Selected
Publications
Selected
Publications
Total: 153
As Published In...
Language Barriers and Access to Hospital Patient Portals in the US. JAMA Netw Open. 2025 Oct 1;8(10):e2537864.
Chen DW, Watanabe M, Xie S, Huston-Paterson HH, Banerjee M, Haymart MR.
ABSTRACT
Importance: Although patient portals are becoming important tools in health care delivery, there is a lack of published data on the language accessibility of these digital platforms.
Objective: To examine the language accessibility of hospitals' patient portals.
Design, setting, and participants: This cross-sectional study identified 51 counties in the 17 US states (5 western states, 2 midwestern, 4 northeastern, and 6 southern) with at least 300 000 residents with limited English proficiency. From eligible hospitals with public-facing patient portal platforms, the following data were obtained between September and December 2024: the URL (uniform resource locator) and language accessibility of the patient portal (ie, of the login prompts), portal vendor, and whether the availability of secure portal messaging was explicitly described.
Main outcomes and measures: The primary outcome was language accessibility of the portal login page (binary variable: only English vs in at least 2 languages). Multivariable logistic regression analysis was performed to determine factors associated with accessibility of the portal login page in at least 2 languages.
Results: Among 514 eligible hospitals (194 [38.0%] in West census region), 511 (99.4%) had public-facing patient portal platforms and were thus included in the analytic cohort; 429 (84.0%) were nonteaching hospitals. Patient portals were accessible in only English at 150 hospitals (29.4%); in English and Spanish only at 305 hospitals (59.7%); and in English, Spanish, and at least 1 additional language at 56 hospitals (10.9%). Only 24 of the 511 hospitals (4.7%) offered portal access in the most common non-English, non-Spanish language of their respective counties. In multivariable logistic regression analysis, teaching hospitals had higher odds of offering portals with multilingual accessibility (odds ratio [OR], 2.21; 95% CI, 1.66-2.95) compared with nonteaching hospitals, while hospitals that used vendors other than Epic MyChart or Cerner had lower odds (OR 0.34; 95% CI, 0.24-0.48 vs Epic).
Conclusions and relevance: In this cross-sectional study of hospitals in 17 states, only a small proportion offered patient portals that were accessible in a non-English, non-Spanish language. As digital health care continues to evolve, prioritizing language accessibility in its design is essential to ensure inclusivity for all patients.
DOI:Â 10.1001/jamanetworkopen.2025.37864
PubMed ID: 41100083
Partnering With Patients to Conduct High-Quality Research - Where Have We Been and Where Are We Going? Health Expect. 2025 Oct;28(5):e70414.
Whibley D, Merritt G, Haymart M, Piechowski P, Larkin K, Williams D.
Unravelling the rise in thyroid cancer incidence and addressing overdiagnosis. Nat Rev Endocrinol. 2025 Sep 3.
Chen DW, Haymart MR.
Hypothyroidism: A Review. JAMA. 2025 Sep 3.Â
Chaker L, Papaleontiou M.
ABSTRACT
Importance: Hypothyroidism is a disease of thyroid hormone deficiency. The prevalence ranges from 0.3% to 12% worldwide, depending on iodine intake, and it is more common in women and older adults. Untreated hypothyroidism can cause serious health complications such as heart failure and myxedema coma.
Observations: Hashimoto thyroiditis (an autoimmune disease) is the cause of primary hypothyroidism in up to 85% of patients with hypothyroidism living in areas with adequate nutritional iodine levels. The risk of developing hypothyroidism is associated with genetic factors (having a first-degree relative with hypothyroidism), environmental factors (iodine deficiency), undergoing neck surgery or receiving radiation therapy, pregnancy in the setting of underlying autoimmune thyroid disease, and with the use of certain medications (eg, immune checkpoint inhibitors and amiodarone). Patients with hypothyroidism may have nonspecific symptoms due to metabolic slowing, including fatigue (68%-83%), weight gain (24%-59%), cognitive issues (45%-48%) such as memory loss and difficulty concentrating, and menstrual irregularities (approximately 23%) such as oligomenorrhea and menorrhagia. Hypothyroidism can cause insulin resistance and hyperglycemia in patients with diabetes, increase the risk for cardiovascular events, such as heart failure, and negatively affect female reproductive health, causing disrupted ovulation, infertility, and increased risk of miscarriage. Untreated hypothyroidism may progress to severe hypothyroidism with decompensation (myxedema coma), which is a condition associated with hypothermia, hypotension, and altered mental status that requires treatment in an intensive care unit and has a mortality rate of up to 30%. Hypothyroidism is diagnosed based on biochemical testing; a high thyrotropin (TSH) level and a low free thyroxine (T4) level indicate overt primary hypothyroidism. Screening for hypothyroidism is not recommended for asymptomatic individuals. Targeted testing is recommended for patients who are considered high risk (eg, patients with type 1 diabetes). First-line treatment for hypothyroidism is synthetic levothyroxine to normalize thyrotropin levels. Initial dosages should be tailored to patient-specific factors. Lower starting doses should be used for older patients or those with atrial fibrillation and coronary artery disease. Thyrotropin monitoring should be performed 6 to 8 weeks after initiating levothyroxine treatment, or when changing the dose, and then annually once the thyrotropin level is at goal to avoid overtreatment or undertreatment, both of which are associated with cardiovascular health risks.
Conclusions and relevance: Hypothyroidism may be associated with fatigue, weight gain, memory loss, difficulty concentrating, cardiovascular disease such as heart failure, menstrual irregularities, infertility, and increased risk of miscarriage. Levothyroxine is the first-line treatment to normalize the thyrotropin level and improve clinical manifestations due to hypothyroidism.
PubMed ID: 40900603
Neck Ultrasound in Older Adults With Thyroid Nodules: Considering Risk of Death From Other Causes. Endocr Pract. 2025 Sep;31(9):1105-1109.
Francis-Levin N, Shao E, Ortlieb J, Gay B, Banerjee M, Papaleontiou M, Haymart MR.
ABSTRACT
Objective: Thyroid nodules are common in older adults with the majority being benign. Optimal use of neck ultrasound for nodule surveillance in older adults, particularly in the setting of comorbidities and competing causes of death, remains unknown. We aimed to evaluate the use of neck ultrasound for thyroid nodule surveillance in older adults and to assess subsequent cause of death.
Methods: We used a dataset that combines the Centers for Medicare & Medicaid Services data with the health data of University of Michigan Medicine patients between 2016 and 2021. We identified patients aged ≥ 65 with thyroid nodule(s) (median follow-up 2 years, range 0-6 years). Demographic characteristics, number of comorbidities (range 0-6), frequency of neck ultrasound, and cause of death were analyzed.
Results: Of the 18 001 patients diagnosed with thyroid nodules, median age was 75 years (range 65-105), and 71.2% were female. Only 29 (0.2%) died of thyroid cancer and 2387 (13.3%) died of other causes. Patients who died of other causes had more comorbidities (mean comorbidities 1.73, range 0-5 vs mean comorbidities in entire cohort 1.2, range 0-6). During the study period, those who died of other causes received a mean of 1.31 neck ultrasounds (range 0-12) whereas the rest of the cohort received a mean of 2.41 neck ultrasounds (range 0-26), P < .001.
Conclusions: Older adults with thyroid nodules are more likely to die of causes other than thyroid cancer. Neck ultrasound for surveillance should be tailored to the patient, with consideration for comorbidities and life expectancy.
DOI: 10.1016/j.eprac.2025.06.007
PubMed ID: 40663032
2025 American Thyroid Association Management Guidelines for Adult Patients with Differentiated Thyroid Cancer. Thyroid. 2025 Aug;35(8):841-985.
Ringel MD, Sosa JA, Baloch Z, Bischoff L, Bloom G, Brent GA, Brock PL, Chou R, Flavell RR, Goldner W, Grubbs EG, Haymart M, Larson SM, Leung AM, Osborne J, Ridge JA, Robinson B, Steward DL, Tufano RP, Wirth LJ.
ABSTRACT
Background: Differentiated thyroid cancer (DTC) is the most prevalent cancer of thyroid and is among the most frequently diagnosed cancers in the United States. The practice guidelines of the American Thyroid Association (ATA) for DTC management in adult patients (previously combined with thyroid nodules) were published initially in 1996, with subsequent revisions based on advances in the field. The goal of this update is to provide clinicians, patients, researchers, and those involved in health policy with rigorous, comprehensive, and contemporary guidelines to assist in the management of adult patients with DTC, emphasizing the patient journey beginning with a thyroid cancer diagnosis. Methods: The questions addressed were based, in part, on prior versions of the guidelines, with input from a larger, more diverse complement of stakeholders. The panel included members from multiple specialties involved in thyroid cancer care, including a patient advocate and an expert in systematic reviews/meta-analyses/guidelines who educated and supported task force members. The panel conducted systematic literature reviews to inform the recommendations and commissioned two additional systematic reviews. Published English-language articles were eligible for inclusion, with a final search date of July 1, 2024. A modified Grading of Recommendations Assessment, Development and Evaluation system was used for critical appraisal of evidence and determining the quality of data. The guidelines panel had editorial independence from the ATA. Competing interests of task force members were pre-vetted, regularly updated, communicated with task force members, and assessed and managed by ATA leadership and the Clinical Practice Guidelines and Statements Committee. Results: These revised guidelines begin with the initial cancer diagnosis and continue with recommendations for staging and risk assessment, initial treatment decisions, assessment of treatment responses, monitoring approaches, diagnostic testing, and subsequent therapies based on the strength of evidence for response and consideration of side effects and outcomes. Patient-reported outcomes and identified areas of need for additional high-quality research are highlighted. Conclusions: These revised evidence-based recommendations inform clinical decision-making in the management of DTC that reflect the changing science and optimize the evidence-based clinical care of patients throughout their journey with DTC. Critical areas of need for additional research are highlighted.
DOI: 10.1177/10507256251363120
PubMed ID: 40844370
Use of Neck Ultrasound as Surveillance in Older Adults With Thyroid Cancer. Endocr Pract. 2025 Aug;31(8):1033-1037.
Francis-Levin N, Shao E, Ortlieb J, Gay B, Banerjee M, Papaleontiou M, Haymart MR.
ABSTRACT
Objective: Close to one-quarter of thyroid cancers occur in older adults (ie, aged ≥ 65). This group also has other comorbidities and higher risk of death from other causes. Data on optimal neck ultrasound use for thyroid cancer surveillance in older adults are limited.
Methods: We identified patients aged ≥ 65 years diagnosed with thyroid cancer using data from the Centers for Medicare & Medicaid Services linked to health data from University of Michigan between 2016-2021 (median follow-up 3 years, range 0-6 years). We assessed demographic characteristics, comorbidities, frequency of neck ultrasound, and cause of death.
Results: Of the 2007 patients diagnosed with thyroid cancer, median age was 74 years (range 65-100) and 65.1% were female. Overall, 76 (3.8%) died of thyroid cancer, and 259 (12.9%) died of other causes. There were more comorbidities in the cohort who died of other causes during the study period, eg, 179 (69.1%) in the cohort who died of other causes had heart disease compared with 868 (43.3%) of those in the entire cohort. Patients who died of other causes received a mean of 1.36 neck ultrasounds (range 0-12) and the remainder of the cohort received a mean of 2.38 neck ultrasounds (range 0-26) during the study period, P < .001.
Conclusions: Older adults with thyroid cancer are more likely to die of causes other than thyroid cancer. To improve high-value care in older adults with thyroid cancer and high-risk of death from other causes, there is need for individualized plans for neck ultrasound use.
DOI: 10.1016/j.eprac.2025.04.020
PubMed ID: 40316140
NCCN Guidelines® Insights: Thyroid Carcinoma, Version 1.2025 J Natl Compr Canc Netw. 2025 Jul;23(7):e250033.
Haddad RI, Bischoff L, Applewhite M, Bernet V, Blomain E, Brito M, Busaidy NL, Campbell M, DeLozier O, Duh QY, Ehya H, Grady E, Guo T, Haymart M, Hunt JP, Kandeel F, Kotwal A, Lamonica DM, Lorch J, Mandel SJ, Markovina S, Mydlarz W, Nabell L, Raeburn CD, Rezaee R, Ridge JA, Ritter H, Roth MY, Salgado SA, Scheri RP, Shah JP, Sipos JA, Sippel R, Sturgeon C, Wirth LJ, Wong RJ, Worden F, Yeh MW, Darlow S, Cassara CJ, Sliker B.
ABSTRACT
The NCCN Guidelines for Thyroid Carcinoma address the management of different types of thyroid carcinoma, including papillary, follicular, oncocytic, medullary, and anaplastic carcinoma. The NCCN Thyroid Carcinoma Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights focus on the panel's most recent recommendations regarding systemic therapies for thyroid carcinoma as well as the supporting clinical data.
PubMed ID: 40639400
Considerations in the Diagnosis and Management of Thyroid Dysfunction in Older Adults. Thyroid. 2025 Jun;35(6):624-632.
Jasim S, Papaleontiou M.
ABSTRACT
Background: Thyroid dysfunction is common in older adults and poses diagnostic and management challenges for clinicians. In this narrative review, we present published data focusing on special considerations in the diagnosis and management of hypothyroidism and hyperthyroidism in older adults. Methods: A comprehensive literature search of the PubMed and Ovid MEDLINE databases was conducted from January 2000 to December 2024 to identify pertinent articles in English for this narrative review. Results: Due to significant cardiovascular risk if untreated, both overt hypothyroidism and hyperthyroidism should be treated in older adults. Findings from observational studies do not support treating older adults with subclinical hypothyroidism with a thyrotropin (TSH) <7 mIU/L. However, observational data have demonstrated an increased risk of cardiovascular mortality and stroke in older adults with subclinical hypothyroidism with TSH 7.0-9.9 mIU/L and of coronary heart disease, cardiovascular mortality, and heart failure in those with TSH ≥10 mIU/L, suggesting levothyroxine treatment in these individuals should be considered. Data from clinical trials failed to show improvement with levothyroxine in hypothyroidism symptoms or fatigue in older adults with subclinical hypothyroidism compared with placebo. Over- and under-replacement with thyroid hormone is common and should be avoided, as population-based studies have shown associations with adverse cardiovascular and skeletal events. Subclinical hyperthyroidism with a TSH <0.1 mIU/L should be treated in older individuals as it has been associated with increased cardiovascular risk and bone density loss based on observational data. Randomized controlled trials have shown that long-term low-dose methimazole is a viable alternative to radioactive iodine in older adults with hyperthyroidism. Conclusions: A personalized approach should be undertaken in the diagnosis and management of thyroid dysfunction in older adults. Multiple factors should be considered, including physiological age-related changes in thyroid function, comorbidities, and polypharmacy. Care should be taken to maintain euthyroidism in order to avoid adverse events.
PubMed ID: 40376729
Letter to the Editor: New Current Procedural Terminology Codes for Radiofrequency Ablation of Thyroid Nodules Will Negatively Affect American Patients According to the Executive Council of the North American Society for Interventional Thyroidology. Thyroid. 2025 Feb;35(2):225-226.
Russell JO, Huber T, Noel J, Papaleontiou M, Baldwin CK, Banuchi VM, Dhillon V, Dream S, Hodak SP, Kandil E, Kuo JH, Patel KN, Sinclair CF, Tufano RP. Â
Physician-reported barriers and facilitators to thyroid hormone deprescribing in older adults. J Am Geriatr Soc. 2025 Feb;73(2):566-573.Â
Moretti B, Livecchi R, Taylor SR, Pitt SC, Gay BL, Haymart MR, Bhan A, Perkins J, Papaleontiou M.
ABSTRACT
Background: Thyroid hormone is one of the most commonly prescribed medications in the United States. Misuse of and overtreatment with thyroid hormone is common in older adults and can lead to cardiovascular and skeletal adverse events. Even though deprescribing can reduce inappropriate care, no studies have yet explored specific barriers and facilitators to guide thyroid hormone deprescribing in older adults (defined as discontinuation of thyroid hormone when initiated without an appropriate indication or dose reduction in those overtreated).
Methods: We conducted semi-structured interviews with 19 endocrinologists, geriatricians, and primary care physicians who prescribe thyroid hormone. Interviews were completed between July 2020 and December 2021 via two-way video conferencing. We used both an inductive and deductive content analysis guided by the Theoretical Domains Framework to evaluate transcribed and coded participant responses. Thematic analysis characterized themes related to barriers and facilitators to thyroid hormone deprescribing practices in older adults.
Results: The most commonly reported barriers to thyroid hormone deprescribing were related to patient-level factors, followed by physician- and system-level factors. Patient factors included patients' perceived need for thyroid hormone use and patient anxiety/concerns about potential side effects related to thyroid hormone dose reduction, patient lack of knowledge, and misinformation regarding deprescribing. Physician- and system-level barriers included clinic visit time constraints, physician inertia, physician lack of knowledge about deprescribing, perceived lack of sufficient patient follow-up, and electronic health record limitations. The most prominent physician-reported facilitators to thyroid hormone deprescribing were effective physician-to-patient communication, and positive physician-patient relationship, including patients' trust in their treating physician.
Conclusion: Barriers and facilitators to thyroid hormone deprescribing in older adults were reported at multiple levels including patient-, physician-, and system-level factors. Interventions to improve thyroid hormone deprescribing in older adults should aim to improve patient education and expectations, increase multidisciplinary physician awareness, and overcome physician inertia.
DOI:Â 10.1111/jgs.19219
PubMed ID: 39392046
Performance of Afirma Genomic Sequencing Classifier in Binary Subcategories of Atypia of Undetermined Significance Thyroid Nodules: Single Versus Repeat Diagnosis. Thyroid. 2025 Jan;35(1):41-49.Â
Jin X, Broome DT, Lew M, Heider A, Haymart MR, Papaleontiou M, Chen D, Iyengar JJ, Esfandiari N, Sandouk Z, Douyon L, Hughes DT, Smola B, Jing X.
ABSTRACT
Background: Afirma Genomic Sequencing Classifier (GSC) testing has been utilized for further risk stratification of thyroid nodules categorized as atypia of undetermined significance (AUS). The 2023 Bethesda system subcategorizes AUS diagnosis into AUS with nuclear atypia (AUS-N) and other atypia (AUS-O). The current study aims to determine if performance of GSC testing differs between the two AUS subcategories and between single AUS cohort and repeat AUS cohort. Methods: This retrospective study analyzed consecutive thyroid nodule fine-needle aspiration with a single or a repeat AUS diagnosis and a diagnostic GSC testing result (benign vs. suspicious). All AUS nodules were divided into AUS-N or AUS-O subcategory and followed by either surgical intervention or at least 12 months of clinical and/or ultrasound monitoring. We then assessed performance of GSC testing in each subcategory and subsequently compared the individual performance in AUS-N or AUS-O subcategory between single AUS cohort and repeat AUS cohort. Results: The study identified a total of 365 thyroid nodules subcategorized as AUS-N (N = 106) and AUS-O (N = 259). Both cohorts showed a significantly lower GSC benign call rate (BCR) in AUS-N nodules compared with AUS-O nodules (43% vs. 71% in single AUS, p = 0.001; 58% vs. 74% in repeat AUS, p = 0.02). The proportion of histology-proven malignancies associated with a suspicious GSC result tended to be greater in AUS-N nodules than AUS-O nodules (28% vs. 10% in single AUS, p = 0.09; 38% vs. 27% in repeat AUS, p = 0.3). Compared with AUS-N nodules, AUS-O cohorts demonstrated significantly higher specificity in the single AUS group (73% vs. 51%, p = 0.01). In both subcategories, the repeat AUS cohort yielded greater specificity, positive predictive value, and diagnostic accuracy compared with the single AUS group. However, the differences did not reach statistical significance. Conclusions: GSC BCR and diagnostic performance of GSC testing may vary in AUS-N versus AUS-O subcategories. However, there were no statistically significant differences in GSC performance between single and repeat AUS cohorts.
DOI:Â 10.1089/thy.2024.0277
PubMed ID: 39630538
Examining Why Thyroid Cancer Incidence Is High in Women. Thyroid. 2024 Dec;34(12):1449-1450.
Sinha SH, Haymart MR.
Thyroid Function and Cognitive Decline: A Narrative Review. Endocr Pract. 2024 Nov;30(11):1113-1118.
Sinha SH, Zietlow K, Papaleontiou M.
ABSTRACT
Objective: As the population of older adults in the United States continues to rise, understanding modifiable risk factors that contribute to cognitive decline and dementia becomes increasingly important. This narrative review summarizes existing literature on the association between thyroid function in the euthyroid range, hypothyroidism and hyperthyroidism, and cognitive outcomes in older adults.
Methods: A comprehensive literature search of the PubMed and Ovid/Medline databases was conducted. Randomized controlled trials, systematic reviews, meta-analyses, and observational studies published in English between January 2000 and December 2023 were included.
Results: Overall, existing studies yielded conflicting results, failing to delineate a concrete relationship between thyroid function and cognitive outcomes and/or dementia in older adults. There may be a possible association between higher thyroid stimulating hormone in the reference range and lower risk of incident dementia, which may be more pronounced in women. Majority of studies elucidated a possible association between low thyroid stimulating hormone and incident dementia, with suggestion that duration of hyperthyroidism may contribute to increasing dementia risk. Even though evidence on the association of hypothyroidism and cognitive decline are disparate, current data do not support treatment of subclinical hypothyroidism to improve cognitive outcomes in older adults.
Conclusion: Despite numerous studies, there is no conclusive evidence that supports a direct relationship between hyperthyroidism or hypothyroidism and cognitive decline. Study limitations include heterogeneity in study designs, measurement methodologies, and cognitive assessment tools. Future research is needed to better delineate whether an association exists and whether treatment of thyroid dysfunction ameliorates cognitive impairment.
DOI:Â 10.1016/j.eprac.2024.07.013
PubMed ID: 39111592
Endocrine Disorders During Pregnancy. Endocrinol Metab Clin North Am. 2024 Sep;53(3):xv-xvii.
Pessah-Pollack R, Papaleontiou M.
Survival Prognostication in Patients with Differentiated Thyroid Cancer and Distant Metastases: A SEER Population-Based Study. Thyroid. 2024 Jul;34(7):837-845.Â
Chen DW, Carr G, Worden FP, Veenstra CM, Haymart MR, Banerjee M.
ABSTRACT
Background: For patients with thyroid cancer, distant metastasis is a significant predictor of poor outcome. Since distant metastasis occurs in less than 10% of patients with differentiated thyroid cancer, correlates of survival in this vulnerable patient population remain understudied. This study aimed to identify prognostic groups among patients with differentiated thyroid cancer and distant metastases and to determine the role of, and interactions between, patient and tumor characteristics in determining survival. Methods: We identified adult patients diagnosed with differentiated thyroid cancer with distant metastases from the U.S. SEER-17 cancer registry (2010-2019). Analyses were performed using Cox proportional hazards regression, survival trees, and random survival forest. Relative importance of patient and tumor factors important for disease-specific and overall survival was assessed based on the random survival forest analyses. Results: Cohort consisted of 2411 patients with differentiated thyroid cancer with distant metastases followed for a median of 62 months. Most common histopathologic subtype (86.0%) was papillary thyroid cancer, and the most common sites of distant metastasis were the lungs (33.7%) and bone (18.9%). Cox proportional hazards model illustrated significant associations between survival and the following: patient age (p < 0.001), tumor size (p < 0.01), and site of distant metastasis (p < 0.05). Survival tree analyses identified three distinct prognostic groups based on disease-specific survival (DSS) (5-year survival of the prognostic groups was 92%, 64%, and 41%; p < 0.001) and four distinct prognostic groups based on overall survival (OS) (5-year survival of the prognostic groups was 96%, 84%, 57%, and 31%; p < 0.001). The first split in the survival trees for DSS and OS was by age at diagnosis (≤57 years vs. ≥58 years) with subsequent splits based on presence/absence of lung metastases, tumor size (≤4 cm vs. >4 cm), and patient age. A total of 558 patients (23.1%) died from thyroid cancer, and 757 patients (31.4%) died from all causes during the study period. Conclusions: This study identifies distinct prognostic groups for patients with differentiated thyroid cancer with distant metastases and highlights the importance of patient age, lung metastases, and tumor size for determining both disease-specific and overall survival. These findings inform risk stratification and treatment decision-making in this understudied patient population.
DOI:Â 10.1089/thy.2023.0709
PubMed ID: 38757633
Access to New Clinic Appointments for Patients With Cancer. JAMA Netw Open. 2024 Jun 3;7(6):e2415587.Â
Chen DW, Banerjee M, Gay B, Wang YC, Miranda L, Watanabe M, Veenstra CM, Haymart MR.
ABSTRACT
Importance: Racial and ethnic disparities have been observed in the outpatient visit rates for specialist care, including cancer care; however, little is known about patients' experience at the critical step of attempting to access new clinic appointments for cancer care.
Objective: To determine simulated English-speaking, Spanish-speaking, and Mandarin-speaking patient callers' ability to access new clinic appointments for 3 cancer types (colon, lung, and thyroid cancer) that disproportionately impact Hispanic and Asian populations.
Design, setting, and participants: This cross-sectional audit study was conducted between November 2021 and March 2023 using 479 clinic telephone numbers that were provided by the hospital general information personnel at 143 hospitals located across 12 US states. Using standardized scripts, trained research personnel assigned to the roles of English-speaking, Spanish-speaking, and Mandarin-speaking patients called the telephone number for a clinic that treats colon, lung, or thyroid cancer to inquire about a new clinic appointment. Data analysis was conducted from June to September 2023.
Main outcomes and measures: The primary outcome was whether the simulated patient caller was able to access cancer care (binary variable, yes or no), which was defined to include being provided with a clinic appointment date or scheduling information. Multivariable logistic regression analysis was performed to determine factors independently associated with simulated patient callers being able to access cancer care.
Results: Of 985 total calls (399 English calls; 302 Spanish calls; 284 Mandarin calls), simulated patient callers accessed cancer care in 409 calls (41.5%). Differences were observed based on language type, with simulated English-speaking patient callers significantly more likely to access cancer care compared with simulated Spanish-speaking and Mandarin-speaking patient callers (English, 245 calls [61.4%]; Spanish, 110 calls [36.4%]; Mandarin, 54 calls [19.0%]; P < .001). A substantial number of calls ended due to linguistic barriers (291 of 586 Spanish or Mandarin calls [49.7%]) and workflow barriers (239 of 985 calls [24.3%]). Compared with English-speaking simulated patient callers, the odds of accessing cancer care were lower for Spanish-speaking simulated patient callers (adjusted odds ratio [aOR], 0.34; 95% CI, 0.25-0.46) and Mandarin-speaking simulated patient callers (aOR, 0.13; 95% CI, 0.09-0.19). Compared with contacting clinics affiliated with teaching hospitals, callers had lower odds of accessing cancer care when contacting clinics that were affiliated with nonteaching hospitals (aOR, 0.53; 95% CI, 0.40-0.70).
Conclusions and relevance: In this cross-sectional audit study, simulated patient callers encountered substantial barriers when attempting to access clinic appointments for cancer care. These findings suggest that interventions focused on mitigating these barriers are necessary to increase access to cancer care for all patients.
DOI: 10.1001/jamanetworkopen.2024.15587
PubMed ID: 38848062
Access to New Clinic Appointments for Patients With Cancer. JAMA Netw Open. 2024 Jun 3;7(6):e2415587.Â
Chen DW, Banerjee M, Gay B, Wang YC, Miranda L, Watanabe M, Veenstra CM, Haymart MR.
ABSTRACT
Importance: Racial and ethnic disparities have been observed in the outpatient visit rates for specialist care, including cancer care; however, little is known about patients' experience at the critical step of attempting to access new clinic appointments for cancer care.
Objective: To determine simulated English-speaking, Spanish-speaking, and Mandarin-speaking patient callers' ability to access new clinic appointments for 3 cancer types (colon, lung, and thyroid cancer) that disproportionately impact Hispanic and Asian populations.
Design, setting, and participants: This cross-sectional audit study was conducted between November 2021 and March 2023 using 479 clinic telephone numbers that were provided by the hospital general information personnel at 143 hospitals located across 12 US states. Using standardized scripts, trained research personnel assigned to the roles of English-speaking, Spanish-speaking, and Mandarin-speaking patients called the telephone number for a clinic that treats colon, lung, or thyroid cancer to inquire about a new clinic appointment. Data analysis was conducted from June to September 2023.
Main outcomes and measures: The primary outcome was whether the simulated patient caller was able to access cancer care (binary variable, yes or no), which was defined to include being provided with a clinic appointment date or scheduling information. Multivariable logistic regression analysis was performed to determine factors independently associated with simulated patient callers being able to access cancer care.
