Secondary Logo

Institutional members access full text with Ovid®

Share this article on:

Oncological Benefits of Neoadjuvant Chemoradiation With Gemcitabine Versus Upfront Surgery in Patients With Borderline Resectable Pancreatic Cancer: A Prospective, Randomized, Open-label, Multicenter Phase 2/3 Trial

Jang, Jin-Young, MD, PhD*; Han, Youngmin, MS*; Lee, Hongeun, MD*; Kim, Sun-Whe, MD, PhD*; Kwon, Wooil, MD, PhD*; Lee, Kyung-Hun, MD, PhD; Oh, Do-Youn, MD, PhD; Chie, Eui Kyu, MD, PhD; Lee, Jeong Min, MD, PhD§; Heo, Jin Seok, MD, PhD; Park, Joon Oh, MD, PhD||; Lim, Do Hoon, MD, PhD**; Kim, Seong Hyun, MD, PhD††; Park, Sang Jae, MD, PhD‡‡; Lee, Woo Jin, MD, PhD‡‡; Koh, Young Hwan, MD, PhD‡‡; Park, Joon Seong, MD, PhD§§; Yoon, Dong Sup, MD, PhD§§; Lee, Ik Jae, MD, PhD¶¶; Choi, Seong Ho, MD, PhD

doi: 10.1097/SLA.0000000000002705
FEATURES

Objective: This study was performed to determine whether neoadjuvant treatment increases survival in patients with BRPC.

Summary Background Data: Despite many promising retrospective data on the effect of neoadjuvant treatment for borderline resectable pancreatic cancer (BRPC), no high-level evidence exists to support the role of such treatment.

Methods: This phase 2/3 multicenter randomized controlled trial was designed to enroll 110 patients with BRPC who were randomly assigned to gemcitabine-based neoadjuvant chemoradiation treatment (54 Gray external beam radiation) followed by surgery or upfront surgery followed by chemoradiation treatment from four large-volume centers in Korea. The primary endpoint was the 2-year survival rate (2-YSR). Interim analysis was planned at the time of 50% case enrollment.

Results: After excluding the patients who withdrew consent (n = 8) from the 58 enrolled patients, 27 patients were allocated to neoadjuvant treatment and 23 to upfront surgery groups. The overall 2-YSR was 34.0% with a median survival of 16 months. In the intention-to-treat analysis, the 2-YSR and median survival were significantly better in the neoadjuvant chemoradiation than the upfront surgery group [40.7%, 21 months vs 26.1%, 12 months, hazard ratio 1.495 (95% confidence interval 0.66–3.36), P = 0.028]. R0 resection rate was also significantly higher in the neoadjuvant chemoradiation group than upfront surgery (n = 14, 51.8% vs n = 6, 26.1%, P = 0.004). The safety monitoring committee decided on early termination of the study on the basis of the statistical significance of neoadjuvant treatment efficacy.

Conclusion: This is the first prospective randomized controlled trial on the oncological benefits of neoadjuvant treatment in BRPC. Compared to upfront surgery, neoadjuvant chemoradiation provides oncological benefits in patients with BRPC.

*Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea

Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea

Department of Radiation Oncology, Seoul National University Hospital, Seoul, Republic of Korea

§Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

||Department of Internal Medicine Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

**Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

††Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

‡‡Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea

§§Department of Surgery, Gangnam Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea

¶¶Department of Radiation Oncology, Yonsei University Health System, Seoul, Republic of Korea.

Reprints: Seong Ho Choi, MD, PhD, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea; E-mail: sh3468.choi@samsung.com; Jin-Young Jang, MD, PhD, Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Chongno-gu, Seoul 03080, South Korea; E-mail: jangjy4@snu.ac.kr.

J-YJ and YH equally contributed to this study.

This study was supported by grants from the Korean Health Technology R&D Project (HI14C2640) and the National R&D Program for Cancer Control (1120310), Ministry of Health & Welfare, Republic of Korea.

The web-based randomization program and central database was developed and supported by the Medical Research Collaborating Center (MRCC) at the Seoul National University Hospital.

Authors’ Contribution: J-YJ contributed in study concept and design, analysis and interpretation of data, critical revision of the manuscript for important intellectual content, study supervision, final approval of the manuscript; YH contributed in acquisition of data, statistical analysis, and interpretation of data, manuscript drafting, final approval of the manuscript; HL contributed in manuscript drafting, interpretation of data, final approval of the manuscript; S-WK contributed in acquisition of data, critical revision of the manuscript for important intellectual content, final approval of the manuscript; WK contributed in acquisition of data, critical revision of the manuscript, final approval of the manuscript; K-HL contributed in acquisition of data, critical revision of the manuscript, final approval of the manuscript; D-YO contributed in acquisition of data, critical revision of the manuscript, final approval of the manuscript; EKC contributed in acquisition of data, critical revision of the manuscript, final approval of the manuscript; JML contributed in acquisition of data, critical revision of the manuscript, final approval of the manuscript; JSH contributed in acquisition of data, critical revision of the manuscript, final approval of the manuscript; JOP contributed in acquisition of data, critical revision of the manuscript, final approval of the manuscript; DHL contributed in acquisition of data, critical revision of the manuscript, final approval of the manuscript; SHK contributed in acquisition of data, critical revision of the manuscript, final approval of the manuscript; SJP contributed in acquisition of data, critical revision of the manuscript, final approval of the manuscript; WJL contributed in acquisition of data, critical revision of the manuscript, final approval of the manuscript; YHKcontributed in acquisition of data, critical revision of the manuscript, final approval of the manuscript; JSP contributed in acquisition of data, critical revision of the manuscript, final approval of the manuscript; DSY contributed in acquisition of data, critical revision of the manuscript, final approval of the manuscript; IJL contributed in acquisition of data, critical revision of the manuscript, final approval of the manuscript; SHC contributed in study concept and design, acquisition of data, critical revision of the manuscript, study supervision, final approval of the manuscript

The authors declare no conflict of interests.

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.