The PACT-ES study
PACT-ES: Personalised Approach to Chemotherapy Treatment for Ewing’s Sarcoma
Background
Ewing's sarcoma, an aggressive bone cancer that mostly affects children and adolescents, is currently treated with a multimodal treatment approach involving chemotherapy and local therapy. Often, modifications to dosage and timing of chemotherapy are necessary due to therapy-related side effects or based on individual preferences of the child/parents. However, the impact of such modifications has not been thoroughly investigated, resulting in a lack of certainty regarding the actual treatment outcomes, leading to important concerns of patients and parents.
Aims
To bridge this knowledge gap, this research project aims to employ advanced medical statistics methodology to develop a novel Personalised Approach to Chemotherapy Treatment for Ewing’s Sarcoma (PACT-ES). PACT-ES will investigate the longitudinal relationship between dose-reductions/delays in chemotherapy and multiple side effects, and their impact on survival outcomes. Data from the Euro Ewing 2012 international multicentre trial will be analysed, offering a valuable opportunity to study a contemporary cohort treated according to the current state-of-the-art systemic and local therapy.
The PACT-ES study will develop a longitudinal approach to detect differences and variability in actual treatment administration and overall toxicity among patients. The impact of the administered therapy on survival will then be investigated. Finally, a dynamic prediction model for conditional survival based on patients’ unique clinical history throughout the course of treatment will be developed.
Relevance for cancer research
The PACT-ES study will shed light on whether (i) treatment delays and dose reductions recommended by guidelines can be accepted without compromising outcomes, reassuring patients and parents regarding concerns about the potential impact of treatment modifications; or (ii), if a more rigorous adherence to treatment schedule, potentially accepting higher toxicity levels if feasible, can improve survival chances.
PACT-ES will therefore help guide treatment decisions, improve patient’s care, and provide reassurance to patients and parents, ultimately improving the management and outcomes of this difficult disease.
Scientific Personnel
Prof.dr. M. Fiocco - Methodological Project Leader
Mathematical Institute of Leiden University, Leiden University Medical Center (Biomedical Data Sciences) & Princess Máxima Center for Pediatric OncologyProf.dr. J.H.M. Merks - Clinical Project Leader
Princess Máxima Center for Pediatric Oncology & University Medical Center UtrechtDr. M. Spreafico - Co-Investigator
Mathematical Institute of Leiden University & Leiden University Medical Center (Biomedical Data Sciences)Prof. B. Brennan - Co-Investigator
Department of Paediatric Oncology and Haematology, Royal Manchester Children’s Hospital (Manchester, UK)
Chief Investigator of the Euro Ewing 2012 trialProf.dr. M.A.J. van de Sande
Leiden University Medical Center (Orthopaedic Surgery) & Princess Máxima Center for Pediatric OncologyProf.dr. H. Gelderblom
Leiden University Medical Center (Medical Oncology)
Collaborators
Laura Kirton
Cancer Research Clinical Trials Unit, University of Birmingham (Birmingham, UK)Piers Gaunt
Cancer Research Clinical Trials Unit, University of Birmingham (Birmingham, UK)Dr. L. Haveman
Princess Máxima Center for Pediatric OncologyDr. R. Dávila Fajardo
Princess Máxima Center for Pediatric Oncology & University Medical Center UtrechtVereniging Kinderkanker Nederland (Utrecht, NL)
Funding
The project "PACT-ES: Personalised Approach to Chemotherapy Treatment for Ewing’s Sarcoma" is funded by KiKa KinderKankervrij [2024-grant 485].
