Smyth, E. C., Fassan, M., Cunningham, D., Allum, W. H., Okines, A. F. C., Lampis, A., Hahne, J. C., Rugge, M., Peckitt, C., Nankivell, M., Langley, R., Ghidini, M., Braconi, C., Wotherspoon, A., Grabsch, H. I., Valeri, N. (2016) Effect of Pathologic Tumor Response and Nodal Status on Survival in the Medical Research Council Adjuvant Gastric Infusional Chemotherapy Trial. JOURNAL OF CLINICAL ONCOLOGY, 34 (23). pp. 2721-2727. ISSN 0732-183X

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Abstract

Purpose The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial established perioperative epirubicin, cisplatin, and fluorouracil chemotherapy as a standard of care for patients with resectable esophagogastric cancer. However, identification of patients at risk for relapse remains challenging. We evaluated whether pathologic response and lymph node status after neoadjuvant chemotherapy are prognostic in patients treated in the MAGIC trial. Materials and Methods Pathologic regression was assessed in resection specimens by two independent pathologists using the Mandard tumor regression grading system (TRG). Differences in overall survival (OS) according to TRG were assessed using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate analyses using the Cox proportional hazards method established the relationships among TRG, clinical-pathologic variables, and OS. Results Three hundred thirty resection specimens were analyzed. In chemotherapy-treated patients with a TRG of 1 or 2, median OS was not reached, whereas for patients with a TRG of 3, 4, or 5, median OS was 20.47 months. On univariate analysis, high TRG and lymph node metastases were negatively related to survival (Mandard TRG 3, 4, or 5: hazard ratio [HR], 1.94; 95% CI, 1.11 to 3.39; P = .0209; lymph node metastases: HR, 3.63; 95% CI, 1.88 to 7.0; P < . 001). On multivariate analysis, only lymph node status was independently predictive of OS (HR, 3.36; 95% CI, 1.70 to 6.63; P < .001). Conclusion Lymph node metastases and not pathologic response to chemotherapy was the only independent predictor of survival after chemotherapy plus resection in the MAGIC trial. Prospective evaluation of whether omitting postoperative chemotherapy and/or switching to a noncross-resistant regimen in patients with lymph node-positive disease whose tumor did not respond to preoperative epirubicin, cisplatin, and fluorouracil may be appropriate. (C) 2016 by American Society of Clinical Oncology.

Item Type:	Article
Authors (ICR Faculty only):	Valeri, Nicola
All Authors:	Smyth, E. C., Fassan, M., Cunningham, D., Allum, W. H., Okines, A. F. C., Lampis, A., Hahne, J. C., Rugge, M., Peckitt, C., Nankivell, M., Langley, R., Ghidini, M., Braconi, C., Wotherspoon, A., Grabsch, H. I., Valeri, N.
Additional Information:	ISI Document Delivery No.: DU8MF Times Cited: 0 Cited Reference Count: 34 Smyth, Elizabeth C. Fassan, Matteo Cunningham, David Allum, William H. Okines, Alicia F. C. Lampis, Andrea Hahne, Jens C. Rugge, Massimo Peckitt, Clare Nankivell, Matthew Langley, Ruth Ghidini, Michele Braconi, Chiara Wotherspoon, Andrew Grabsch, Heike I. Valeri, Nicola Cancer Research UK [CEA A18052]; European Union FP7 [CIG 334261]; National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at The Royal Marsden NHS Foundation Trust; NIHR ICR/RMH BRC; Institute of Cancer Research [A62, A100, A101] Supported by Cancer Research UK (CEA A18052), European Union FP7 (CIG 334261), and the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research (grants A62, A100, A101) to N.V. E.C.S., D.C., C.P., A.W., and N.V. acknowledge funding from the NIHR ICR/RMH BRC. 0 AMER SOC CLINICAL ONCOLOGY ALEXANDRIA J CLIN ONCOL
Uncontrolled Keywords:	DISEASE-SPECIFIC SURVIVAL PREOPERATIVE CHEMORADIOTHERAPY PERIOPERATIVE CHEMOTHERAPY ESOPHAGOGASTRIC JUNCTION NEOADJUVANT CHEMOTHERAPY ESOPHAGEAL CANCER RECTAL-CANCER F-18-FDG PET PHASE-III CARCINOMA
Research teams:	ICR divisions > Molecular Pathology > Gastrointestinal Cancer Biology and Genomics
Depositing User:	Barry Jenkins
Date Deposited:	18 Oct 2016 12:16
Last Modified:	18 Oct 2016 12:21
URI:	http://publications.icr.ac.uk/id/eprint/15329

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