pd1 antibody sintilimab ± chemoradiotherapy for locally advanced rectal cancer

Conditions: Colorectal Cancer Stage II; Colorectal Cancer Stage III

Summary: in this study, participants with locally advanced rectal cancer patients will be treated according to mmr/msi status. there will be two cohorts in this study: cohort a and cohort b. for cohort a, dmmr or msi-h patients will receive 4 cycles of neoadjuvant pd1 antibody sintilimab,followed by one of the following treatments: (1) surgery and adjuvant treatment, (2）another 4 cycles of sintilimab, followed by radical surgery or observation (only for ccr) . for cohort b, pmmr/mss/msi-l patients will be randomized to receive neoadjuvant chemoradiotherapy ± four cycles of pd1 antibody sintilimab，followed by one of the following treatments: (1) curative surgery and four cycles of adjuvant chemotherapy;(2)four cycles of chemotherapy then observation (only ccr after neoadjuvant therapy)


Eligibility criteria:
inclusion criteria: 1. histologically proven colorectal adenocarcinoma; 2. cohort 1: biopsy tissues with ihc indicates deficient mismatch repair(dmmr),that is,the loss of at least one of the four proteins ,msh1,msh2,msh6,pms2;or gene detection implies msi-h; cohort 2: biopsy tissues with ihc indicates proficient mismatch repair(pmmr),that is positivity of all four proteins ,msh1,msh2,msh6,pms2;or gene detection implies mss/msi-l 3. clinical stage for rectal cancer patients is ct3-4n0m0 or ctxn+m0; 4. preoperative staging methods: all patients need to accept digital rectal examination(dre).patients with rectal cancer undergo high-resolution mri±ultrasound colonoscopy/transrectal ultrasound for preoperative staging. perienteric lymph nodes with short diameter ≥10mm or the shape of lymph nodes and its mri characteristics are consistent with typical lymph node metastasis. if endoscopic ultrasonography is used in combination, and there is a contradiction between staging methods, the data should be submitted to the evaluation team of our center for the accurate staging; 5. no symptoms of ileus; or ileus is alleviated after proximal colostomy. 6. no rectal surgery except preventative stoma; 7. no chemotherapy or radiotherapy; 8. no biotherapy (e.g.monoclonal antibodies), immunotherapy (e.g.anti-pd-1 antibody,anti-pd-l1 antibody,anti-pd-l2 antibody or ctla-4 antibody),or other clinical trials agents; 9. no limit to previous endocrine therapy. 10. age between 18 and 75 years; 11. ecog performance status of 0 or 1; 12. life expectancy: more than 2 years; 13. hematopoietic: wbc\>3×109/l;plt\>80×109/l; hb\>90g/l; 14. hepatic: alt and ast\<2 times upper limit of normal (uln); bilirubin\<1.5 times uln; 15. renal: creatinine \<1.5 times uln or creatinine clearance ≥ 60 ml/min. exclusion criteria: 1. arrhythmias require antiarrhythmic therapy (with the exception of β-blockers or digoxin), symptomatic coronary artery disease or local myocardial ischemia (myocardial infarction within the past 6 months) or congestive heart failure exceeding nyha ii; 2. severe hypertension with poor control after medication; 3. a known history of testing positive for hiv or chronic hepatitis b or c (high copy virus dna) at active stage; 4. patients with active tuberculosis (tb) are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year before screening; 5. other active severe clinical infections (nci-ctc5.0); 6. apparent distant metastasis away from the pelvic before surgery; 7. cachexia, organ function decompensation; 8. previous pelvic or abdominal radiotherapy; 9. multiple primary colorectal cancers; 10. epilepsy require medical treatment (such as steroid or antiepileptic therapy); 11. other malignancy within the past 5 years with the exception of effectively treated carcinoma in situ of the cervix or basal cell carcinoma of the skin; 12. drug abuse and medical, psychological or social factors that may interfere with patients' participation in the study or affect the evaluation of the study; 13. patients have any active autoimmune diseases or a history of autoimmune diseases(including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism and decreased thyroid function; patients with vitiligo or with complete remission of asthma in childhood and without any intervention in adulthood may be included; patients with asthma requiring bronchodilators intervention are not included. 14. received any anti-infection vaccine (e.g. influenza vaccine, chickenpox vaccine, etc.) within 4 weeks before enrollment; 15. complications require long-term treatment with immunosuppressive drugs, or requiring systemic or local use of immunosuppressive corticosteroids(\>10mg/day prednisone or other therapeutic hormones); 16. known or suspected allergy to the study drugs or to any drugs related to this trial; 17. any unstable condition or which endangers the patients' safety and compliance; 18. pregnant or breast-feeding women who are fertile without effective contraception; 19. refuse to sign the informed consent.