Early relapses after adjuvant chemotherapy suggests primary chemoresistance in diffuse gastric cancer

PLoS One. 2017 Sep 18;12(9):e0183891. doi: 10.1371/journal.pone.0183891. eCollection 2017.

Abstract

Background: Survival from gastric cancer remains poor, particularly in Western populations. Previous pre-clinical and subgroup analyses of clinical trials have suggested differing benefits from fluoropyrimidine-based chemotherapeutics for diffuse and intestinal gastric cancer. This analysis examines patterns of relapse with and without adjuvant chemotherapy after curative resection for gastric cancer in these subtypes to explore the Lauren classification as a predictive marker of benefit for fluoropyrimidine-based adjuvant chemotherapy.

Patients and methods: Gastric cancer patients enrolled in an ongoing tissue banking study were analysed, 164 patients who would currently be considered for adjuvant therapy after curative resection were included in the analysis. Patients who did and did not receive adjuvant chemotherapy were compared. The primary end point was relapse free survival.

Results: Approximately 50% of patients received adjuvant chemotherapy, the majority receiving a fluoropyrimidine-based regimen. The comparison of Kaplan-Meier curves for patients who did and did not receive adjuvant chemotherapy are different between patients with intestinal and diffuse gastric cancer, and suggest that there may be a benefit in intestinal gastric cancer. The hazard ratio for adjuvant chemotherapy for intestinal gastric cancer was 0.56, (95% CI 0.27-1.17), suggesting a trend towards benefit that was lacking in diffuse gastric cancer patients (1.26, 95% CI 0.70-2.38). The patterns of relapse after adjuvant chemotherapy also differed between diffuse and intestinal gastric cancer. More than 50% of diffuse gastric cancer patients who received adjuvant chemotherapy relapsed within 12 months of surgery despite similar surgical parameters.

Conclusions: Lauren classification is prognostic in gastric cancer. This analysis adds further evidence that it may also be predictive of benefit for fluoropyrimidine-based chemotherapeutics, with lower chemosensitivity seen in diffuse gastric cancer. Treating diffuse and intestinal gastric cancer as separate entities, with identification of efficacious treatments for diffuse gastric cancer will help in improving outcomes from gastric cancer.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Chemotherapy, Adjuvant*
  • Disease-Free Survival
  • Drug Resistance, Neoplasm / drug effects*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local* / classification
  • Neoplasm Recurrence, Local* / drug therapy
  • Neoplasm Recurrence, Local* / mortality
  • Stomach Neoplasms* / classification
  • Stomach Neoplasms* / drug therapy
  • Stomach Neoplasms* / mortality
  • Survival Rate

Grants and funding

Collection and curation of the study cohort has been funded through a number of grants – National Health and Medical Research Council (NHMRC) project grants (2004-2006 ID288714; 2007-2009 ID454584); 2009-2011 Cancer Australia ID570996; 2012-2014 Peter Mac Foundation grant ID APP1030980. S Pattison was supported a NHMRC post-graduate scholarship APP1039393. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.