Cancer Management and Research (Oct 2018)
The high pCR rate of sandwich neoadjuvant treatment in locally advanced rectal cancer may translate into a better long-term survival benefit: 5-year outcome of a Phase II clinical trial
Abstract
Yong-Hong Hu,1,2,* Jia-Wang Wei,1–3,* Hui Chang,1,2,* Wei-Wei Xiao,1,2 Jun-Zhong Lin,1,4 Mu-Yan Cai,1,5 Pei-Qiang Cai,1,6 Ling-Heng Kong,1,4 Gong Chen,1,4 Zhi-Zhong Pan,1,4 Zhi-Fan Zeng,1,2 Pei-Rong Ding,1,4 Yuan-Hong Gao1,2 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People’s Republic of China; 2Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 3Departments of Oncology, Ganzhou People’s Hospital, Ganzhou, Jiangxi, People’s Republic of China; 4Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 5Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 6Department of Medical Imaging and Interventional Radiology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China *These authors contributed equally to this work Background: In a Phase II clinical trial, we reported the effectiveness and safety of a sandwich neoadjuvant treatment based on a modified oxaliplatin plus capecitabine (XELOX) regimen for locally advanced rectal cancer (LARC). The pathologic complete response (pCR) rate was 42.2%, and no patient presented Grade 4 acute toxicities. This study was performed to evaluate whether the high pCR rate could translate into an improved long-term survival benefit by analyzing the 5-year follow-up results of the trial.Methods: Fifty-one patients with LARC were initially enrolled in the trial. Of these, 2 cases were eliminated due to distant metastasis before treatment. In addition, 4 cases were eliminated for refusing surgery after neoadjuvant chemoradiotherapy (NACRT). Finally, a total of 45 patients were treated with the sandwich NACRT plus total mesorectal excision. We followed up these patients and calculated their overall survival (OS) and disease-free survival (DFS) through a Kaplan–Meier approach. A log-rank test and multivariate survival analysis based on a Cox proportional hazard model were performed to explore the risk factors influencing distant metastasis.Results: The median follow-up time was 60.8 months, and among the 45 patients analyzed, 1 (2.2%) patient suffered local recurrence, and 9 (20.0%) suffered distant metastasis. The 3-year OS and DFS were 95.6% and 84.4%, respectively. In addition, the 5-year OS and DFS were 91.1% and 80.0%, respectively. In the multivariate analysis, postsurgical pathological N stage and carbohydrate antigen 19–9 before treatment maintained statistical significance on distant metastasis.Conclusions: The sandwich NACRT with XELOX regimen might reduce distant metastasis and improve the survival of LARC patients. However, long-term benefits should be verified through further Phase III clinical trials. Keywords: rectal neoplasms, neoadjuvant chemoradiotherapy, locally advanced, neoadjuvant therapy, prognosis