sintilimab plus hypofractionated radiotherapy for msi-h/dmmr rectal cancer

Conditions: Anti-PD-1 Antibody; Radiotherapy; Rectal Cancer; MSI-H; Mmr Deficiency

Summary: this prospective, single-arm study is conducted to investigate the safety and efficacy of sintilimab combined with hypofractionated radiotherapy in patients with microsatellite instability-high (msi-h)/ dna mismatch repair-deficient (dmmr) non-metastatic rectal cancer.

the patients meet the inclusion criteria. after signing the informed consent, they are given radiotherapy 5gyx5 and sintilimab 200mg ivgtt d1, d15, d29. radical surgery is performed 6-8 weeks after radiotherapy.

Eligibility criteria:
inclusion criteria: 1. histologically confirmed rectal adenocarcinoma; 2. with dna mismatch repair-deficient (dmmr) or microsatellite instability-high (msi-h) status, whether or not being lynch syndrome; 3. not received any anti-rectal cancer treatment previously; for patients with lynch syndrome, not received any anti-tumor therapy about rectal cancer diagnosed this time; 4. no distant metastasis except for lateral lymph nodes on thoracic and abdominal enhanced computed tomography (ct) scans; the distance between tumor's lower edge and anus within 15cm; clinical t stage ≥t2 on high-resolution pelvic magnetic resonance imaging (mri)； 5. men and women ≥18 years of age; 6. eastern cooperative oncology group performance status score 0 or 1; 7. adequate hematologic, hepatic, renal, thyroid and cardiac function: hemoglobin ≥90 g/l, neutrophils ≥1500/mm3, platelets ≥75,000/mm3; aspartate aminotransferase and alanine aminotransferase ≤3.0 × upper limit of normal (uln), bilirubin ≤1.5 × uln; creatinine ≤1.5 × uln, creatinine clearance ≥50 ml/min; activated partial thromboplastin time, prothrombin time and international normalized ratio ≤1.5 × uln; serum albumin ≥28 g/l；thyroid stimulating hormone and free thyroxine within ±10% of normal levels; no obvious abnormality in electrocardiogram; 8. not received blood, blood products and hematopoietic growth factor (e.g. granulocyte colony-stimulating factor) within 2 weeks before inclusion; 9. informed consent form signed; 10. life expectancy of ≥3 months. exclusion criteria: 1. allergic disease history, severe hypersensitivity to drugs, antibody products or sintilimab; 2. other malignancy history with disease free survival \<5 years, except for curative in situ cervical cancer, curative skin basal cell carcinoma and curative gastrointestinal cancer by endoscopic mucoresection; 3. current or past history of autoimmune diseases, including but not limited to: interstitial lung disease, uveitis, enteritis，active hepatitis (hbv dna≥103 copies/ml after regular antiviral therapy)，nephritis, hyperthyroidism and hypothyroidism; 4. immunosuppressant or corticosteroid (systemic or local) use to suppress immune function within 2 weeks before inclusion; 5. severe infection needing intravenous antibiotics, antifungal agents or antiviral drugs, et al; 6. congenital or acquired immunodeficiency such as hiv infection; active hepatitis b (hbv dna≥103 copies/ml after regular antiviral therapy); 7. having one of the following complications: massive gastrointestinal hemorrhage, gastrointestinal perforation or obstruction; symptomatic heart diseases including unstable angina, myocardial infarction and heart failure; uncontrollable diabetes mellitus or hypertension; uncontrollable diarrhea (interfering with daily activities although receiving adequate treatment); 8. bleeding tendency or receiving thrombolytic or anticoagulant therapy; 9. pregnant or breastfeeding female; male and female unwilling to take any contraceptive measures; 10. psychiatric disorders that would interfere with cooperation with the requirements of the study; 11. other conditions that investigators consider not suitable for this study.