Node-Sparing Low-Dose Radiotherapy Concurrent With Chemotherapy and PD-1 Inhibitor in pMMR
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 n
| Condition(s) | Colon Cancer, Neoadjuvant Therapies, Immune Checkpoint Therapy, Radiation Therapy |
|---|---|
| Status | Recruiting |
| Phase | Phase 2 |
| Study type | Interventional |
| Summary | 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 adapt |
| Who can participate | Inclusion Criteria: 1. Voluntarily signed written informed consent. 2. Age ≥ 18 years and ≤ 75 years at the time of enrollment. 3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. 4. Life expectancy \> 2 years. 5. Histologically confirmed adenocarcinoma of the colon (without squamous or sarcomatoid components). 6. Tumor biopsy immunohistochemistry (IHC) indicates pMMR (proficient Mismatch Repair), defined as positive expression of all four proteins: MSH1, MSH2, MSH6, and PMS2; or genetic testing indicates MSS (Microsatellite Stable). 7. Staged as T4 and/or N+ (Stage IIB-III) according to the AJCC 8th edition, as evaluated by imaging (contrast-enhanced CT or MRI). 8. Prior to enrollment, the subject must be evaluated by a surgeon responsible for the operation ba |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Lead sponsor | Sixth Affiliated Hospital, Sun Yat-sen University |
| Locations | Guangzhou, Guangdong, China |
| Start date | 2025-11-26 |
| NCT ID | NCT07279077 |
| Official listing | https://clinicaltrials.gov/study/NCT07279077 |