Results: Of 985 total calls (399 English calls; 302 Spanish calls; 284 Mandarin calls), simulated patient callers accessed cancer care in 409 calls (41.5%). Differences were observed based on language type, with simulated English-speaking patient callers significantly more likely to access cancer care compared with simulated Spanish-speaking and Mandarin-speaking patient callers (English, 245 calls [61.4%]; Spanish, 110 calls [36.4%]; Mandarin, 54 calls [19.0%]; P < .001). A substantial number of calls ended due to linguistic barriers (291 of 586 Spanish or Mandarin calls [49.7%]) and workflow barriers (239 of 985 calls [24.3%]). Compared with English-speaking simulated patient callers, the odds of accessing cancer care were lower for Spanish-speaking simulated patient callers (adjusted odds ratio [aOR], 0.34; 95% CI, 0.25-0.46) and Mandarin-speaking simulated patient callers (aOR, 0.13; 95% CI, 0.09-0.19). Compared with contacting clinics affiliated with teaching hospitals, callers had lower odds of accessing cancer care when contacting clinics that were affiliated with nonteaching hospitals (aOR, 0.53; 95% CI, 0.40-0.70).
Conclusions and relevance: In this cross-sectional audit study, simulated patient callers encountered substantial barriers when attempting to access clinic appointments for cancer care. These findings suggest that interventions focused on mitigating these barriers are necessary to increase access to cancer care for all patients.
DOI: 10.1001/jamanetworkopen.2024.15587
PubMed ID: 38848062
The Potential of Wearable Devices in Cancer Care Delivery. JAMA Oncol. 2024 May 1;10(5):573-574.
Hawley ST, Haymart MR.Â
Team-Based Care for Thyroid Cancer: What Is the Role of the Primary Care Physician? Endocr Pract. 2024 May;30(5):476-478.
Radhakrishnan A, Haymart MR.
Levothyroxine Prescribing: Why Simple Is so Complex. J Clin Endocrinol Metab. 2024 Apr 19;109(5):e1406-e1407.
Esfandiari NH, Papaleontiou M.
All-Cause and Cause-Specific Mortality Among Low-Risk Differentiated Thyroid Cancer Survivors in the United States. Thyroid. 2024 Feb;34(2):215-224.
Tran TV, Schonfeld SJ, Pasqual E, Haymart MR, Morton LM, Kitahara CM.
ABSTRACT
Background: Despite the excellent disease-specific survival associated with low-risk differentiated thyroid cancer (DTC), its diagnosis and management have been linked to patient concerns about cancer recurrence, treatment-related health risks, and mortality. Lack of information regarding long-term health outcomes can perpetuate these concerns. Therefore, we assessed all-cause and cause-specific mortality in a large cohort of individuals diagnosed with low-risk DTC. Methods: From the U.S. Surveillance, Epidemiology, and End Results-12 cancer registry database (1992-2019), we identified 51,854 individuals (81.8% female) diagnosed with first primary DTC at low risk of recurrence (≤4 cm, localized). We estimated cause-specific cumulative mortality by time since diagnosis, accounting for competing risks. Standardized mortality ratios (SMRs) and CIs were used to compare observed mortality rates in DTC patients with expected rates in the matched U.S. general population, overall and by time since DTC diagnosis. We used Cox proportional hazards models to examine associations between radioactive iodine (RAI) treatment and cause-specific mortality. Results: During follow-up (median = 8.8, range 0-28 years), 3467 (6.7%) deaths were recorded. Thyroid cancer accounted for only 4.3% of deaths (n = 148). The most common causes of death were malignancies (other than thyroid cancer) (n = 1031, 29.7%) and cardiovascular disease (CVD; n = 912, 26.3%). The 20-year cumulative mortality rate from thyroid cancer, malignancies (other than thyroid or nonmelanoma skin cancer), and CVD was 0.6%, 4.6%, and 3.9%, respectively. Lower than expected mortality was observed for all causes excluding thyroid cancer (SMR = 0.69 [CI 0.67-0.71]) and most specific causes, including all malignancies combined (other than thyroid cancer; SMR = 0.80 [CI 0.75-0.85]) and CVD (SMR = 0.64 [CI 0.60-0.69]). However, mortality rates were elevated for specific cancers, including pancreas (SMR = 1.58 [CI 1.18-2.06]), kidney and renal pelvis (SMR = 1.85 [CI 1.10-2.93]), and brain and other nervous system (SMR = 1.62 [CI 0.99-2.51]), and myeloma (SMR = 2.35 [CI 1.46-3.60]) and leukemia (SMR = 1.62 [CI 1.07-2.36]); these associations were stronger ≥10 years after diagnosis. RAI was not associated with risk of cause-specific death, but numbers of events were small and the range of administered activities was likely narrow. Conclusions: Overall, our findings provide reassurance regarding low overall and cause-specific mortality rates in individuals with low-risk DTC. Additional research is necessary to confirm and understand the increased mortality from certain subsequent cancers.
PubMed ID: 38149602
Disentangling the Association Between Excess Thyroid Hormone and Cognition in Older Adults. JAMA Intern Med. 2023 Dec 1;183(12):1332-1333.Â
Papaleontiou M, Brito JP.
Updates in thyroid healthcare delivery: advancing patient-centered care. Curr Opin Endocrinol Diabetes Obes. 2023 Oct 1;30(5):217.
Papaleontiou M, Haymart MR.
General Principles for the Safe Performance, Training, and Adoption of Ablation Techniques for Benign Thyroid Nodules: An American Thyroid Association Statement. Thyroid. 2023 Oct;33(10):1150-1170.Â
Sinclair CF, Baek JH, Hands KE, Hodak SP, Huber TC, Hussain I, Lang BH, Noel JE, Papaleontiou M, Patel KN, Russ G, Russell J, Spiezia S, Kuo JH.
ABSTRACT
Background: The primary goal of this interdisciplinary consensus statement is to provide a framework for the safe adoption and implementation of ablation technologies for benign thyroid nodules.
Summary: This consensus statement is organized around three key themes: (1) safety of ablation techniques and their implementation, (2) optimal skillset criteria for proceduralists performing ablative procedures, and (3) defining expectations of success for this treatment option given its unique risks and benefits. Ablation safety considerations in pre-procedural, peri-procedural, and post-procedural settings are discussed, including clinical factors related to patient selection and counseling, anesthetic and technical considerations to optimize patient safety, peri-procedural risk mitigation strategies, post-procedural complication management, and safe follow-up practices. Prior training, knowledge, and steps that should be considered by any physician who desires to incorporate thyroid nodule ablation into their practice are defined and discussed. Examples of successful clinical practice implementation models of this emerging technology are provided.
Conclusions: Thyroid ablative procedures provide valid alternative treatment strategies to conventional surgical management for a subset of patients with symptomatic benign thyroid nodules. Careful patient and nodule selection are critical to the success of these procedures as is extensive pre-procedural patient counseling. Although these emerging technologies hold great promise, they are not without risk and require the development of a unique skillset and environment for optimal, safe performance and consistent outcomes.
PubMed ID: 37642289
Hidden Disparities: How Language Influences Patients' Access to Cancer Care. J Natl Compr Canc Netw. 2023 Sep;21(9):951-959.e1.
Chen DW, Banerjee M, He X, Miranda L, Watanabe M, Veenstra CM, Haymart MR.
ABSTRACT
Background: Patients with limited English proficiency, a vulnerable patient population, remain understudied in the literature addressing cancer disparities. Although it is well documented that language discordance between patients and physicians negatively impacts the quality of patient care, little is known about how patients' preferred spoken language impacts their access to cancer care.
Patients and methods: Between November 2021 and June 2022, we conducted an audit study of 144 hospitals located across 12 demographically diverse states. Using a standardized script, trained investigators assigned to the roles of English-speaking, Spanish-speaking, and Mandarin-speaking patients called the hospital general information telephone line seeking to access care for 3 cancer types that disproportionately impact Hispanic and Asian populations (colon, lung, and thyroid cancer). Primary outcome was whether the simulated patient caller was provided with the next steps to access cancer care, defined as clinic number or clinic transfer. We used chi-square tests and logistic regression analysis to test for associations between the primary outcome and language type, region type, hospital teaching status, and cancer care requested. We used multivariable logistic regression analysis to determine factors associated with simulated patient callers being provided the next steps.
Results: Of the 1,296 calls, 52.9% (n=686) resulted in simulated patient callers being provided next steps to access cancer care. Simulated non-English-speaking (vs English-speaking) patient callers were less likely to be provided with the next steps (Mandarin, 27.5%; Spanish, 37.7%; English, 93.5%; P<.001). Multivariable logistic regression found significant associations of the primary outcome with language spoken (Mandarin: odds ratio [OR], 0.02 [95% CI, 0.01-0.04] and Spanish: OR, 0.04 [95% CI, 0.02-0.06] vs English) and hospital teaching status (nonteaching: OR, 0.43 [95% CI, 0.32-0.56] vs teaching).
Conclusions: Linguistic disparities exist in access to cancer care for non-English-speaking patients, emphasizing the need for focused interventions to mitigate systems-level communication barriers.
PubMed ID: 37673110
Real-World Use of Systemic Therapies for the Treatment of Advanced Thyroid Cancers. Endocr Pract. 2023 Nov;29(11):868-874.
Chen DW, Banerjee M, Xu T, Worden FP, Haymart MR.
ABSTRACT
Objective: In the last decade, new systemic treatment options have been made available for patients with advanced thyroid cancer. However, little is known about the real-world utilization of these systemic therapies.
Methods: We used Optum's de-identified Clinformatics® Data Mart Database to characterize trends in the use of 15 systemic therapies that are available for the treatment of advanced thyroid cancer between 2013 and 2021. Joinpoint regression was used to calculate annual percentage changes in the use of systemic therapy by patients' race/ethnicity. The sequence of therapies was determined by the date of prescription claims.
Results: Between 2013 and 2021, the annual number of patients treated for advanced thyroid cancer with systemic therapy increased from 45 patients in 2013 to 114 patients in 2021 (N of total cohort = 885). Most patients were female (54.7%) and non-Hispanic White (62.1%). Between 2013 and 2021, there was a significant decrease in the proportion of non-Hispanic White patients treated for advanced thyroid cancer with systemic therapy (annual percentage change -3.9%, 95% confidence intervals, -6.0% to -1.8%). Since its approval by the US Food and Drug Administration (FDA) in 2015, lenvatinib remains the most frequently prescribed first-line therapy for the treatment of radioiodine-refractory thyroid cancer (48.8% of patients between 2017 and 2021). Between 2017 and 2021, most patients (79.7%) were initiated on 1 of the 10 FDA-approved agents and 81.7% received only a first-line therapy.
Conclusions: Between 2013 and 2021, the use of systemic treatment options for advanced thyroid cancer increased significantly, largely driven by the prescription of lenvatinib following its approval by the FDA in 2015, with an increasing trend for use in non-White patients.
DOI: 10.1016/j.eprac.2023.08.005
PubMed ID: 37619826
Performance of Afirma genomic sequencing classifier and histopathological outcome in Bethesda category III thyroid nodules: Initial versus repeat fine-needle aspiration. Diagn Cytopathol. 2023 Nov;51(11):698-704.
Jin X, Lew M, Pantanowitz L, Iyengar JJ, Haymart MR, Papaleontiou M, Broome D, Sandouk Z, Raja SS, Hughes DT, Smola B, Jing X.
ABSTRACT
Background: There is limited data comparing the performance of Afirma Genomic Sequencing Classifier (GSC) in thyroid nodules carrying an initial versus a repeat diagnosis of atypia of undetermined significance (AUS). This study reported an institutional experience in this regard.
Materials and methods: This retrospective study included consecutive thyroid nodules that had an initial or a repeat AUS diagnosis and had a subsequent GSC diagnostic result (benign or suspicious) from 2017 to 2021. All nodules were followed by surgical intervention or by clinical and/or ultrasound monitoring. GSC's benign call rate (BCR), rate of histology-proven malignancy associated with a suspicious GSC result, and diagnostic parameters of GSC were calculated and compared between the two cohorts (initial versus repeat AUS). Statistical significance was defined with a p-value of <.05 for all analysis.
Results: A total of 202 cases fulfilled inclusion criteria, including 67 and 135 thyroid nodules with an initial and a repeat AUS diagnosis, respectively. BCR was 67% and 66% in initial and repeat AUS cohorts, respectively. Rate of histology-proven malignancy associated with a suspicious GSC result were 22% and 24% in initial and repeat AUS cohorts, respectively. Compared with the repeat AUS cohort, the initial AUS cohort showed slightly lower sensitivity (83% vs. 100%), specificity (70% vs. 73%), PPV (23% vs. 24%), NPV (98% vs. 100%), and diagnostic accuracy (72% vs. 75%). Nevertheless, these differences did not reach statistical significance.
Conclusion: GSC demonstrated comparable performance in thyroid nodules with a repeat AUS diagnosis versus nodules with an initial AUS diagnosis.
DOI: 10.1002/dc.25203
PubMed ID: 37519144
The psychosocial impact of thyroid cancer. Curr Opin Endocrinol Diabetes Obes. 2023 Oct 1;30(5):252-258.
Haymart P, Levin NJ, Haymart MR.
ABSTRACT
Purpose of review: This review discusses the psychosocial impact of thyroid cancer diagnosis and management. It summarizes recent findings, presents management options, and briefly discusses future directions.
Recent findings: A thyroid cancer diagnosis and its downstream management can impact patients in a variety of ways, including contributing to distress, worry, worse quality of life, and in some cases, anxiety and depression. Racial/ethnic minorities, those with lower education, women, adolescents/young adults, and individuals with a prior mental health conditions are a few of the patient groups at greater risks for adverse psychosocial effects from their thyroid cancer diagnosis and management. Findings are mixed, but some studies suggest treatment, for example, more intensive treatment as opposed to less, may be associated with a greater psychosocial impact. Clinicians providing care to thyroid cancer patients use a variety of resources and techniques, some more effective than others, to provide support.
Summary: A thyroid cancer diagnosis and its subsequent treatment can greatly impact a patient's psychosocial wellbeing, particularly for at-risk groups. Clinicians can help their patients by informing them of the risks associated with treatments and by offering education and resources for psychosocial support.
DOI: 10.1097/med.0000000000000815
PubMed ID: 37288721
Access Denied: Disparities in Thyroid Cancer Clinical Trials. J Endocr Soc. 2023 May 17;7(6):bvad064.
Chen DW, Worden FP, Haymart MR.
ABSTRACT
For thyroid cancer clinical trials, the inclusion of participants from diverse patient populations is uniquely important given existing racial/ethnic disparities in thyroid cancer care. Since 2011, a paradigm shift has occurred in the treatment of advanced thyroid cancer with the approval of multiple systemic therapies by the US Food and Drug Administration based on their use in the clinical trials setting. Although these clinical trials recruited patients from up to 164 sites in 25 countries, the inclusion of racial/ethnic minority patients remained low. In this mini-review, we provide an overview of barriers to accessing cancer clinical trials, framed in the context of why patients with thyroid cancer may be uniquely vulnerable. Multilevel interventions and increased funding for thyroid cancer research are necessary to increase access to and recruitment of under-represented patient populations into thyroid cancer clinical trials.
PubMed ID: 37256092
Management of Advanced Thyroid Cancer: Overview, Advances, and Opportunities. Am Soc Clin Oncol Educ Book. 2023 May;43:e389708.Â
Agosto Salgado S, Kaye ER, Sargi Z, Chung CH, Papaleontiou M.
ABSTRACT
Thyroid cancer is the most common endocrine malignancy with almost one million people living with thyroid cancer in the United States. Although early-stage well-differentiated thyroid cancers account for the majority of thyroid cancers on diagnosis and have excellent survival rates, the incidence of advanced-stage disease has increased over the past few years and confers poorer prognosis. Until recently, patients with advanced thyroid cancer had limited therapeutic options. However, the landscape of thyroid cancer treatment has dramatically changed in the past decade with the current availability of several novel effective therapeutic options, leading to significant advances and improved patient outcomes in the management of advanced disease. In this review, we summarize the current status of advanced thyroid cancer treatment options and discuss recent advances made in targeted therapies that have proven promising to clinically benefit patients with advanced thyroid cancer.
DOI: 10.1200/edbk_389708
PubMed ID: 37186883
Physician-Reported Barriers to Osteoporosis Screening: A Nationwide Survey. Endocr Pract. 2023 May 6:S1530-891X(23)00403-2.
Choksi P, Gay BL, Haymart MR, Papaleontiou M.
ABSTRACT
Objective: Despite increased awareness, osteoporosis screening rates remain low. The objective of this survey study was to identify physician-reported barriers to osteoporosis screening.
Methods: We conducted a survey of 600 physician members of the Endocrine Society, American Academy of Family Practice, and American Geriatrics Society. The respondents were asked to rate barriers to osteoporosis screening in their patients. We performed multivariable logistic regression analyses to determine correlates with the most commonly reported barriers.
Results: Of 566 response-eligible physicians, 359 completed the survey (response rate, 63%). The most commonly reported barriers to osteoporosis screening included patient nonadherence (63%), physician concern about cost (56%), clinic visit time constraints (51%), low on the priority list (45%), and patient concern about cost (43%). Patient nonadherence as a barrier was correlated with physicians in academic tertiary centers (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.06-5.13), whereas clinic visit time constraints were correlated with physicians in both community-based academic affiliates and academic tertiary care ([OR, 1.96; 95% CI, 1.10-3.50] and [OR, 2.48; 95% CI, 1.22-5.07], respectively). Geriatricians (OR, 0.40; 95% CI, 0.21-0.76) and physicians with >10 years in practice were less likely to report clinic visit time constraints as a barrier (11-20 years: OR, 0.41; 95% CI, 0.20-0.85; >20 years: OR, 0.32; 95% CI, 0.16-0.65). Physicians with more patient-facing time (3-5 compared with 0.5-2 d/wk) were more likely to place screening low on the priority list (OR, 2.66; 95% CI, 1.34-5.29).
Conclusion: Understanding barriers to osteoporosis screening is vital in developing strategies to improve osteoporosis care.
DOI: 10.1016/j.eprac.2023.05.001
PubMed ID: 37156374
Thyroid cancer. Lancet. 2023 May 6;401(10387):1531-1544.Â
Chen DW, Lang BHH, McLeod DSA, Newbold K, Haymart MR.
ABSTRACT
The past 5-10 years have brought in a new era in the care of patients with thyroid cancer, with the introduction of transformative diagnostic and management options. Several international ultrasound-based thyroid nodule risk stratification systems have been developed with the goal of reducing unnecessary biopsies. Less invasive alternatives to surgery for low-risk thyroid cancer, such as active surveillance and minimally invasive interventions, are being explored. New systemic therapies are now available for patients with advanced thyroid cancer. However, in the setting of these advances, disparities exist in the diagnosis and management of thyroid cancer. As new management options are becoming available for thyroid cancer, it is essential to support population-based studies and randomised clinical trials that will inform evidence-based clinical practice guidelines on the management of thyroid cancer, and to include diverse patient populations in research to better understand and subsequently address existing barriers to equitable thyroid cancer care.
DOI: 10.1016/s0140-6736(23)00020-x
PubMed ID: 37023783
Celebrating 20 Years of Women in Thyroidology in the American Thyroid Association. Thyroid. 2023 March 16;33(3):271-272.Â
Busaidy NL, Leung AM, Papaleontiou M.
Setting the Tone-Pretreatment Understanding Is Associated With Treatment-Related Expectations Among Thyroid Cancer Survivors. JAMA Otolaryngol Head Neck Surg. 2023 Feb 1;149(2):120-121.
Genere N, Papaleontiou M.
Banking on Fertility Preservation: Financial Concern for Adolescent and Young Adult Cancer Patients Considering Oncofertility Services. J Adolesc Young Adult Oncol. 2023 Oct;12(5):710-717.Â
Jackson Levin N, Tan CY, Stelmak D, Iannarino NT, Zhang A, Ellman E, Herrel LA, Walling EB, Moravek MB, Chugh R, Haymart MR, Zebrack B.
ABSTRACT
Purpose: Financial concern is a major issue for adolescent and young adult (AYA) cancer patients. Furthermore, unaddressed oncofertility challenges (e.g., infertility) are linked to psychological distress and decreased overall quality of life. Little is known about how financial concern in terms of oncofertility (i.e., concern regarding affording fertility preservation [FP] services) impacts AYAs' decision making and experiences. Methods: AYA cancer patients (n = 27) aged 12-25 years whose cancer treatment conferred risk of infertility were recruited through electronic health record query. Participants completed semi-structured interviews, which were recorded, transcribed, and deductively coded for themes related to information needs, knowledge of treatment effects on fertility, and reproductive concerns after cancer. Emergent, inductive themes related to financial concern were identified. The Institutional Review Board at the University of Michigan approved this study (HUM#00157267). Results: Financial concern was a dominant theme across the qualitative data. Emergent themes included (1) varied access to health insurance, (2) presence of parental/guardian support, (3) reliance upon financial aid, (4) negotiating infertility risk, and (5) lack of preparation for long-term costs. AYAs relied heavily upon parents for out-of-pocket and insurance coverage support. Some participants sought financial aid when guided by providers. Several participants indicated that no financial support existed for their circumstance. Conclusions: Financial consequences in terms of oncofertility are a major issue affecting AYA cancer patients. The incidence and gravity of financial concern surrounding affording oncofertility services merits attention in future research (measuring financial resources of AYAs' parental/support networks), clinical practice (strategically addressing short- and long-term costs; tailored psychosocial support), and health care policy (promoting legislation to mandate pre- and post-treatment FP coverage).
PubMed ID: 36603107
Current Controversies in Low-Risk Differentiated Thyroid Cancer: Reducing Overtreatment in an Era of Overdiagnosis. J Clin Endocrinol Metab. 2023 Jan 17;108(2):271-280.
Ullmann TM, Papaleontiou M, Sosa JA.
ABSTRACT
Context: Low-risk differentiated thyroid cancer (DTC) is overdiagnosed, but true incidence has increased as well. Owing to its excellent prognosis with low morbidity and mortality, balancing treatment risks with risks of disease progression can be challenging, leading to several areas of controversy.
Evidence acquisition: This mini-review is an overview of controversies and difficult decisions around the management of all stages of low-risk DTC, from diagnosis through treatment and follow-up. In particular, overdiagnosis, active surveillance vs surgery, extent of surgery, radioactive iodine (RAI) treatment, thyrotropin suppression, and postoperative surveillance are discussed.
Evidence synthesis: Recommendations regarding the diagnosis of DTC, the extent of treatment for low-risk DTC patients, and the intensity of posttreatment follow-up have all changed substantially in the past decade. While overdiagnosis remains a problem, there has been a true increase in incidence as well. Treatment options range from active surveillance of small tumors to total thyroidectomy followed by RAI in select cases. Recommendations for long-term surveillance frequency and duration are similarly broad.
Conclusion: Clinicians and patients must approach each case in a personalized and nuanced fashion to select the appropriate extent of treatment on an individual basis. In areas of evidential equipoise, data regarding patient-centered outcomes may help guide decision-making.
PubMed ID: 36327392
Editorial: New horizons for thyroid diseases: transformative changes and tailored care. Curr Opin Endocrinol Diabetes Obes. 2022 Oct 1;29(5):440.
Haymart MR.
Evaluating health outcomes in the treatment of hypothyroidism. Front Endocrinol (Lausanne). 2022 Oct 18;13:1026262.
Ettleson MD, Papaleontiou M.
ABSTRACT
Clinical hypothyroidism is defined by the inadequate production of thyroid hormone from the thyroid gland to maintain normal organ system functions. For nearly all patients with clinical hypothyroidism, lifelong treatment with thyroid hormone replacement is required. The primary goal of treatment is to provide the appropriate daily dose of thyroid hormone to restore normal thyroid function for each individual patient. In current clinical practice, normalization of thyrotropin (TSH) level is the primary measure of effectiveness of treatment, however the use of a single biomarker to define adequate thyroid hormone replacement is being reevaluated. The assessment of clinical health outcomes and patient-reported outcomes (PROs), often within the context of intensity of treatment as defined by thyroid function tests (i.e., undertreatment, appropriate treatment, or overtreatment), may play a role in evaluating the effectiveness of treatment. The purpose of this narrative review is to summarize the prominent health outcomes literature in patients with treated hypothyroidism. To date, overall mortality, cardiovascular morbidity and mortality, bone health and cognitive function have been evaluated as endpoints in clinical outcomes studies in patients with treated hypothyroidism. More recent investigations have sought to establish the relationships between these end results and thyroid function during the treatment course. In addition to clinical event outcomes, patient-reported quality of life (QoL) has also been considered in the assessment of adequacy of hypothyroidism treatment. From a health care quality perspective, treatment of hypothyroidism should be evaluated not just on its effectiveness for the individual patients but also to the extent to which patients of different sociodemographic groups are treated equally. Ultimately, more research is needed to explore differences in health outcomes between different sociodemographic groups with hypothyroidism. Future prospective studies of treated hypothyroidism that integrate biochemical testing, PROs, and end result clinical outcomes could provide a more complete picture into the effectiveness of treatment of hypothyroidism.
DOI: 10.3389/fendo.2022.1026262
PubMed ID: 36329885
Towards De-Implementation of low-value thyroid care in older adults. Curr Opin Endocrinol Diabetes Obes. 2022 Oct 1;29(5):483-491.Â
Perkins JM, Papaleontiou M.
ABSTRACT
Purpose of review: This review discusses the current literature regarding low-value thyroid care in older adults, summarizing recent findings pertaining to screening for thyroid dysfunction and management of hypothyroidism, thyroid nodules and low-risk differentiated thyroid cancer.
Recent findings: Despite a shift to a "less is more" paradigm for clinical thyroid care in older adults in recent years, current studies demonstrate that low-value care practices are still prevalent. Ineffective and potentially harmful services, such as routine treatment of subclinical hypothyroidism which can lead to overtreatment with thyroid hormone, inappropriate use of thyroid ultrasound, blanket fine needle aspiration biopsies of thyroid nodules, and more aggressive approaches to low-risk differentiated thyroid cancers, have been shown to contribute to adverse effects, particularly in comorbid older adults.
Summary: Low-value thyroid care is common in older adults and can trigger a cascade of overdiagnosis and overtreatment leading to patient harm and increased healthcare costs, highlighting the urgent need for de-implementation efforts.
DOI: 10.1097/med.0000000000000758
PubMed ID: 35869743
The relative importance of treatment outcomes to surgeons' recommendations for low-risk thyroid cancer. Surgery. 2023 Jan;173(1):183-188.Â
Chiu AS, Saucke MC, Bushaw K, Voils CI, Sydnor J, Haymart M, Pitt SC.
ABSTRACT
Background: The treatment of low-risk thyroid cancer is controversial. We evaluated the importance of treatment outcomes to surgeons' recommendations.
Methods: A cross-sectional survey asked thyroid surgeons for their treatment recommendations for a healthy 45-year-old patient with a solitary, low-risk, 2-cm papillary thyroid cancer. The importance of the 10 treatment outcomes (survival, recurrence, etc.) to their recommendation was evaluated using constant sum scaling, a method where 100 points are allocated among the treatment outcomes; more points indicate higher importance. The distribution of points was compared between surgeons recommending total thyroidectomy and surgeons recommending lobectomy using Hottelling's T2 test.
Results: Of 165 respondents (74.3% response rate), 35.8% (n = 59) recommended total thyroidectomy and 64.2% (n = 106) lobectomy. The importance of the 10 treatment outcomes was significantly different between groups (P < .05). Surgeons recommending total thyroidectomy were most influenced by the risk of recurrence (19.1 points; standard deviation 16.5) and rated this 1.6-times more important than those recommending lobectomy. Conversely, surgeons recommending lobectomy placed high emphasis on need for hormone replacement (14.3 points; standard deviation 15.4), rating this 3.1-times more important than those recommending total thyroidectomy.
Conclusion: Surgeons who recommend total thyroidectomy and those who recommend lobectomy differently prioritize the importance of cancer recurrence and thyroid hormone replacement. Understanding how surgeons' beliefs influence their recommendations is important for ensuring patients receive treatment aligned with their values.
DOI: 10.1016/j.surg.2022.05.002
PubMed ID: 36182602
Variation in the Diagnosis of Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features. J Clin Endocrinol Metab. 2022 Sep 28;107(10):e4072-e4077.
Chen DW, Rob FI, Mukherjee R, Giordano TJ, Haymart MR, Banerjee M.
ABSTRACT
Context: Noninvasive encapsulated follicular variant of papillary thyroid cancer was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in January 2017. The impact of this nomenclature change at a population level remains unknown.
Objective: Examine use of NIFTP across different US regions and populations.
Design: Descriptive epidemiology study using SEER-22 data (2000-2019).
Participants: Individuals diagnosed with papillary or follicular thyroid cancer (2000-2019) or NIFTP (2017-2019).
Main outcome measures: Annual incidence rates of thyroid cancer by subtype and NIFTP. Using 2018-2019 data, (1) rates of NIFTP at the 17 SEER-22 sites and (2) comparison of demographics for patients diagnosed with NIFTP vs papillary and follicular thyroid cancer.
