Abstract
Background: The purpose of this study was to evaluate the clinical outcomes following postoperative chemotherapy (XP) versus chemoradiotherapy (XP-RT) according to mesenchymal subtype based on RNA sequencing in gastric cancer (GC) in a cohort of the Adjuvant chemoRadioTherapy In Stomach Tumor (ARTIST) trial. Methods: Of the 458 patients enrolled in the ARTIST trial, formalin-fixed, paraffin-embedded (FFPE) specimens were available from 106 (23.1%) patients for RNA analysis. The mesenchymal subtype was classified according to a previously reported 71-gene MSS/EMT signature using the NanoString assay. Results: Of the 106 patients analyzed (50 in XP arm, 56 in XP-RT arm), 36 (34.0%) patients were categorized as mesenchymal subtype by NanoString assay. Recurrence-free survival (RFS, p = 0.009, hazard ratio (HR) = 2.11, 95% confidence interval (CI): 1.21–3.70) and overall survival (OS, p = 0.003, HR = 2.28, 95% CI: 1.31–3.96) were significantly lower in the mesenchymal subtype than in the non-mesenchymal subtype. In terms of post-operative radiotherapy (RT), mesenchymal subtype was not an independent variable to predict RFS or OS regardless to the assigned arm (XP with or without RT) in this patient cohort. However, there was a trend in the adjuvant XP arm, which showed higher OS than the XP-RT arm for the mesenchymal subtype and lower OS than the XP-RT arm for the non-mesenchymal subtype. Conclusions: We could not determine any significant differences between the mesenchymal and non-mesenchymal subtypes with respect to the effects of adjuvant XP with or without RT in gastric cancer following curative surgery.
Highlights
Gastric cancer (GC) remains an unresolved major health problem in the world, ranking fifth among the most common cancers, with an estimated incidence of 951,000 cases in 2012 [1]
This study was performed on patients who participated in the Adjuvant chemoRadioTherapy In Stomach Tumor (ARTIST) trial who agreed to have their tissue studied, and whose tissue surgical specimens were available and sufficient for ribonucleic acid (RNA) extraction
Among the 458 patients who participated in the ARTIST trial, a total of 106 (23.1%) formalin-fixed, paraffin-embedded (FFPE) samples that were available for targeted profiling by the NanoString nCounter assay were evaluated and analyzed in the present study
Summary
Gastric cancer (GC) remains an unresolved major health problem in the world, ranking fifth among the most common cancers, with an estimated incidence of 951,000 cases in 2012 [1]. It is the third leading cause of cancer-related deaths, with 723,100 patients dying because of it in 2012. The purpose of this study was to evaluate the clinical outcomes following postoperative chemotherapy (XP) versus chemoradiotherapy (XP-RT) according to mesenchymal subtype based on RNA sequencing in gastric cancer (GC) in a cohort of the Adjuvant chemoRadioTherapy In Stomach Tumor (ARTIST) trial. In terms of post-operative radiotherapy (RT), mesenchymal subtype was not an independent variable to predict RFS or OS regardless to the assigned arm (XP with or without RT) in this patient cohort
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