A randomised Phase II trial comparing proton versus photon-based neoadjuvant chemoradiation, followed by standard therapy, in oesophageal cancer
Oesophageal cancer
Current interventions as of 06/02/2026: Eligible patients will be allocated by a computer devised programme into one of the treatment groups: A) a group receiving proton beam radiotherapy (PBT) or B) a group receiving standard of care treatment photon radiotherapy. All patients will receive 3 weeks of daily radiation and 5-7 courses of chemotherapy once weekly/fortnightly, with/without immunotherapy, followed by surgery. Patients in PBT group will travel to one of the proton beam centres either in Manchester or London. After chemoradiotherapy, all patients will have surgery and they will receive up to 4 fortnightly cycles of chemotherapy and/or immunotherapy for up to 1 year after their surgery, which starts approximately 4 to 12 weeks after surgery. The frequency when the patient should receive immunotherapy, for example, once every 2 or 4 weeks, will depend on the local hospital’s policy. After finishing surgery, all patients will be seen at clinic (follow-up visits) at the first month after the surgery, then every 3 months for up to a 1 year. Further follow-up data will be collected remotely via a data collection service called NHS Digital (NHS England data registries). There is also a translational research component where extra blood will be taken from patients, and tissue samples from the diagnostic biopsy and surgical specimen will be collected for use in research. Previous interventions: Eligible patients will be allocated by a computer devised programme into one of the treatment groups: A) a group receiving proton beam radiotherapy (PBT) or B) a group receiving standard of care treatment photon radiotherapy. All patients will receive 3 weeks of daily radiation and 5 courses of chemotherapy once weekly, followed by surgery. Patients in PBT group will travel to one of the proton beam centres either in Manchester or London. After chemoradiotherapy, all patients will have surgery and if they have a small amount of remaining cancer cells (residual disease) afte
1. 16 years of age or older 2. Histologically confirmed diagnosis of oesophageal adenocarcinoma (OAC) or squamous cell carcinoma (OSCC) 3. Tumour of the thoracic oesophagus or gastroesophageal junction with distal maximum extension no more than 3 cm beyond the gastroesophageal junction 4. cT stage >=2 and/or cN stage >=0-2 defined by AJCC 8th edition 5. ECOG performance status 0–1 6. Suitable for and fit to receive curative neoadjuvant Chemoradiotherapy followed by surgery by an Upper GI MDT 7. Suitable for and fit to receive adjuvant Immunotherapy according to local guidelines 8. Adequate cardiovascular and respiratory function for surgery in the opinion of the surgical team within 4 weeks prior to randomisation 9. Willing and able to give written informed consent and able to comply with treatment and follow up schedule 10. Willing and able to undergo treatment at a PBT centre (i.e. UCLH or The Christie) if randomised to Proton Arm
1. Metastatic disease or extensive nodal disease (N3). 2. Patients who have had previous treatment for invasive oesophageal carcinoma or gastro-oesophageal junction carcinoma (including Photo Dynamic Therapy or laser therapy for high grade dysplasia/carcinoma in-situ). 3. Patients with > 3cm mucosal extension of tumour into the stomach beyond the GOJ or where the superior extent is in the cervical oesophagus 4. Tumour length based on position: 4.1. Length of primary tumour >10 cm in thorax, or 4.2. >12 cm in the gastroesophageal junction or lower third of the oesophagus, or 4.3. Total length of disease (primary tumour and involved lymph nodes) length >14 cm for lower third tumours. 5. Patients with unstable angina, uncontrolled hypertension, cardiac failure or arrhythmia and other clinically significant cardiac disease. 6. Patients with an oesophageal stent (patients requiring a PEG/RIG/feeding jejunostomy for nutritional purposes ARE eligible). 7. No relevant co-morbidities, including Usual Interstitial Pneumonia (UIP) pulmonary fibrosis and connective tissue disorders. 8. History of other malignancy likely to interfere with the protocol treatment (e.g. patients with previously treated malignancy who have been disease-free for < 1 year, or patients with active malignancy undergoing treatment). Exceptions: 8.1. Subjects who have been successfully treated and disease-free for > 3 years, 8.2. A history of treated non-melanoma skin cancer, 8.3. Successfully treated in situ carcinoma, 8.4. CLL in stable remission, or indolent prostate cancer requiring no or only anti-hormonal therapy. 9. Any other situation, which in the opinion of the local PI, makes the patient unsuitable for this trial. 10. Women who are pregnant or breastfeeding. 11. Patients unable to adhere to the contraception guidance in the protocol.