Effect of Pathologic Tumor Response and Nodal Status on Survival in the Medical Research Council Adjuvant Gastric Infusional Chemotherapy Trial

Elizabeth C. Smyth, Matteo Fassan, David Cunningham, William H. Allum, Alicia F. C. Okines, Andrea Lampis, Jens C. Hahne, Massimo Rugge, Clare Peckitt, Matthew Nankivell, Ruth Langley, Michele Ghidini, Chiara Braconi, Andrew Wotherspoon, Heike I. Grabsch, Nicola Valeri*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

150 Citations (Web of Science)

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.

Original languageEnglish
Pages (from-to)2721-2727
Number of pages10
JournalJournal of Clinical Oncology
Volume34
Issue number23
DOIs
Publication statusPublished - 10 Aug 2016

Keywords

  • DISEASE-SPECIFIC SURVIVAL
  • PREOPERATIVE CHEMORADIOTHERAPY
  • PERIOPERATIVE CHEMOTHERAPY
  • ESOPHAGOGASTRIC JUNCTION
  • F-18-FDG PET
  • CANCER
  • REGRESSION
  • ADENOCARCINOMA
  • ESOPHAGEAL
  • CARCINOMA

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