Feasibility

Status: In Set-Up (18/Nov/2025)

CPMS No: 66335

Description: Cancers that are hypoxic (have a high percentage of regions of low local O2 concentration) are refractory to radiotherapy but benefit from hypoxia modification. However, there are no biomarkers to identify patients with hypoxic tumours. The gold standard for determining tissue O2 concentration is the O2-electrode which takes measurements at several sites within the tumour. However, this necessitates insertion of a needle into multiple regions of the tumour so is invasive and provides only a localised hypoxia status. Other hypoxia biomarkers that identify hypoxia have been derived from cell surface protein expression, gene expression or imaging outputs. Proteins expressed on the tumour cell surface of hypoxic cells include CA9 and glut1 but the expression of these proteins is not specific to hypoxia and is highly heterogeneous within tumours. Whilst expression of HIF1 by hypoxic tumours has been shown not to predict benefit from hypoxia-modification (Swartz et al 2022). Gene signatures are a set of genes in which the collective changed expression has been validated to demonstrate diagnosis, prognosis or predict therapeutic response. Gene expression is consistently altered across tumours with high hypoxic fractions meaning that they are robust indicators of hypoxia status. Using RNA extracted from archived material (Formalin fixed paraffin embedded tumour tissue) our gene-expression signature-based biomarkers for bladder, head and neck, prostate, sarcoma, cervical and lung cancers have been validated by demonstrated prognosis in each of the cancer groups. Further the 24 gene bladder cancer hypoxia signature has been shown to be predictive of benefit from hypoxia modification for patients with hypoxic tumours receiving radiotherapy. A recent review of predictive biomarkers in cancer treatment has shown that this is the only predictive biomarker for hypoxia-modification during radiotherapy (Batis et al 2021). Hypoxic regions in tumours can also be identified using MRI techniques including O2-senstive MRI (OE-MRI) and Intravoxel incoherent motion imaging. Combining imaging with gene expression data results in more accurate assessment of hypoxic status and identify tumour subtype which further contributes to personalised clinical decisions. MRI-based techniques also facilitate localized personalization approaches, e.g. for hypoxia-directed focal radiotherapy dose escalation. 

• Status: In Set-Up (18/11/2025)

• CPMS No: 58409

• Description: Breast cancer affects 55,000 patients each year in the UK, and in ~20% of cases, the cancer will have spread to the armpit (axillary) lymph nodes. The current standard treatment for these patients is to remove all the axillary lymph nodes (axillary node clearance), even if only one or two are affected. However, one in three patients will experience life changing complications as a result of this treatment, including permanent swelling of the arm (lymphoedema), long-term pain, and problems with shoulder function. These complications dramatically affect quality of life and are costly to the NHS. Axillary node clearance (ANC) was believed to give patients the best chance of surviving their breast cancer, but there is no evidence to show that this is true if the spread to the axillary lymph nodes is limited. More targeted surgery to the armpit, called a targeted axillary dissection (TAD), in which just the lymph nodes containing cancer and the first draining (sentinel) lymph nodes are removed may be just as safe and reduce the risk of life-changing complications. The TADPOLE study aims to determine whether targeted armpit surgery (TAD) reduces the risk of lymphoedema at 12 months after the operation without increasing the risk of the cancer returning, compared to ANC. 861 patients will be recruited from 40 UK NHS Breast Units. One group will receive ANC (standard care), while the other group will receive TAD. Patients will be assigned to a group by randomisation to ensure that the groups are similar. TADPOLE will compare how many patients have lymphoedema 12 months after surgery, and patients will be followed up for five years to ensure that the risk of the cancer returning after receiving TAD is acceptable. We will also collect information on surgical complications, shoulder function, pain, quality of life and financial costs. 

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• Status: In Set-Up (18 Nov 2025)

• CPMS ID: 55290 

• Description: Malignant pleural mesothelioma (MPM) is a cancer which begins in the tissues lining the lungs. Many patients are under initial surveillance after diagnosis and only receive treatment later when deemed suitable when considering the risk and benefits of the NHS approved treatment options and impact on quality of life. Proton beam therapy (PBT) is a type of radiotherapy which results in less radiation to healthy tissues surrounding the cancer compared to photon radiotherapy. Using PBT to limit these side effects would provide an invaluable way to improve outcomes and life expectancy for these patients whilst maintaining their quality of life. This trial aims to explore PBT as a treatment option for MPM patients who would routinely be put under initial surveillance in the standard of care pathway after diagnosis; to determine how PBT impacts progression free and overall survival, safety and toxicity, quality of life and health economics. Patients will be randomly allocated (1:1 ratio) to receive either PBT (the trial arm), or remain in the standard of care surveillance approach for MPM (the control arm). The PBT will be delivered daily (on weekdays) over 5 weeks at the proton centre in London or Manchester. The trial aims to recruit 148 patients in total. In collaboration with Mesothelioma UK and University of Sheffield, there is also a sub-study for 8-10 patients who are allocated to receive PBT to explore patient expectations and journey with the trial and proton therapy. All patients will be followed up locally at their recruitment centres for two years where tumour assessments with CT scans and blood samples will be collected for biomolecular research. The evidence from this national trial will support the national guidance on best available treatments for mesothelioma to be updated, and further patients to benefit from this in the future.