Results: NIFTP comprised 2.2% and 2.6% of cases in 2018 and 2019, respectively. Between 2018 and 2019, large heterogeneity was observed in the regional use of NIFTP diagnosis, with site-specific incidence rates between 0.0% and 6.2% (median 2.8%, interquartile range 1.3-3.6%). A diagnosis of NIFTP (vs papillary and follicular thyroid cancer) in 2018 and 2019 was significantly associated with older age (P = 0.012 and P = 0.009, respectively), Black race (both Ps < 0.001), and non-Hispanic ethnicity (both Ps < 0.001).
Conclusions: Marked variation exists in the use of the NIFTP diagnosis. The recent 2021 coding change that resulted in NIFTP, a tumor with uncertain malignant potential and for which there is no long-term outcome data available, no longer being a reportable diagnosis to SEER will disproportionately affect vulnerable patient groups such as older patients and Black patients, in addition to patients who reside in regions with higher rates of NIFTP diagnoses.
PubMed ID: 35918064
Thyroid Carcinoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022 Aug;20(8):925-951.
Haddad RI, Bischoff L, Ball D, Bernet V, Blomain E, Busaidy NL, Campbell M, Dickson P, Duh QY, Ehya H, Goldner WS, Guo T, Haymart M, Holt S, Hunt JP, Iagaru A, Kandeel F, Lamonica DM, Mandel S, Markovina S, McIver B, Raeburn CD, Rezaee R, Ridge JA, Roth MY, Scheri RP, Shah JP, Sipos JA, Sippel R, Sturgeon C, Wang TN, Wirth LJ, Wong RJ, Yeh M, Cassara CJ, Darlow S.
ABSTRACT
Differentiated thyroid carcinomas is associated with an excellent prognosis. The treatment of choice for differentiated thyroid carcinoma is surgery, followed by radioactive iodine ablation (iodine-131) in select patients and thyroxine therapy in most patients. Surgery is also the main treatment for medullary thyroid carcinoma, and kinase inhibitors may be appropriate for select patients with recurrent or persistent disease that is not resectable. Anaplastic thyroid carcinoma is almost uniformly lethal, and iodine-131 imaging and radioactive iodine cannot be used. When systemic therapy is indicated, targeted therapy options are preferred. This article describes NCCN recommendations regarding management of medullary thyroid carcinoma and anaplastic thyroid carcinoma, and surgical management of differentiated thyroid carcinoma (papillary, follicular, HĂĽrthle cell carcinoma).
PubMed ID: 35948029
To Radiate or Not to Radiate? Adjuvant External Beam Radiation Therapy for Nonanaplastic Thyroid Cancer. Endocr Pract. 2022 Jul;28(7):732-733.Â
Arida AK, Papaleontiou M.
Hot Topics and Advances in Thyroidology: Looking into the Future. Endocrinol Metab Clin North Am. 2022 Jun;51(2):xv-xvi.
Haymart MR, Papaleontiou M.
Association of Thyroid Hormone Treatment Intensity With Cardiovascular Mortality Among US Veterans. JAMA Netw Open. 2022 May 2;5(5):e2211863.
Evron JM, Hummel SL, Reyes-Gastelum D, Haymart MR, Banerjee M, Papaleontiou M.
ABSTRACT
Importance: Cardiovascular disease is the leading cause of death in the United States. Synthetic thyroid hormones are among the 3 most commonly prescribed medications, yet studies evaluating the association between the intensity of thyroid hormone treatment and cardiovascular mortality are scarce.
Objective: To evaluate the association between thyroid hormone treatment intensity and cardiovascular mortality.
Design, setting, and participants: This retrospective cohort study used data on 705 307 adults who received thyroid hormone treatment from the Veterans Health Administration Corporate Data Warehouse between January 1, 2004, and December 31, 2017, with a median follow-up of 4 years (IQR, 2-9 years). Two cohorts were studied: 701 929 adults aged 18 years or older who initiated thyroid hormone treatment with at least 2 thyrotropin measurements between treatment initiation and either death or the end of the study period, and, separately, 373 981 patients with at least 2 free thyroxine (FT4) measurements. Data were merged with the National Death Index for mortality ascertainment and cause of death, and analysis was conducted from March 25 to September 2, 2020.
Exposures: Time-varying serum thyrotropin and FT4 levels (euthyroidism: thyrotropin level, 0.5-5.5 mIU/L; FT4 level, 0.7-1.9 ng/dL; exogenous hyperthyroidism: thyrotropin level, <0.5 mIU/L; FT4 level, >1.9 ng/dL; exogenous hypothyroidism: thyrotropin level, >5.5 mIU/L; FT4 level, <0.7 ng/dL).
Main outcomes and measures: Cardiovascular mortality (ie, death from cardiovascular causes, including myocardial infarction, heart failure, or stroke). Survival analyses were performed using Cox proportional hazards regression models using serum thyrotropin and FT4 levels as time-varying covariates.
Results: Of the 705 307 patients in the study, 625 444 (88.7%) were men, and the median age was 67 years (IQR, 57-78 years; range, 18-110 years). Overall, 75 963 patients (10.8%) died of cardiovascular causes. After adjusting for age, sex, traditional cardiovascular risk factors (eg, hypertension, smoking, and previous cardiovascular disease or arrhythmia), patients with exogenous hyperthyroidism (eg, thyrotropin levels, <0.1 mIU/L: adjusted hazard ratio [AHR], 1.39; 95% CI, 1.32-1.47; FT4 levels, >1.9 ng/dL: AHR, 1.29; 95% CI, 1.20-1.40) and patients with exogenous hypothyroidism (eg, thyrotropin levels, >20 mIU/L: AHR, 2.67; 95% CI, 2.55-2.80; FT4 levels, <0.7 ng/dL: AHR, 1.56; 95% CI, 1.50-1.63) had increased risk of cardiovascular mortality compared with individuals with euthyroidism.
Conclusions and relevance: This study suggests that both exogenous hyperthyroidism and exogenous hypothyroidism were associated with increased risk of cardiovascular mortality. These findings emphasize the importance of maintaining euthyroidism to decrease cardiovascular risk and death among patients receiving thyroid hormone treatment.
DOI: 10.1001/jamanetworkopen.2022.11863
PubMed ID: 35552725
Concurrent Use of Thyroid Hormone Therapy and Interfering Medications in Older US Veterans. J Clin Endocrinol Metab. 2022 Jun 16;107(7):e2738-e2742.
Livecchi R, Coe AB, Reyes-Gastelum D, Banerjee M, Haymart MR, Papaleontiou M.
ABSTRACT
Context: Thyroid hormone management in older adults is complicated by comorbidities and polypharmacy.
Objective: Determine the prevalence of concurrent use of thyroid hormone and medications that can interfere with thyroid hormone metabolism (amiodarone, prednisone, prednisolone, carbamazepine, phenytoin, phenobarbital, tamoxifen), and patient characteristics associated with this practice.
Design: Retrospective cohort study between 2004 and 2017 (median follow-up, 56 months).
Setting: Veterans Health Administration Corporate Data Warehouse.
Participants: A total of 538 137 adults ≥ 65 years prescribed thyroid hormone therapy during the study period.
Main outcome measure: Concurrent use of thyroid hormone and medications interfering with thyroid hormone metabolism.
Results: Overall, 168 878 (31.4%) patients were on at least 1 interfering medication while on thyroid hormone during the study period. In multivariable analyses, Black/African-American race (odds ratio [OR], 1.25; 95% CI, 1.21-1.28, compared with White), Hispanic ethnicity (OR, 1.12; 95% CI, 1.09-1.15, compared with non-Hispanic), female (OR, 1.11; 95% CI, 1.08-1.15, compared with male), and presence of comorbidities (eg, Charlson/Deyo Comorbidity Score ≥ 2; OR, 2.50; 95% CI, 2.45-2.54, compared with 0) were more likely to be associated with concurrent use of thyroid hormone and interfering medications. Older age (eg, ≥ 85 years; OR, 0.48; 95% CI, 0.47-0.48, compared with age 65-74 years) was less likely to be associated with this practice.
Conclusions and relevance: Almost one-third of older adults on thyroid hormone were on medications known to interfere with thyroid hormone metabolism. Our findings highlight the complexity of thyroid hormone management in older adults, especially in women and minorities.
PubMed ID: 35396840
Active Surveillance Versus Thyroid Surgery for Differentiated Thyroid Cancer: A Systematic Review. Thyroid. 2022 Apr;32(4):351-367.
Chou R, Dana T, Haymart M, Leung AM, Tufano RP, Sosa JA, Ringel MD.
ABSTRACT
Background: Active surveillance has been proposed as an appropriate management strategy for low-risk differentiated thyroid cancer (DTC), due to the typically favorable prognosis of this condition. This systematic review examines the benefits and harms of active surveillance vs. immediate surgery for DTC, to inform the updated American Thyroid Association guidelines. Methods: A search on Ovid MEDLINE, Embase, and Cochrane Central was conducted in July 2021 for studies on active surveillance vs. immediate surgery. Studies of surgery vs. no surgery for DTC were assessed separately to evaluate relevance to active surveillance. Quality assessment was performed, and evidence was synthesized narratively. Results: Seven studies (five cohort studies [N = 5432] and two cross-sectional studies [N = 538]) of active surveillance vs. immediate surgery, and seven uncontrolled treatment series of active surveillance (N = 1219) were included. One cross-sectional study was rated fair quality, and the remainder were rated poor quality. In patients with low risk (primarily papillary), small (primarily ≤1 cm) DTC, active surveillance, and immediate surgery were associated with similar, low risk of all-cause or cancer-specific mortality, distant metastasis, and recurrence after surgery. Uncontrolled treatment series reported no cases of mortality in low-risk DTC managed with active surveillance. Among patients managed with active surveillance, rates of tumor growth were low; rates of subsequent surgery varied and primarily occurred due to patient preference rather than tumor progression. Four cohort studies (N = 88,654) found that surgery associated with improved all-cause or thyroid cancer mortality compared with nonsurgical management, but findings were potentially influenced by patient age and tumor risk category and highly susceptible to confounding by indication; eligibility for, and receipt of, active surveillance; and timing of surgery was unclear. Conclusions: In patients with small low-risk (primarily papillary) DTC, active surveillance and immediate surgery may be associated with similar mortality, risk of recurrence, and other outcomes, but methodological limitations preclude strong conclusions. Studies of no surgery vs. surgery are difficult to interpret due to clinical heterogeneity and potential confounding factors and are unsuitable for assessing the utility of active surveillance. Research is needed to clarify the benefits and harms of active surveillance and determine outcomes in nonpapillary DTC, larger (>1 cm) cancers, and older patients.
PubMed ID: 35081743
Radiofrequency Ablation for Thyroid Nodules and Cancer in the United States: Balancing a Transformation of Thyroid Care With Risk for Misuse. Endocr Pract. 2022 Feb;28(2):233-234.
Haymart MR, Papaleontiou M.
Optimal Thyrotropin Following Lobectomy for Papillary Thyroid Cancer: Does It Exist? Thyroid. 2022 Feb;32(2):117-118.
Bischoff L, Haymart MR.
Physician Specialties Involved in Thyroid Cancer Diagnosis and Treatment: Implications for Improving Health Care Disparities. J Clin Endocrinol Metab. 2022 Feb 17;107(3):e1096-e1105.
Radhakrishnan A, Reyes-Gastelum D, Abrahamse P, Gay B, Hawley ST, Wallner LP, Chen DW, Hamilton AS, Ward KC, Haymart MR.
ABSTRACT
Context: Little is known about provider specialties involved in thyroid cancer diagnosis and management.
Objective: Characterize providers involved in diagnosing and treating thyroid cancer.
Design/setting/participants: We surveyed patients with differentiated thyroid cancer from the Georgia and Los Angeles County Surveillance, Epidemiology and End Results registries (N = 2632, 63% response rate). Patients identified their primary care physicians (PCPs), who were also surveyed (N = 162, 56% response rate).
Main outcome measures: (1) Patient-reported provider involvement (endocrinologist, surgeon, PCP) at diagnosis and treatment; (2) PCP-reported involvement (more vs less) and comfort (more vs less) with discussing diagnosis and treatment.
Results: Among thyroid cancer patients, 40.6% reported being informed of their diagnosis by their surgeon, 37.9% by their endocrinologist, and 13.5% by their PCP. Patients reported discussing their treatment with their surgeon (71.7%), endocrinologist (69.6%), and PCP (33.3%). Physician specialty involvement in diagnosis and treatment varied by patient race/ethnicity and age. For example, Hispanic patients (vs non-Hispanic White) were more likely to report their PCP informed them of their diagnosis (odds ratio [OR]: 1.68; 95% CI, 1.24-2.27). Patients ≥65 years (vs <45 years) were more likely to discuss treatment with their PCP (OR: 1.59; 95% CI, 1.22-2.08). Although 74% of PCPs reported discussing their patients' diagnosis and 62% their treatment, only 66% and 48%, respectively, were comfortable doing so.
Conclusions: PCPs were involved in thyroid cancer diagnosis and treatment, and their involvement was greater among older patients and patients of minority race/ethnicity. This suggests an opportunity to leverage PCP involvement in thyroid cancer management to improve health and quality of care outcomes for vulnerable patients.
PubMed ID: 34718629
Clearing Up the Fog: Insights Into Brain Fog Experienced by Patients With Hypothyroidism. Endocr Pract. 2022 Mar;28(3):349-350.
Chen DW, Papaleontiou M.
Understanding Worry About Risks Associated With Thyroid Hormone Therapy: A National Survey of Endocrinologists, Family Physicians, and Geriatricians. Endocr Pract. 2022 Jan;28(1):25-29.Â
Shah K, Reyes-Gastelum D, Gay BL, Papaleontiou M.
ABSTRACT
Objective: Thyroid hormone use is widespread, and prior studies have shown that over- and undertreatment with thyroid hormone are common. Our objective was to understand physician worry regarding risks associated with thyroid hormone therapy, specifically overtreatment or undertreatment.
Methods: A nationwide survey was administered to physician members of the Endocrine Society, the American Academy of Family Practice, and the American Geriatrics Society. Participants were asked how often they were worried about various risks that may be associated with thyroid hormone over- or undertreatment, that is, cardiovascular complications, bone complications, and poor quality of life due to overtreatment or undertreatment with thyroid hormone. Multivariable regression analyses were conducted to determine physician characteristics associated with each worry.
Results: The response rate was 63% (359 of 566); of those who responded, 128 (36%) were primary care physicians, 114 (32%) were endocrinologists, and 113 (32%) were geriatricians. Overall, 74 (21%) physicians reported that they frequently or always worried about cardiovascular complications, 74 (21%) about bone complications, 111 (31%) about the poor quality of life due to symptoms from undertreatment with thyroid hormone, and 87 (24%) about the poor quality of life due to symptoms from overtreatment with thyroid hormone. Endocrinologists were more likely to frequently or always worry about the patients' poor quality of life due to symptoms from overtreatment (odds ratio, 2.05; 95% confidence interval, 1.09-3.93) compared with primary care physicians.
Conclusion: Up to one third of the physicians frequently or always worried about risks resulting from the thyroid hormone overtreatment or undertreatment. More research is needed across specialties to understand physician perceptions of how thyroid hormone therapy impacts the patients' quality of life.
DOI: 10.1016/j.eprac.2021.08.007
PubMed ID: 34438052
Year in Thyroidology-Recent Developments and Future Challenges: Clinical Science Review. Thyroid. 2022 Jan;32(1):9-13.
Haymart MR.
ABSTRACT
Background: The 2021 Year in Thyroidology-Recent Developments and Future Challenges: Clinical Science Review featured key clinical research within five categories: Thyroid Nodules and Cancer, Thyroid Function and Thyroid Eye Disease, Thyroid and Pregnancy, Thyroid and Pediatrics, and Disparities in Thyroid. Methods: A literature search of PubMed from November 2019 to August 2021 was performed to identify relevant peer-reviewed articles published in English and with a focus on human subjects. Results: There were three nominees for each of the five categories and one featured article per category. The featured articles had the most potential to change clinical practice, focused on a novel topic, and/or included of strong methodology. Conclusions: There were many strong publications on thyroid between November 2019 and August 2021; the 15 nominees and 5 featured articles span a breadth of topics and methodological approaches. The featured articles all have potential to change practice patterns or to stimulate further research that will ultimately change practice patterns.
PubMed ID: 34806424
Progress and Challenges in Thyroid Cancer Management. Endocr Pract. 2021 Dec;27(12):1260-1263.
Haymart MR.
ABSTRACT
The state of thyroid cancer in 2021 is reviewed including the prevalence of thyroid cancer, vulnerable patient groups such as women and young adults, and known and hypothesized risk factors for thyroid cancer. Understanding the overdiagnosis and overtreatment of thyroid cancer and recent efforts to reduce harms secondary to overdiagnosis and overtreatment are addressed with optimism that future work will continue to evaluate and improve the care of patients with thyroid cancer.
DOI: 10.1016/j.eprac.2021.09.006
PubMed ID: 34562612
Non-surgical management of thyroid nodules - the role of ablative therapies. J Clin Endocrinol Metab. 2022 Apr 19;107(5):1417-1430.
Stan MN, Papaleontiou M, Schmitz JJ, Castro MR.
ABSTRACT
Context: After a thorough evaluation most thyroid nodules are deemed of no clinical consequence and can be observed. However, when they are compressive, toxic, or involved by papillary thyroid carcinoma surgery or radioactive iodine (RAI) (if toxic) are the treatments of choice. Both interventions can lead to hypothyroidism and other adverse outcomes (eg, scar, dysphonia, logistical limitation with RAI). Active surveillance might be used for papillary thyroid microcarcinoma (PTMC) initially, but anxiety leads many cases to surgery later. Several ablative therapies have thus evolved over the last few years aimed at treating these nodules while avoiding described risks.
Cases: We present 4 cases of thyroid lesions causing concern (compressive symptoms, thyrotoxicosis, anxiety with active surveillance of PTMC). The common denominator is patients' attempt to preserve thyroid function, bringing into focus percutaneous ethanol injection (PEI) and thermal ablation techniques (radiofrequency ablation [RFA] being the most common). We discuss the evidence supporting these approaches and compare them with standard therapy, where evidence exists. We discuss additional considerations for the utilization of these therapies, their side-effects, and conclude with a simplified description of how these procedures are performed.
Conclusion: Thermal ablation, particularly RFA, is becoming an attractive option for managing a subgroup of solid thyroid nodules, while PEI has a role in managing thyroid cysts and a select group of PTMC. Their role in the algorithm of thyroid nodule management is still being refined and technical expertise will be essential to reproduce the reported results into everyday practice.
PubMed ID: 34953163
Change in worry over time among Hispanic women with thyroid cancer. J Cancer Surviv. 2022 Aug;16(4):844-852.
Jackson Levin N, Zhang A, Reyes-Gastelum D, Chen DW, Hamilton AS, Zebrack B, Haymart MR.
ABSTRACT
Purpose: The purpose of this study is to assess change in worry over time in Hispanic women with thyroid cancer.
Methods: Worry about recurrence, quality of life, family at risk, death, and harm from treatments was assessed in 273 Hispanic women with thyroid cancer diagnosed in 2014-2015. Subjects were recruited from Surveillance, Epidemiology, and End Results (SEER) Los Angeles. Participants were surveyed at two points in time (time 1: 2017-2018 and time 2: 2019). Multivariable logistic regression was used to determine correlates with high worry (somewhat, quite a bit, very much) versus low worry (not at all, a little) at time 2.
Results: For the five worry items, 20.1-39.6% had high worry at both time 1 and time 2. An additional 7.6-13.4% had low worry at time 1 that became high worry at time 2. In multivariable logistic regression controlling for age, recurrence status, education level, and number of complications or side effects symptoms, younger age (20-39) as compared to older (40-79) was associated with high worry about thyroid cancer recurrence (OR 2.16, 95% CI 1.12-4.17). History of recurrent or persistent disease was associated with high worry about harms from treatment (OR 2.94, 95% CI 1.29-6.67). Greater number of complications or side effects of symptoms was associated with more worry across all five items.
Conclusions: Some Hispanic women with thyroid cancer have persistently high worry, with young adult Hispanic women vulnerable to worry about recurrence.
Implications for cancer survivors: Hispanic women with thyroid cancer may benefit from targeted psychosocial support during survivorship, with interventions informed by patient and cancer characteristics.
DOI: 10.1007/s11764-021-01078-8
PubMed ID: 34633638
Decision Making in Subclinical Thyroid Disease. Med Clin North Am. 2021 Nov;105(6):1033-1045.Â
Evron JM, Papaleontiou M.
ABSTRACT
Subclinical thyroid disease is frequently encountered in clinic practice. Although overt thyroid dysfunction has been associated with adverse clinical outcomes, uncertainty remains about the implications of subclinical thyroid disease. Available data suggest that subclinical hypothyroidism may be associated with increased risk of cardiovascular disease and death. Despite this finding, treatment with thyroid hormone has not been consistently demonstrated to reduce cardiovascular risk. Subclinical hyperthyroidism has been associated with increased risk of atrial fibrillation and osteoporosis, but the association with cardiovascular disease and death is uncertain. The decision to treat depends on the degree of thyroid-stimulating hormone suppression and underlying comorbidities.
DOI: 10.1016/j.mcna.2021.05.014
PubMed ID: 34688413
Assessment of surveillance versus etiologic factors in the reciprocal association between papillary thyroid cancer and breast cancer. Cancer Epidemiol. 2021 Jul 16;74:101985.Â
Advani PG, Morton LM, Kitahara CM, Berrington de Gonzalez A, Ramin C, Haymart MR, Curtis RE, Schonfeld SJ.
ABSTRACT
Background: Mutually increased risks for thyroid and breast cancer have been reported, but the contribution of etiologic factors versus increased medical surveillance to these associations is unknown.
Methods: Leveraging large-scale US population-based cancer registry data, we used standardized incidence ratios (SIRs) to investigate the reciprocal risks of thyroid and breast cancers among adult females diagnosed with a first primary invasive, non-metastatic breast cancer (N = 652,627) or papillary thyroid cancer (PTC) (N = 92,318) during 2000-2017 who survived ≥1-year.
Results: PTC risk was increased 1.3-fold [N = 1434; SIR = 1.32; 95 % confidence interval (CI) = 1.25-1.39] after breast cancer compared to the general population. PTC risk declined significantly with time since breast cancer (Poisson regression = Ptrend <0.001) and was evident only for tumors ≤2 cm in size. The SIRs for PTC were higher after hormone-receptor (HR)+ (versus HR-) and stage II or III (versus stage 0-I) breast tumors. Breast cancer risk was increased 1.2-fold (N = 2038; SIR = 1.21; CI = 1.16-1.26) after PTC and was constant over time since PTC but was only increased for stage 0-II and HR + breast cancers.
Conclusion: Although some of the patterns by latency, stage and size are consistent with heightened surveillance contributing to the breast-thyroid association, we cannot exclude a role of shared etiology or treatment effects.
DOI: 10.1016/j.canep.2021.101985
PubMed ID: 34280845
Thyroid Hormone Therapy and Incident Stroke. J Clin Endocrinol Metab. 2021 Sep 27;106(10):e3890-e3900.
Papaleontiou M, Levine DA, Reyes-Gastelum D, Hawley ST, Banerjee M, Haymart MR.
ABSTRACT
Context: Stroke is a leading cause of death and disability and there is a need to identify modifiable risk factors.
Objective: We aimed to determine the relationship between thyroid hormone treatment intensity and incidence of atrial fibrillation and stroke.
Methods: We conducted a retrospective cohort study using data from the Veterans Health Administration between 2004 and 2017, with a median follow-up of 59 months. The study population comprised 733 208 thyroid hormone users aged ≥18 years with at least 2 thyroid stimulating hormone (TSH) measurements between thyroid hormone initiation and incident event (atrial fibrillation or stroke) or study conclusion (406 030 thyroid hormone users with at least 2 free thyroxine [T4] measurements).
Results: Overall, 71 333/643 687 (11.08%) participants developed incident atrial fibrillation and 41 931/663 809 (6.32%) stroke. In multivariable analyses controlling for pertinent factors such as age, sex, and prior history of atrial fibrillation, higher incidence of stroke was associated with low TSH or high free T4 levels (ie, exogenous hyperthyroidism; eg, TSH <0.1 mIU/L; OR 1.33; 95% CI, 1.24-1.43; free T4>1.9 ng/dL, OR 1.17, 95% CI 1.06-1.30) and high TSH or low free T4 levels (ie, exogenous hypothyroidism; eg, TSH >5.5 mIU/L; OR 1.29; 95% CI, 1.26-1.33; free T4 <0.7 ng/dL; OR 1.29; 95% CI, 1.22-1.35) compared with euthyroidism (TSH >0.5-5.5 mIU/L and free T4 0.7-1.9 ng/dL). Risk of developing atrial fibrillation and stroke was cumulative over time for both patients with exogenous hyperthyroidism and hypothyroidism.
Conclusion: Both exogenous hyper- and hypothyroidism were associated with increased risk of stroke, highlighting the importance of patient medication safety.
PubMed ID: 34137866
Breaking Down or Waking Up? Psychological Distress and Sleep Disturbance in Patients with Thyroid Nodules and Cancer. J Clin Endocrinol Metab. 2021 Sep 27;106(10):e4278-e4280.
Pitt SC, Haymart MR.
Surgeons' Attitudes on Total Thyroidectomy vs Lobectomy for Management of Papillary Thyroid Microcarcinoma. JAMA Otolaryngol Head Neck Surg. 2021 Jul 1;147(7):667-669.
Rosko AJ, Gay BL, Reyes-Gastelum D, Hamilton AS, Ward KC, Haymart MR.Â
ABSTRACT
This survey study assessed surgeons’ preference for total thyroidectomy vs lobectomy to treat patients with papillary thyroid cancer.
DOI: 10.1001/jamaoto.2021.0525
PubMed ID: 33885723
Thyrotropin Suppression for Papillary Thyroid Cancer: A Physician Survey Study. Thyroid. 2021 Sep;31(9):1383-1390.
Papaleontiou M, Chen D, Banerjee M, Reyes-Gastelum D, Hamilton AS, Ward KC, Haymart MR.
ABSTRACT
Background: Current guidelines recommend against thyrotropin (TSH) suppression in low-risk differentiated thyroid cancer patients; however, physician practices remain underexplored. Our objective was to understand treating physicians' approach to TSH suppression in patients with papillary thyroid cancer. Methods: Endocrinologists and surgeons identified by thyroid cancer patients from the Surveillance, Epidemiology, and End Results registries of Georgia and Los Angeles were surveyed in 2018-2019. Physicians were asked to report how likely they were to recommend TSH suppression (i.e., TSH <0.5 mIU/L) in three clinical scenarios: patients with intermediate-risk, low-risk, and very low-risk papillary thyroid cancer. Responses were measured on a 4-point Likert scale (extremely unlikely to extremely likely). Multivariable logistic regressions were performed to determine physician characteristics associated with recommending TSH suppression in each of the aforementioned scenarios. Results: Response rate was 69% (448/654). Overall, 80.4% of physicians were likely/extremely likely to recommend TSH suppression for a patient with an intermediate-risk papillary thyroid cancer, 48.8% for a patient with low-risk papillary thyroid cancer, and 29.7% for a patient with very low-risk papillary thyroid cancer. Surgeons were less likely to recommend TSH suppression for an intermediate-risk papillary thyroid cancer patient (odds ratio [OR] = 0.36 [95% confidence interval, CI, 0.19-0.69]) compared with endocrinologists. Physicians with higher thyroid cancer patient volume were less likely to suppress TSH in low-risk and very low-risk papillary thyroid cancer patients (i.e., >40 patients per year, OR = 0.53 [CI 0.30-0.96]; OR = 0.49 [CI 0.24-0.99], respectively, compared with 0-20 patients per year). Physicians who estimated higher likelihood of recurrence were more likely to suppress TSH in a patient with very low-risk papillary thyroid cancer (OR = 2.34 [CI 1.91-4.59]). Conclusions: Many patients with low-risk thyroid cancer continue to be treated with suppressive doses of thyroid hormone, emphasizing the need for more high-quality research to guide thyroid cancer management, as well as better understanding of barriers that hinder guideline adoption.
PubMed ID: 33779292
Competing Causes of Death in Older Adults with Thyroid Cancer. Thyroid. 2021 Sep;31(9):1359-1365.
Papaleontiou M, Norton EC, Reyes-Gastelum D, Banerjee M, Haymart MR.
