Most colorectal cancers belong to the microsatellite stable (MSS) or proficient mismatch repair (pMMR) subtypes, with limited response to PD-1 inhibitors. Radiotherapy can increase the release of tumor-associated antigens, thereby improve responsiveness to PD-1 blockade in MSS/pMMR rectal cancer. Tumor-draining lymph nodes are important sites for PD-1 inhibitors to exert antitumor effects, and studies have reported that direct radiation-induced damage and fibrosis can inhibit lymph node drainage and anti-tumor function. Accumulating evidence indicates that low-dose radiotherapy reprograms the tumor microenvironment (TME), transforming immunosuppressive 'cold' tumors into immunostimulatory 'hot' tumors. This transition is mediated by modulating the gut microbiota, eliciting innate and adaptive immune responses, inhibiting immunosuppressive cells, and promoting the infiltration of T and B lymphocytes.Therefore, this study aims to evaluate whether node-sparing low-dose radiotherapy (1Gy/8f) concurrent with chemotherapy and PD-1 inhibitor can improve the pathological complete response (pCR) rate, enhance tolerability, and improve prognosis in patients with pMMR/MSS high-risk locally advanced colon cancer.
Voluntarily signed written informed consent.
Age ≥ 18 years and ≤ 75 years at the time of enrollment.
Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
Life expectancy > 2 years.
Presence of suspicious metastatic lesions or locally advanced unresectable disease, regardless of disease stage.
Subjects who have had other malignancies within 5 years prior to enrollment, excluding colorectal cancer. This excludes subjects with other malignancies cured by local therapy, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the breast.
Receipt of any investigational drug or investigational device therapy within 4 weeks prior to the first dose of the study drug.
Presence of intestinal obstruction, bowel perforation, or intestinal bleeding requiring emergency surgical intervention.
Single group
Node-Sparing Low-Dose Radiotherapy Concurrent With Chemotherapy and PD-1 Inhibitor
Combination productPatients will receive 4 cycles of neoadjuvant therapy: In D1, D2: node-sparing low-dose radiotherapy (1Gy\*2d), concurrent with CAPOX chemotherapy and PD-1 inhibitor(200mg). After that, patients will undergo partial colectomy at the site of tumor.
Pathological Complete Response(pCR) Rate
Evaluate whether 8Gy/8F node-sparing low-dose radiotherapy concurrent with chemotherapy and PD-1 inhibitor as total neoadjuvant therapy can better improve the pathological complete response(pCR) rate or not in colon cancer.
Tumor regression grade (TRG)
Tumor downstaging rate
R0 resection rate
3-year overall survival (OS) rate
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