Role of microsatellite instability and HER2 positivity in locally advanced esophago-gastric cancer patients treated with peri-operative chemotherapy

• Lorenzo Gervaso ^[1] ; Luca Bottiglieri ^[2] ; Monica Isabel Meneses-Medina ^[1] ; Stefania Pellicori ^[1] ; Roberto Biffi ^[3] ; Uberto Fumagalli Romario ^[3] ; Stefano De Pascale ^[3] ; Isabella Sala ^[4] ; Vincenzo Bagnardi ^[4] ; Massimo Barberis ^[5] ; Chiara Alessandra Cella ^[1] ; Nicola Fazio ^[1]
  1. [1] Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO IRCCS, Via Ripamonti 435, Milan, Italy
  2. [2] Division of Pathology, European Institute of Oncology IRCCS, Milan, Italy
  3. [3] Division of Digestive Surgery, IEO, European Institute of Oncology IRCCS, Milan, Italy
  4. [4] Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy
  5. [5] Pathology Unit, European Institute of Oncology IRCCS, Milan, Italy

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 25, Nº. 11 (November), 2023, págs. 3287-3295
• Idioma: inglés
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• Resumen

  • Purpose Neoadjuvant chemotherapy (NAC) significantly improved the prognosis of patients with locally advanced gastric cancer (LAGC). Several biomarkers, including HER2 and MMR/MSI are crucial for treatment decisions in the advanced stage but, currently, no biomarkers can guide the choice of NAC in clinical practice. Our aim was to evaluate the role of MSI and HER2 status on clinical outcomes.

    Methods We retrospectively collected LAGC patients treated with NAC and surgery +/- adjuvant chemotherapy from 2006 to 2018. HER2 and MSI were assessed on endoscopic and surgical samples. Pathologic complete response (pCR) rate, overall survival (OS), and event‐free survival (EFS) were estimated and evaluated for association with downstaging and MSI.

    Results We included 76 patients, 8% were classified as MSI-H, entirely consistent between endoscopic and surgical samples. Six percent of patients were HER2 positive on endoscopic and 4% on surgical samples. Tumor downstaging was observed in 52.5% of cases, with three pCR (5.1%), none in MSI-H cancers. According to MSI status, event-free survival (EFS) and overall survival (OS) were higher for MSI-H patients to MSS [EFS not reached vs 30.0 months, p = 0.08; OS not reached vs 39.6 months, p = 0.10].

    Conclusion Our work confirms the positive prognostic effect of MSI-H in the curative setting of LAGC, not correlated with pathologic tumor downstaging. Prospective ad-hoc trial and tumor molecular profiling are eagerly needed.