ABSTRACT
Background: Understanding the impact of comorbidities and competing risks of death when caring for older adults with thyroid cancer is key for personalized management. The objective of this study was to determine whether older adults with thyroid cancer are more likely to die from thyroid cancer or other etiologies, and determine patient factors associated with each. Methods: The Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used to identify patients aged ≥66 years diagnosed with thyroid cancer (papillary, follicular, Hürthle cell, medullary, anaplastic, and other) between 2000 and 2015 (median follow-up, 50 months). We analyzed time to event (i.e., death from other causes or death from thyroid cancer) using cumulative incidence functions. Competing risk hazards regression was used to determine the association between patient (e.g., age at diagnosis and specific comorbidities) and tumor characteristics (e.g., SEER stage) with two competing mortality outcomes: death from other causes and death from thyroid cancer. Results: Of 21,509 patients with a median age of 72 years (range 66-106), 4168 (19.4%) died of other causes and 2644 (12.3%) died of thyroid cancer during the study period. For differentiated thyroid cancer patients, likelihood of dying from other causes exceeds likelihood of dying from thyroid cancer, whereas the opposite is true for anaplastic thyroid cancer. For medullary thyroid cancer, after 6.25 years patients are more likely to die from other etiologies than thyroid cancer. Using competing risks hazards regression, male sex (hazards ratio [HR] 1.47; 95% confidence interval [CI 1.37-1.57]), black race (HR 1.30; CI [1.16-1.46]), and comorbidities (e.g., heart disease, HR 1.34; CI [1.25-1.44]; chronic lower respiratory disease, HR 1.25; CI [1.17-1.34]) were associated with death from other causes. Tumor characteristics such as histology, tumor size, and stage correlated with death from thyroid cancer (e.g., distant SEER stage compared with localized, HR 12.65; CI [10.91-14.66]). Conclusions: The clinical context, including patients' specific comorbidities, should be considered when diagnosing and managing thyroid cancer. Our findings can be used to develop decision models that account for competing causes of death, as an aid for clinical decision making.
PubMed ID: 33764188
Multi-level factors associated with more intensive use of radioactive iodine for low-risk thyroid cancer. J Clin Endocrinol Metab. 2021 May 13;106(6):e2402-e2412.Â
Wallner LP, Banerjee M, Reyes-Gastelum D, Hamilton AS, Ward KC, Lubitz C, Hawley ST, Haymart MR.
ABSTRACT
Context: The use of radioactive iodine (RAI) for low-risk thyroid cancer is common, and variation in its use exists, despite the lack of benefit for low-risk disease and potential harms and costs.
Objective: To simultaneously assess patient- and physician-level factors associated with patient-reported receipt of RAI for low-risk thyroid cancer.
Methods: This population-based survey study of patients with newly diagnosed differentiated thyroid cancer identified via the Surveillance Epidemiology and End Results (SEER) registries of Georgia and Los Angeles County included 989 patients with low-risk thyroid cancer, linked to 345 of their treating general surgeons, otolaryngologists, and endocrinologists. We assessed the association of physician- and patient-level factors with patient-reported receipt of RAI for low-risk thyroid cancer.
Results: Among this sample, 48% of patients reported receiving RAI, and 23% of their physicians reported they would use RAI for low-risk thyroid cancer. Patients were more likely to report receiving RAI if they were treated by a physician who reported they would use RAI for low-risk thyroid cancer compared with those whose physician reported they would not use RAI (adjusted OR: 1.84; 95% CI, 1.29-2.61). The odds of patients reporting they received RAI was 55% lower among patients whose physicians reported they saw a higher volume of patients with thyroid cancer (40+ vs 0-20) (adjusted OR: 0.45; 0.30-0.67).
Conclusions: Physician perspectives and attitudes about using RAI, as well as patient volume, influence RAI use for low-risk thyroid cancer. Efforts to reduce overuse of RAI in low-risk thyroid cancer should include interventions targeted toward physicians, in addition to patients.
PubMed ID: 33687063
Unmet Information Needs Among Hispanic Women with Thyroid Cancer. J Clin Endocrinol Metab. 2021Â Jun 16;106(7):e2680-e2687.
Chen DW, Reyes-Gastelum D, Hawley ST, Wallner LP, Hamilton AS, Haymart MR.Â
ABSTRACT
Context: Thyroid cancer is the second most common cancer in Hispanic women.
Objective: To determine the relationship between acculturation level and unmet information needs among Hispanic women with thyroid cancer.
Design: Population-based survey study.
Participants: Hispanic women from Los Angeles Surveillance Epidemiology and End Results registry with thyroid cancer diagnosed in 2014-2015 who had previously completed our thyroid cancer survey in 2017-2018 (N = 273; 80% response rate).
Main outcome measures: Patients were asked about 3 outcome measures of unmet information needs: (1) internet access, (2) thyroid cancer information resources used, and (3) ability to access information. Acculturation was assessed with the Short Acculturation Scale for Hispanics (SASH). Health literacy was measured with a validated single-item question.
Results: Participants' median age at diagnosis was 47 years (range 20-79) and 48.7% were low-acculturated. Hispanic women were more likely to report the ability to access information "all of the time" if they preferred thyroid cancer information in mostly English compared to mostly Spanish (88.5% vs 37.0%, P < 0.001). Low-acculturated (vs high-acculturated) Hispanic women were more likely to have low health literacy (47.2% vs 5.0%, P < 0.001) and report use of in-person support groups (42.0% vs 23.1%, P = 0.006). Depending on their level of acculturation, Hispanic women accessed the internet differently (P < 0.001) such that low-acculturated women were more likely to report use of only a smartphone (34.0% vs 14.3%) or no internet access (26.2% vs 1.4%).
Conclusions: Low-acculturated (vs high-acculturated) Hispanic women with thyroid cancer have greater unmet information needs, emphasizing the importance of patient-focused approaches to providing medical information.
PubMed ID: 33660770
Understanding Osteoporosis Screening Practices in Men: A Nationwide Physician Survey. Endocr Pract. 2020 Nov;26(11):1237-1243.Â
Choksi P, Gay BL, Reyes-Gastelum D, Haymart MR, Papaleontiou M.
ABSTRACT
Objective: To understand osteoporosis screening practices, particularly in men, by a diverse cohort of physicians, including primary care physicians, endocrinologists, and geriatricians.
Methods: We surveyed randomly selected members of the American Academy of Family Practice, Endocrine Society, and American Geriatrics Society. Respondents were asked to rate how often they would screen for osteoporosis in four different clinical scenarios by ordering a bone density scan. Multivariable logistic regression analyses were conducted to determine factors associated with offering osteoporosis screening in men in each clinical scenario. Physicians were also asked to note factors that would lead to osteoporosis screening in men.
Results: Response rate was 63% (359/566). While 90% respondents reported that they would always or frequently screen for osteoporosis in a 65-year-old post-menopausal woman, only 22% reported they would screen a 74-year-old man with no significant past medical history. Endocrinologists were more likely to screen a 74-year-old man compared to primary care physicians (odds ratio, 2.32; 95% confidence interval, 1.10 to 4.88). In addition to chronic steroid use (94%), history of nontraumatic fractures (88%), and androgen-deprivation therapy for prostate cancer (82%), more than half the physicians reported suppressive doses of thyroid hormone (64%) and history of falls (52%) as factors leading to screening for osteoporosis in men.
Conclusions: Our survey results highlight heterogeneity in osteoporosis screening in men, with underscreening in some scenarios compared to women, and identify factors that lead to screening in men. These findings can help design interventions to improve osteoporosis screening in men.
DOI: 10.4158/ep-2020-0123
PubMed ID: 33471653
Physician Confidence in Neck Ultrasonography for Surveillance of Differentiated Thyroid Cancer Recurrence. JAMA Otolaryngol Head Neck Surg. 2020 Dec 23;147(2):166-72.
Kovatch KJ, Reyes-Gastelum D, Sipos JA, Caoili EM, Hamilton AS, Ward KC, Haymart MR.
ABSTRACT
Importance: Neck ultrasonography, a mainstay of long-term surveillance for recurrence of differentiated thyroid cancer (DTC), is routinely used by endocrinologists, general surgeons, and otolaryngologists; however, physician confidence in their ability to use ultrasonography to identify lymph nodes suggestive of cancer recurrence remains unknown.
Objective: To evaluate physicians' posttreatment surveillance practices for DTC recurrence, specifically their use of and confidence in ultrasonography.
Design, setting, and participants: Cross-sectional study of 448 physicians in private and academic hospitals who completed a survey on DTC posttreatment practices from October 2018 to August 2019 (response rate, 69%) and self-reported involvement in long-term surveillance for thyroid cancer recurrence. Physicians were identified by patients affiliated with the Surveillance, Epidemiology, and End Results Program registries in Georgia State and Los Angeles County. Of the respondents, 320 physicians who reported involvement with DTC surveillance were included in the analysis.
Main outcomes and measures: Physician-reported long-term surveillance practices for DTC, including frequency of use and level of confidence in ultrasonography for detecting lymph nodes suggestive of cancer recurrence.
Results: In the cohort of 320 physicians who reported involvement with DTC surveillance, 186 (60%) had been in practice for 10 years to less than 30 years; 209 (68%) were White; and 212 (66%) were men. The physicians included 170 (56%) endocrinologists, 67 (21%) general surgeons, and 75 (23%) otolaryngologists. Just 84 (27%) physicians reported personally performing bedside ultrasonography. Only 57 (20%) had high confidence (rated quite or extremely confident) in their ability to use bedside ultrasonography to identify lymph nodes suggestive of recurrence; 94 (33%) did not report high confidence in either their ability or a radiologist's ability to use ultrasonography to detect recurrence. Higher confidence in ultrasonography was associated with the general surgery subspecialty (odds ratio [OR], 5.7; 95% CI, 2.2-14.4; reference endocrinology) and with treating a higher number of patients per year (>50 patients: OR, 14.4; 95% CI, 4.4-47.4; 31-50 patients: OR, 8.4; 95% CI, 2.6-26.7; 11-30 patients: OR, 4.3; 95% CI, 1.5-12.1; reference 0-10 patients).
Conclusions and relevance: Given the importance of neck ultrasonography in long-term surveillance for thyroid cancer, these findings of physicians' low confidence in their own ability and that of radiologists to use ultrasonography to detect recurrence point to a major obstacle to standardizing long-term DTC surveillance practices.
DOI: 10.1001/jamaoto.2020.4471
PubMed ID: 33355635
Barriers to the Use of Active Surveillance for Thyroid Cancer Results of a Physician Survey. Ann Surg. 2022 Jul 1;276(1):e40-e47.
Hughes DT, Reyes-Gastelum D, Ward KC, Hamilton AS, Haymart MR.
ABSTRACT
Objective: The aim of this study was to determine physician-reported use of and barriers to active surveillance for thyroid cancer.
Summary background data: It is not clear whether active surveillance for thyroid cancer is widely used.
Methods: Surgeons and endocrinologists identified by thyroid cancer patients from the Surveillance, Epidemiology, and End Results (SEER) registries of Georgia and Los Angeles County were surveyed between 2018 and 2019. Multivariable weighted logistic regression analyses were conducted to determine physician acceptance and use of active surveillance. Results: Of the 654 eligible physicians identified, 448 responded to the survey (69% response rate). The majority (76%) believed that active surveillance was an appropriate management option, but only 44% used it in their practice. Characteristics of physicians who stated that active surveillance was appropriate management, but did not report using it included more years in practice (reference group <10 years in practice): 10 to 19 years [odds ratio, OR 0.50 [95% confidence interval, CI 0.28-0.92]; 20 to 29 years [OR 0.31 (95% CI 0.15-0.62)]; >30 years [OR 0.30 (95% CI 0.15-0.61)] and higher patient volume 11 to 30 patients per year [OR 0.39 (95% CI 0.21 -0.70)] and >50 patients per year [OR 0.33 (95% CI 0.16-0.71)] compared to < 10, with no significant difference in those seeing 31 to 50 patients. Physicians reported multiple barriers to implementing active surveillance including patient does not want (80.3%), loss to follow-up concern (78.4%), more patient worry (57.6%), and malpractice lawsuit concern (50.9%).
Conclusion and relevance: Despite most physicians considering active surveillance to be appropriate management, more than half are not using it. Addressing existing barriers is key to improving uptake.
DOI: 10.1097/sla.0000000000004417
PubMed ID: 33074908
Thyroid Cancer Clinical Guidelines and the De-escalation of Care. JAMA Otolaryngol Head Neck Surg. 2020 Nov 1;146(11):1082-1083.Â
Haymart MR, Goldner WS.
Physician management of thyroid cancer patients' worry. J Cancer Surviv. 2021 Jun;15(3):418-426.Â
Papaleontiou M, Zebrack B, Reyes-Gastelum D, Rosko AJ, Hawley ST, Hamilton AS, Ward KC, Haymart MR.
ABSTRACT
Purpose: The purpose of this study is to understand physician management of thyroid cancer-related worry.
Methods: Endocrinologists, general surgeons, and otolaryngologists identified by Surveillance, Epidemiology, and End Results (SEER) patients were surveyed 2018-2019 (response rate 69% (448/654)) and asked to rate in general their patients' worry at diagnosis and actions they take for worried patients. Multivariable-weighted logistic regressions were conducted to determine physician characteristics associated with reporting thyroid cancer as "good cancer" and with encouraging patients to seek help managing worry outside the physician-patient relationship.
Results: Physicians reported their patients as quite/very worried (65%), somewhat worried (27%), and a little/not worried (8%) at diagnosis. Half of the physicians tell patients their thyroid cancer is a "good cancer." Otolaryngology (odds ratio (OR) 1.87, 95% confidence interval (CI) 1.08-3.21, versus endocrinology), private practice (OR 2.48, 95% CI 1.32-4.68, versus academic setting), and Los Angeles (OR 2.24, 95% CI 1.45-3.46, versus Georgia) were associated with using "good cancer." If patients are worried, 97% of physicians make themselves available for discussion, 44% refer to educational websites, 18% encourage communication with family/friends, 13% refer to support groups, and 7% refer to counselors. Physicians who perceived patients being quite/very worried were less likely to use "good cancer" (OR 0.54, 95% CI 0.35-0.84) and more likely to encourage patients to seek help outside the physician-patient relationship (OR 1.82, 95% CI 1.17-2.82).
Implications for cancer survivors: Physicians perceive patient worry as common and address it with various approaches, with some approaches of unclear benefit. Efforts are needed to develop tailored interventions targeting survivors' psychosocial needs.
DOI: 10.1007/s11764-020-00937-0
PubMed ID: 32939685
 Financial Hardship Among Hispanic Women with Thyroid Cancer. Thyroid. 2021 May;31(5):752-759.
Chen DW, Reyes-Gastelum D, Veenstra CM, Hamilton AS, Banerjee M, Haymart MR.
ABSTRACT
Background: Little is known about financial hardship among Hispanic women with thyroid cancer. The goal of this study was to determine the prevalence of financial hardship and to identify correlates of financial hardship in this understudied patient group. Methods: We surveyed Hispanic women who had diagnoses of thyroid cancer reported to the Los Angeles Surveillance Epidemiology and End Results (SEER) registry in 2014-2015, and who had previously completed our thyroid cancer survey in 2017-2018 (N = 273; 80% response rate). Acculturation was assessed with the Short Acculturation Scale for Hispanics (SASH). Patients were asked about three outcome measures since their thyroid cancer diagnosis: (i) financial status, (ii) insurance status, and (iii) material measures of financial hardship, collapsed into a single composite measure of financial hardship. We used multivariable logistic regression to identify correlates of financial hardship. Results: Patients' median age at diagnosis was 47 years (range 20-79 years); 49% were low-acculturated and 47% reported financial hardship. Since their thyroid cancer diagnosis, 31% and 12% of the cohort reported being worse off regarding financial and insurance status, respectively. In multivariable analysis, high-acculturated older women were less likely to experience financial hardship compared with high-acculturated 20-year-old women. While financial hardship decreased with age for high-acculturated women (p = 0.002), financial hardship remained elevated across all age groups for low-acculturated women (p = 0.54). Conclusions: Our findings suggest that across all age groups, low-acculturated Hispanic women with thyroid cancer are vulnerable to financial hardship, emphasizing the need for tailored patient-focused interventions.
PubMed ID: 32838705
Salivary and lacrimal dysfunction after radioactive iodine for differentiated thyroid cancer: American Head and Neck Society Endocrine Surgery Section and Salivary Gland Section joint multidisciplinary clinical consensus statement of otolaryngology, ophthalmology, nuclear medicine and endocrinology. Head Neck. 2020 Nov;42(11):3446-3459.
Singer MC, Marchal F, Angelos P, Bernet V, Boucai L, Buchholzer S, Burkey B, Eisele D, Erkul E, Faure F, Freitag SK, Gillespie MB, Harrell RM, Hartl D, Haymart M, Leffert J, Mandel S, Miller BS, Morris J, Pearce EN, Rahmati R, Ryan WR, Schaitkin B, Schlumberger M, Stack BC, Van Nostrand D, Wong KK, Randolph G.
ABSTRACT
Background: Postoperative radioactive iodine (RAI) administration is widely utilized in patients with differentiated thyroid cancer. While beneficial in select patients, it is critical to recognize the potential negative sequelae of this treatment. The prevention, diagnosis, and management of the salivary and lacrimal complications of RAI exposure are addressed in this consensus statement.
Methods: A multidisciplinary panel of experts was convened under the auspices of the American Head and Neck Society Endocrine Surgery and Salivary Gland Sections. Following a comprehensive literature review to assess the current best evidence, this group developed six relevant consensus recommendations.
Results: Consensus recommendations on RAI were made in the areas of patient assessment, optimal utilization, complication prevention, and complication management.
Conclusion: Salivary and lacrimal complications secondary to RAI exposure are common and need to be weighed when considering its use. The recommendations included in this statement provide direction for approaches to minimize and manage these complications.
DOI: 10.1002/hed.26417
PubMed ID: 32812307
Physician-Reported Misuse of Thyroid Ultrasonography. JAMA Surg. 2020 Oct 1;155(10):984-986.
Chen DW, Reyes-Gastelum D, Radhakrishnan A, Hamilton AS, Ward KC, Haymart MR.
ABSTRACT
This cohort study surveyed practicing physicians in the US about their use of thyroid ultrasonography to examine the rate at which misuse occurs.
DOI: 10.1001/jamasurg.2020.2507
PubMed ID: 32804996
Primary care provider involvement in thyroid cancer survivorship care. J Clin Endocrinol Metab. 2020 Sep 1;105(9):e3300–6.
Radhakrishnan A, Reyes-Gastelum D, Gay B, Hawley ST, Hamilton AS, Ward KC, Wallner LP, Haymart MR.
ABSTRACT
Context: While prior research has examined how primary care providers (PCPs) can care for breast and colon cancer survivors, little is known about their role in thyroid cancer survivorship.
Objective: To understand PCP involvement and confidence in thyroid cancer survivorship care.
Design/setting/participants: We surveyed PCPs identified by thyroid cancer patients from the Georgia and LA SEER registries (n = 162, response rate 56%). PCPs reported their involvement in long-term surveillance and confidence in handling survivorship care (role of random thyroglobulin levels and neck ultrasound, and when to end long-term surveillance and refer back to the specialist). We examined: 1) PCP-reported factors associated with involvement using multivariable analyses; and 2) bivariate associations between involvement and confidence in handling survivorship care.
Main outcome measures: PCP involvement (involved vs not involved) and confidence (high vs low).
Results: Many PCPs (76%) reported being involved in long-term surveillance. Involvement was greater among PCPs who noted clinical guidelines as the most influential source in guiding treatment (OR 4.29; 95% CI, 1.56-11.82). PCPs reporting high confidence in handling survivorship varied by aspects of care: refer patient to specialist (39%), role of neck ultrasound (36%) and random thyroglobulin levels (27%), and end long-term surveillance (14%). PCPs reporting involvement were more likely to report high confidence in discussing the role of random thyroglobulin levels (33.3% vs 7.9% not involved; P < 0.01).
Conclusions: While PCPs reported being involved in long-term surveillance, gaps remain in their confidence in handling survivorship care. Thyroid cancer survivorship guidelines that delineate PCP roles present one opportunity to increase confidence about their participation.
PubMed ID: 32639557
Disparities Research in Thyroid Cancer: Challenges and Strategies for Improvement. Thyroid. 2020 Sep;30(9):1231-1235.
Chen DW, Haymart MR.
ABSTRACT
Until recently, thyroid cancer was one of the most rapidly increasing cancers in the United States. Disparities exist in many aspects of thyroid cancer care as a result of the multifactorial interplay of systemic, patient, and physician factors. To better understand the management of thyroid cancer in populations at risk for health disparities and subsequently implement changes that will lead to health equity for all patients with thyroid cancer, health services research with innovative approaches is necessary.
PubMed ID: 32340582
The Relationship Between Imaging and Thyroid Cancer Diagnosis and Survival. Oncologist. 2020 Sep;25(9):765-771.
Haymart MR, Reyes-Gastelum D, Caoili E, Norton EC, Banerjee M.
ABSTRACT
Background: Controversy exists over whether there has been a true increase in the occurrence of thyroid cancer or overdiagnosis secondary to imaging practices. Because cancer overdiagnosis is associated with detection of indolent disease, overdiagnosis can be associated with perceived improvement in survival.
Materials and methods: Surveillance, Epidemiology, and End Results-Medicare linked database was used to determine the relationship between type of imaging leading to thyroid cancer diagnosis and survival. Disease-specific and overall survival were evaluated in 11,945 patients aged ≥66 years with differentiated thyroid cancer diagnosed between January 1, 2001, and September 30, 2015, who prior to their cancer diagnosis initially underwent thyroid ultrasound versus other imaging capturing the neck. Analyses were performed using the Kaplan-Meier method and Cox proportional hazards model with propensity score.
Results: Patients who underwent thyroid ultrasound as compared with other imaging had improved disease-specific and overall survival (p < .001, p < .001). However, those who underwent thyroid ultrasound were less likely to have comorbidities (p < .001) and more likely to be younger (p < .001), be female (p < .001), have localized cancer (p < .001), and have tumor size ≤1 cm (p < .001). After using propensity score analysis and adjusting for tumor characteristics, type of initial imaging still correlated with better overall survival but no longer correlated with better disease-specific survival.
Conclusion: There is improved disease-specific survival in patients diagnosed with thyroid cancer after thyroid ultrasound as compared with after other imaging. However, better disease-specific survival is related to these patients being younger and healthier and having lower-risk cancer, suggesting that thyroid ultrasound screening contributes to cancer overdiagnosis.
Implications for practice: The findings from this study have implications for patients, physicians, and policy makers. Patients who have thyroid ultrasound as their initial imaging are fundamentally different from those who are diagnosed after other imaging. Because patients undergoing ultrasound are younger and healthier and are diagnosed with lower-risk thyroid cancer, they are less likely to die of their thyroid cancer. However, being diagnosed with thyroid cancer can lead to cancer-related worry and create risks for harm from treatments. Thus, efforts are needed to reduce inappropriate use of ultrasound, abide by the U.S. Preventive Services Task Force recommendations, and apply nodule risk stratification tools when appropriate.
DOI: 10.1634/theoncologist.2020-0159
PubMed ID: 32329106
Patient Report of Recurrent and Persistent Thyroid Cancer. Thyroid. 2020 Sep;30(9):1297-1305.
Papaleontiou M, Evron JM, Esfandiari NH, Reyes-Gastelum D, Ward KC, Hamilton AS, Worden F, Haymart MR.
ABSTRACT
Background: Despite the excellent survival of most patients with differentiated thyroid cancer (DTC), recurrent and persistent disease remain major concerns for physicians and patients. However, studies on patient report of recurrent and persistent disease are lacking. Methods: Between February 1, 2017, and October 31, 2018, we surveyed eligible patients who were diagnosed with DTC between 2014 and 2015 from the Georgia and Los Angeles Surveillance, Epidemiology, and End Results cancer registries (N = 2632; response rate, 63%). Patients who reported current disease status were included in this study (n = 2454). Patient-reported data were linked to registry data. A multivariable, multinomial logistic regression analysis was conducted to determine patient and tumor characteristics associated with recurrent and persistent thyroid cancer. Quality of life was evaluated using the Patient-Reported Outcomes Measurement Information System-Global Health v1.2 questionnaire. Meaningful change in global health was defined as a minimal difference of a half standard deviation or 5 points compared with the mean (T score = 50) of a sample population matching the United States 2000 General Census. Results: Of the 2454 patients completing the survey, 95 (4.1%) reported recurrent disease and 137 (5.8%) reported persistent disease. In multinomial analyses, T3/T4 classification and cervical lymph node involvement (N1) were associated with both report of recurrent (adjusted relative risk ratio [RRR] 1.99, 95% confidence interval [CI 1.16-3.42]; adjusted RRR 2.03 [CI 1.29-3.21], respectively) and persistent disease (adjusted RRR 3.48 [CI 1.96-6.20]; adjusted RRR 3.56 [CI 2.41-5.24], respectively). Additionally, Hispanic ethnicity was associated with report of recurrent disease (adjusted RRR 1.99 [CI 1.23-3.24]). Regarding quality of life, the median scores in patients with persistent disease met criteria for meaningful change in global physical health (T-score = 44.9) and global mental health (T-score = 43.5) when compared with the general population norms. Median scores in patients with cured or recurrent disease did not meet criteria for meaningful change. Conclusions: Patient report is a reasonable method of assessing recurrent and persistent disease. Impact on quality of life is more marked for patients with reported persistent disease. Our findings will help personalize treatment and long-term follow-up in these patients.
PubMed ID: 32183609
Fragility Fractures in Male Veterans on Thyroid Hormone Therapy. Endocr Pract. 2020 Mar;26(3):359-361.
Papaleontiou M, Reyes-Gastelum D, Haymart MR.
Too Much of a Good Thing? A Cautionary Tale of Thyroid Cancer Overdiagnosis and Overtreatment. Thyroid. 2020 May;30(5):651-652.
Papaleontiou M, Haymart MR.
Retrospective Cohort Study of 1947 Thyroid Nodules: A Comparison of the 2017 American College of Radiology TI-RADS and the 2015 American Thyroid Association Classifications. AJR Am J Roentgenol. 2020 Apr;214(4):900-906.
Pandya A, Caoili EM, Jawad-Makki F, Wasnik AP, Shankar PR, Bude R, Haymart MR, Davenport MS.
ABSTRACT
OBJECTIVE. The objective of our study was to compare diagnostic accuracy and reliability of the 2017 American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) and 2015 American Thyroid Association (ATA) classifications for thyroid nodules. MATERIALS AND METHODS. This study was a retrospective cohort study of 1947 consecutive thyroid nodules sampled with fine-needle aspiration (FNA) from 2007 to 2016. Reviewers assigned TI-RADS scores to all nodules while blinded to clinical outcome and histologic diagnosis and compared TI-RADS scores with nodule-specific ATA scores from the same cohort. Five blinded radiologists independently assigned TI-RADS scores to a subset of 151 nodules (interrater agreement). The primary outcome was a comparison of the diagnostic accuracy of the TI-RADS and ATA classifications using ROC curve analysis. The reference standard was cytopathologic diagnosis according to the Bethesda system. Interrater agreement was determined using intraclass correlation (ICC) and kappa statistics. RESULTS. Of 1947 sampled thyroid nodules, 31.8% (n = 620) met TI-RADS criteria for FNA, 28.0% (n = 545) met TI-RADS criteria for follow-up, and 40.2% (n = 782) met TIRADS criteria to be ignored. Applying the 2015 ATA criteria resulted in recommendations of immediate FNA procedures for more nodules than applying the 2017 TI-RADS (ATA vs TIRADS: 62.3% [1213/1947] vs 31.8% [620/1947], p < 0.0001). Diagnostic accuracies (AUCs: TI-RADS score, 0.684 [95% CI, 0.644-0.724]; ATA, 0.686 [95% CI, 0.646-0.725]) and false-negative rates (TI-RADS, 2.2% [43/1947]; ATA, 2.4% [47/1947]) for the two classifications were similar (p = 0.75). Overall interrater agreement was fair for both (ICCs: TI-RADS, 0.437 [95% CI, 0.357-0.520]; ATA classification, 0.460 [95% CI, 0.391-0.533]). CONCLUSION. The 2017 ACR TI-RADS and 2015 ATA classifications have similar diagnostic accuracies and interrater agreement, but TI-RADS results in fewer nodules being recommended for immediate FNAs and more nodules being recommended for imaging surveillance.
DOI: 10.2214/ajr.19.21904
PubMed ID: 32069084
Disparities in risk perception of thyroid cancer recurrence and death. Cancer. 2020 Apr 1;126(7):1512-1521.
Chen DW, Reyes-Gastelum D, Wallner LP, Papaleontiou M, Hamilton AS, Ward KC, Hawley ST, Zikmund-Fisher BJ, Haymart MR.
ABSTRACT
Background: To the authors' knowledge, studies regarding risk perception among survivors of thyroid cancer are scarce.
