Implementation, optimisation and evaluation of proton therapy in esophageal cancer

The standard treatment for locally advanced esophageal cancer consists of neoadjuvant chemoradiotherapy followed by surgery. However, this trimodality treatment comes at a price of increased toxicity.  Nowadays, radiation treatment is delivered using photon-based radiotherapy. The latter is characterized by an energy deposition that follows a decreasing exponential as a function of the penetration depth into the patient. Subsequently, significant doses are absorbed by organs located upstream and downstream of the tumor. Proton therapy is an innovative modality with the property of depositing a narrow peak of energy at the required depth (Bragg peak), thus reducing doses to the surrounding healthy organs. Our research group participates in the European, multicenter, randomized phase III PROTECT (PROton versus photon Therapy for Esophageal Cancer: a Trimodality strategy) trial. The general aim of this trial is to show a reduction in radiotherapy-related toxicity by replacing photon-based radiotherapy with proton therapy. This research project aims at using the results of the PROTECT trial to compare our previously published predictive models with the observed outcomes after photon-based radiotherapy and proton therapy. Moreover, we aim to identify imaging and biological markers predictive for toxicity and outcome. The latter will be studied on serial blood samples and biopsies taken from the patients randomized in the trial. The identified markers will then be used to enrich our current prediction models. Upon validation, these prediction models will enable an evidence-based selection of patients who will benefit most from proton therapy.