Effect of Pathologic Tumor Response and Nodal Status on Survival in the Medical Research Council Adjuvant Gastric Infusional Chemotherapy Trial.
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Authors
Smyth, EC
Fassan, M
Cunningham, D
Allum, WH
Okines, AFC
Lampis, A
Hahne, JC
Rugge, M
Peckitt, C
Nankivell, M
Langley, R
Ghidini, M
Braconi, C
Wotherspoon, A
Grabsch, HI
Valeri, N
Fassan, M
Cunningham, D
Allum, WH
Okines, AFC
Lampis, A
Hahne, JC
Rugge, M
Peckitt, C
Nankivell, M
Langley, R
Ghidini, M
Braconi, C
Wotherspoon, A
Grabsch, HI
Valeri, N
Document Type
Journal Article
Date
2016-08-10
Date Accepted
2016-04-07
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.
Citation
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2016, 34 (23), pp. 2721 - 2727
Source Title
Publisher
AMER SOC CLINICAL ONCOLOGY
ISSN
0732-183X
eISSN
1527-7755
Research Team
Signal Transduction & Molecular Pharmacology
Medicine (RMH Smith Cunningham)
Evolutionary Genomics & Modelling
Gastrointestinal Cancer Biology and Genomics
Medicine (RMH Smith Cunningham)
Evolutionary Genomics & Modelling
Gastrointestinal Cancer Biology and Genomics