Methods: The authors surveyed patients who were diagnosed with differentiated thyroid cancer from the Surveillance, Epidemiology, and End Results registries of Georgia and Los Angeles County (2632 patients; 63% response rate). The analytic cohort was defined by a ≤5% risk of disease recurrence and mortality (1597 patients). Patients estimated their recurrence and mortality risks separately (increments of 10% and endpoints of ≤5% and ≥95%). Both outcomes were dichotomized between reasonably accurate estimates (risk perception of ≤5% or 10%) versus overestimation (risk perception of ≥20%). Multivariable logistic regression was used to identify factors associated with risk overestimation, and the relationships between overestimation and both worry and quality of life were evaluated.
Results: In the current study sample, 24.7% of patients overestimated their recurrence risk and 12.5% overestimated their mortality risk. A lower educational level was associated with overestimating disease recurrence (≤high school diploma: odds ratio [OR], 1.64 [95% CI, 1.16-2.31]; and some college: OR, 1.36 [95% CI, 1.02-1.81]) and mortality (≤high school diploma: OR, 1.86 [95% CI, 1.18-2.93]) risk compared with those attaining at least a college degree. Hispanic ethnicity was found to be associated with overestimating recurrence risk (OR, 1.44, 95% CI 1.02-2.03) compared with their white counterparts. Worry about recurrence and death was found to be greater among patients who overestimated versus those who had a reasonably accurate estimate of their risk of disease recurrence and mortality, respectively (P < .001). Patients who overestimated mortality risk also reported a decreased physical quality of life (mean T score, 43.1; 95% CI, 41.6-44.7) compared with the general population.
Conclusions: Less educated patients and Hispanic patients were more likely to report inaccurate risk perceptions, which were associated with worry and a decreased quality of life.
DOI: 10.1002/cncr.32670
PubMed ID: 31869452
A Survey of American Thyroid Association Members Regarding the 2015 Adult Thyroid Nodule and Differentiated Thyroid Cancer Clinical Practice Guidelines. Thyroid. 2020 Jan;(1):25-33.
Sawka AM, Gagliardi AR, Haymart MR, Sturgeon C, Bernet V, Hoff KC, Angelos P, Brito JP, Haugen BR MD, Kim BW, Kopp PA, Mandel SJ, Ross DS, Samuels M, Sarne DH MD, Sinclair CF, Jonklaas J.
ABSTRACT
Background: The 2015 American Thyroid Association (ATA) clinical practice guidelines (CPGs) on management of thyroid nodules (TNs) and differentiated thyroid cancer (DTC) in adults were developed to inform clinicians, patients, researchers, and health policy makers about the best available evidence, and its limitations, relating to management of these conditions. Methods: We conducted a cross-sectional electronic survey of ATA members' perspectives of these CPGs, using a standardized survey (Clinician Guidelines Determinant Questionnaire) developed by the Guidelines International Network. A survey link was electronically mailed to members in February of 2019, with reminders sent to nonrespondents 2 and 5 weeks later. Data were descriptively summarized, after excluding missing responses. Results: The overall response rate was 19.8% (348/1761). The effective response rate was 20.2% (348/1720), after excluding a recently deceased member and individuals who had either invalid e-mail addresses or whose e-mails were returned. Of the respondents, 37.9% (132/348) were female, 60.4% (209/346) were endocrinologists, 27.5% (95/346) were surgeons, and 3.5% (12/346) were nuclear medicine specialists. The majority of respondents (71.9%; 250/348) were at a mid- or advanced-career level, and more than half were in academia (57.5%; 195/339). The majority (69.8%; 243/348) practiced in North America. The vast majority of respondents indicated that the CPGs explained the underlying evidence (92.3%; 298/323) and 92.9% (300/323) agreed or strongly agreed with the content. Most respondents stated that they regularly used the CPGs in their practice (83.0%; 268/323). Most respondents (83.0%; 268/323) also agreed or strongly agreed that the recommendations were easy to incorporate in their practice. The most popular CPG format was an electronic desktop file (78.8%; 252/320). Shorter more frequent CPGs were favored by 55.0% (176/320) of respondents, and longer traditional CPGs were favored by 39.7% (127/320). Conclusions: The clinical content and evidence explanations in the adult TN and DTC CPGs are widely accepted and applied among ATA survey respondents. Future ATA CPG updates need to be optimized to best meet users' preferences regarding format, frequency, and length.
PubMed ID: 31830853
Thyroid nodules and cancer during pregnancy, post-partum and preconception planning: Addressing the uncertainties and challenges. Best Pract Res Clin Endocrinol Metab. 2019 Nov 22:101363.
Papaleontiou M, Haymart MR.
ABSTRACT
Thyroid nodules and thyroid cancer have become increasingly common worldwide. When discovered during pregnancy, they pose unique diagnostic and therapeutic challenges for both the treating physician and the patient. The benefits of treatment should be carefully weighed against risks that may adversely impact maternal and fetal health. In this review, we present current knowledge and controversies surrounding the management of thyroid nodules and thyroid cancer in pregnancy, in the post-partum period and during preconception planning.
DOI: 10.1016/j.beem.2019.101363
PubMed ID: 31786102
Energy level and fatigue after surgery for thyroid cancer: A population-based study of patient-reported outcomes. Surgery. 2020 Jan;167(1):102-109.
Hughes DT, Reyes-Gastelum D, Kovatch KJ, Hamilton AS, Ward KC, Haymart MR.
ABSTRACT
Introduction: The relationship between treatment for differentiated thyroid cancer and patient-report of decreased energy and fatigue remains unclear.
Methods: Patients diagnosed with differentiated thyroid cancer from 2014 to 2015 included in the Georgia and Los Angeles, California cancer registries of the Surveillance, Epidemiology, and End Results program were surveyed 2 to 4 years after diagnosis, and responses were linked to data from the Surveillance, Epidemiology, and End Results registry. Multivariable logistic regression analysis determined characteristics associated with the report of worse energy level at 2 to 4 years compared to before treatment and current fatigue severity using adjusted odds ratios with 95% confidence intervals.
Results: Of the 2,584 respondents, 988 (38.2%) reported much worse or somewhat worse energy and 1,310 (50.7%) reported moderate to very severe fatigue. The majority of patients were treated with total thyroidectomy with or without nodal dissection (total thyroidectomy with lymph node removal [49.3%] or total thyroidectomy [38.3%]). Only 12.3% had a thyroid lobectomy. Just over half were treated with radioactive iodine therapy (56.7%) and thyroid hormone suppression (50.2%) after the thyroidectomy. Younger age, history of depression, thyroid hormone suppression (odds ratio 1.48 [confidence interval 1.21-1.82]), and receipt of radioiodine (odds ratio 1.31 [confidence interval 1.10-1.56]) correlated with worse energy. Similarly, correlates of substantial fatigue included younger age, more comorbidities, history of depression, and thyroid hormone suppression (odds ratio 1.63 [confidence interval 1.34-1.99]). The presence of low serum calcium levels for >3 months after thyroidectomy was associated with worse energy (odds ratio 1.26 [confidence interval 1.02-1.54]) and substantial fatigue (odds ratio 1.49 [confidence interval 1.21-1.84]).
Conclusion: In addition to accepted risk factors such as depression and comorbidities, receiving radioactive iodine and reporting low calcium after thyroidectomy for differentiated thyroid cancer were associated with reports of worse energy compared to preoperative levels; thyroid hormone suppression was associated with reports of both worse energy and substantial post-treatment fatigue.
DOI: 10.1016/j.surg.2019.04.068
PubMed ID: 31582311
Role of Patient Maximizing-Minimizing Preferences in Thyroid Cancer Surveillance. J Clin Oncol. 2019 Nov 10;37(32):3042-3049.
Evron JM, Reyes-Gastelum D, Banerjee M, Scherer LD, Wallner LP, Hamilton AS, Ward KC, Hawley ST, Zikmund-Fisher BJ, Haymart MR.
ABSTRACT
Purpose: To understand the effect of patient preferences on thyroid cancer surveillance intensity.
Patients and methods: Eligible patients diagnosed with thyroid cancer between January 1, 2014, and December 31, 2015, from the Georgia and Los Angeles County SEER registries were surveyed between February 2017 and October 2018 (N = 2,632; response rate, 63%). Patient reports on health care utilization in the past year and responses to the validated Medical Maximizer-Minimizer Scale were linked to SEER data in the 2,183 disease-free patients. Ordered logistic regression was performed using a cumulative logit with nonproportional odds.
Results: Of disease-free patients, 31.6% were classified as minimizers, 42.5% as moderate maximizers, and 25.9% as strong maximizers. In the past year, 25.2%, 27.3%, and 38.5% of minimizers, moderate maximizers, and strong maximizers, respectively, had ≥ 4 doctor visits, and 18.3%, 24.9%, and 29.5%, respectively, had ≥ 2 neck ultrasounds. When controlling for age, sex, race and ethnicity, comorbidity, stage, and SEER site, strong maximizers (compared with minimizers) were significantly more likely to report ≥ 4 doctor visits (odds ratio [OR], 1.45; 95% CI, 1.10-1.92), ≥ 2 neck ultrasounds (OR, 1.58; 95% CI, 1.17-2.14), ≥ 1 radioactive iodine scan (OR, 1.73; 95% CI, 1.19-2.50), and ≥ 1 additional imaging study (OR, 2.06; 95% CI, 1.56-2.72).
Conclusion: Among patients with thyroid cancer who have been declared disease free, preference for a more maximal versus minimal approach to medical care is associated with increased number of physician visits and imaging tests. Because increased surveillance does not clearly correlate with improved outcomes, poses potential risks to patients, and contributes to increased healthcare costs, stronger consideration of the role of patient preferences is necessary when framing discussions on surveillance.
DOI: 10.1200/jco.19.01411
PubMed ID: 31573822
Patient Requests for Tests and Treatments Impact Physician Management of Hypothyroidism. Thyroid. 2019 Nov;29(11):1536-1544.
Esfandiari NH, Reyes-Gastelum D, Hawley ST, Haymart MR, Papaleontiou M.
ABSTRACT
Background: Levothyroxine is one of the most commonly prescribed medications in the United States. Although prior research focused on over- and undertreatment and patient dissatisfaction with thyroid hormone, little is known about physician-reported barriers to managing thyroid hormone therapy. In addition, the impact of patient requests for tests and treatments on hypothyroidism management remains unexplored. Methods: We randomly surveyed physician members of the Endocrine Society, American Academy of Family Practice and American Geriatrics Society. Respondents were asked to rate barriers to management of thyroid hormone therapy. We conducted multivariable logistic regression analyses to determine correlates with physician report of the most commonly reported barriers, including patient requests. Results: Response rate was 63% (359/566). Almost half of the physicians reported that patient requests for tests and treatments were somewhat to very likely to being a barrier to appropriate management of thyroid hormone therapy (46%). Endocrinologists (odds ratio [OR] = 2.29 [95% confidence interval, CI 1.03-5.23], compared with primary care physicians) and physicians with more than 25% of patients on thyroid hormone therapy per year (OR = 1.90 [CI 1.05-3.46], compared with those with <25% patients per year) were more likely to report patient requests as a barrier. Physicians with more years in practice were less likely to do so (11-20 years: OR = 0.44 [CI 0.21-0.89]; >20 years: OR = 0.24 [CI 0.12-0.46], compared with ≤10 years). Physician-reported patient requests included requests for preparations other than synthetic thyroxine (52%), adjusting thyroid hormone dose based on symptoms when biochemically euthyroid (52%), maintaining thyrotropin level below the reference range (32%), and adjusting dose according to serum T3 level (21%). Physicians who reported receiving patient requests for the former three unconventional practices were more likely to execute them (p < 0.001, p = 0.014, p < 0.001, respectively). Conclusions: Physicians reported patient requests for tests and treatments as a common barrier to appropriate thyroid hormone management. In some scenarios, physician adherence to patient requests may be a driver for inappropriate care and lead to harm. Understanding physician-reported barriers to thyroid hormone management and factors associated with physician perception that patient requests are a barrier is key to improving patient care.
PubMed ID: 31436135
Factors Associated With Diagnosis and Treatment of Thyroid Microcarcinomas. J Clin Endocrinol Metab. 2019 Dec 1;104(12):6060-6068.
Esfandiari NH, Hughes DT, Reyes-Gastelum D, Ward KC, Hamilton AS, Haymart MR.
ABSTRACT
Context: Nearly one-third of all thyroid cancers are ≤1 cm.
Objective: To determine diagnostic pathways for microcarcinomas vs larger cancers.
Design/setting/participants: Patients from Georgia and Los Angeles Surveillance, Epidemiology, and End Results (SEER) registries with differentiated thyroid cancer diagnosed in 2014 or 2015 were surveyed. Survey data were linked to SEER data on tumor and treatment characteristics. Multivariable logistic regression analysis was performed.
Main outcome measures: Method of nodule discovery; reason for thyroid surgery.
Results: Of patients who underwent surgery, 975 (38.2%) had cancers ≤1 cm, and 1588 cancers (61.8%) were >1 cm. The reported method of nodule discovery differed significantly between patients with cancers ≤1 cm and those with cancers >1 cm (P < 0.001). Cancer ≤1 cm was associated with nodule discovery on thyroid ultrasound (compared with other imaging, OR, 1.59; 95% CI, 1.21 to 2.10), older patient age (45 to 54 years vs ≤44, OR, 1.45; 95% CI, 1.16 to 1.82), and female sex (OR, 1.51; 95% CI, 1.22 to 1.87). Hispanic ethnicity (OR, 0.71; 95% CI, 0.57 to 0.89) and Asian race (OR, 0.67; 95% CI, 0.49 to 0.92) were negative correlates. Cancers ≤1 cm were associated with lower likelihood of surgery for a nodule suspicious or consistent with cancer (OR, 0.48; 95% CI, 0.40 to 0.57).
Conclusion: Thyroid microcarcinomas are more likely to be detected by ultrasound and less likely to be associated with surgery scheduled for known thyroid cancer. Understanding diagnostic pathways allows for targeted interventions to decrease overdiagnosis and overtreatment.
PubMed ID: 31415089
Assessment of Voice Outcomes Following Surgery for Thyroid Cancer. JAMA Oto. 2019 Sep 1;145(9):823-829.
Kovatch KJ, Reyes-Gastelum D, Hughes DT, Hamilton AS, Ward KC, Haymart MR.
ABSTRACT
Importance: An increasing number of surgeries are being performed for differentiated thyroid cancer (DTC). Long-term voice abnormalities are a known risk of thyroid surgery; however, few studies have used validated scales to quantify voice outcomes after surgery.
Objective: To identify the prevalence, severity, and factors associated with poor voice outcomes following surgery for DTC.
Design, setting, and participants: A cross-sectional, population-based survey was distributed via a modified Dillman method to 4185 eligible patients and linked to Surveillance, Epidemiology and End Results (SEER) data from SEER sites in Georgia and Los Angeles, California, from February 1, 2017, to October 31, 2018. Multivariable logistic regression and zero-inflated negative binomial analysis were performed to determine factors associated with abnormal voice. Participants included patients undergoing surgery for DTC between January 1, 2014, and December 31, 2015, excluding those with voice abnormalities before surgery.
Main outcomes and measures: Abnormal Voice Handicap Index (VHI-10) score, defined as greater than 11. The VHI-10 is designed to quantify 10 psychosocial consequences of voice disorders on a Likert scale (0, never; to 4, always).
Results: A total of 2632 patients (63%) responded to the survey and 2325 met the inclusion criteria. With data reported as unweighted number and weighted percentage, 1792 were women (77.4%); weighted mean (SD) age was 49.4 (14.4) years. Of these, 599 patients (25.8%) reported voice changes lasting more than 3 months following surgery, 272 patients (12.7%) were identified as having an abnormal VHI-10 score, and 105 patients (4.7%) reported vocal fold motion impairment diagnosed by laryngoscopy. In multivariable analysis, factors associated with an abnormal VHI-10 score included age 45 to 54 years (reference, ≤44 years; odds ratio [OR], 1.49; 95% CI, 1.05-2.11), black race (OR, 1.73; 95% CI, 1.14-2.62), Asian race (OR, 1.66; 95% CI, 1.08-2.54), gastroesophageal reflux disease (OR, 1.67; 95% CI, 1.15-2.43), and lateral neck dissection (OR, 1.99; 95% CI, 1.11-3.56).
Conclusions and relevance: A high prevalence of abnormal voice per validation with the VHI-10 emphasizes the need for heightened awareness of voice abnormalities following surgery and warrants consideration in the preoperative risk-benefit discussion, planned extent of surgery, and postoperative rehabilitation.
DOI: 10.1001/jamaoto.2019.1737
PubMed ID: 31318375
Patient-Perceived Lack of Choice in Receipt of Radioactive Iodine for Treatment of Differentiated Thyroid Cancer. J Clin Oncol. 2019 Aug 20;37(24):2152-2161.
Wallner LP, Reyes-Gastelum D, Hamilton AS, Ward KC, Hawley ST, Haymart MR.
ABSTRACT
Purpose: For many patients with differentiated thyroid cancer, use of radioactive iodine (RAI) does not improve survival or reduce recurrence risk. Yet there is wide variation in RAI use, emphasizing the importance of understanding patient perspectives regarding RAI decision making.
Patients and methods: All eligible patients diagnosed with thyroid cancer from 2014 to 2015 from the Georgia and Los Angeles SEER registries were surveyed (N = 2,632; response rate, 63%). Patients in whom selective RAI use is recommended were included in this analysis (n = 1,319). Patients were asked whether they felt like they had a choice to receive RAI (yes or no), how strongly their physician recommended RAI (5-point Likert-type scale), whether they received RAI (yes or no), and how satisfied they were with their RAI decision (more [score of 4 or greater] v less). Multivariable, weighted logistic regression with multiple imputation was used to assess the associations between patient characteristics and perception of no RAI choice and between perception of no RAI choice with receipt of RAI and decision satisfaction.
Results: More than half of respondents (55.8%) perceived they did not have an RAI choice, and the majority of patients (75.9%) received RAI. The odds of perceiving no RAI choice was greater among those whose physician strongly recommended RAI (adjusted odds ratio [OR], 1.56; 95% CI, 1.13 to 2.17). Patients who perceived they did not have an RAI choice were more likely to receive RAI (adjusted OR, 2.50; 95% CI, 1.64 to 3.82) and report lower decision satisfaction (adjusted OR, 2.31; 95% CI, 1.67 to 3.20).
Conclusion: Many patients did not feel they had a choice about whether to receive RAI. Patients who perceived they did not have a choice were more likely to receive RAI and report lower decision satisfaction, suggesting a need for more shared decision making to reduce overtreatment.
DOI: 10.1200/jco.18.02228
PubMed ID: 31283406
Worry in Thyroid Cancer Survivors with a Favorable Prognosis. Thyroid. 2019 Aug;29(8):1080-1088.
Papaleontiou M, Reyes-Gastelum D, Gay BL, Ward KC, Hamilton AS, Hawley ST, Haymart MR.
ABSTRACT
Background: Little is known about cancer-related worry in thyroid cancer survivors with favorable prognosis. Methods: A diverse cohort of patients diagnosed with differentiated thyroid cancer in 2014-2015 from the Surveillance, Epidemiology, and End Results (SEER) Program registries of Georgia and Los Angeles County were surveyed two to four years after diagnosis. Main outcomes were any versus no worry about harms from treatments, quality of life, family at risk for thyroid cancer, recurrence, and death. After excluding patients with recurrent, persistent, and distant disease, multivariable logistic regression was used to identify correlates of worry in 2215 disease-free survivors. Results: Overall, 41.0% reported worry about death, 43.5% worry about harms from treatments, 54.7% worry about impaired quality of life, 58.0% worry about family at risk, and 63.2% worry about recurrence. After controlling for disease severity, in multivariable analyses with separate models for each outcome, there was more worry in patients with lower education (e.g., worry about recurrence, high school diploma and below: odds ratio [OR] 1.78, 95% confidence interval [CI 1.36-2.33] compared with college degree and above). Older age and male sex were associated with less worry (e.g., worry about recurrence, age ≥65 years: OR 0.28 [CI 0.21-0.39] compared with age ≤44 years). Worry was associated with being Hispanic or Asian (e.g., worry about death, Hispanic: OR 1.41 [CI 1.09-1.83]; Asian: OR 1.57 [CI 1.13-2.17] compared with whites). Conclusions: Physicians should be aware that worry is a major issue for thyroid cancer survivors with favorable prognosis. Efforts should be undertaken to alleviate worry, especially among vulnerable groups, including female patients, younger patients, those with lower education, and racial/ethnic minorities.
PubMed ID: 31232194
Risk of Osteoporosis and Fractures in Patients with Thyroid Cancer: A Case-Control Study in U.S. Veterans. Oncologist. 2019 Sep;24(9):1166-1173.
Papaleontiou M, Banerjee M, Reyes-Gastelum D, Hawley ST, Haymart MR.
ABSTRACT
Background: Data on osteoporosis and fractures in patients with thyroid cancer, especially men, are conflicting. Our objective was to determine osteoporosis and fracture risk in U.S. veterans with thyroid cancer.
Materials and methods: This is a case-control study using the Veterans Health Administration Corporate Data Warehouse (2004-2013). Patients with thyroid cancer (n = 10,370) and controls (n = 10,370) were matched by age, sex, weight, and steroid use. Generalized linear mixed-effects regression model was used to compare the two groups in terms of osteoporosis and fracture risk. Next, subgroup analysis of the patients with thyroid cancer using longitudinal thyroid-stimulating hormone (TSH) was performed to determine its effect on risk of osteoporosis and fractures. Other covariates included patient age, sex, median household income, comorbidities, and steroid and androgen use.
Results: Compared with controls, osteoporosis, but not fractures, was more frequent in patients with thyroid cancer (7.3% vs. 5.3%; odds ratio [OR], 1.33; 95% confidence interval [CI], 1.18-1.49) when controlling for median household income, Charlson/Deyo comorbidity score, and androgen use. Subgroup analysis of patients with thyroid cancer demonstrated that lower TSH (OR, 0.93; 95% CI, 0.90-0.97), female sex (OR, 4.24; 95% CI, 3.53-5.10), older age (e.g., ≥85 years: OR, 17.18; 95% CI, 11.12-26.54 compared with <50 years), and androgen use (OR, 1.63; 95% CI, 1.18-2.23) were associated with osteoporosis. Serum TSH was not associated with fractures (OR, 1.01; 95% CI, 0.96-1.07).
Conclusion: Osteoporosis, but not fractures, was more common in U.S. veterans with thyroid cancer than controls. Multiple factors may be contributory, with low TSH playing a small role.
Implications for practice: Data on osteoporosis and fragility fractures in patients with thyroid cancer, especially in men, are limited and conflicting. Because of excellent survival rates, the number of thyroid cancer survivors is growing and more individuals may experience long-term effects from the cancer itself and its treatments, such as osteoporosis and fractures. The present study offers unique insight on the risk for osteoporosis and fractures in a largely male thyroid cancer cohort. Physicians who participate in the long-term care of patients with thyroid cancer should take into consideration a variety of factors in addition to TSH level when considering risk for osteoporosis.
DOI: 10.1634/theoncologist.2019-0234
PubMed ID: 31164453
A History of Thyroid Cancer Does Not Meaningfully Complicate Pregnancy. Thyroid. 2019;29(6):758-759.
Korevaar TIM, Haymart MR.
American Head and Neck Society Endocrine Section clinical consensus statement: North American quality statements and evidence-based multidisciplinary workflow algorithms for the evaluation and management of thyroid nodules. Head Neck. 2019;41(4):843-856.
Meltzer CJ, Irish J, Angelos P, Busaidy NL, Davies L, Dwojak S, Ferris RL, Haugen BR, Harrell RM, Haymart MR, McIver B, Mechanick JI, Monteiro E, Morris JC 3rd, Morris LGT, Odell M, Scharpf J, Shaha A, Shin JJ, Shonka DC Jr, Thompson GB, Tuttle RM, Urken ML, Wiseman SM, Wong RJ, Randolph G.
ABSTRACT
Background: Care for patients with thyroid nodules is complex and multidisciplinary, and research demonstrates variation in care. The objective was to develop clinical guidelines and quality metrics to reduce unwarranted variation and improve quality.
Methods: Multidisciplinary expert consensus and modified Delphi approach. Source documents were workflow algorithms from Kaiser Permanente Northern California and Cancer Care of Ontario based on the 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer.
Results: A consensus-based, unified preoperative, perioperative, and postoperative workflow was developed for North American use. Twenty-one panelists achieved consensus on 16 statements about workflow-embedded process and outcomes metrics addressing safety, access, appropriateness, efficiency, effectiveness, and patient centeredness of care.
Conclusion: A panel of Canadian and United States experts achieved consensus on workflows and quality metric statements to help reduce unwarranted variation in care, improving overall quality of care for patients diagnosed with thyroid nodules.
DOI: 10.1002/hed.25526
PubMed ID: 30561068
NCCN Guidelines Insights: Thyroid Carcinoma, Version 2.2018. JNCCN. 2018;16(12):1429-1440.
Haddad RI, Nasr C, Bischoff L, Busaidy NL, Byrd D, Callender G, Dickson P, Duh QY, Ehya H, Goldner W, Haymart M, Hoh C, Hunt JP, Iagaru A, Kandeel F, Kopp P, Lamonica DM, McIver B, Raeburn CD, Ridge JA, Ringel MD, Scheri RP, Shah JP, Sippel R, Smallridge RC, Sturgeon C, Wang TN, Wirth LJ, Wong RJ, Johnson-Chilla A, Hoffmann KG, Gurski LA.
ABSTRACT
The NCCN Guidelines for Thyroid Carcinoma provide recommendations for the management of different types of thyroid carcinoma, including papillary, follicular, HĂĽrthle cell, medullary, and anaplastic carcinomas. These NCCN Guidelines Insights summarize the panel discussion behind recent updates to the guidelines, including the expanding role of molecular testing for differentiated thyroid carcinoma, implications of the new pathologic diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features, and the addition of a new targeted therapy option for BRAF V600E-mutated anaplastic thyroid carcinoma.
PubMed ID: 30545990
Thyroid Ultrasound and the Increase in Diagnosis of Low-Risk Thyroid Cancer. J Clin Endocrinol Metab.2019;104(3):785-792.
Haymart MR, Banerjee M, Reyes-Gastelum D, Caoili E, Norton EC.
ABSTRACT
Context: Thyroid cancer incidence increased with the greatest change in adults aged ≥65 years.
Objective: To determine the relationship between area-level use of imaging and thyroid cancer incidence over time.
Design, setting and participants: Longitudinal imaging patterns in Medicare patients aged ≥65 years residing in Surveillance, Epidemiology, and End Results (SEER) regions were assessed in relationship to differentiated thyroid cancer diagnosis in patients aged ≥65 years included in SEER-Medicare. Linear mixed-effects modeling was used to determine factors associated with thyroid cancer incidence over time. Multivariable logistic regression was used to determine patient characteristics associated with receipt of thyroid ultrasound as initial imaging.
Main outcome measure: Thyroid cancer incidence.
Results: Between 2002 and 2013, thyroid ultrasound use as initial imaging increased (P < 0.001). Controlling for time and demographics, use of thyroid ultrasound was associated with thyroid cancer incidence (P < 0.001). Findings persisted when cohort was restricted to papillary thyroid cancer (P < 0.001), localized papillary thyroid cancer (P = 0.004), and localized papillary thyroid cancer with tumor size ≤1 cm (P = 0.01). Based on our model, from 2003 to 2013, at least 6594 patients aged ≥65 years were diagnosed with thyroid cancer in the United States due to increased use of thyroid ultrasound. Thyroid ultrasound as initial imaging was associated with female sex and comorbidities.
Conclusion: Greater thyroid ultrasound use led to increased diagnosis of low-risk thyroid cancer, emphasizing the need to reduce harms through reduction in inappropriate ultrasound use and adoption of nodule risk stratification tools.
PubMed ID: 30329071
Association of the Word Cancer With Thyroid Cancer Treatment Decisions-A Rose by Any Other Name. JAMA Oto. 2018;144(10):896.
Haymart MR.
South Korean Thyroid Cancer Trends: Good News and Bad. Thyroid. 2018;28(9):1081-1082.
Haymart MR, Davies L.
Limitations of the 2015 ATA Guidelines for Prediction of Thyroid Cancer: A Review of 1,947 Consecutive Aspirations. J Clin Endocrinol Metab. 2018;103(9):3496-3502.
Pandya A, Caoili EM, Jawad-Makki F, Wasnik AP, Shankar PR, Bude R, Haymart MR, Davenport MS.
ABSTRACT
Background: The 2015 American Thyroid Association (ATA) guidelines have been proposed to aid in the management of thyroid nodules by determining whether fine needle aspiration is indicated.
Objective: To determine whether the ATA guidelines contribute to the overdiagnosis of thyroid cancer.
