Overview

Research Objectives and Principles: Through a prospective study, explore the effectiveness and safety of stereotactic body radiation therapy (SBRT) in the treatment of unresectable locally recurrent rectal cancer (ULRRC), providing high-level evidence for the use of SBRT in ULRRC treatment.

Primary Objective: R0 resection rate. Secondary Objectives: 1-year local progression-free survival (LPFS) and overall survival (OS), 2-year LPFS and OS, and side effects of the treatment.

Study Design: A single-arm, open-label, prospective phase II study. Study Population and Expected Enrollment: Patients with unresectable locally recurrent rectal adenocarcinoma, with an expected enrollment of 20 patients.

Scheduled Visits and Duration: December 2024 to November 2026. Trial Duration: December 2024 to November 2026. Intervention: SBRT for unresectable locally recurrent rectal cancer. Statistical Hypothesis: Enrolled patients are those with unresectable recurrent rectal cancer. Based on previous literature reports and retrospective clinical data from our center, it is hypothesized that the R0 resection rate for patients with unresectable locally recurrent colorectal cancer who do not receive SBRT is 20%, while the R0 resection rate for those receiving SBRT intervention is 50%. Using Simon's optimal two-stage study design, a single-arm study, with α set at 0.05 and 1-β at 0.80, and an expected loss to follow-up rate of 10%.

Eligibility

Inclusion Criteria:

1. Written informed consent;
2. 18-75 years of age;
3. Histologically, cytologically, or radiologically confirmed tumor recurrence, and the MDT assesses that the recurrent lesion cannot achieve R0 resection (unresectable defined as: 1) Pelvic MRI shows infiltration of S2 or above, 2) and/or lateral pelvic invasion, 3) and/or neurovascular invasion of the pelvic, 4) No indication for R0 resection after MDT discussion);
4. No clear distant metastasis at the time of diagnosis of locally recurrent rectal adenocarcinoma or MDT assesses that oligometastatic lesions are resectable or controlable (UICC 8th edition);
5. No previous radiotherapy for initial treatment, or more than 6 months between completion of initial radiotherapy and start of re-radiotherapy, with a previous radiotherapy dose of less than 50.4 Gy, and no grade 3-4 radiotherapy side effects in the small intestine or bladder;
6. ECOG score for performance status is 0-1 (Appendix 1);
7. Peripheral blood cell counts and liver and kidney function within the following acceptable ranges (tested within 15 days before treatment):
   • White blood cell count more than 3.0×10\^9/L or neutrophils more than 1.5×10\^9/L;
     • Hemoglobin more than 80 g/L; ③ Platelets more than 100×10\^9/L; ④ ALT or AST less than 3 times the upper limit of normal; ⑤ Total bilirubin less than 1.5 times the upper limit of normal; ⑥ Creatinine less than 1.5 times the upper limit of normal;
8. No history of other malignant tumors, non-pregnant or lactating patients, participants must use effective contraception during the study and for 6 months after the last treatment;
9. Expected survival more than 12 months.

Exclusion Criteria:

1. Patients with a history of severe allergies to drugs, including platinum-based drugs, 5-FU, LV, and 5-HT3 receptor antagonists;
2. Patients who have participated in or are participating in other clinical trials within 4 weeks of enrollment;
3. Severe electrolyte abnormalities;
4. Presence of gastrointestinal diseases, such as active ulcers in the stomach or duodenum, ulcerative colitis, or unresected tumors that are actively bleeding; or other conditions that may lead to gastrointestinal bleeding or perforation; or unhealed gastrointestinal perforation after surgical treatment;
5. History of arterial thrombosis or deep vein thrombosis within 6 months; evidence of bleeding history or bleeding tendency within 2 months;
6. Pregnant or lactating women or women with a positive pregnancy test before the first medication; or female participants and their partners unwilling to strictly use contraception during the study;
7. Brain metastases with a diameter greater than 3 cm or a total volume greater than 30 cc;
8. Clinical or radiological evidence of spinal cord compression, or tumors within 3 mm of the spinal cord on MRI;
9. History of other active malignant tumors (except for those who have received curative treatment and have been disease-free for over 3 years or in situ cancers that can be cured with adequate treatment);
10. Severe ECG abnormalities, active coronary artery disease, or severe and uncontrolled angina, newly diagnosed angina, or myocardial infarction within 12 months before participating in the study, congestive heart failure of NYHA class II or above;
11. Patients with active infections (fever above 38°C due to infection);
12. Patients with poorly controlled hypercalcemia, high blood pressure, or diabetes;
13. Patients with severe pulmonary diseases (interstitial pneumonia, pulmonary fibrosis, severe emphysema, etc.);
14. Patients with mental disorders affecting clinical treatment or a history of central nervous system diseases;
15. Patients with severe complications (intestinal obstruction, renal failure, liver failure, cerebrovascular disorders, etc.);
16. Any unresolved toxicity from previous treatments that is grade 2 or higher according to CTCAE (excluding anemia, alopecia, skin pigmentation);
17. Any medical condition that is unstable or may affect patient safety and study compliance;
18. Patients deemed unsuitable for participation in this study by the investigator.