Patient case (clinical description): A 63-year-old man comes to the clinic for recent unintentional weight loss. The patient also has epigastric discomfort after meals. He has no known medical problems and takes no medications. His blood pressure is 130/75 and pulse rate is 88/min. He is not febrile. Upper endoscopy shows a lesion in the stomach that shows typical features of diffuse-type adenocarcinoma presenting with signet ring cells that do not form glands.

Patient's own account: I went to the clinic because I had been losing so much weight that it was concerning. I'm a 63-year-old guy, and it is something rather unusual. I'm always suffering from stomachache after every meal. I've never been sick, and I don't take any medicine. The doctor took my blood pressure and told me it was 130/75, and my pulse rate was 88/min. I'm not febrile! I also had to do an endoscopy, and they found a lesion in my stomach that shows typical features of stomach cancer. I'm totally devastated...

Clinical trial: Neoadjuvant Chemoradiation Plus PD-1 Antibody(SHR-1210) in Locally Advanced Proximal Stomach Adenocarcinoma

Eligibility criteria:
Inclusion Criteria:

          1. histologically documented gastric adenocarcinoma.

          2. primary lesion is in proximal stomach, including gastroesophageal junction, fundus and
             upper body.

          3. clinically diagnosed stage T3-4aN+M0 according to ultrasound endoscopy or enhanced
             CT/MRI scan.

          4. at least one evaluable lesion in abdominal CT/MRI according to RESIST 1.1 is required.

          5. surgeons participating in this study consider the lesion a resectable one.

          6. Karnofsky score≥ 80.

          7. Physical condition and adequate organ function to ensure the success of abdominal
             surgery.

          8. Adequate hematological function: Neutrophil count ≥ 1.5 × 109/L, Platelets ≥ 100 ×
             109/L and Hemoglobin ≥90g/L.

          9. Adequate liver function: Total bilirubin ≤ 1.5 × upper limit of normal (ULN); AST
             (SGOT) and ALT (SGPT) < 2.5 × ULN in the absence of liver metastases, or < 5 × ULN in
             case of liver metastases. ALP ≤ 2.5 × upper limit of normal (ULN); ALB ≥30g/L.

         10. Adequate renal function: Serum creatinine ≤ 1.5 x ULN, and creatinine clearance ≥ 60
             ml/min.

         11. Adequate coagulation function: INR/PT≤ 1.5 x ULN, aPTT≤ 1.5 x ULN.

         12. No serious concomitant disease that will threaten the survival of patients to less
             than 5 years.

         13. Male or female. Age ≥ 18 years and ≤75 years.

         14. Written (signed) informed consent.

         15. Good compliance with the study procedures, including lab and auxiliary examination and
             treatment.

         16. Female patients should not be pregnant or breast feeding.

         17. Agree to take contraception measures during treatment and in 120 days after last dose
             of SHR-1210 or in 180 days after last dose of chemo.

        Exclusion Criteria:

          1. patients with distant metastasis or unresectable primary lesion.

          2. patients with T1, T2 lesion according to CT/MRI or ultrasound endoscopy.

          3. history of chemo, radiation, immune therapy or radical resection for the stomach
             adenocarcinoma, except steroids.

          4. patients with active autoimmune disease or history of refractory autoimmune disease.

          5. patients with active malignant tumor in recent 2 years, except the tumor studied in
             this research or cured locally tumor like resected basal cell or squamous cell skin
             cancer, superficial bladder cancer, cervical or breast carcinoma in situ.

          6. uncontrollable pleural effusion, pericardial effusion, or ascites in 2 weeks before
             recruitment.

          7. patients who have digestive tract bleeding in 2 weeks before recruitment or with high
             risk of bleeding.

          8. perforation / fistula of GI tract in 6 months before recruitment.

          9. patients with upper GI tract obstruction or functional abnormality or malabsorption
             syndrome, which can affect absorption of capecitabine.

         10. losing over 20% body weight in 2 months before recruitment.

         11. pulmonary disease history: interstitial pulmonary disease, non-infective pneumonitis,
             pulmonary fibrosis, acute pulmonary disease.

         12. uncontrollable systemic diseases, including diabetes, hypertension, etc.

         13. severe chronic or active infections in need of systemic antibacterial, antifungal, or
             antiviral treatment, including TB or HIV, etc.

         14. patients with untreated chronic hepatitis B or HBV DNA over 500 IU/ml or positive HCV
             RNA.

         15. patients with any cardiovascular risk factors below:

               1. cardiac chest pain occurring in 28 days before recruitment, defined as moderate
                  pain that limits daily activity.

               2. pulmonary embolism with symptoms occurring in 28 days before recruitment.

               3. acute myocardial infarction occurring in 6 months before recruitment.

               4. any history of heart failure reaching grade 3/4 of NYHA in 6 months before
                  recruitment.

               5. ventricular arrhythmias of Grade 2 or grater in 6 months before recruitment, or
                  accompanied by supraventricular tachyarrhythmias requiring medical treatment.

               6. cerebrovascular accident within 6 months before recruitment.

         16. patients with peripheral neuropathy NCI CTC AE grade 1, except those with only deep
             tendon reflex disappearing.

         17. moderate or severe renal injury [creatinine clearance rate≤50 ml/min (according to
             Cockroft & Gault equation)], or Scr>ULN.

         18. dipyrimidine dehydrogenase (DPD) deficiency.

         19. allergic to any drug in this study.

         20. history of allogeneic stem cell transplantation or organ transplantation.

         21. use of steroids (dosage>10mg/d prednisone) or other systemic immune suppressive
             therapy in 14 days before recruitment, except patients treated with regimens below: a.
             steroids for hormone replacement (dosage>10mg/d prednisone); b. steroids for local
             application with little systemic absorption; c. short -term (≤ 7 days) steroids for
             preventing allergy or vomiting.

         22. vaccinated with live vaccine in 4 weeks before recruitment.

         23. receiving immune (interleukin, interferon, thymin) treatment or treatment of other
             trials in 28 days before recruitment.

         24. receiving palliative radiation in 14 days before recruitment.

         25. history of anti PD-1, PD-L1, PD-L2 or any other specific T cell co-stimulation or
             checkpoint pathway targeted treatment.

         26. receiving operation in 28 days before recruitment, only if the operation is a
             minimally invasive one e.g. PICC.

         27. for patients with uncontrolled epilepsy, CNS diseases or history of mental disorder,
             researchers should evaluate whether their diseases will impede their signing of
             informed consent or compliance of treatment.

         28. existing of potential situation which will impede drug administration or affect
             toxicity analysis or alcohol/ drug abuse.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.
Subject must be at most 75 Years

Eligibility (NLI label): Entailment