CRUK/22/011: PROTIEUS - Proton Beam Therapy and adjuvant Immunotherapy in Oesophageal cancer

Background Oesophageal cancer comprising mainly of oesophageal adenocarcinoma and squamous cell carcinoma is one of the most lethal cancers with rising incidence and high mortality (1 in 18 cancer deaths).

It ranks 7th in incidence of cancer worldwide in 2020 with 604,100 new cases and 6th in mortality with 544,076 deaths were attributed to OEC in 2020. Oesophageal cancer is a strategic priority for CRUK and a serious health problem world-wide. Preoperative therapy consists of chemotherapy or chemoradiation, but the optimal regimen is under research.

The incidence of severe toxicity of the multimodality treatment is >60% and impacts oncological outcomes. Protons are a means of reducing toxicity and need prospective investigation. Immune treatments are standard of care after chemoradiation and surgery in oesophageal cancer.

Aims This study aims to investigate if moderate hypofractionated proton beam therapy (PBT) and chemotherapy (carboplatin-taxol) in the preoperative setting of OEC significantly reduces risk of pulmonary toxicity and permits timely initiation of adjuvant immunotherapy when compared with moderate hypofractionated radiotherapy delivered as part of triple modality therapy.

Methods This is a phase II two-arm randomised controlled trial, where 170 patients with locally advanced operable oesophageal cancer will be randomized 1:1 into the experimental arm (proton beam therapy delivered with pencil beam scanning 40Gy in 15 fractions over 3 weeks + carboplatin/paclitaxel 5 doses + surgery) and control arm (intensity modulated photon radiotherapy 40 Gy in 15 fractions over 3 weeks + carboplatin/paclitaxel 5 doses + surgery).

Patients eligible for adjuvant immunotherapy will then receive a maximum of 12 months of treatment as per standard of care.

How the results of this research will be used Trial results will be disseminated via national and international conferences and meetings for presentations/posters, as well as high impact factor peer-reviewed journals.

Patients associations will also be contacted to discuss dissemination of trial results via existing newsletters, journals, and bulletins.