Related Experiment Video
Updated: Sep 15, 2025
Robot-assisted Total Mesorectal Excision and Lateral Pelvic Lymph Node Dissection for Locally Advanced Middle-low Rectal Cancer
Published on: February 12, 2022
Total neoadjuvant therapy integrating long-course radiotherapy with trifluridine/tipiracil for locally advanced
Xue Dou1, Lina Zhao2, Zhenyu Ma1,3
1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Background:
Total neoadjuvant therapy (TNT) is recommended for locally advanced rectal cancer (LARC) with high-risk factors. The objective of this multi-center phase 2 study is to evaluate the impact of a newly designed TNT consist of TAS-102 concurrent with long-course radiotherapy followed by consolidative TAS-102 and oxaliplatin on the pathological complete response (pCR) rate in patients with LARC.
Methods:
Patients with LARC were to receive a newly designed TNT consisting of radiotherapy (50 Gy/25 fractions) concurrently with oral TAS-102 (35 mg/m2 given twice a day on days 1-5 during the 1st, 3rd and 5th week of radiotherapy) followed by 2 cycles of consolidation chemotherapy (oxaliplatin 85 mg/m2 on day 1 and TAS-102 35 mg/m2 twice a day on days 1-5, repeated on a 14-day cycle), with total mesorectal excision to follow within 7-11 weeks after radiotherapy completion. The primary endpoint was the pCR (ypT0 ypN0) rate. This trial is registered with Chinese Clinical Trial Registry, ChiCTR2200063142.
Findings:
From September 1, 2022 through January 11, 2024, 50 patients were enrolled and treated; 44 (88%) received surgery. Among all 50 patients, the overall complete response rate (pCR and clinical complete response [cCR]) was 32% (95% confidence interval [CI] 20-47). Among the 44 patients who underwent surgery, the pCR rate was 32% (95% CI 19-48), exceeding the hypothesized standard pCR rate of 13%. The major pathological regression rate was 52% (95% CI 37-68), and the pathological complete lymph node regression rate was 61% (95% CI 45-76). Of the 6 patients who did not receive surgery, 2 achieved cCR followed by observation, 1 was confirmed to have high microsatellite instability and refused surgery, and 3 refused surgery for personal reasons. Grade 3 hematologic toxicity was recorded in 10 patients (20%) and grade 4 in 3 (6%), consisting largely of myelosuppression. Most patients had mild gastrointestinal toxicity; the most common grade 3 and 4 toxicity was diarrhea (14%). No patients had hand-foot skin reactions.
Interpretation:
We found that TAS-102 concurrent with preoperative radiotherapy led to a high pCR rate (32%) with acceptable toxicity among patients with stage Ⅱ/Ⅲ rectal cancer. Prospective randomized controlled trials comparing fluoropyrimidine-based and TAS-102-based TNT are warranted.
Funding:
National Natural Science Foundation of China and Shandong Provincial Natural Science Foundation.
