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Recurrence Risk Stratification After Preoperative Chemoradiation of Esophageal Adenocarcinoma

Xi, Mian, MD*,†; Hallemeier, Christopher L., MD; Merrell, Kenneth W., MD; Liao, Zhongxing, MD*; Murphy, Mariela A. Blum, MD§; Ho, Linus, MD, PhD§; Hofstetter, Wayne L., MD; Mehran, Reza, MD; Lee, Jeffrey H., MD||; Bhutani, Manoop S., MD||; Weston, Brian, MD||; Maru, Dipen M., MD**; Komaki, Ritsuko, MD*; Ajani, Jaffer A., MD§; Lin, Steven H., MD, PhD*

doi: 10.1097/SLA.0000000000002352

Objective: To discern recurrence risk stratification and investigate its influence on postoperative surveillance in patients with esophageal adenocarcinoma (EAC) after neoadjuvant chemoradiotherapy (CRT).

Background: Reports documenting recurrence risk stratification in EAC after neoadjuvant CRT are scarce.

Methods: Between 1998 and 2014, 601 patients with EAC who underwent neoadjuvant CRT followed by esophagectomy were included for analysis. The pattern, site, timing, and frequency of the first recurrence and potential prognostic factors for developing recurrences were analyzed. This cohort was used as the training set to propose a recurrence risk stratification system, and the stratification was further validated in another cohort of 172 patients.

Results: A total of 150 patients (25.0%) achieved pathologic complete response (pCR) after neoadjuvant CRT and the rest were defined as the non-pCR group (n = 451) in the training cohort. After a median follow-up of 63.6 months, the pCR group demonstrated a significantly lower locoregional (4.7% vs 19.1%) and distant recurrence rate (22.0% vs.44.6%) than the non-pCR group (P < 0.001). Based on independent prognostic factors, patients were stratified into 4 recurrence risk categories: pCR with clinical stage I/II, pCR with clinical stage III, non-pCR with pN0, and non-pCR with pN+, with corresponding 5-year recurrence-free survival rates of 88.7%, 65.8%, 55.3%, and 33.0%, respectively (P < 0.001). The risk stratification was reproducible in the validation cohort.

Conclusions: We proposed a recurrence risk stratification system for EAC patients based on pathologic response and pretreatment clinical stage. Risk-based postoperative surveillance strategies could be developed for different risk categories.

*Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China

Department of Radiation Oncology, Mayo Clinic, Rochester, MN

§Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX

||Department of Gastroenterology, The University of Texas MD Anderson Cancer Center, Houston, TX

**Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Reprints: Steven H. Lin, MD, PhD, Department of Radiation Oncology, Unit 97, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. E-mail:

Authors’ contributions: Conception and design—SHL, MX; provision of study materials or patients—CLH, KWM, ZL, MABM, LH, WLH, RM, JHL, MSB, BW, DMM, RK, JAA, and SHL; collection and assembly of data: MX, SHL, ZL, MABM, and LH; data analysis and interpretation—all authors; manuscript writing and final approval of manuscript—all authors.

Funding: This work was supported in part by the Mabuchi Research Fund and the University of Texas MD Anderson Cancer Center and by the National Cancer Institute Cancer Center Support Grant CA016672.

Conflicts of Interest and Source of Funding: SHL has received research funding from Elekta, STCube Pharmaceuticals, Peregrine Pharmaceuticals, Hitachi Chemical, and Roche/Genentech, has served as consultant for AstraZeneca, and received honoraria from US Oncology and ProCure. All other authors have no conflicts of interest to declare.

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