TY - JOUR
T1 - Response to neoadjuvant chemotherapy and survival in molecular subtypes of resectable gastric cancer
T2 - a post hoc analysis of the D1/D2 and CRITICS trials
AU - Biesma, Hedde D
AU - Soeratram, Tanya T D
AU - Sikorska, Karolina
AU - Caspers, Irene A
AU - van Essen, Hendrik F
AU - Egthuijsen, Jacqueline M P
AU - Mookhoek, Aart
AU - van Laarhoven, Hanneke W M
AU - van Berge Henegouwen, Mark I
AU - Nordsmark, Marianne
AU - van der Peet, Donald L
AU - Warmerdam, Fabienne A R M
AU - Geenen, Maud M
AU - Loosveld, Olaf J L
AU - Portielje, Johanneke E A
AU - Los, Maartje
AU - Heideman, Daniëlle A M
AU - Meershoek-Klein Kranenbarg, Elma
AU - Hartgrink, Henk H
AU - van Sandick, Johanna
AU - Verheij, Marcel
AU - van de Velde, Cornelis J H
AU - Cats, Annemieke
AU - Ylstra, Bauke
AU - van Grieken, Nicole C T
N1 - Publisher Copyright: © 2022, The Author(s).
PY - 2022/5
Y1 - 2022/5
N2 - 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. 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. 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. 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.
AB - 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. 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. 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. 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.
KW - Epstein–Barr virus (EBV)
KW - Histopathological response
KW - Microsatellite instability (MSI)
KW - Mucinous differentiation
KW - Stomach neoplasms
U2 - 10.1007/s10120-022-01280-2
DO - 10.1007/s10120-022-01280-2
M3 - Article
SN - 1436-3291
VL - 25
SP - 640
EP - 651
JO - Gastric cancer
JF - Gastric cancer
IS - 3
ER -