Advanced Rectal Cancer

The goal of this clinical trial is conducted to evaluate the neoadjuvant regimen of short-course radiotherapy (SCRT) followed by NALIRIFOX chemotherapy plus Pucotenlimab immunotherapy for high-risk locally advanced rectal cancer. The main questions it aims to answer are: 1. Does this regimen increase the complete response rate ? 2. What medical problems (adverse events) do participants have when receiving this treatment? Researchers will evaluate this regimen compared to historical standard neoadjuvant chemoradiotherapy to see if it achieves a higher complete response rate and improves sphincter preservation. Participants will: 1. Receive short-course radiotherapy (25Gy/5f) over 5 consecutive days. 2. Then receive NALIRIFOX chemotherapy every 2 weeks for 9 cycles and Pucotenlimab immunotherapy every 3 weeks for 6 cycles (total treatment duration approximately 6 months). 3. Regular checkups and tests during treatment. 4. Keep a diary of their symptoms and the number of times they use a rescue inhaler.

This is a prospective, single-center, single-arm study evaluating the combination regimen of liposomal irinotecan, capecitabine, and enlonstobart combined with short-course radiotherapy as neoadjuvant therapy for locally advanced rectal cancer.

In the treatment of locally advanced rectal cancer, the short-term and long-term efficacy of the traditional sandwich regimen has not reached satisfactory efficacy. For this reason, the concept of reducing the dose of postoperative chemotherapy or directly moving forward the full amount of postoperative chemotherapy was proposed, which is called total neoadjuvant therapy (TNT). However, TNT also includes the high toxicity of oxaliplatin in the whole process and the long time interval between the end of radiotherapy and the operation, which leads to fibrosis of the surrounding tissue, which increases the difficulty of surgical resection and makes it difficult to ensure good surgical specimen quality. In addition to this, there are issues that may increase the risk of potential disease progression in patients with poor treatment withdrawal. Therefore, appropriately reducing the intensity of chemotherapy and controlling the total duration of preoperative neoadjuvant therapy during radiotherapy is expected to alleviate the side effects of neoadjuvant therapy. Here, the investigators synthesized the characteristics of TNT and sandwich regimens and proposed a XELOX regimen and capecitabine alternate administration combined with preoperative intensity modulated radiation therapy.

Although patients with locally advanced rectal cancer and resectable liver/pulmonary metastasis could benefit from surgery resection, these patients still have a poorer prognosis compared to those without distal metastasis. Based on previous studies, there is no confirmation of whether these patients could benefit from preoperative immunotherapy combined with conventional chemoradiotherapy. This study proposes a combination therapy, preoperative short-course radiotherapy followed by neoadjuvant chemotherapy and anti-PD-1 immunotherapy, for microsatellite-stable patients with locally advanced rectal cancer and resectable liver/pulmonary metastasis, to assess its impact on tumor retreat, decline of postoperative metastasis and recurrence, and the disease-free survival and overall survival of patients. Besides, this study will provide high-level medical evidence for future clinical treatment of patients with advanced rectal cancer.