Overview

Colorectal cancer has an annual incidence surpassing 700,000 cases globally, ranking as the fourth most prevalent cancer with the second-highest mortality rate. Rectal cancer accounts for approximately one-third of newly diagnosed colorectal cancer cases. Stages II (cT3-4/N0) and III (cT1-4/N1-3) rectal cancer are commonly classified as Locally Advanced Rectal Cancer (LARC), characterized by a high risk of local recurrence post-surgery. Neoadjuvant chemoradiotherapy (CRT) combined with Total Mesorectal Excision Surgery (TME) has reduced the 5-year local recurrence rate in LARC from 25% to 5%-10%. Currently, neoadjuvant CRT+TME+postoperative adjuvant chemotherapy effectively controls local recurrence in LARC. However, it is associated with low Pathological Complete Regression (pCR) rates, suboptimal sphincter preservation, increased distant metastasis, heterogeneous adherence to adjuvant chemotherapy, and limited long-term survival benefits.

Further optimization of neoadjuvant treatment strategies holds promise for promoting tumor regression and improving prognosis. In neoadjuvant therapy, the extent of rectal tumor regression is highly dependent on radiotherapy, with higher radiation doses correlating with increased rates of pathological regression. This study aims to investigate the role of MRI-guided radiotherapy with a simultaneous integrated boost in enhancing tumor pCR in neoadjuvant treatment for locally advanced rectal cancer.

Eligibility

Inclusion Criteria:

• Histopathologically confirmed rectal adenocarcinoma.
• Tumor located ≤10cm from the anal verge.
• Age ≥18 years.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1.
• Primary treatment-naive tumor confirmed by endorectal ultrasound (ERUS) or -
• Magnetic resonance imaging (MRI) as cT3-4/N+ according to the 8th edition of AJCC staging.
• Ability to provide tissue and blood samples for translational research.
• Anticipated survival of ≥6 months.
• Normal major organ function (within 14 days prior to enrollment) and suitability for receiving chemoradiotherapy.

Exclusion Criteria:

• History of prior chemotherapy, radiotherapy, or surgical treatment for rectal cancer, including transanal tumor resection.
• Locally recurrent rectal cancer.
• History of familial adenomatous polyposis.
• Active Crohn's disease or ulcerative colitis.
• Allergy or hypersensitivity history to 5-fluorouracil (fluorouracil) and/or oxaliplatin.
• History of difficulty or inability to take or absorb oral medications.
• Diagnosis of malignancy other than rectal cancer within the past 5 years (excluding completely cured basal cell carcinoma, squamous cell carcinoma of the skin, and/or in situ carcinoma treated with radical resection).
• Confirmed distant metastasis, i.e., cM1, through imaging or biopsy.
• History of pelvic radiotherapy.
• Pregnant or lactating women.
• Presence of any severe or uncontrollable systemic illness.