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Response to neoadjuvant chemotherapy and survival in molecular subtypes of resectable gastric cancer: a post hoc analysis of the D1/D2 and CRITICS trials.

Hedde D Biesma ,
Tanya T D Soeratram ,
Karolina Sikorska ,
Irene A Caspers ,
Hendrik F van Essen ,
Jacqueline M P Egthuijsen ,
Aart Mookhoek ,
Hanneke W M van Laarhoven ,
Mark I van Berge Henegouwen ,
Marianne Nordsmark ,
Donald L van der Peet ,
Fabienne A R M Warmerdam ,
Maud M Geenen ,
Olaf J L Loosveld ,
Johanneke E A Portielje ,
Maartje Los ,
Daniëlle A M Heideman ,
Elma Meershoek-Klein Kranenbarg ,
Henk H Hartgrink ,
Johanna van Sandick ,
Marcel Verheij ,
Cornelis J H van de Velde ,
Annemieke Cats ,
Bauke Ylstra ,
Nicole C T van Grieken

Abstract

METHODS

EBV and MSI status were determined on tumor samples collected from 447 patients treated with surgery only in the D1/D2 trial, and from 451 patients treated perioperatively in the CRITICS trial. Results were correlated to histopathological response, morphological tumor characteristics, and survival.

CONCLUSIONS

In resectable GC, MSI-high had favorable outcome compared to EBV-/MSS, both in patients treated with surgery only, and in those treated with perioperative chemo(radio)therapy. Substantial histopathological response was restricted to mucinous MSI-high tumors. The mucinous phenotype might be a relevant parameter in future clinical trials for MSI-high patients.

RESULTS

In the D1/D2 trial, 5-year cancer-related survival was 65.2% in 47 patients with EBV+, 56.7% in 47 patients with MSI-high, and 47.6% in 353 patients with EBV-/MSS tumors. In the CRITICS trial, 5-year cancer-related survival was 69.8% in 25 patients with EBV+, 51.7% in 27 patients with MSI-high, and 38.6% in 402 patients with EBV-/MSS tumors. Interestingly, all three MSI-high tumors with moderate to complete histopathological response (3/27, 11.1%) had substantial mucinous differentiation. No EBV+ tumors had a mucinous phenotype. 115/402 (28.6%) of EBV-/MSS tumors had moderate to complete histopathological response, of which 23/115 (20.0%) had a mucinous phenotype.

BACKGROUND

Epstein-Barr virus positivity (EBV+) and microsatellite instability (MSI-high) are positive prognostic factors for survival in resectable gastric cancer (GC). However, benefit of perioperative treatment in patients with MSI-high tumors remains topic of discussion. Here, we present the clinicopathological outcomes of patients with EBV+, MSI-high, and EBV-/MSS GCs who received either surgery only or perioperative treatment.

More about this publication

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association

Volume 25
Issue nr. 3
Pages 640-651
Publication date 01-05-2022

Full text links

Publisher website (DOI) 10.1007/s10120-022-01280-2
Europe PubMed Central 35129727
Pubmed 35129727

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