Patients and methods: This was a retrospective cohort study of ultrasound-imaged thyroid nodules (n = 1947) consecutively aspirated at a tertiary care center from 1 October 2009 to 22 February 2016. Nodules were retrospectively reviewed, assigned a 2015 ATA morphology, and placed into one of five 2015 ATA categories of risk (ATA-1, <1% risk of malignancy; ATA-2, <3% risk; ATA-3, 5% to 10% risk, ATA-4: 10% to 20% risk; ATA-5, >70% to 90% risk) by a reader who was blinded to cytology. ATA category was compared with cytopathology. The positive predictive value (PPV) of each ATA category was calculated with respect to cancer. Numbers needed to aspirate and Pearson correlations were calculated. Interrater agreement for ATA category across five readers was assessed.
Results: The PPV for cancer increased by ATA category [category 1 to 5, respectively: 0% (0/14), 2% (4/249), 5% (36/733), 12% (104/850), 28% (28/101)]. The number needed to sample to detect one papillary cancer was 125 (ATA-2), 49 (ATA-3), 13 (ATA-4), and 5 (ATA-5). The overall interrater agreement for ATA score across all five readers was fair (intraclass correlation coefficient 0.460).
Conclusions: The 2015 ATA guidelines stratify risk for thyroid cancer; however, the stratification system is overly optimistic regarding cancer detection rates for the higher-risk nodules, and there is only fair interrater agreement.
PubMed ID: 29982716
Treatment-Free Survival in Patients With Differentiated Thyroid Cancer. J Clin Endocrinol Metab. 2018;103(7):2720-2727.
Banerjee M, Reyes-Gastelum D, Haymart MR.
ABSTRACT
Objective: Cancer recurrence is a primary concern for patients with differentiated thyroid cancer; however, population-level data on recurrent or persistent disease do not currently exist. The objective of this study was to determine treated recurrent or persistent thyroid cancer by using a population-based registry, identify correlates of poor treatment-free survival, and define prognostic groups for treatment-free survival.
Methods: In this population-based study, we evaluated treatment-free survival in 9273 patients from the Surveillance, Epidemiology, and End Results Program-Medicare with a diagnosis of differentiated thyroid cancer between 1998 and 2012. Treated recurrence was defined by treatment of recurrent or persistent differentiated thyroid cancer with surgery, radioactive iodine, or radiation therapy at ≥1 year after diagnosis. Multivariable analysis was performed with Cox proportional hazards regression, survival trees, and random survival forests.
Results: In this cohort the median patient age at time of diagnosis was 69 years, and 75% of the patients were female. Using survival tree analyses, we identified five distinct prognostic groups (P < 0.001), with a prediction accuracy of 88.7%. The 5-year treatment-free survival rates of these prognostic groups were 96%, 91%, 85%, 72%, and 52%, respectively, and the 10-year treatment-free survival rates were 94%, 87%, 80%, 64%, and 39%. Based on survival forest analysis, the most important factors for predicting treatment-free survival were stage, tumor size, and receipt of radioactive iodine.
Conclusion: In this population-based cohort, five prognostic groups for treatment-free survival were identified. Understanding treatment-free survival has implications for the care and long-term surveillance of patients with differentiated thyroid cancer.
PubMed ID: 29788217
Is BRAF V600E Mutation the Explanation for Age-Associated Mortality Risk in Patients With Papillary Thyroid Cancer? J Clin Oncol. 2018;36(5):433-434.
Haymart MR.
Active Surveillance for Low-Risk Cancers - A Viable Solution to Overtreatment? N Engl J Med. 2017;377(3):203-206.
Haymart MR, Miller DC, Hawley ST.
Controversies in the Management of Low-Risk Differentiated Thyroid Cancer. Endocr Rev. 2017;38(4):351-378.
Haymart MR, Esfandiari NH, Stang MT, Sosa JA.
ABSTRACT
Controversy exists over optimal management of low-risk differentiated thyroid cancer. This controversy occurs in all aspects of management, including surgery, use of radioactive iodine for remnant ablation, thyroid hormone supplementation, and long-term surveillance. Limited and conflicting data, treatment paradigm shifts, and differences in physician perceptions contribute to the controversy. This lack of physician consensus results in wide variation in patient care, with some patients at risk for over- or undertreatment. To reduce patient harm and unnecessary worry, there is a need to design and implement studies to address current knowledge gaps.
PubMed ID: 28633444
Referral of Older Thyroid Cancer Patients to a High-Volume Surgeon: Results of a Multidisciplinary Physician Survey. Endocr Pract. 2017;23(7):808-815.
Papaleontiou M, Gauger PG, Haymart MR.
ABSTRACT
Objective: Surgical outcomes of thyroid cancer patients are improved with high-volume surgeons. However, age disparities in referral to specialist surgical centers still exist. The factors that influence decision making regarding referral of older thyroid cancer patients to high-volume surgeons remain unknown.
Methods: We surveyed members of the Endocrine Society, American College of Physicians, and American Academy of Family Practice.
Results: Overall, 270 physicians completed the survey. Patient preference (69%), transportation barriers (62%), and confidence in local surgeon (54%) were the most cited factors decreasing likelihood of referral to a high-volume surgeon. In clinical scenarios, referral rates to a high-volume surgeon were similar for patients aged 40 and 65 years with a 1-cm thyroid nodule diagnostic of thyroid cancer (n = 137 [54%]; n = 132 [52%], respectively) as for an 85-year-old with a 4-cm nodule (n = 148 [59%]). When comorbidities were introduced, more physicians (n = 186 [74%]) would refer a 65-year-old with a 4-cm thyroid nodule and comorbidities, compared to an 85-year-old with the same nodule size without comorbidi-ties. In multivariable analysis, treating >10 thyroid cancer patients/year (P<.001; P<.005) and endocrinology specialty (P = .003; P = .003) were associated with referral to a high-volume surgeon for a 65-year-old with comorbidities and an 85-year-old without comorbidities, respectively.
Conclusion: Understanding surgical referral patterns of older thyroid cancer patients is vital in identifying obstacles in the referral process. We found that patient factors including comorbidities and physician factors including specialty and patient volume influence these patterns. This is the first step towards developing targeted interventions for these patients.
DOI: 10.4158/ep171788.or
PubMed ID: 28534681
Population-Based Assessment of Complications following Surgery for Thyroid Cancer. J Clin Endocrinol Metab. 2017;102(7):2543-2551.
Papaleontiou M, Hughes DT, Guo C, Banerjee M, Haymart MR.
ABSTRACT
Context: As thyroid cancer incidence rises, more patients undergo thyroid surgery. Although postoperative complication rates have been reported in single institution studies, population-based data are limited.
Objective: To determine thyroid cancer surgery complication rates and identify at-risk populations.
Design/setting/patients: Using the Surveillance, Epidemiology, and End Results-Medicare database, we evaluated general complications within 30 days and thyroid surgery-specific complications within 1 year in 27,912 patients who underwent surgery for differentiated or medullary thyroid cancer between 1998 and 2011. Multivariable analyses of patient characteristics associated with postoperative complications were performed.
Main outcome measures: General and thyroid surgery-specific complications.
Results: Overall, 1820 (6.5%) patients developed general postoperative complications and 3427 (12.3%) developed thyroid surgery-specific complications. In multivariable analyses, general and thyroid surgery-specific complications were significantly higher in patients >65 years [odds ratio (OR), 2.61; 95% confidence interval (CI), 2.31 to 2.95; OR, 3.12; 95% CI, 2.85 to 3.42], those with a Charlson/Deyo comorbidity score of 1 (OR, 2.40; 95% CI, 1.66 to 3.49; OR, 1.88; 95% CI, 1.53 to 2.31) and ≥2 (OR, 7.05; 95% CI, 5.33 to 9.56; OR, 3.62; 95% CI, 3.11 to 4.25), and those with regional (OR, 1.18; 95% CI, 1.03 to 1.35; OR, 1.31; 95% CI, 1.19 to 1.45) or distant disease (OR, 2.83; 95% CI, 2.30 to 3.47; OR, 1.85; 95% CI, 1.54 to 2.21), respectively.
Conclusions: The rates of thyroid cancer surgery complications are higher than predicted, and patients with older age, more comorbidities, and advanced disease are at greatest risk. Efforts to reduce complications are needed.
PubMed ID: 28460061
Skeletal Complications and Mortality in Thyroid Cancer: A Population-Based Study. J Clin Endocrinol Metab. 2017;102(4):1254-1260.
Choksi P, Papaleontiou M, Guo C, Worden F, Banerjee M, Haymart M.
ABSTRACT
Context: Although bone is a common site for tumor metastases, the burden of bone events [bone metastases and skeletal-related events (SREs)] in patients with thyroid cancer is not well known.
Objective: To measure the prevalence of bone events and their impact on mortality in patients with thyroid cancer.
Patients, design, and setting: We identified patients diagnosed with thyroid cancer between 1991 and 2011 from the linked Surveillance Epidemiology and End Results-Medicare dataset. Multivariable logistic regression was used to identify the risk factors for bone metastases and SREs. We used Cox proportional hazards regressions to assess the impact of these events on mortality, after adjusting for patient and tumor characteristics.
Results: Of the 30,063 patients with thyroid cancer, 1173 (3.9%) developed bone metastases and 1661 patients (5.5%) developed an SRE. Compared with papillary thyroid cancer, the likelihood of developing bone metastases or an SRE was higher in follicular thyroid cancer [odds ratio (OR), 2.25; 95% confidence interval (CI), 1.85 to 2.74 and OR, 1.40; 95% CI, 1.15 to 1.68, respectively] and medullary thyroid cancer (OR, 2.16; 95% CI, 1.60 to 2.86 and OR, 1.62; 95% CI, 1.23 to 2.11, respectively). The occurrence of a bone event was associated with greater risk of overall and disease-specific mortality [hazard ratio (HR), 2.14; 95% CI, 1.94 to 2.36 and HR, 1.59; 95% CI, 1.48 to 1.71, respectively]. Bone events were a poor prognostic indicator even when compared with patients with other distant metastases (P < 0.001 and P < 0.001 for overall and disease-specific mortality, respectively).
Conclusions: Bone events in patients with thyroid cancer are a poor prognostic indicator. Patients with follicular and medullary thyroid cancers are at especially high risk for skeletal complications.
DOI: 10.1210/jc.2016-3906
PubMed ID: 28324052
How Much Should Thyroid Cancer Impact Plans for Pregnancy? Thyroid. 2017;27(3):312-314.
Haymart MR, Pearce EN.
Inappropriate use of Suppressive Doses of Thyroid Hormone in Thyroid Nodule Management: Results from a Nationwide Survey. Endo Pract. 2016;22(11):1358-1360.
Papaleontiou M, Haymart MR.
Use of imaging tests after primary treatment of thyroid cancer in the United States: Population based retrospective cohort study evaluating death and recurrence. BMJ, 2016;354:i3839.
Banerjee M, Wiebel JL, Guo C, Gay B, Haymart MR.
ABSTRACT
Objective: To determine whether the use of imaging tests after primary treatment of differentiated thyroid cancer is associated with more treatment for recurrence and fewer deaths from the disease.
Design: Population based retrospective cohort study.
Setting: Surveillance Epidemiology and End Results-Medicare database in the United States.
Participants: 28 220 patients diagnosed with differentiated thyroid cancer between 1998 and 2011. The study cohort was followed up to 2013, with a median follow-up of 69 months.
Main outcome measures: Treatment for recurrence of differentiated thyroid cancer (additional neck surgery, additional radioactive iodine treatment, or radiotherapy), and deaths due to differentiated thyroid cancer. We conducted propensity score analyses to assess the relation between imaging (neck ultrasound, radioiodine scanning, or positron emission tomography (PET) scanning) and treatment for recurrence (logistic model) and death (Cox proportional hazards model).
Results: From 1998 until 2011, we saw an increase in incident cancer (rate ratio 1.05, 95% confidence interval 1.05 to 1.06), imaging (1.13, 1.12 to 1.13), and treatment for recurrence (1.01, 1.01 to 1.02); the change in death rate was not significant. In multivariable analysis, use of neck ultrasounds increased the likelihood of additional surgery (odds ratio 2.30, 95% confidence interval 2.05 to 2.58) and additional radioactive iodine treatment (1.45, 1.26 to 1.69). Radioiodine scans were associated with additional surgery (odds ratio 3.39, 95% confidence interval 3.06 to 3.76), additional radioactive iodine treatment (17.83, 14.49 to 22.16), and radiotherapy (1.89, 1.71 to 2.10). Use of PET scans was associated with additional surgery (odds ratio 2.31, 95% confidence interval 2.09 to 2.55), additional radioactive iodine treatment (2.13, 1.89 to 2.40), and radiotherapy (4.98, 4.52 to 5.49). Use of neck ultrasounds or PET scans did not significantly affect disease specific survival (hazard ratio 1.14, 95% confidence interval 0.98 to 1.27, and 0.91, 0.77 to 1.07, respectively). However, radioiodine scans were associated with an improved disease specific survival (hazard ratio 0.70, 95% confidence interval 0.60 to 0.82).
Conclusions: The marked rise in use of imaging tests after primary treatment of differentiated thyroid cancer has been associated with an increased treatment for recurrence. However, with the exception of radioiodine scans in presumed iodine avid disease, this association has shown no clear improvement in disease specific survival. These findings emphasize the importance of curbing unnecessary imaging and tailoring imaging after primary treatment to patient risk.
DOI: 10.1136/bmj.i3839
PubMed ID: 27443325
Retrospective Study of Sirolimus and Cyclophosphamide in Patients with Advanced Differentiated Thyroid Cancers. J Thyroid Disord Ther. 2015;4(3);188.
Manohar PM, Beesley LJ, Taylor JM, Hesseltine E, Haymart MR, Esfandiari NH, Hanauer DA, Worden FP.
ABSTRACT
Background: We hypothesize that the combination of an mTOR inhibitor, sirolimus, with a well-known cytotoxic agent, cyclophosphamide, provides a well-tolerated and promising alternative treatment for advanced, differentiated thyroid cancers (DTC).
Methods: This retrospective review extracted data from patients treated for advanced DTC at the University of Michigan Comprehensive Cancer Center from 1995 through 2013. Fifteen patients treated with combination sirolimus and cyclophosphamide were identified as the sirolimus+cyp group. Seventeen patients treated with standard of care and enrolled in clinical trials were identified as the comparison group.
Results: The one-year progression free survival rate (PFS) was 0.45, 95% CI [0.26, 0.80] in the sirolimus+cyp population and 0.30, 95% CI [0.13, 0.67] in the comparison population. The hazard ratio for PFS from initiation of treatment was 1.47, 95% CI [0.57, and 3.78]. In patients treated as first line, one-year PFS rate was 0.57, 95% CI [0.30, 1.00] in the sirolimus+cyp group and relatively unchanged at 0.29, 95% CI [0.11, 0.74] in the comparison group. The hazard ratio for PFS for first line patients was 1.10, 95% CI[ 0.4, and 3.5]. In patients with 3 or fewer sites of metastases, the one year PFS was 0.58, 95% CI [0.33, 1.00] in the sirolimus+cyp group, and 0.37, 95% CI [0.17, 0.80] in the comparison group. The average number of toxicities was 0.87 in the sirolimus+cyp patients and 1.71 in the comparison group.
Conclusions: The combination of sirolimus and cyclophosphamide was generally well tolerated with similar progression free survival, highlighting its applicability in patients with limited options.
DOI: 10.4172/2167-7948.1000188
PubMed ID: 27088062
The Impact of age in the Management of Hypothyroidism: Results of a Nationwide Survey. Endocr Pract. 2016 Jun;22(6):708-15.
Papaleontiou M, Gay BL, Esfandiari NH, Hawley ST, Haymart MR.
ABSTRACT
Objective: Evidence exists that thyroid-stimulating hormone (TSH) increases with age and lowering the TSH goal in older patients on thyroid hormone may cause over-treatment. Risks of overtreatment include cardiac and skeletal events. We assessed practice patterns regarding TSH goals and explored factors influencing physicians' decision making when managing hypothyroidism.
Methods: Members of the American College of Physicians, the American Academy of Family Practice, and the Endocrine Society were surveyed to determine goal TSH when treating hypothyroidism.
Results: Fifty-three percent of physicians reported factoring patient age into their decision making when managing hypothyroidism. Patient age was prioritized third (53%), following patient symptoms (69.2%) and cardiac arrhythmias (65.7%). In multivariable analysis, endocrinologists (P = .002), internists (P = .049), physicians in academic settings (P = .003), and high-volume physicians (P = .021) were more likely to consider patient age when determining goal TSH. When presented with scenarios differing in patient gender and age, 90% of physicians targeted a TSH ≤3.0 mIU/L in 30-year-old patients. Fifty-three percent of respondents targeted a TSH ≤3.0 mIU/L in octogenarians, but 90% targeted a TSH >1.5 mIU/L in this group. Regardless of gender, physician-reported TSH goal ranges (0.1 to 0.5, 0.6 to 1.5, 1.6 to 3.0, and 3.1 to 5.0 mIU/L) increased in a direct relationship to patient age (P<.001).
Conclusion: Just over half of physicians consider patient age when determining TSH goal. When presented with scenarios differing in patient age and gender, physicians targeted a higher TSH goal in octogenarians. This may indicate an attempt to avoid overtreatment in this group. Consensus is needed among physicians regarding the role of patient age in hypothyroidism management.
DOI: 10.4158/ep151021.or
PubMed ID: 26866707
Safety and tolerability of sorafenib in patients with radioactive-refractory thyroid cancer. Endocr Relat Cancer. 2015;22(6):877-87.
Worden F, Fassnacht M, Shi Y, Hadjieva T, Bonichon F, et al.
ABSTRACT
Effective adverse event (AE) management is critical to maintaining patients on anticancer therapies. The DECISION trial was a multicenter, randomized, double-blind, placebo-controlled, Phase 3 trial which investigated sorafenib for treatment of progressive, advanced, or metastatic radioactive iodine-refractory, differentiated thyroid carcinoma. Four hundred and seventeen adult patients were randomized (1:1) to receive oral sorafenib (400 mg, twice daily) or placebo, until progression, unacceptable toxicity, noncompliance, or withdrawal. Progression-free survival, the primary endpoint of DECISION, was reported previously. To elucidate the patterns and management of AEs in sorafenib-treated patients in the DECISION trial, this report describes detailed, by-treatment-cycle analyses of the incidence, prevalence, and severity of hand-foot skin reaction (HFSR), rash/desquamation, hypertension, diarrhea, fatigue, weight loss, increased serum thyroid stimulating hormone, and hypocalcemia, as well as the interventions used to manage these AEs. By-cycle incidence of the above-selected AEs with sorafenib was generally highest in cycle 1 or 2 then decreased. AE prevalence generally increased over cycles 2-6 then stabilized or declined. Among these AEs, only weight loss tended to increase in severity (from grade 1 to 2) over time; severity of HFSR and rash/desquamation declined over time. AEs were mostly grade 1 or 2, and were generally managed with dose interruptions/reductions, and concomitant medications (e.g. antidiarrheals, antihypertensives, dermatologic preparations). Most dose interruptions/reductions occurred in early cycles. In conclusion, AEs with sorafenib in DECISION were typically grade 1 or 2, occurred early during the treatment course, and were manageable over time.
DOI: 10.1530/erc-15-0252
PubMed ID: 26370187
Effect of Thyrotropin Suppression Therapy on Bone in Thyroid Cancer Patients. The Oncologist, 2016;21(2)165-71.
Papaleonitou M, Hawley ST, Haymart MR.
ABSTRACT
Background: The thyroid cancer incidence is rising. Despite current guidelines, controversy exists regarding the degree and duration of thyrotropin suppression therapy. Also, its potential skeletal effects remain a concern to physicians caring for thyroid cancer patients. We conducted a review of published data to evaluate existing studies focusing on the skeletal effects of thyrotropin suppression therapy in thyroid cancer patients.
Materials and methods: A systematic search of the PubMed, Ovid/Medline, and Cochrane Central Register of Controlled Trials databases was conducted. The retained studies were evaluated for methodological quality, and the study populations were categorized into premenopausal women, postmenopausal women, and men.
Results: Twenty-five pertinent studies were included. Seven studies were longitudinal and 18 were cross-sectional. Of the 25 included studies, 13 were assigned an excellent methodological quality score. Three of 5 longitudinal studies and 3 of 13 cross-sectional studies reported decreased bone mineral density (BMD) in premenopausal women; 2 of 4 longitudinal studies and 5 of 13 cross-sectional studies reported decreased BMD in postmenopausal women. The remaining studies showed no effect on BMD. The only longitudinal study of men showed bone mass loss; however, cross-sectional studies of men did not demonstrate a similar effect.
Conclusion: Studies to date have yielded conflicting results on the skeletal effects of thyrotropin suppression therapy and a knowledge gap remains, especially for older adults and men. Existing data should be cautiously interpreted because of the variable quality and heterogeneity. Identifying groups at risk of adverse effects from thyrotropin suppression therapy will be instrumental to providing focused and tailored thyroid cancer treatment.
DOI: 10.1634/theoncologist.2015-0179
PubMed ID: 26659220
NCCN Anaplastic Thyroid Carcinoma Version 2, Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network, 2015;13(9):1140-50.
Haddad RI, Lydiatt WM, Ball DW, Busaidy NL, Byrd D, Callender G, Dickson P, Duh QY, Ehya H, Haymart M, et al.
ABSTRACT
This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Thyroid Carcinoma focuses on anaplastic carcinoma because substantial changes were made to the systemic therapy recommendations for the 2015 update. Dosages and frequency of administration are now provided, docetaxel/doxorubicin regimens were added, and single-agent cisplatin was deleted because it is not recommended for patients with advanced or metastatic anaplastic thyroid cancer.
PubMed ID: 26358798
Evaluating Positron Emission Tomography Use in Differentiated Thyroid Cancer. Thyroid, 2015;25(9):1026-32.
Wiebel J, Esfandiari N, Papaleontiou M, Worden F, Haymart MR.
ABSTRACT
Background: Using the Surveillance, Epidemiology, and End Results-Medicare database, a substantial increase was found in the use of positron emission tomography (PET) scans after 2004 in differentiated thyroid cancer (DTC) patients. The reason for the increased utilization of the PET scan was not clear based on available the data. Therefore, the indications for and outcomes of PET scans performed at an academic institution were evaluated.
Methods: A retrospective cohort study was performed of DTC patients who underwent surgery at the University of Michigan Health System from 2006 to 2011. After identifying patients who underwent a PET scan, indications, rate of positive PET scans, and impact on management were evaluated. For positive scans, the location of disease was characterized, and presence of disease on other imaging was determined.
Results: Of the 585 patients in the cohort, 111 (19%) patients had 200 PET scans performed for evaluation of DTC. Indications for PET scan included: elevated thyroglobulin and negative radioiodine scan in 52 scans (26.0%), thyroglobulin antibodies in 13 scans (6.5%), rising thyroglobulin in 18 scans (9.0%), evaluation of abnormality on other imaging in 22 scans (11.0%), evaluation of extent of disease in 33 scans (16.5%), follow-up of previous scan in 57 scans (28.5%), other indications in two scans (1.0%), and unclear indications in three scans (1.5%). The PET scan was positive in 124 studies (62.0%); positivity was identified in the thyroid bed on 25 scans, cervical or mediastinal lymph nodes on 105 scans, lung on 28 scans, bone on four scans, and other areas on 14 scans. Therapy following PET scan was surgery in 66 cases (33.0%), chemotherapy or radiation in 23 cases (11.5%), observation in 110 cases (55.0%), and palliative care in one case (0.5%). Disease was identifiable on other imaging in 66% of cases. PET scan results changed management in 59 cases (29.5%).
Conclusions: In this academic medical center, the PET scan was utilized in 19% of patients. Indications for the PET scan included conventional indications, such as elevated thyroglobulin with noniodine avid disease, and more controversial uses, such as evaluation of extent of disease or abnormalities on other imaging tests. PET scan results changed management in about 30% of cases.
PubMed ID: 26133765
Inappropriate use of radioactive iodine for low-risk papillary thyroid cancer in most common in regions with poor access to health care. Thyroid, 2016;25(7):865-6.
Marti JL, Davies L, Haymart MR, Roman BR, Tuttle RM, Morris LGT.
Maintaining physical activity during head and neck cancer treatment: Results of a pilot controlled trial. Head Neck. 2016 Apr;38 Suppl 1(Suppl 1):E1086-96.
Zhao SG, Alexander NB, Djuric Z, Zhou J, Tao Y, Schipper M, Feng FY, Eisbruch A, Worden FP, Strath SJ, Jolly S.
ABSTRACT
Background: Concurrent chemoradiotherapy (concurrent CRT) to treat head and neck cancer is associated with significant reductions of weight, mobility, and quality of life (QOL). An intervention focusing on functional exercise may attenuate these losses.
Methods: We allocated patients to a 14-week functional resistance and walking program designed to maintain physical activity during cancer treatment (MPACT group; n = 11), or to usual care (control group; n = 9). Outcomes were assessed at baseline, and 7 and 14 weeks.
Results: Compared to controls, the MPACT participants had attenuated decline or improvement in several strength, mobility, physical activity, diet, and QOL endpoints. These trends were statistically significant (p < .05) in knee strength, mental health, head and neck QOL, and barriers to exercise.
Conclusion: In this pilot study of patients with head and neck cancer undergoing concurrent CRT, MPACT training was feasible and maintained or improved function and QOL, thereby providing the basis for larger future interventions with longer follow-up. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1086-E1096, 2016.
DOI: 10.1002/hed.24162
PubMed ID: 26445898
Treatment strategies for radioactive iodine-refractory differentiated thyroid cancer. Ther Adv Med Oncol. 2014;6(6);267-79.
Worden F.
ABSTRACT
Until recently, no truly effective treatment options have existed for patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), a serious disease with poor prognosis. In November 2013, the targeted multikinase inhibitor, sorafenib, was approved for use in these patients based on substantially improved progression-free survival compared with placebo. A number of other targeted agents, including lenvatinib, are being investigated in phase II and phase III trials. With the advent of these new treatment options, practitioners are faced with making important decisions in determining which patients are candidates for systemic treatment and the optimal timing for treatment initiation. Since patients may remain asymptomatic for a protracted period of time, tumor size and growth rate are the primary considerations for making these choices. Proactive management of side effects is also critical in optimizing the effectiveness of treatment. Here we review targeted systemic agents that are either in use or are under investigation for RAI-refractory DTC and provide recommendations on the rationale for initiating systemic treatment and on managing adverse events. Four illustrative case studies are provided.
PubMed ID: 25364392
A phase II study evaluating axitinib in patients with unresectable, recurrent or metastatic head and neck cancer. Invest New Drugs, 2015;33(6):1248-56.
Swiecicki PL, Zhao L, Belile E, Sacco AG, Chepeha DB, Dobrosotskaya I, Spector M, Shuman A, Malloy K, Moyer J, McKean E, McLean S, Wolf GT, Eisbruch A, Prince M, Bradford C, Carey T, Worden FP.
ABSTRACT
Background: Axitinib is an oral, potent, small molecule tyrosine kinase inhibitor with selective inhibition of VEGFR 1,2, 3, as well as inhibition of potential downstream effectors of the EGFR pathway. Given the upregulation of EGFR and VEGFR in head and neck squamous cell carcinoma, treatment with axitinib holds promise as a rational targeted therapy.
Patients and methods: Patients with unresectable, recurrent or metastatic head and neck squamous cell carcinoma were included in this open label, single arm, phase II trial. Primary endpoint was 6 month progression free survival. All patients received single agent axitinib with planned dose escalation based on tolerability. A planned interim efficacy analysis was performed after enrollment of 30 patients.
Results: Forty-two patients were registered, 30 were evaluable. While treatment was well-tolerated with no severe bleeding events, only 19 patients were able to achieve full planned dose. The best overall response rate was 6.7% (two partial responses) with a disease control rate of 76.7%. Median progression free survival was 3.7 months (95% Confidence Interval (CI): 3.5-5.7) and overall survival was 10.9 months (95% CI: 6.4-17.8). Exploratory analysis demonstrated that patients with a smaller sum of diameter of target lesions experienced improved response rates, and better progression-free and overall survival.
Conclusion: Treatment with single agent axitinib should be considered due to acceptable toxicity profile and favorable median overall survival compared to standard therapies.
DOI: 10.1007/s10637-015-0293-8
PubMed ID: 26453566
Cumulative cisplatin dose in concurrent chemoradiotherapy for head and neck cancer: A systematic review. Head Neck. 2016 Apr;38 Suppl 1:E2151-8.
Strojan P, Vermorken JB, Beitler JJ, Saba NF, Haigentz M Jr, Bossi P, Worden FP, Langendijk JA, Eisbruch A, Mendenhall WM, Lee AW, Harrison LB, Bradford CR, Smee R, Silver CE, Rinaldo A, Ferlito A.
