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Multi-institutional Analysis of Recurrence and Survival After Neoadjuvant Chemoradiotherapy of Esophageal Cancer

Impact of Histology on Recurrence Patterns and Outcomes

Xi, Mian, MD*; Yang, Yadi, MD; Zhang, Li, PhD*; Yang, Hong, MD; Merrell, Kenneth W., MD§; Hallemeier, Christopher L., MD§; Shen, Robert K., MD; Haddock, Michael G., MD§; Hofstetter, Wayne L., MD||; Maru, Dipen M., MD**; Ho, Linus, MD, PhD††; Wu, Carol C., MD‡‡; Liu, Mengzhong, MD*; Lin, Steven H., MD, PhD§§

doi: 10.1097/SLA.0000000000002670
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Objective: To determine the impact of histology on pathologic response, survival outcomes, and recurrence patterns in patients with esophageal cancer (EC) who received neoadjuvant chemoradiotherapy (CRT).

Summary of Background Data: There is a paucity of data regarding comparative outcomes after neoadjuvant CRT between esophageal squamous cell carcinoma (SCC) and adenocarcinoma.

Methods: Between 2002 and 2015, 895 EC patients who underwent neoadjuvant CRT followed by esophagectomy at 3 academic institutions were retrospectively reviewed, including 207 patients with SCC (23.1%) and 688 patients with adenocarcinoma (76.9%). Pathologic response, survival, recurrence pattern, and potential prognostic factors were compared.

Results: Pathologic complete response (pCR) rate was significantly higher for SCC compared with adenocarcinoma (44.9% vs 25.9%, P < 0.001). After a median follow-up of 52.9 months, 71 patients (34.3%) with SCC versus 297 patients (43.2%) with adenocarcinoma had recurrent disease (P = 0.023). For patients who achieved a pCR, no significant differences were found in recurrence pattern, sites, or survival end-points between the 2 histology groups. For non-pCR patients, the SCC group demonstrated significantly higher regional and supraclavicular recurrence rates but a lower hematogenous metastasis rate than adenocarcinoma patients, whereas the adenocarcinoma patients had a more favorable locoregional failure-free survival (P = 0.005) and worse distant metastasis-free survival (P = 0.024). No differences were found in overall survival (P = 0.772) or recurrence-free survival (P = 0.696) between groups.

Conclusions: SCC was associated with a significantly higher pCR rate than adenocarcinoma. Recurrence pattern and survival outcomes were significantly different between the 2 histology subtypes in non-pCR patients.

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

Departments of Imaging Diagnosis and Interventional Center, Sun Yat-sen University, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China

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

§Departments of Radiation Oncology, Department of Surgery, Mayo Clinic, Rochester, MN

Division of General Thoracic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN

||Departments of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, TX

**Departments of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX

††Departments of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX

‡‡Departments of Diagnostic Radiology, University of Texas MD Anderson Cancer Center, Houston, TX

§§Departments of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX.

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

MX, YY, LZ, and HY are the first 3 authors who contributed equally to this study.

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.

SHL has received research funding from STCube Pharmaceuticals, Peregrine Pharmaceuticals, Hitachi Chemical, and Roche/Genentech, is on the advisory board for AstraZeneca, and received honoraria from US Oncology and ProCure. The authors declare no conflicts of interest.

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