A clinical trial to investigate if proton beam therapy with chemotherapy given before surgery for patients with oesophageal cancer that has spread to the surrounding tissues, significantly reduces the severe side effects to the heart and lungs and allows immunotherapy to be started sooner after surgery when compared with standard radiotherapy and chemotherapy before surgery, and whether this delivers value to the NHS and patients

INTERVENTION: 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) after surgery, they will receive immunotherapy for up to 1 year after their surgery, 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 and tissue samples will be taken from patients. CONDITION: Oesophageal cancer ; Cancer PRIMARY OUTCOME: Frequency and percentage of patients that experience severe post operative complications prior to or at the follow‐up assessment 3 months after surgery measured using adverse event data entered on the database by sites which is graded using both the CTCAE and the Clavien Dindo Scale SECONDARY OUTCOME: Preliminary data on longer term efficacy outcomes following 1 year of adjuvant immunotherapy for patients that do not achieve pathologic complete response at surgery measured using survival data and the number and percentages of different types of disease recurrences INCLUSION CRITERIA: 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