Short-course Radiotherapy Combined With CapeOx and PD-1 Inhibitor After Local Excision for High-risk Early Rectal Cancer (TORCH-LE)

Short-course Radiotherapy Combined With CapeOx and PD-1 Inhibitor After Local Excision for High-risk Early Rectal Cancer (TORCH-LE)

This is a single arm phase II study to explore the 3y LRFS and safety for high-risk early rectal cancer after local excision with short-course radiotherapy and chemo-immunotherapy.

A total of 60 patients with high-risk pathologic stage pT1 or pT2 cancer after local excision but refused radical surgery will be included.

Eligibility criteria include a histological diagnosis of adenocarcinoma located ≤7 cm from the anal verge, pT1 after local excision of the primary rectal cancer, with one of the high-risk features including margin positivity/very close margin (<1mm) at time of local excision, depth of invasion >1 mm or SM3 invasion (submucosal invasion to the lower third of the submucosal level), high grade or poorly differentiated, lymphovascular invasion, perineural invasion, tumour budding, or pT2 tumor.

They will receive 5*5Gy short-course radiotherapy, followed by 4 cycles of capecitabine plus oxaliplatin (CAPOX) chemotherapy and PD-1 antibody.

Inclusion Criteria:

1. age 18-75 years old, female and male
2. pathological confirmed adenocarcinoma
3. the distance from anal verge ≤ 7 cm
4. pT1 after local excision of the primary rectal cancer, with at least one of the high-risk features including margin positivity/very close margin (<1mm) at time of local excision, depth of invasion >1 mm or SM3 invasion (submucosal invasion to the lower third of the submucosal level), high grade or poorly differentiated, lymphovascular invasion, perineural invasion, tumour budding, or pT2 tumor.
5. refuse radical surgery
6. without pelvic or distance metastases
7. KPS >=70
8. with good compliance
9. microsatellite repair status is MSS/pMMR
10. without previous anti-cancer therapy or immunotherapy
11. signed the inform consent

Exclusion Criteria:

1. pregnancy or breast-feeding women
2. pathological confirmed signet ring cell carcinoma
3. history of other malignancies within 5 years
4. serious medical illness, such as severe mental disorders, cardiac disease, uncontrolled infection, etc.
5. immunodeficiency disease or long-term using of immunosuppressive agents
6. baseline blood and biochemical indicators do not meet the following criteria: neutrophils≥1.5×10^9/L, Hb≥90g/L, PLT≥100×10^9/L, ALT/AST ≤2.5 ULN, Cr≤ 1 ULN
7. DPD deficiency
8. allergic to any component of the therapy