ABSTRACT
Background: The optimal cumulative dose and timing of cisplatin administration in various concurrent chemoradiotherapy protocols for nonmetastatic head and neck squamous cell carcinoma (HNSCC) has not been determined.
Methods: The absolute survival benefit at 5 years of concurrent chemoradiotherapy protocols versus radiotherapy alone observed in prospective randomized trials reporting on the use of cisplatin monochemotherapy for nonnasopharyngeal HNSCC was extracted. In the case of nonrandomized studies, the outcome results at 2 years were compared between groups of patients receiving different cumulative cisplatin doses.
Results: Eleven randomized trials and 7 nonrandomized studies were identified. In 6 definitive radiotherapy phase III trials, a statistically significant association (p = .027) between cumulative cisplatin dose, independent of the schedule, and overall survival benefit was observed for higher doses.
Conclusion: Results support the conclusion that the cumulative dose of cisplatin in concurrent chemoradiation protocols for HNSCC has a significant positive correlation with survival. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2151-E2158, 2016.
DOI: 10.1002/hed.24026
PubMed ID: 25735803
American Association of Clinical Endocrinologists and American College of Endocrinology Disease State Clinical Review: The increasing incidence of Thyroid Cancer. Endocrine Practice, 2015;21:686-96.
Davies L, Morris LGT, Haymart M, Chen AY, Goldenberg D, Morris J, Ogilvie JB, Terris DJ, Netterville J, Wong RJ, Randolph G.
ABSTRACT
Objective: (1) Describe current epidemiology of thyroid cancer in the United States; (2) evaluate hypothesized causes of the increased incidence of thyroid cancer; and (3) suggest next steps in research and clinical action.
Methods: Analysis of data from Surveillance, Epidemiology and End Results System and the National Center for Vital Statistics. Literature review of published English-language articles through December 31, 2013.
Results: The incidence of thyroid cancer has tripled over the past 30 years, whereas mortality is stable. The increase is mainly comprised of smaller tumors. These facts together suggest the major reason for the increased incidence is detection of subclinical, nonlethal disease. This has likely occurred through: health care system access, incidental detection on imaging, more frequent biopsy, greater volumes of and extent of surgery, and changes in pathology practices. Because larger-size tumors have increased in incidence also, it is possible that there is a concomitant true rise in thyroid cancer incidence. The only clearly identifiable contributor is radiation exposure, which has likely resulted in a few additional cases annually. The contribution of the following causes to the increasing incidence is unclear: iodine excess or insufficiency, diabetes and obesity, and molecular disruptions. The following mechanisms do not currently have strong evidence to support a link with the development of thyroid cancer: estrogen, dietary nitrate, and autoimmune thyroid disease.
Conclusion: Research should focus on illuminating which thyroid cancers need treatment. Patients should be advised of the benefits as well as harms that can occur with treatment of incidentally identified, small, asymptomatic thyroid cancers.
DOI: 10.4158/ep14466.dscr
PubMed ID: 26135963
Trends in Imaging After Diagnosis of Thyroid Cancer. Cancer, 2015;121(9):1387-94.
Wiebel JL, Banerjee M, Muenz DG, Worden FP, Haymart MR.
ABSTRACT
Background: The largest growth noted among differentiated thyroid cancer (DTC) diagnosis is in low-risk cancers. Trends in imaging after the diagnosis of DTC are understudied. Hypothesizing a reduction in imaging use due to rising low-risk disease, the authors evaluated postdiagnosis imaging patterns over time and patient characteristics that are associated with the likelihood of imaging.
Methods: Using the Surveillance, Epidemiology, and End Results-Medicare database, the authors identified patients diagnosed with localized, regional, or distant DTC between 1991 and 2009. Medicare claims were reviewed for use of neck ultrasound, iodine-131 (I-131) scan, or positron emission tomography (PET) scan within 3 years after diagnosis. Trends in imaging use were evaluated using regression analyses. Multivariable logistic regression was used to estimate the likelihood of imaging based on patient characteristics.
Results: A total of 23,669 patients were included. Compared with patients diagnosed between 1991 and 2000, those diagnosed between 2001 and 2009 were more likely to have localized disease (P<.001) and tumors measuring <1 cm (P<.001). Use of neck ultrasound and I-131 scans increased in patients with localized disease (P ≤.001 and P = .003, respectively), regional disease (P<.001 and P<.001, respectively), and distant metastasis (P = .001 and P = .015, respectively). Patients diagnosed after 2000 were more likely to undergo neck ultrasound (odds ratio, 2.15; 95% confidence interval, 2.02-2.28) and I-131 scan (odds ratio, 1.44; 95% confidence interval, 1.35-1.54). Compared with 1996 through 2004, PET scan use from 2005 to 2009 increased 32.4-fold (P≤.001) in patients with localized disease, 13.1-fold (P<.001) in patients with regional disease, and 33.4-fold (P<.001) in patients with distant DTC.
Conclusions: Despite an increase in the diagnosis of low-risk disease, the use of postdiagnosis imaging increased among patients with all stages of disease. The largest growth observed was in the use of PET after 2004.
DOI: 10.1002/cncr.29210
PubMed ID: 25565063
Thyroid carcinoma, version 2.2014. J Natl Compr Canc Netw. 2014 Dec;12(12):1671-80; quiz 1680.Â
Tuttle RM, Haddad RI, Ball DW, Byrd D, Dickson P, Duh QY, Ehya H, Haymart M, Hoh C, Hunt JP, Iagaru A, Kandeel F, Kopp P, Lamonica DM, Lydiatt WM, McCaffrey J, Moley JF, Parks L, Raeburn CD, Ridge JA, Ringel MD, Scheri RP, Shah JP, Sherman SI, Sturgeon C, Waguespack SG, Wang TN, Wirth LJ, Hoffmann KG, Hughes M.
ABSTRACT
These NCCN Guidelines Insights focus on some of the major updates to the 2014 NCCN Guidelines for Thyroid Carcinoma. Kinase inhibitor therapy may be used to treat thyroid carcinoma that is symptomatic and/or progressive and not amenable to treatment with radioactive iodine. Sorafenib may be considered for select patients with metastatic differentiated thyroid carcinoma, whereas vandetanib or cabozantinib may be recommended for select patients with metastatic medullary thyroid carcinoma. Other kinase inhibitors may be considered for select patients with either type of thyroid carcinoma. A new section on "Principles of Kinase Inhibitor Therapy in Advanced Thyroid Cancer" was added to the NCCN Guidelines to assist with using these novel targeted agents.
PubMed ID: 25505208
Conditional Survival in Patients with Thyroid Cancer. Thyroid, 2014;24(12):1784-9.
Banerjee M, Muenz DG, Worden F, Wong SL, Haymart MR.Â
ABSTRACT
Background: Thyroid cancer is an increasingly common malignancy. Although likelihood of survival from well-differentiated thyroid cancer can vary by disease severity, it is not known how patients' life expectancies change the farther they are from time of diagnosis.
Methods: Using data from the Surveillance, Epidemiology, End Results (SEER) registry, we selected patients diagnosed with well-differentiated thyroid cancer (N=43,392) between 1998 and 2005. Patients were followed for up to 12 years. Conditional survival estimates by SEER stage and age were obtained based on Cox proportional hazards regression model of disease-specific survival.
Results: Patients with localized thyroid cancer have excellent conditional 5-year survival, irrespective of where they are in their survivorship phase. Patients with regional thyroid cancer have relatively stable conditional 5-year survival, whereas for patients with distant thyroid cancer there is gradual improvement the farther from time of diagnosis. Age and gender influence conditional survival. Similarly, age has a strong effect on disease-specific survival for patients with thyroid cancer with localized (hazard ratio [HR] 88.7 [95% confidence interval {CI} 26.3-552), comparing age ≥80 with <30 years), regional (HR 105 [95% CI 52.6-250]), and distant disease [HR 86.8 (95% CI 32.5-354)]. Male gender is also associated with a significantly worse disease-specific survival among patients with regional disease (HR 1.56 [95% CI 1.31-1.85]) but not among patients with localized or distant disease.
Conclusion: Cancer stage, gender, age at diagnosis, and length of time already survived can influence conditional survival for patients with thyroid cancer. Understanding the conditional 5-year disease-specific survival of well-differentiated thyroid cancer is key to creating treatment plans and tailoring surveillance.
PubMed ID: 25208475
ACR Appropriateness Criteria thyroid carcinoma. Oral Oncol., 2014;50(6):577-86.
Salama JK, Golden DW, Yom SS, Garg MK, Lawson J, McDonald MW, Quon H, Saba N, Smith RV, Worden F, et al.
ABSTRACT
The ACR Head and Neck Cancer Appropriateness Criteria Committee reviewed relevant medical literature to provide guidance for those managing patients with thyroid carcinoma. The American College of Radiology Appropriateness Criteriaare evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Thyroid cancer is the most common endocrine malignancy in the United States, most often presenting as a localized palpable nodule. Surgery is the mainstay of treatment for WDTC, with most patients undergoing complete resection of their disease having good outcomes. Following surgery thyroxine supplementation should begin to suppress TSH, which unchecked can stimulate residual disease and/or metastatic progression, Adjuvant treatment with radioactive iodine (RAI) using iodine-131 ((131)I) is frequently used for diagnostic and therapeutic purposes. The use of EBRT for thyroid cancer has not been tested in well-designed, randomized, controlled trials and should, therefore, be considered on a case-by-case basis. Chemotherapy plays a minimal role in the management of WDTC. Novel biologic agents, such as systemic therapy options, are being actively investigated, and patients with metastatic thyroid cancer that is not iodine avid should be encouraged to enroll in clinical trials exploring novel systemic agents.
DOI: 10.1016/j.oraloncology.2013.12.004
PubMed ID: 24824115
Ectopic Cushing syndrome secondary to metastatic medullary thyroid cancer in a child with multiple endocrine neoplasia syndrome type 2B: clues to early diagnosis of the paraneoplastic syndromes. J Pediatr Endocrinol Metab., 2014;27(9-10):993-6.
Singer K, Heiniger N, Thomas I, Worden FP, Menon RK, Chen M.
ABSTRACT
We describe a 13-year-old male with multiple endocrine neoplasia syndrome type 2B with medullary thyroid carcinoma who was diagnosed with ectopic adrenocorticotropin-dependent Cushing syndrome. This report highlights the importance of monitoring for paraneoplastic syndrome in MEN and clues to the diagnosis of this complication provided by growth patterns.
PubMed ID: 24859505
Phase I trial of radiotherapy concurrent with twice-weekly gemcitabine for head and neck cancer: translation from preclinical investigations aiming to improve the therapeutic ratio. Transl Oncol. 2014 Aug;7(4):479-83.
Popovtzer A, Normolle D, Worden FP, Prince ME, Chepeha DB, Wolf GT, Bradford CR, Lawrence TS, Eisbruch A.
ABSTRACT
Background: Once-weekly gemcitabine concurrent with radiotherapy was highly effective in the treatment of head and neck cancer (HNC) but limited by high mucosal toxicity. Pre-clinical investigations suggested that delivering gemcitabine at substantially lower doses twice weekly during radiotherapy improved the therapeutic ratio. We sought to translated these preclinical findings to a phase I trial.
Methods: Twenty-five patients with non-resectable HNC were scheduled to receive gemcitabine twice weekly during the last 2 weeks (total 5 infusions) of hyperfractionated radiotherapy delivering 1.2 Gy twice daily to total 76.8 Gy. Tumor biopsies to measure active intracellular (phosphorylated) gemcitabine were planned after the first drug delivery. Patients were assigned to escalating dose cohorts using the Continuous Reassessment Method.
Results: Twenty-one patients evaluable for toxicity were divided into cohorts receiving twice weekly treatment with 10, 20, 33, or 50 mg/m(2) gemcitabine. Dose-limiting toxicity was grade 3-4 confluent mucositis/pharyngitis, and the maximally tolerated dose (MTD) was 20 mg/m(2). Median survival was 20 months, with no difference between cohorts receiving lower (10, 20 mg/m(2)) or higher (33, 50 mg/m(2)) gemcitabine doses. Tumor biopsies after the first drug delivery showed only a minority of tumor cells in the specimens.
Conclusion: These findings validate preclinical models that show that gemcitabine is radiation sensitizer at doses far below those used for systemic chemotherapy. However, the improvement in the therapeutic ratio predicted from the preclinical study did not translate into a substantial relative increase in the MTD of the drug in the clinical phase I trial.
DOI: 10.1016/j.tranon.2014.04.016
PubMed ID: 25171890
The combination of insulin-like growth factor receptor 1 (IGF1R) antibody cixutumumab and mitotane as a first-line therapy for patients with recurrent/metastatic adrenocortical carcinoma: a multi-institutional NCI-sponsored trial. Horm Cancer. 2014 Aug;5(4):232-9.
Lerario AM, Worden FP, Ramm CA, Hesseltine EA, Stadler WM, Else T, Shah MH, Agamah E, Rao K, Hammer GD.
ABSTRACT
Adrenocortical carcinoma (ACC) is an aggressive malignancy, which lacks an effective systemic treatment. Abnormal activation of insulin-like growth factor receptor 1 (IGF1R) has been frequently observed. Preclinical studies demonstrated that pharmacological inhibition of IGF1R signaling in ACC has antiproliferative effects. A previous phase I trial with an IGF1R inhibitor has demonstrated biological activity against ACC. The objective of this study is to assess the efficacy of the combination of the IGF1R inhibitor cixutumumab (IMC-A12) in association with mitotane as a first-line treatment for advanced/metastatic ACC. We conducted a multicenter, randomized double-arm phase II trial in patients with irresectable recurrent/metastatic ACC. The original protocol included two treatment groups: IMC-A12 + mitotane and mitotane as a single agent, after an initial single-arm phase for safety evaluation with IMC-A12 + mitotane. IMC-A12 was dosed at 10 mg/kg intravenously every 2 weeks. The starting dose for mitotane was 2 g daily, subsequently adjusted according to serum levels/symptoms. The primary endpoint was progression-free survival (PFS) according to RECIST (Response Evaluation Criteria in Solid Tumors). This study was terminated before the randomization phase due to slow accrual and limited efficacy. Twenty patients (13 males, 7 females) with a median age of 50.2 years (range 21.9-79.6) were enrolled for the single-arm phase. Therapeutic effects were observed in 8/20 patients, including one partial response and seven stable diseases. The median PFS was 6 weeks (range 2.66-48). Toxic events included two grade 4 (hyperglycemia and hyponatremia) and one grade 5 (multiorgan failure). Although the regimen demonstrated activity in some patients, the relatively low therapeutic efficacy precluded further studies with this combination of drugs.
DOI: 10.1007/s12672-014-0182-1
PubMed ID: 24849545
Tree-Based Model for Thyroid Cancer Prognostication. J Clin Endocrinol Metab, 2014;99(10):3737-45.
Banerjee M, Muenz DG, Chang JT, Papaleontiou M, Haymart MR.
ABSTRACT
Background: Death is uncommon in thyroid cancer patients, and the factors important in predicting survival remain inadequately studied. The objective of this study was to assess prognostic effects of patient, tumor, and treatment factors and to determine prognostic groups for thyroid cancer survival.
Methods: Using data from the Surveillance, Epidemiology, and End Results Program (SEER), we evaluated overall and disease-specific survival (DSS) in 43 392 well-differentiated thyroid cancer patients diagnosed from 1998 through 2005. Multivariable analyses were performed using Cox proportional hazards regression, survival trees, and random survival forest. Similar analyses were performed using National Cancer Data Base data, with overall survival (OS) evaluated in 131 484 thyroid cancer patients diagnosed from 1998 through 2005. Relative importance of factors important to survival was assessed based on the random survival forest analyses.
Results: Using survival tree analyses, we identified 4 distinct prognostic groups based on DSS (P < .0001). The 5-year DSS of these prognostic groups was 100%, 98%, 91%, 64%, whereas the 10-year survival was 100%, 96%, 85%, and 50%. Based on random survival forest analyses, the most important factors for DSS were SEER stage and age at diagnosis. For OS, important prognostic factors were similar, except age at diagnosis demonstrated marked importance relative to SEER stage. Similar results for OS were found using National Cancer Data Base data.
Conclusion: This study identifies distinct prognostic groups for thyroid cancer and illustrates the importance of patient age to both disease-specific and OS. These findings have implications for patient education and thyroid cancer treatment.
DOI: 10.1210/jc.2014-2197
PubMed ID: 25033070
New insights in risk stratification of differentiated thyroid cancer. Current Opinion in Oncology, 2014;26(1):1-7.
Papaleontiou M, Haymart MR.
ABSTRACT
Purpose of review: Numerous staging and scoring systems exist for differentiated thyroid cancer (DTC), but all harbor limitations. This has prompted investigation for new factors with prognostic implications for DTC.
Recent findings: Several new factors that may be involved in DTC risk stratification have emerged, such as thyroid stimulating hormone and molecular markers. In addition, others are controversial and being challenged, such as age, sex and lymph node involvement.
Summary: The purpose of this review is to present recent updates in the literature on new potential risk stratification predictors for DTC.
DOI: 10.1097/cco.0000000000000022
PubMed ID: 24285100
The Effect of Extent of Surgery and Number of Lymph Node Metastases on Overall Survival in Patients with Medullary Thyroid Cancer. J Clin Encrinol Metab, 2014;99(2):448-54.
Esfandiari NH, Hughes DT, Banerjee M, Haymart MR.
ABSTRACT
Context: Total thyroidectomy with central lymph node dissection is recommended in patients with medullary thyroid cancer (MTC). However, the relationship between disease severity and extent of resection on overall survival remains unknown.
Objective: The aim of the study was to identify the effect of surgery on overall survival in MTC patients.
Methods: Using data from 2968 patients with MTC diagnosed between 1998 and 2005 from the National Cancer Database, we determined the relationship between the number of cervical lymph node metastases, tumor size, distant metastases, and extent of surgery on overall survival in patients with MTC.
Results: Older patient age (5.69 [95% CI, 3.34-9.72]), larger tumor size (2.89 [95% CI, 2.14-3.90]), presence of distant metastases (5.68 [95% CI, 4.61-6.99]), and number of positive regional lymph nodes (for ≥16 lymph nodes, 3.40 [95% CI, 2.41-4.79]) were independently associated with decreased survival. Overall survival rate for patients with cervical lymph nodes resected and negative, cervical lymph nodes not resected, and 1-5, 6-10, 11-16, and ≥16 cervical lymph node metastases was 90, 76, 74, 61, 69, and 55%, respectively. There was no difference in survival based on surgical intervention in patients with tumor size ≤ 2 cm without distant metastases. In patients with tumor size > 2.0 cm and no distant metastases, all surgical treatments resulted in a significant improvement in survival compared to no surgery (P < .001). In patients with distant metastases, only total thyroidectomy with regional lymph node resection resulted in a significant improvement in survival (P < .001).
Conclusions: The number of lymph node metastases should be incorporated into MTC staging. The extent of surgery in patients with MTC should be tailored to tumor size and distant metastases.
DOI: 10.1210/jc.2013-2942
PubMed ID: 24276457
Marginal treatment benefit in anaplastic thyroid cancer. Cancer, 2013;119(17):3133-39.
Haymart MR, Banerjee M, Yin H, Worden F, Griggs JJ.
ABSTRACT
Background: Because anaplastic thyroid cancer is a rare malignancy with a high mortality rate, the benefit of multimodality treatment was evaluated.
Methods: Overall survival was determined in the 2742 patients captured by the National Cancer Database who were diagnosed with anaplastic thyroid cancer between 1998 and 2008. Kaplan-Meier analysis and then Cox proportional hazard regression was performed, controlling for patient characteristics and treatment.
Results: Only older age (adjusted hazard ratio [AHR] for ≥ 85 years = 3.43, 95% confidence interval [CI] = 2.34-5.03; for 75-84 years, AHR = 2.85, 95% CI = 1.97-4.11; for 65-74 years, AHR = 2.20, 95% CI = 1.53-3.15; for 45-64 years, AHR = 2.08, 95% CI = 1.47-2.95) and omission of treatment were associated with greater mortality (omission of surgery: AHR = 1.79, 95% CI = 1.61-1.99; omission of radiation therapy: AHR = 1.56; 95% CI = 1.41-1.73; and omission of chemotherapy: AHR = 1.28, 95% CI = 1.15-1.43). In subgroup analysis of patients with American Joint Committee on Cancer stage IVA, IVB, and IVC anaplastic thyroid cancer, combination therapy with surgery, radiation, and chemotherapy was associated a difference in median survival of months.
Conclusions: Multimodality management of anaplastic thyroid cancer results in a marginal treatment benefit. The poor overall survival of all anaplastic thyroid cancer patients, regardless of treatment, emphasizes the need for informed patients whose preferences are incorporated into treatment decision-making.
DOI: 10.1002/cncr.28187
PubMed ID: 23839797
Clinical practice guideline: improving voice outcomes after thyroid surgery. Otolaryngol Head Neck Surg, 2013;148(6 Suppl):S1-37.
Chandrasekhar SS, Randolph GW, Seidman MD, Rosenfeld RM, Angelos P, et al.
ABSTRACT
Objective: Thyroidectomy may be performed for clinical indications that include malignancy, benign nodules or cysts, suspicious findings on fine needle aspiration biopsy, dysphagia from cervical esophageal compression, or dyspnea from airway compression. About 1 in 10 patients experience temporary laryngeal nerve injury after surgery, with longer lasting voice problems in up to 1 in 25. Reduced quality of life after thyroid surgery is multifactorial and may include the need for lifelong medication, thyroid suppression, radioactive scanning/treatment, temporary and permanent hypoparathyroidism, temporary or permanent dysphonia postoperatively, and dysphagia. This clinical practice guideline provides evidence-based recommendations for management of the patient's voice when undergoing thyroid surgery during the preoperative, intraoperative, and postoperative period.
Purpose: The purpose of this guideline is to optimize voice outcomes for adult patients aged 18 years or older after thyroid surgery. The target audience is any clinician involved in managing such patients, which includes but may not be limited to otolaryngologists, general surgeons, endocrinologists, internists, speech-language pathologists, family physicians and other primary care providers, anesthesiologists, nurses, and others who manage patients with thyroid/voice issues. The guideline applies to any setting in which clinicians may interact with patients before, during, or after thyroid surgery. Children under age 18 years are specifically excluded from the target population; however, the panel understands that many of the findings may be applicable to this population. Also excluded are patients undergoing concurrent laryngectomy. Although this guideline is limited to thyroidectomy, some of the recommendations may extrapolate to parathyroidectomy as well.
Results: The guideline development group made a strong recommendation that the surgeon should identify the recurrent laryngeal nerve(s) during thyroid surgery. The group made recommendations that the clinician or surgeon should (1) document assessment of the patient's voice once a decision has been made to proceed with thyroid surgery; (2) examine vocal fold mobility, or refer the patient to a clinician who can examine vocal fold mobility, if the patient's voice is impaired and a decision has been made to proceed with thyroid surgery; (3) examine vocal fold mobility, or refer the patient to a clinician who can examine vocal fold mobility, once a decision has been made to proceed with thyroid surgery if the patient's voice is normal and the patient has (a) thyroid cancer with suspected extrathyroidal extension, or (b) prior neck surgery that increases the risk of laryngeal nerve injury (carotid endarterectomy, anterior approach to the cervical spine, cervical esophagectomy, and prior thyroid or parathyroid surgery), or (c) both; (4) educate the patient about the potential impact of thyroid surgery on voice once a decision has been made to proceed with thyroid surgery; (5) inform the anesthesiologist of the results of abnormal preoperative laryngeal assessment in patients who have had laryngoscopy prior to thyroid surgery; (6) take steps to preserve the external branch of the surperior laryngeal nerve(s) when performing thyroid surgery; (7) document whether there has been a change in voice between 2 weeks and 2 months following thyroid surgery; (8) examine vocal fold mobility or refer the patient for examination of vocal fold mobility in patients with a change in voice following thyroid surgery; (9) refer a patient to an otolaryngologist when abnormal vocal fold mobility is identified after thyroid surgery; (10) counsel patients with voice change or abnormal vocal fold mobility after thyroid surgery on options for voice rehabilitation. The group made an option that the surgeon or his or her designee may monitor laryngeal electromyography during thyroid surgery. The group made no recommendation regarding the impact of a single intraoperative dose of intravenous corticosteroid on voice outcomes in patients undergoing thyroid surgery.
PubMed ID: 23733893
The Relationship Between Extent of Thyroid Cancer Surgery and Use of Radioactive Iodine. Ann Surg, 2013;258(2):354-8.
Haymart MR, Banerjee M, Yang D, Stewart AK, Doherty GM, Koenig RJ, Griggs JJ.
ABSTRACT
By linking surgeon surveys to the National Cancer Database, we found that surgeons' tendency to perform more extensive thyroid resection is associated with greater use of radioactive iodine for stage I thyroid cancer.
Objective: To determine the relationships between surgeon recommendations for extent of resection and radioactive iodine use in low-risk thyroid cancer.
Background: There has been an increase in thyroid cancer treatment intensity; the relationship between extent of resection and medical treatment with radioactive iodine remains unknown.
Methods: We randomly surveyed thyroid surgeons affiliated with 368 hospitals with Commission on Cancer-accredited cancer programs. Survey responses were linked to the National Cancer Database. The relationship between extent of resection and the proportion of the American Joint Committee on Cancer stage I well-differentiated thyroid cancer patients treated with radioactive iodine after total thyroidectomy was assessed with multivariable weighted regression, controlling for hospital and surgeon characteristics.
Results: The survey response rate was 70% (560/804). Surgeons who recommend total thyroidectomy over lobectomy for subcentimeter unifocal thyroid cancer were significantly more likely to recommend prophylactic central lymph node dissection for thyroid cancer regardless of tumor size (P < 0.001). They were also more likely to favor radioactive iodine in patients with intrathyroidal unifocal cancer ≤1 cm (P = 0.001), 1.1-2 cm (P = 0.004), as well as intrathyroidal multifocal cancer ≤1 cm (P = 0.004). In multivariable analysis, high hospital case volume, fewer surgeon years of experience, general surgery specialty, and preference for more extensive resection were independently associated with greater hospital-level use of radioactive iodine for stage I disease.
Conclusions: In addition to surgeon experience and specialty, surgeons' tendency to perform more extensive thyroid resection is associated with greater use of radioactive iodine for stage I thyroid cancer.
DOI: 10.1097/sla.0b013e31826c8915
PubMed ID: 23567930
Variation in the Management of Thyroid Cancer. J Clin Endocrinol Metab, 2013;98(5):2001-8.
Haymart MR, Banerjee M, Yang D, Stewart AK, Sisson JC, Koenig RJ, Doherty GM, Griggs JJ.
ABSTRACT
Context: Little is known about practice patterns in thyroid cancer, a cancer that is increasing in incidence.
Objective: We sought to identify aspects of thyroid cancer management that have the greatest variation.
Design/setting/participants: We surveyed 944 physicians involved in thyroid cancer care from 251 hospitals affiliated with the US National Cancer Database. Physicians were asked questions in the following four domains: thyroid surgery, radioactive iodine use, thyroid hormone replacement postsurgery, and long-term thyroid cancer management. We calculated the ratio of observed variation to hypothetical maximum variation under the assumed distribution of the response. Ratios closer to 1 indicate greater variation.
Results: We had a 66% response rate. We found variation in multiple aspects of thyroid cancer management, including the role of central lymph node dissections (variation, 0.99; 95% confidence interval [CI], 0.98-1.00), the role of pretreatment scans before radioactive iodine treatment (variation, 1.00; 95% CI, 0.98-1.00), and all aspects of long-term thyroid cancer management, including applications of ultrasound (variation, 0.97; 95% CI, 0.93-0.99) and radioactive iodine scans (variation, 0.99; 95% CI, 0.97-1.00). For the management of small thyroid cancers, variation exists in all domains, including optimal extent of surgery (variation, 0.91; 95% CI, 0.88-0.94) and the role of both radioactive iodine treatment (variation, 0.91; 95% CI, 0.89-0.93) and suppressive doses of thyroid hormone replacement (variation, 1.00; 95% CI, 0.99-1.00).
Conclusion: We identified areas of variation in thyroid cancer management. To reduce the variation and improve the management of thyroid cancer, there is a need for more research and more research dissemination.
DOI: 10.1210/jc.2012-3355
PubMed ID: 23539722
Referral patterns for patients with high-risk thyroid cancer. Endocr Pract, 2013;19(4):638-43.
Haymart MR, Banerjee M, Yang D, Stewart AK, Griggs JJ, Sisson JC, Koenig RJ.
ABSTRACT
Objective: Knowledge of referral patterns for specialty cancer care is sparse. Information on both the need and reasons for referral of high-risk, well-differentiated thyroid cancer patients should provide a foundation for eliminating obstacles to appropriate patient referrals and improving patient care.
