Chemoimmunotherapy Followed by Surgery for Oligometastatic Esophagogastric Cancer: (TORO Protocol)

Inclusion Criteria:

• Histologically-proven cT1-4aN0-3M1 adenocarcinoma or squamous cell carcinoma of theesophagus, or EGJ according to the 8th edition of the Union for International CancerControl (UICC) TNM classification for Esophageal Cancer;

• Oligometastatic disease, which is defined as a maximum of five metastatic lesions,that is treatable by surgical resection or radiation. These five lesions can bepresent in a maximum of two organs (eg, liver, lung or adrenal gland). Lymph nodesare not counted as an organ. If metastatic retroperitoneal or supraclavicular lymphnodes are present, this lymph node site counts as one metastatic lesion, andtogether with the possible metastases in organs cannot exceed the number of fivelesions.

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;

• Adequate cardiac and respiratory function by standard electrocardiogram andadditional diagnostics in case of cardiopulmonary complaints or comorbidity (i.e.lung function test, or echocardiography)

• Adequate blood work parameters for systemic therapy as per treating medicaloncologist in terms of ANC, platelet count and hemoglobin.

• Adequate renal function (glomerular filtration rate >50 mL/min or serum creatinine ≤1.5x upper level of normal (ULN)) and adequate liver function (total bilirubin < 2.5x ULN and alanine transaminase (ALT) < 3x ULN);

• A negative serum pregnancy test in women of child-bearing potential during screeningperiod.

• Age >18 and <80 years old

Exclusion Criteria:

• Patients with overt peritoneal or pleural dissemination, as detected on PET-CT orregular CT-scan. In patients in whom a diagnostic laparoscopy is indicated (toassess gastric involvement and the possibility to perform gastric tubereconstruction or to exclude peritoneal disease), tumor-positive cytology peritonealfluid is also an exclusion criteria. Of note, positive microscopic peritonealcytology which converts to negative after treatment is not an exclusion criteria (i.e. peritoneal or pleural fluid cytology must be negative at the time ofenrollment, with no gross disease identified initially).

• Multiple bone or brain metastases - up to one solitary bone met and/one solitarybrain met is allowable as a metastatic site, if curative ablative radiotherapy canbe given at the discretion of the treating physicians. Patients with multiple brainmetastases or multiple bone metastases will be excluded.

• Any other condition that, in the opinion of the investigator, would make the patientunsuitable for the study; particularly any condition that would make the patientunfit for surgery, radiation, chemotherapy or a combination thereof.

• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressivedrugs) except vitiligo or resolved childhood asthma/atopy. Replacement therapy, suchas thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenalor pituitary insufficiency, is not considered a form of systemic treatment and isallowed. Use of non-systemic steroids is permitted.

• Patients with active pregnancy, or lactation.