Long-course neoadjuvant chemoradiotherapy with versus without a concomitant boost in locally advanced rectal cancer: a randomized, multicenter, phase II trial (FDRT-002)

Jingwen Wang,Zhen Zhang,Juying Zhou,Chao Li,Ji Zhu,Senxiang Yan,Weilie Gu,Sanjun Cai,Dan Huang,Yun Guan,Tong Tong

doi:10.1186/s13014-019-1420-z

Abstract

BackgroundThis study was designed to explore whether an intensified chemoradiotherapy (CRT) led to a better clinical outcome in locally advanced rectal cancer.MethodsPatients with stage II/III rectal cancer were randomly allocated to receive either pelvic intensity-modulated radiation therapy (IMRT) of 50 Gy/25Fx concurrently with capecitabine and oxaliplatin (Arm A), or pelvic radiation of 50 Gy/25Fx with a concomitant boost of 5 Gy to the primary lesion, followed by a cycle of XELOX 2 weeks after the end of CRT (Arm B). All patients were planned to receive a definitive operation 8 weeks after the completion of CRT and a total of six perioperative chemotherapy cycles of capecitabine and oxaliplatin regardless of pathological result. Pathological complete response (ypCR) was the primary endpoint.ResultsFrom February 2010 to December 2011, 120 patients from three centers were enrolled in this study. Ninety-five percent patients completed a full-dose chemoradiotherapy as planning. Then 53 and 57 patients received a radical surgery, and 8 and 14 cases were confirmed as ypCR in two groups (P = 0.157). The other 10 patients failed to receive a definitive resection because of unresectable disease. Similar toxicities were observed between two groups and more incision healing delay were found in Arm B (3 vs.13, P = 0.011). No statistical differences were observed in local-regional control (P = 0.856), disease-free survival (P = 0.349) and overall survival (P = 0.553). Mesorectal fascia (MRF) involvement was an independent prognostic factor for survival in multivariate analysis.ConclusionsA concomitant boost to oxalipatin-combined preoperative chemoradiotherapy demonstrated a slightly higher pCR rate but delayed incision healing after surgery. The impact of MRF involvement on survival merits further investigations.Trial registrationNCT01064999 (ClinicalTrials.gov).

Highlights

With report of results from a series of large randomized clinical trials comparing neoadjuvant pelvic radiotherapy (RT) alone versus RT plus concurrent 5-fluorouracil (5FU), the standard modality for stage II/III rectal cancer has shifted to preoperative chemoradiotherapy (CRT), followed by total mesorectal excision (TME) and postoperative chemotherapy, which leads to preservation of normal tissue, improvement of tumor regression and excellent local control [1]
In some views, tumor downstaging, especially pCR, was regarded as a goal in neoadjuvant treatment of locally advanced rectal cancer, which motivated the combination of systemic chemotherapy and advanced RT technique in this approaches
Baseline characteristics From February 2010 to December 2011, 120 eligible patients in three centers (Fudan University Shanghai Cancer Center, Shanghai, China; The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China; The First Affiliated Hospital of Suzhou University, Suzhou, China) were randomly assigned in the trial, and the final analysis was performed in ITT set including all 120 cases (Fig. 2)

Summary

Introduction

With report of results from a series of large randomized clinical trials comparing neoadjuvant pelvic radiotherapy (RT) alone versus RT plus concurrent 5-fluorouracil (5FU), the standard modality for stage II/III rectal cancer has shifted to preoperative chemoradiotherapy (CRT), followed by total mesorectal excision (TME) and postoperative chemotherapy, which leads to preservation of normal tissue, improvement of tumor regression and excellent local control [1].The German CAO/ARO/AIO-94 study is the milestone of preoperative CRT [2]. With report of results from a series of large randomized clinical trials comparing neoadjuvant pelvic radiotherapy (RT) alone versus RT plus concurrent 5-fluorouracil (5FU), the standard modality for stage II/III rectal cancer has shifted to preoperative chemoradiotherapy (CRT), followed by total mesorectal excision (TME) and postoperative chemotherapy, which leads to preservation of normal tissue, improvement of tumor regression and excellent local control [1]. The EORTC 22921 trial [3] and FFCD9203 trial [4] suggested 5-FU-based CRT resulted in a lower local recurrence rate compared with long-course RT alone, in spite of similar long-term survival. This study was designed to explore whether an intensified chemoradiotherapy (CRT) led to a better clinical outcome in locally advanced rectal cancer

Methods

Results

Conclusion