PROton Versus Photon Therapy for Esophageal Cancer - a Trimodality Strategy

Inclusion Criteria:

* Patients with histologically verified squamous cell carcinoma or adenocarcinoma (including signet cell carcinoma and large cell carcinoma, not further specified) of the esophagus (E) or gastro-esophageal junction (GEJ).

  * FDG PET/CT performed.
  * Tumor stage according to TNM (8th edition): cT1-4a and/or cN+, cM0.
  * Age ≥18 years.
  * Performance status WHO ≤2.
  * Adequate laboratory findings: hematological: hemoglobin \> 90 g/L, absolute neutrophil count (ANC) ≥ 1,5 x 109/L, platelets ≥ 75 x 109/L hepatic: bilirubin ≤ 1.5 x upper limit of normal (ULN), ALAT ≤ 3 x ULN renal: creatinine ≤ 1.5 x ULN, GFR (may be calculated) \> 30 ml/min
  * MDT decision on suitability to undergo curatively intended nCXT or nCPT followed by surgery.
  * Planned transthoracic esophagectomy or gastrectomy being open, minimally invasive of combination of both.
  * Ability to adhere to procedures for study and follow-up.
  * Patients with low risk cancers with a life expectancy above 5 years (e.g. low risk prostate cancer) are allowed in the study. Adequately treated diagnoses such as cervix uteri carcinoma in situ, in situ urothelial carcinoma or localized non-melanoma skin cancer are allowed, regardless of time of diagnosis.
  * Patients of childbearing potential: pregnancy prevention according to the standards of each country. Patients of childbearing potential must present a negative pregnancy test. Patients and their partners must use effective contraception. Patients of childbearing potential included in the study must use oral contraceptives, intrauterine devices, depot injection of progestin subdermal implantation, a hormonal vaginal ring, or transdermal patch during the study treatment and one month after.

Exclusion Criteria:

Patients who meet one or more of the following exclusion criteria cannot be included in the study:

* Prior thoracic XT or PT, chemotherapy or surgical resection in the esophageal/gastric region (previous EMR or ESD is allowed).
* Tumor \< 3 cm from oropharyngeal sphincter.
* Planned transhiatal resection
* Patients with other previous malignancies are excluded unless a complete remission or complete resection was achieved at least 5 years prior to study entry.
* Any unstable systemic disease (including clinically significant lung and cardiovascular disease, unstable angina, New York Heart Association (NYHA) grade III-IV congestive heart, severe hepatic, renal or metabolic disease or active inflammatory bowel disease).
* Symptomatic peripheral neuropathy greater than grade 1 (scored according to CTCAE v5.0).
* Any other serious or uncontrolled illness, which, in the opinion of the investigator, makes it undesirable for the patient to enter the trial.
* Unable to understand and digest study patient information or comply with study treatment and safety instructions.
* Gastro-esophageal stent within the irradiated volume.