Methods: We surveyed 370 endocrinologists involved in thyroid cancer management. From information in a clinical vignette, respondents were asked to identify the reasons they would need to refer a high-risk patient to a more specialized facility for care. We performed multivariable analysis controlling for hospital and physician characteristics.
Results: Thirty-two percent of respondents reported never referring thyroid cancer patients to another facility. Of those that would refer a high-risk patient to another facility, the opportunity for a patient to enter a clinical trial was the most common reason reported (44%), followed by high-dose radioactive iodine (RAI) with or without dosimetry (33%), lateral neck dissection (24%), and external beam radiation (15%). In multivariable analysis, endocrinologists with a higher percentage of their practice devoted to thyroid cancer care were significantly less likely to refer patients to another facility (P = .003).
Conclusion: The majority of endocrinologists treating thyroid cancer patients report referring a high-risk patient to another facility for some or all of their care. Knowledge of the patterns of physician referrals and the likelihood of need for referral are key to understanding discrepancies in referral rates and obstacles in the referral process.
DOI: 10.4158/ep12288.or
PubMed ID: 23512381
Disease severity and radioactive iodine use for thyroid cancer. J Clin Endocrinol Metab, 2013;98(2):678-86.
Haymart MR, Muenz DG, Stewart AK, Griggs JJ, Banerjee M.
ABSTRACT
Context: Although variation in radioactive iodine (RAI) use for thyroid cancer has been demonstrated, the role of region and nonclinical correlates of use within risk groups has not been investigated.
Objective: The objective of the study was to determine the correlates of RAI use within risk groups.
Design/setting/patients: Use of RAI was evaluated across 9 US regions in 85 948 patients with well-differentiated thyroid cancer diagnosed between 2004 and 2008 at 986 hospitals associated with the US National Cancer Database. Cancers were then categorized as low risk (tumor size ≤ 1 cm and American Joint Committee on Cancer stage I disease), medium risk (neither low nor high-risk), and high risk (American Joint Committee on Cancer stage III or IV). Within each risk stratum, the role of region and nonclinical correlates of RAI use were evaluated using hierarchical logistic regression.
Main outcome measure: Use of RAI was measured.
Results: Rates of RAI use varied across geographic regions from 49% to 66%. Regional differences persisted after controlling for patient and hospital characteristics and evaluating less vs more intensive regions within low-risk [odds ratio (OR) 0.36 (95% confidence interval [CI] 0.25-0.53)], medium-risk [OR 0.23 (95% CI 0.16-0.34)], and high-risk cancers [OR 0.30 (95% CI 0.19-0.49)]. Patterns of RAI use were similar in medium- and high-risk patients. The most nonclinical correlates of use were in low-risk patients.
Conclusion: Similar treatment patterns for the heterogeneous medium-risk thyroid cancer patients compared with the high-risk patients suggest more intensive management in patients with medium-risk disease. The large number of nonclinical correlates of RAI use, including region, imply controversy over indications for RAI.
DOI: 10.1210/jc.2012-3160
PubMed ID: 23322816
Surgeon training and use of radioactive iodine in stage I thyroid cancer patients. Ann Surg Oncol, 2013;20(3):733-8.
Schuessler KM, Banerjee M, Yang D, Stewart AK, Doherty GM, Haymart MR.
ABSTRACT
Background: The majority of thyroid cancer diagnoses in the United States are stage I well-differentiated cancer. The use of radioactive iodine (RAI) in these low-risk patients has increased over time. The role of surgeon training in decision making regarding treatment with RAI is unknown.
Methods: Thyroid surgeons affiliated with 368 hospitals associated with the US National Cancer Database (NCDB) were surveyed. Survey data were linked to the NCDB data. A multivariable weighted analysis controlling for surgeon and hospital characteristics was conducted to examine the relationship between surgeon training, continuing education and hospital-level RAI use for stage I well-differentiated thyroid cancer.
Results: The response rate was 70% (560 of 804). In both univariate and multivariable analysis controlling for hospital case volume, practice setting and surgeon specialty, training with a thyroid surgeon was associated with less RAI use for stage I thyroid cancer (P = 0.022 and 0.028, respectively). Attending one or more professional society meetings a year was associated with a lower rate of hospital-level RAI use in univariate analysis (P = 0.044) but not multivariable analysis.
Conclusions: Training with a surgeon or group of surgeons who focus on thyroid surgery was associated with a lower proportion of stage I thyroid cancer patients receiving RAI after total thyroidectomy. This study emphasizes the importance of surgeon training in hospital practice patterns.
DOI: 10.1245/s10434-012-2745-0
PubMed ID: 23224826
Factors that influence radioactive iodine use for thyroid cancer. Thyroid, 2013;23(2):219-24.
Papaleontiou M, Banerjee M, Yang D, Sisson JC, Koenig RJ, Haymart MR.
ABSTRACT
Background: There is variation in the use of radioactive iodine (RAI) as treatment for well-differentiated thyroid cancer. The factors involved in physician decision-making for RAI remain unknown.
Methods: We surveyed physicians involved in postsurgical management of patients with thyroid cancer from 251 hospitals. Respondents were asked to rate the factors important in influencing whether a thyroid cancer patient receives RAI. Multivariable analyses controlling for physician age, gender, specialty, case volume, and whether they personally administer RAI, were performed to determine correlates of importance placed on patients' and physicians' worry about death from cancer and differences between low- versus higher-case-volume physicians.
Results: The survey response rate was 63% (534/853). Extent of disease, adequacy of surgical resection, patients' willingness to receive RAI, and patients' age were the factors physicians were most likely to report as quite or very important in influencing recommendations for RAI to patients with thyroid cancer. Interestingly, both physicians' and patients' worry about death from thyroid cancer were also important in determining RAI use. Physicians with less thyroid cancer cases per year were more likely than higher-volume physicians to report patients' (p<0.001) and physicians' worry about death (p=0.016) as quite or very important in decision-making. Other factors more likely to be of greater importance in determining RAI use for physicians with lower thyroid cancer patient volume versus higher include the accepted standard at the affiliated hospital (p=0.020), beliefs about RAI expressed by colleagues comanaging patients (p=0.003), and patient distance from the nearest facility administering RAI (p=0.012).
Conclusion: In addition to the extent of disease and adequacy of surgical resection, physicians place importance on physician and patient worry about death from thyroid cancer when deciding whether to treat a patient with RAI. The factors important to physician decision-making differ based on physician thyroid-cancer case-volume, with worry about death being more influential for low-case-volume physicians. As the mortality from thyroid cancer is low, the importance placed on death in decision making may be unwarranted.
PubMed ID: 23134514
The role of clinicians in determining radioactive iodine use for low-risk thyroid cancer. Cancer, 2013;119(2):259-65.
Haymart MR, Banerjee M, Yang D, Stewart AK, Koenig RJ, Griggs JJ.
ABSTRACT
Background: There is controversy regarding the optimal management of thyroid cancer. The proportion of patients with low-risk thyroid cancer who received radioactive iodine (RAI) treatment increased over the last 20 years, and little is known about the role played by clinicians in hospital-level RAI use for low-risk disease.
Methods: Thyroid surgeons affiliated with 368 hospitals that had Commission on Cancer-accredited cancer programs were surveyed. Survey data were linked to data reported to the National Cancer Database. A multivariable analysis was used to assess the relation between clinician decision makers and hospital-level RAI use after total thyroidectomy in patients with stage I, well differentiated thyroid cancer.
Results: The survey response rate was 70% (560 of 804 surgeons). The surgeon was identified as the primary decision maker by 16% of the surgeons; the endocrinologist was identified as the primary decision maker by 69%, and a nuclear medicine, radiologist, or other physician was identified as the primary decision maker by 15%. In a multivariable analysis controlling for hospital case volume and hospital type, when the primary decision maker was in a specialty other than endocrinology or surgery, there was greater use of RAI at the hospital (P < .001). A greater number of providers at the hospital where RAI was administered and having access to a tumor board also were associated with increased use of RAI (P < .001 and P = .006, respectively).
Conclusions: The specialty of the primary decision maker, the number of providers administering RAI, and having access to a tumor board were associated significantly with the use of RAI for stage I thyroid cancer. The findings have implications for addressing nonclinical variation between hospitals, with a marked heterogeneity in decision making suggesting that standardization of care will be challenging.
DOI: 10.1002/cncr.27721
PubMed ID: 22744940
Approach to and treatment of thyroid disorders in the elderly. Med Clin North Am, 2012; 96(2):297-310.
Papaleontiou M, Haymart MR.
ABSTRACT
Thyroid gland dysfunction is prevalent in older adults and may be associated with significant morbidity if misdiagnosed and left untreated. Because of a decreased number of symptoms at presentation, an increased susceptibility to adverse events if not treated, and a greater likelihood of harm from treatment, the diagnosis and management of thyroid disorders in older adults can be challenging. This review focuses on the epidemiology, clinical presentation, risks and complications, and management of thyroid disorders in older adults, including hyperthyroidism, hypothyroidism, thyroid nodules, and thyroid cancer.
DOI: 10.1016/j.mcna.2012.01.013
PubMed ID: 22443977
American Thyroid Association consensus review and statement regarding the anatomy, terminology, and rationale for lateral neck dissection in differentiated thyroid cancer. Thyroid, 2012;22(5):501-8.
Stack BC Jr, Ferris RL, Goldenberg D, Haymart MR, et. al.
ABSTRACT
Background: Cervical lymph node metastases from differentiated thyroid cancer (DTC) are common. Thirty to eighty percent of patients with papillary thyroid cancer harbor lymph node metastases, with the central neck being the most common compartment involved. The goals of this study were to: (1) identify appropriate methods for determining metastatic DTC in the lateral neck and (2) address the extent of lymph node dissection for the lateral neck necessary to control nodal disease balanced against known risks of surgery.
Methods: A literature review followed by formulation of a consensus statement was performed.
Results: Four proposals regarding management of the lateral neck are made for consideration by organizations developing management guidelines for patients with thyroid nodules and DTC including the next iteration of management guidelines developed by the American Thyroid Association (ATA). Metastases to lateral neck nodes must be considered in the evaluation of the newly diagnosed thyroid cancer patient and for surveillance of the previously treated DTC patient.
Conclusions: Lateral neck lymph nodes are a significant consideration in the surgical management of patients with DTC. When current guidelines formulated by the ATA and by other international medical societies are followed, initial evaluation of the DTC patient with ultrasound (or other modalities when indicated) will help to identify lateral neck lymph nodes of concern. These findings should be addressed using fine-needle aspiration biopsy. A comprehensive neck dissection of at least nodal levels IIa, III, IV, and Vb should be performed when indicated to optimize disease control.
PubMed ID: 22435914
Use of radioactive iodine for thyroid cancer. JAMA, 2011;306(7):721-8.
Haymart MR, Banerjee M, Stewart AK, Koenig RJ, Birkmeyer JD, Griggs JJ.
ABSTRACT
Context: Substantial uncertainty persists about the indications for radioactive iodine for thyroid cancer. Use of radioactive iodine over time and the correlates of its use remain unknown.
Objective: To determine practice patterns, the degree to which hospitals vary in their use of radioactive iodine, and factors that contribute to this variation.
Design, setting, and patients: Time trend analysis of radioactive iodine use in a cohort of 189,219 patients with well-differentiated thyroid cancer treated at 981 hospitals associated with the US National Cancer Database between 1990 and 2008. We used multilevel analysis to assess the correlates of patient and hospital characteristics on radioactive iodine use in the cohort treated from 2004 to 2008.
Main outcome measure: Use of radioactive iodine after total thyroidectomy.
Results: Between 1990 and 2008, across all tumor sizes, there was a significant increase in the proportion of patients with well-differentiated thyroid cancer receiving radioactive iodine (1373/3397 [40.4%] vs 11,539/20,620 [56.0%]; P < .001). Multivariable analysis of patients treated from 2004 to 2008 found that there was a statistical difference in radioactive iodine use between American Joint Committee on Cancer stages I and IV (odds ratio [OR], 0.34; 95% confidence interval [CI], 0.31-0.37) but not between stages II/III and IV (for stage II vs stage IV, OR, 0.97; 95% CI, 0.88-1.07 and for stage III vs stage IV, OR, 1.06; 95% CI, 0.95-1.17). In addition to patient and tumor characteristics, hospital volume was associated with radioactive iodine use. Wide variation in radioactive iodine use existed, and only 21.1% of this variation was accounted for by patient and tumor characteristics. Hospital type and case volume accounted for 17.1% of the variation. After adjusting for available patient, tumor, and hospital characteristics, 29.1% of the variance was attributable to unexplained hospital characteristics.
Conclusion: Among patients treated for well-differentiated thyroid cancer at hospitals in the National Cancer Database, there was an increase in the proportion receiving radioactive iodine between 1990 and 2008; much of the variation in use was associated with hospital characteristics.
PubMed ID: 21846853
The most commonly occurring papillary thyroid cancer in the United States is now a microcarcinoma in a patient older than 45 years. Thyroid, 2011;21(3):231-6.
Hughes DT, Haymart MR, Miller BS, Gauger PG, Doherty GM.
ABSTRACT
Background: The incidence of papillary thyroid cancer (PTC) is growing at a faster rate than any other malignancy. However, it is unknown what effect age is having on the changing PTC incidence rates. With the goal of understanding the role of age in thyroid cancer incidence, this study analyzes the changing demographics of patients with PTC over the past three decades.
Methods: This was a retrospective evaluation of the incidence rates of PTC from 1973 to 2006 reported by the National Cancer Institute's Surveillance, Epidemiology, and End Results database.
Results: From 1973-2006 the age group most commonly found to have PTC has shifted from patients in their 30s to patients in the 40-50-year-old age group. In 1973 60% of PTC cases were found in patients younger than 45, and the majority of cases continued to occur in younger patients until 1999. After 1999 PTC became more common in patients older than 45 years, and in 2006, 61% of PTC cases were in patients older than 45 years. From 1988 to 2003 there has been an increasing incidence of all sizes of PTC in all age groups with the largest increase in tumors <1 cm in patients older than 45. Forty-three percent of tumors in patients older than 45 are now <1 cm, whereas only 34% are <1 cm in patients younger than 45. Of the nearly 20,000 thyroid cancer cases in 2003, 24% were microcarcinomas in patients over the age of 45.
Conclusions: The incidence of PTC is increasing disproportionally in patients older than 45 years. The number of PTC tumors smaller than 1 cm is increasing in all age groups, and now the most commonly found PTC tumor in the United States is a microcarcinoma in a patient older than 45 years. These changing patterns relating age and incidence have important prognostic and treatment implications for patients with PTC.
PubMed ID: 21268762
A phase II study of imatinib in patients with advanced anaplastic thyroid cancer. Thyroid, 2010;20(9):975-80.
Ha HT, Lee JS, Urba S, Koenig RJ, Sisson J, Giordano T, Worden FP.
ABSTRACT
Background: Currently, there is no standard treatment for metastatic anaplastic thyroid cancer (ATC). DNA microarray analysis has shown platelet-dervived growth factor receptor (PDGFR) overexpression in ATC relative to well-differentiated thyroid cancer. In p53-mutated/deficient ATC cell lines, cABL is overexpressed, and selective inhibition of cABL results in a cytostatic effect. Imatinib inhibits tyrosine kinase activity of Bcr-ABL and PDGF. We hypothesize that patients with ATC that over-expresses PDGF receptors or cABL will respond to imatinib.
Methods: Patients with histologically confirmed ATC who had measurable disease and whose disease expressed PDGF receptors by immunohistochemistry were eligible for study. Imatinib was administered at 400 mg orally twice daily without drug holiday. Response to treatment was assessed every 8 weeks. Patients with complete response, partial responses, or stable disease were treated until disease progression. The study was terminated early due to poor accrual.
Results: From February 2004 to May 2007, 11 patients were enrolled and were started on imatinib. At baseline, 4/11 had locoregional disease, 5/11 had distant metastases, and 2/11 had both. Nine of 11 had prior chemoradiation, and 7/11 had thyroidectomy. Eight of 11 were evaluable for response; 4 were excluded for lack of follow-up with radiologic evaluation. The overall response rates at 8 weeks were complete response 0/8, partial response 2/8, and stable disease 4/8. The median time to follow-up was 26 months (ranges 23-30 months). The rate of 6-month progression-free survival was 36% (95% confidence interval, 9%-65%). The rate of 6-month overall survival was 45% (95% confidence interval, 16%-70%). The most common grade 3 toxicity was edema in 25%; other grade 3 toxicities included fatigue and hyponatremia (12.5% each). There were no grade 4 toxicities or treatment related deaths.
Conclusions: Imatinib appears to have activity in advanced ATC and is well tolerated. Due to difficulty of accruing patients with a rare malignancy at a single institution, further investigation of imatinib in ATC may be warranted in a multi-institutional setting.
PubMed ID: 20718683
Papillary thyroid microcarcinomas: big decisions for a small tumor. Ann Surg Oncol, 2009;16(11):3132-9.
Haymart MR, Cayo M, Chen H.
ABSTRACT
Background: The clinical significance of papillary thyroid microcarcinoma (PTMC) is debated, and therefore the rise in incidence of PTMC creates management dilemmas. The following study evaluates factors influencing decisions to treat.
Materials and methods: Between 1994 and 2007, 1361 patients underwent thyroid surgery at a single institution. Of these patients, 107 were diagnosed with PTMC. The type of surgical intervention, likelihood of referral to an endocrinologist, use of radioactive iodine, and administration of suppressive doses of levothyroxine (LT4) were analyzed in relation to patient and tumor characteristics.
Results: Multifocality and larger size were predictive of which patients underwent total thyroidectomy on multivariable logistic regression (P=.004 and P=.001, respectively). Larger mean tumor size, 0.62+/-0.004 versus 0.34+/-0.006 cm, was independently associated with increased likelihood of endocrine referral (P=.029). Multifocality, diagnosis via FNA preoperatively, larger mean size of PTMC, and endocrine referral were independently associated with increased likelihood of receiving radioactive iodine (RAI). On multivariable analysis, only total thyroidectomy and endocrine referral were independently associated with treatment with suppressive doses of LT4 (P=.001 and .001, respectively). In the 47 patients with unifocal PTMC<0.8 cm diameter, the mean size of tumor focus was larger in the subgroup undergoing total thyroidectomy (P=.004). Surprisingly, in these very low risk PTMC patients, the likelihood of RAI for remnant ablation was independently associated with younger patient age (P=.029). In the subgroup with unifocal<0.8 cm disease, the mean age of patients receiving RAI was 34+/-3.3 years versus 48+/-2.3 years in those not receiving RAI (P=.003).
Conclusions: The decision tree in the management of PTMC is beginning at the time of surgery, and referral to endocrinology is associated with a more aggressive course. Younger age is predictive of RAI administration in the lowest-risk PTMC patients.
DOI: 10.1245/s10434-009-0647-6
PubMed ID: 19653044
Understanding the relationship between age and thyroid cancer. Oncologist, 2009;14(3);216-21.
Haymart MR.
ABSTRACT
Unique among malignancies, age is a key prognostic indicator for well-differentiated thyroid cancer. Patients aged <45 years can have the same degree of disease involvement and a distinctly different prognosis than those aged >45. Although the reason for the association between age and outcome is not entirely clear, it does imply that there is something intrinsic to either the cancer or the treatment that is age dependent. This article explores the characteristics of the normal thyroid and thyroid cancer that are age dependent. It then provides theories for the relationship between advanced age and poor prognosis, in addition to treatment options tailored to age at diagnosis.
DOI: 10.1634/theoncologist.2008-0194
PubMed ID: 19270027
Higher serum TSH in thyroid cancer patients occurs independent of age and correlates with extrathyroidal extension. Clin Endocrinol (Oxf), 2009;71(3):434-9.
Haymart MR, Glinberg SL, Liu J, Sippel RS, Jaume JC, Chen H.
ABSTRACT
Background: It has previously been shown that higher serum TSH is associated with increased thyroid cancer incidence and advanced-stage disease. In the healthy adult population, mean TSH increases with age. As age over 45 years is a known prognostic indicator for thyroid cancer, it is important to know whether higher TSH in patients with thyroid cancer occurs independent of age.
Objective: To determine the relationship between higher TSH, cancer and age.
Design: A retrospective cohort study.
Patients and methods: A total of 1361 patients underwent thyroid surgery between May 1994 and December 2007 at a single institution. Of these patients, 954 had pathological data, preoperative TSH and complete surgical history available. Data were analysed in relation to age and TSH.
Results: Mean TSH was significantly higher in cancer patients regardless of age < 45 years or >or= 45 years (P = 0.046 and P = 0.027, respectively). When examining age groups < 20, 20-44, 45-59 and >or= 60 years, there was a trend of rising mean TSH with age. Despite the rise in the benign subgroups, mean TSH was consistently higher in those with cancer vs. those without. On multivariate analysis, higher TSH was independently associated with cancer (P = 0.039) and pathological features of Hashimoto's thyroiditis (P = 0.001) but not with age (P = 0.557). On multivariate analysis of high-risk features associated with poor prognosis, there was a significant association between higher TSH and extrathyroidal extension (P = 0.002), whereas there was no clear relationship with age, tumour size > 4 cm, and distant metastases.
Conclusion: Independent of age, thyroid cancer incidence correlates with higher TSH. Higher TSH is associated with extrathyroidal extension of disease.
DOI: 10.1111/j.1365-2265.2008.03489.x
PubMed ID: 19067720
Valproic acid activates Notch1 signaling and induces apoptosis in medullary thyroid cancer cells. Ann Surg, 2008;247(6):1036-40.
Greenblatt DY, Cayo MA, Adler JT, Ning L, Haymart MR, Kunnimalaiyaan M, Chen H.
ABSTRACT
Objective: To examine the effects of valproic acid (VPA) on Notch1 expression and cancer cell proliferation in medullary thyroid cancer (MTC) cells.
Background: Other than surgery, there are no effective treatments for MTC, a neuroendocrine malignancy that frequently metastasizes. We have previously shown that over-expression of Notch1 in MTC cells inhibits cell growth and hormone production. VPA, a drug long used for the treatment of epilepsy, has recently been identified as a potential Notch1 activator. We hypothesized that VPA might activate Notch1 signaling in MTC cells, with antiproliferative effects.
Methods: Human MTC cells were treated with VPA (0-5 mM) and Western blotting was performed to measure levels of Notch1 pathway proteins and neuroendocrine tumor markers. After confirming that VPA is a Notch1 activator in MTC cells, we performed cell proliferation assay. Finally, to determine the mechanism of growth inhibition, we measured protein levels of various markers of apoptosis.
Results: Notch1 was absent in MTC cells at baseline. VPA treatment resulted in an increase in both full-length and active Notch1 protein. Notch1 activation with VPA suppressed 2 neuroendocrine tumor markers, ASCL1 and chromogranin A. Importantly, VPA inhibited the growth of MTC cells in a dose-dependent manner. Immunoblot analysis demonstrated caspase activation and poly(ADP-ribose) polymerase cleavage, indicating the induction of apoptosis.
Conclusions: VPA activates Notch1 signaling in MTC cells and inhibits their growth by inducing apoptosis. As the safety of VPA in human beings is well established, a clinical trial using this drug to treat patients with advanced MTC could be initiated in the near future.
DOI: 10.1097/sla.0b013e3181758d0e
PubMed ID: 18520232
The role of intraoperative frozen section if suspicious for papillary thyroid cancer. Thyroid, 2008;18(4):419-23.
Haymart MR, Greenblatt DY, Elson DF, Chen H.
ABSTRACT
Background: Optimal surgical intervention is straightforward when a fine-needle aspiration (FNA) is diagnostic for papillary thyroid cancer (PTC). However, if there are characteristics of an aspirate suspicious for PTC but not meeting criteria for diagnosis of PTC, the management is less clear.
Methods: Of the 1,051 patients who underwent thyroid surgery at the University of Wisconsin between May 24, 1994, and October 21, 2004, 102 had preoperative FNA cytology that was diagnostic or suspicious for PTC. Within the subgroups of diagnostic for PTC and suspicious for PTC, we evaluated the accuracy of FNA, the utility of frozen section (FS), and the predictive value of demographic and pathologic variables.
Results: When diagnostic for PTC, FNA was 97% accurate and FS did not alter management. However, if an FNA was interpreted as suspicious for PTC, there was a 57% (17/30) likelihood of PTC on permanent histology. In this subgroup, FS led to the optimal operative procedure in 96% (25/26) of cases. With the exception of size greater than 4 cm, demographic and pathologic variables did not predict malignancy or increase the likelihood of an FNA being diagnostic for PTC.
Conclusion: Intraoperative FS is a useful diagnostic tool when an FNA is suspicious for PTC.
PubMed ID: 18352821
Higher serum thyroid stimulating hormone level in thyroid nodule patients is associated with greater risks of differentiated thyroid cancer and advanced tumor stage. J Clin Endocrinol Metab, 2008;93(3):809-14.
Haymart MR, Repplinger DJ, Leverson GE, Elson DF, Sippel RS, Jaume JC, Chen H.
ABSTRACT
Context: TSH is a known thyroid growth factor, but the pathogenic role of TSH in thyroid oncogenesis is unclear.
Objective: The aim was to examine the relationship between preoperative TSH and differentiated thyroid cancer (DTC).
Design: The design was a retrospective cohort.
Setting, participants: Between May 1994 and January 2007, 1198 patients underwent thyroid surgery at a single hospital. Data from the 843 patients with preoperative serum TSH concentration were recorded.
Main outcome measures: Serum TSH concentration was measured with a sensitive assay. Diagnoses of DTC vs. benign thyroid disease were based on surgical pathology reports.
Results: Twenty-nine percent of patients (241 of 843) had DTC on final pathology. On both univariate and multivariable analyses, risk of malignancy correlated with higher TSH level (P=0.007). The likelihood of malignancy was 16% (nine of 55) when TSH was less than 0.06 mIU/liter vs. 52% (15 of 29) when 5.00 mIU/liter or greater (P=0.001). When TSH was between 0.40 and 1.39 mIU/liter, the likelihood of malignancy was 25% (85 of 347) vs. 35% (109 of 308) when TSH was between 1.40 and 4.99 mIU/liter (P=0.002). The mean TSH was 4.9+/-1.5 mIU/liter in patients with stage III/IV disease vs. 2.1+/-0.2 mIU/liter in patients with stage I/II disease (P=0.002).
Conclusions: The likelihood of thyroid cancer increases with higher serum TSH concentration. Even within normal TSH ranges, a TSH level above the population mean is associated with significantly greater likelihood of thyroid cancer than a TSH below the mean. Shown for the first time, higher TSH level is associated with advanced stage DTC.
DOI: 10.1210/jc.2007-2215
PubMed ID: 18160464
Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J Clin Oncol. 2008;26(29):4708-13.
Cohen EE, Rosen LS, Vokes EE, Kies MS, Forastiere AA, Worden FP, et.al.
ABSTRACT
Purpose: Patients with advanced, incurable thyroid cancer not amenable to surgery or radioactive iodine ((131)I) therapy have few satisfactory therapeutic options. This multi-institutional study assessed the activity and safety of axitinib, an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 in patients with advanced thyroid cancer.
Patients and methods: Patients with thyroid cancer of any histology that was resistant or not appropriate for (131)I were enrolled onto a single-arm phase II trial to receive axitinib orally (starting dose, 5 mg twice daily). Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors was the primary end point. Secondary end points included duration of response, progression-free survival (PFS), overall survival, safety, and modulation of soluble (s) VEGFR.
Results: Sixty patients were enrolled. Partial responses were observed in 18 patients, yielding an ORR of 30% (95% CI, 18.9 to 43.2). Stable disease lasting > or = 16 weeks was reported in another 23 patients (38%).
Objective: responses were noted in all histologic subtypes. Median PFS was 18.1 months (95% CI, 12.1 to not estimable). Axitinib was generally well tolerated, with the most common grade > or = 3 treatment-related adverse event being hypertension (n = 7; 12%). Eight patients (13%) discontinued treatment because of adverse events. Axitinib selectively decreased sVEGFR-2 and sVEGFR-3 plasma concentrations versus sKIT, demonstrating its targeting of VEGFR.
Conclusion: Axitinib is a selective inhibitor of VEGFR with compelling antitumor activity in all histologic subtypes of advanced thyroid cancer.
PubMed ID: 18541897
Tumor suppressor role of notch1 and raf-1 signaling in medullary thyroid cancer cells. Transl Oncogenomics, 2007;2:43-7.
Kunnimalaiyaan M, Haymart MR, Chen H.
ABSTRACT
There is a growing body of literature suggesting that signaling based therapy might be a potential approach for medullary thyroid cancer (MTC). In this review we focus on the tumor suppressor role of Notch1 and Raf-1 signaling in MTC. Interestingly these two pathways are minimally active or absent in these tumors and activation of Notch1 and Raf-1 significantly reduces tumor growth in vitro. Therefore, identification of compounds that induce these pathways could be a potential strategy to treat patients with MTC.
PubMed ID: 23641144