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The Influence of Histopathologic Tumor Viability on Long-term Survival and Recurrence Rates Following Neoadjuvant Therapy for Esophageal Adenocarcinoma

Francis, Ashleigh M. MD*; Sepesi, Boris MD*; Correa, Arlene M. PhD*; Blum, Mariela A. MD; Erasmus, Jeremy J. MD; Lee, Jeffrey H. MD§; Maru, Dipen M. MD; Mehran, Reza J. MD*; Rice, David C. MD*; Roth, Jack A. MD*; Vaporciyan, Ara A. MD*; Walsh, Garrett L. MD*; Welsh, James W. MD; Swisher, Stephen G. MD*; Hofstetter, Wayne L. MD*; The University of Texas MD Anderson Esophageal Cancer Group

doi: 10.1097/SLA.0b013e3182a196f4
Papers of the 133rd ASA Annual Meeting

Objective: Our aim was to validate the effect of histopathologic tumor viability (HTV) on extended survival outcomes and assess the prognostic ability of the current staging system in patients receiving preoperative chemoradiotherapy (CRT).

Background: The American Joint Committee on Cancer, 7th Edition, esophageal carcinoma staging system is derived from patients treated with surgery alone and does not account for the treatment effect of CRT. The extent of HTV after CRT is based on response to neoadjuvant therapy and has been shown to correlate with patient outcome.

Methods: Medical records of 1278 patients who underwent esophagectomy (1990–2011) were reviewed; 784 patients underwent preoperative CRT. Histologic tumor viability was assessed in 602 patients and classified as 0% to 10%, 11% to 50%, and more than 50%. Survival was estimated using the Kaplan-Meier method at potential median follow-up of 67 months. Univariate and multivariate analyses identified variables associated with survival.

Results: Multivariate analysis identified HTV of greater than 50% (P < 0.001, HR 2.5), positive pathologic nodal status (P < 0.001, HR 1.6), and positive clinical nodal status (P = 0.002, HR 1.5) but not pathologic T status (P = 0.816, HR 1.2) to be independently associated with survival. Actuarial 5- and 10-year survival was 52% and 43% (HTV of 0%–10%), 45% and 33% (HTV of 11%–50%), and 16% for both (HTV of >50%). The best 5-year survival 56% was achieved in N0 patients with HTV of 0% to 10% (P = 0.056, HR 1.0), contrary to 6% observed in node-positive patients with HTV of greater than 50% (P < 0.001, HR 3.1). Patients with HTV of greater than 50% demonstrated distant recurrence more frequently than those with HTV of less than 50% (51% vs 33%, P = 0.010, OR: 2.2)

Conclusions: After preoperative chemoradiation, long-term outcomes of esophageal carcinoma are best predicted utilizing histologic tumor viability; HTV may be a practical early endpoint predicting efficacy of therapy.

Current American Joint Committee on Cancer, 7th Edition, esophageal carcinoma staging system is derived from patients treated with surgery alone and therefore does not account for the treatment effect of preoperative chemoradiotherapy (CRT). Our study identified histopathologic tumor viability (HTV) as a strong predictor of long-term survival after neoadjuvant CRT for esophageal adenocarcinoma; HTV may be a practical early endpoint predicting efficacy of therapy.

Departments of *Thoracic and Cardiovascular Surgery,

GI Medical Oncology,

Diagnostic Radiology,

§GI Medicine & Nutrition,

Pathology,

Radiation Therapy, and

**Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.

Reprints: Wayne L. Hofstetter, MD, Esophageal Surgery Program, Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Ave, Houston, TX 77030. E-mail: whofstetter@mdanderson.org.

Members of The University of Texas MD Anderson Esophageal Cancer Group include the authors listed above and the following: Jaffer A. Ajani, MD,† Diana M. Palacio, MD,‡ Sonia L. Betancourt-Cuellar, MD,‡ Manoop Bhutani, MD,§ Ritsuko Komaki, MD,‖ Steven H. Lin, MD, PhD,‖ and Hubert H. Chuang, MD, PhD **

Disclosure: The authors declare no conflicts of interest.

© 2013 by Lippincott Williams & Wilkins.