The Ave-CRT Study for Newly Diagnosed Metastatic Esophageal Squamous Cell Carcinoma

Inclusion Criteria: * To be eligible for inclusion, patients must fulfill the following criteria: 1. Histologically proved squamous cell carcinoma of esophagus 2. Metastatic disease, which are defined by TNM system of American Joint Committee on Cancer (AJCC) Cancer Staging System (8th edition) in 2017, involving distant lymph node (para-aortic or cervical) metastasis and/or visceral metastasis (lung, liver) documented by radiological examinations 3. Age ≥ 20 years 4. ECOG Performance Status 0 or 1 5. Adequate bone marrow reserves within 2 weeks prior to registration, defined as:a. absolute neutrophil count (ANC) ≥ 1.5×109/L (1,500/μl)b. platelets ≥ 100×109/L (100,000/µl)c. hemoglobin ≥ 9.0 g/dl (may have been transfused) 6. Adequate liver function reserves within 2 weeks prior to registration, defined as: 1. hepatic transaminases (AST and ALT) ≤ 2.5 × upper limit of normal (ULN) or ≤ 5 × ULN for subjects with documented metastatic disease to liver 2. serum total bilirubin ≤ 2.5 × upper limit of normal (ULN) 7. Adequate renal function within 2 weeks prior to registration: Creatinine ≤1.5 mg/dL 8. Negative serum or urine pregnancy test for women of childbearing potential 9. Women of childbearing potential and male participants must practice highly effective contraception throughout the study and for at least 30 days after last avelumab treatment administration if the risk of conception exists 10. Patients must be able to comply with the study protocol and follow-up schedules and provide study-specific informed consent Exclusion Criteria: * Patients fulfill any of the following criteria will be excluded from this trial 1. Prior radiotherapy to head and neck, chest, or abdomen 2. Tumor invasion to adjacent structures (T4 lesion) 3. Adenocarcinoma of esophagus or gastroesophageal junction. 4. No measurable metastatic target lesion(s) by RECIST criteria 5. Synchronously or metachronously diagnosed squamous cell carcinoma of aerodigestive way, other than esophageal cancer 6. Prior invasive malignancy 7. Prior organ transplantation including allogenic stem-cell transplantation 8. Current use of immunosuppressive medication, EXCEPT for the following: 1. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection) 2. systemic corticosteroids at physiologic doses '≤ 10 mg/day of prednisone or equivalent 3. steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication). 9. Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible. 10. Severe, active comorbidities which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and adverse events of the protocol, or limit compliance with study requirements, defined as follows: 1. Uncontrolled active infection requiring intravenous antibiotics at the time of registration 2. Transmural myocardial infarction \< 6 months prior to registration 3. Unstable angina or congestive heart failure requiring hospitalization \< 6 months prior to registration 4. Life-threatening uncontrolled clinically significant cardiac arrhythmias 5. Cerebral vascular accident/stroke (\< 6 months prior to enrollment) 6. Congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication. 7. Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects 8. Chronic obstructive pulmonary disease exacerbation or other respiratory illness including pulmonary fibrosis requiring hospitalization or precluding study therapy at the time of registration 9. Uncontrolled psychiatric disorder including recent (within the past year) or active suicidal ideation or behavior 10. Laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results 11. Immune colitis, inflammatory bowel disease, immune pneumonitis 11. Known history of testing positive for HIV or known acquired immunodeficiency syndrome." 12. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive) 13. Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines 14. Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3)" 15. Women of childbearing potential and male participants who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the radiation treatment involved in this study may be significantly teratogenic