Sun Yat-Sen University Cancer Center Guangzhou, Guangdong
S. Liu1,2, X. Wang3, Y. Zhuang4, S. Bai5, H. Yu1,2, X. Wu2,6, Y. Ye7, H. Luo1,2, Q. X. Wang8,9, H. Chang8,9, P. Cai2,10, Z. Pan2,6, Y. Gao8,9, G. Chen2,6, and W. Xiao8,9; 1Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China, 2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China, 3epartment of General Surgery, Shantou Central Hospital, Shantou, Shantou, Guangdong, China, 4Department of Abdominal Surgery, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China, 5Department of Radiation Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China, 6Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China, 7Department of Radiation Oncology, Zhongshan Peoples Hospital, Zhongshan, Guangdong, China, 8Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China, 9State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China, 10Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
Purpose/Objective(s): The objective of TESS trial is to increase complete clinical response rate (cCR) and organ preservation with a new total neoadjuvant treatment (TNT) strategy for locally advanced rectal cancer (LARC) patients. Materials/
Methods: In this prospective, open label, multicenter, single arm, phase 2 trial, we enrolled 98 low (less than 5cm from anal verge) LARC patients (cT3-4aNany or cT1-4aN+ without lateral lymph node metastasis). All patients were treated with the new sandwich TNT strategy with 2 cycles of neoadjuvant chemotherapy Capeox (capecitabine + oxaliplation) before, during and after radiotherapy 50Gy/25 fractions (NeoCT-CRT-NeoCT), followed by total mesorectal excision (TME) surgery or Watch & Wait (W&W) strategy, and 2 cycles of adjuvant chemotherapy capecitabine. W & W strategy were recommended for those cCR patients. Primary endpoint of this trial was the cCR rate. Secondary endpoints were sphincter preservation rate, pathological complete response (pCR) rate, survival outcomes, etc. Results: All patients (female: 34, male: 64) were enrolled between February 2019 and December 2021. Median age was 55.1 years (range 45.3-64.9). All patients received radiotherapy and 78 patients (79.6%) received 6 cycles of neoadjuvant chemotherapy. There were 46 patients (46.9%) with cCR, 7 patients (7.1%) with near-cCR (near complete clinical response), and 45 patients (45.9%) with non-cCR (non-complete clinical response). Among 46 cCR patients, 31 patients (67.4%) accepted W&W strategy as recommended. Three patients developed regrowth after cCR assessment with 10.5 months, 10.75 months, 15 months’ intervals, respectively. Two of them received surgery for regrowth, and the other one patient received re-irradiation to avoid surgery. The remaining 28 patients (90.3%) sustained cCR until the end of follow-up. The other 15 patients (32.6%) who was assessed as cCR received TME surgery. Of note, there was only one patient without pCR. There was no metastasis event in all cCR patients. Overall organ preservation rate was 83% (82/98 patients). The pCR rate was 46.4% (26 patients) of 56 patients who underwent TME surgery. The total CR rate (pCR and cCR retained for at least 1.5 years) was 55.1% (54 patients). Grade 3-4 hematologic toxicities were 27.6% (27/98 patients). Local recurrence free survival rate, distant metastases free survival rate, and overall survival rate was 95.9% (94/98 patients), 96.9% (95/98 patients), and 99.0% (97/98 patients), respectively. Conclusion: The novel and promising sandwich TNT strategy of NeoCT-CRT-NeoCT results in high rates of cCR, pCR and organ preservation with acceptable acute toxicity and regrowth rate. This trial was registered at clinicaltrials.gov (NCT03840239).
