This study aims to evaluate the efficacy and safety of short-course radiotherapy combined with CAPOX plus bevacizumab with or without a PD-1 inhibitor in patients with locally advanced rectal cancer (LARC). The hypothesis is that the addition of immunotherapy (PD-1 inhibitor) can significantly improve the complete response (CR) rate and enhance local control while reducing the incidence of distant metastasis. This study will compare the effects of sequential chemoradiotherapy and targeted therapy with or without immunotherapy following short-course radiotherapy, aiming to explore the optimal regimen for total neoadjuvant therapy.
Histopathologically confirmed rectal adenocarcinoma with no prior antitumor therapy.
Exclusion of patients with BRAF mutations or MSI-H status, as determined by pre-enrollment genetic testing including RAS, BRAF, and MSI analysis. RAS mutation status is permitted regardless.
Absence of severe intestinal obstruction symptoms and no evidence of distant metastasis confirmed by imaging examinations such as CT, MRI, or PET/CT.
Confirmation as locally advanced rectal cancer by rectal MRI, meeting one or more of the following criteria: T3c-d or T4, N2, EMVI(+), MRF(+), lateral lymph node metastasis; or patients with low-lying rectal cancer (≤5 cm from the anal verge) unsuitable for sphincter-preserving surgery prior to neoadjuvant therapy.
Patients found to have BRAF mutations or MSI-H status.
Patients who have previously received chemotherapy, radiotherapy, immunotherapy, targeted therapy, or surgical resection for colorectal cancer prior to enrollment.
History or presence of another malignancy (except for early-stage basal cell carcinoma or carcinoma in situ of the cervix) within the past 3 years, with the disease not under control.
Patients who are pregnant (confirmed by serum or urine β-HCG test) or breastfeeding.
Parallel
PD-1 inhibitor based immunotherapy
DrugShort-course radiotherapy (25Gy/5Fx) followed by 4 cycles of CAPOX regimen (Oxaliplatin 130mg/m² IV infusion, Capecitabine 1000mg/m² orally for 14 days, Q3w) combined with Bevacizumab (7.5mg/kg IV infusion, D1, Q3w) + PD-1 inhibitor (Toripalimab 240mg IV infusion, D1, Q3w).
Complete Response rate
Measurement Methods: Chi-square test, Fisher's exact test, multivariate regression analysis (Cox regression model). Description: For pCR and cCR, chi-square test or Fisher's exact test was used to compare differences between the two groups. Multivariate regression analysis (Cox regression model) was employed to assess the relationship between the intervention and the CR rate.
Disease-Free Survival (DFS)
Measurement Method: Kaplan-Meier survival analysis, Log-rank test to compare survival curves between the two groups. Methods for Handling Missing Values: * For missing data, the Last Observation Carried Forward (LOCF) method or multiple imputation method will be applied. * For subjects with significant non-compliance or loss to follow-up, sensitivity analysis will be considered to assess the impact on results.
Distant Metastasis Rate
Measurement Method: Kaplan-Meier survival analysis, Log-rank test to compare survival curves between the two groups. Methods for Handling Missing Values: * For missing data, the Last Observation Carried Forward (LOCF) method or multiple imputation method will be applied. * For subjects with significant non-compliance or loss to follow-up, sensitivity analysis will be considered to assess the impact on results.
Local Recurrence Rate
Measurement Method: Kaplan-Meier survival analysis, Log-rank test to compare survival curves between the two groups. Methods for Handling Missing Values: * For missing data, the Last Observation Carried Forward (LOCF) method or multiple imputation method will be applied. * For subjects with significant non-compliance or loss to follow-up, sensitivity analysis will be considered to assess the impact on results.
Overall Survival (OS)
Measurement Method: Kaplan-Meier survival analysis, Log-rank test to compare survival curves between the two groups. Methods for Handling Missing Values: * For missing data, the Last Observation Carried Forward (LOCF) method or multiple imputation method will be applied. * For subjects with significant non-compliance or loss to follow-up, sensitivity analysis will be considered to assess the impact on results.
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