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Sexual Difference Matters: Females with High Microsatellite Instability Show Increased Survival after Neoadjuvant Chemotherapy in Gastric Cancer

SIMPLE SUMMARY: Here we report a sex- and age-specific analysis of 717 patients with gastric/gastro-esophageal adenocarcinomas treated with or without neoadjuvant chemotherapy (CTx) regarding overall survival (OS) and response to CTx. The analysis was also performed in molecular subtypes determined...

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Autores principales: Kohlruss, Meike, Ott, Katja, Grosser, Bianca, Jesinghaus, Moritz, Slotta-Huspenina, Julia, Novotny, Alexander, Hapfelmeier, Alexander, Schmidt, Thomas, Gaida, Matthias M., Weichert, Wilko, Keller, Gisela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958600/
https://www.ncbi.nlm.nih.gov/pubmed/33801374
http://dx.doi.org/10.3390/cancers13051048
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author Kohlruss, Meike
Ott, Katja
Grosser, Bianca
Jesinghaus, Moritz
Slotta-Huspenina, Julia
Novotny, Alexander
Hapfelmeier, Alexander
Schmidt, Thomas
Gaida, Matthias M.
Weichert, Wilko
Keller, Gisela
author_facet Kohlruss, Meike
Ott, Katja
Grosser, Bianca
Jesinghaus, Moritz
Slotta-Huspenina, Julia
Novotny, Alexander
Hapfelmeier, Alexander
Schmidt, Thomas
Gaida, Matthias M.
Weichert, Wilko
Keller, Gisela
author_sort Kohlruss, Meike
collection PubMed
description SIMPLE SUMMARY: Here we report a sex- and age-specific analysis of 717 patients with gastric/gastro-esophageal adenocarcinomas treated with or without neoadjuvant chemotherapy (CTx) regarding overall survival (OS) and response to CTx. The analysis was also performed in molecular subtypes determined previously. Females demonstrated a significantly increased OS particularly in the group of patients treated with neoadjuvant CTx. Specifically in this patient group and taken into account the molecular subtypes, females with high microsatellite instability (MSI-H) showed the best survival followed by the male MSI-H, the female microsatellite stable (MSS) group and the male MSS group. Thus, we show an effect of sex on OS in gastric/gastro-esophageal cancer in particular for patients treated with neoadjuvant CTx. The superior survival of women with MSI-H tumors among the CTx patients implies that the combined consideration of these factors could contribute to an individualized treatment of the patients. ABSTRACT: We aimed to investigate patients with gastric/gastro-esophageal adenocarcinomas for sex- and age-specific differences regarding overall survival (OS) and response to neoadjuvant chemotherapy (CTx) under consideration of tumor specific molecular subtypes. Overall, 717 patients were analyzed, including 426 patients treated with and 291 treated without neoadjuvant CTx. Microsatellite instability (MSI) and Epstein-Barr virus positivity (EBV+) were determined previously. Females demonstrated a significantly increased OS (p = 0.035), particularly in the subgroup treated with CTx (p = 0.054). No significant differences regarding age were found. In the molecular subgroups, no sex-related differences were observed in the non-CTx group. However in the CTx group, females with MSI-high (H) tumors showed the best OS (p = 0.043), followed by the male MSI-H (p = 0.198) and female MSS (p = 0.114) compared to the male MSS group as reference. The interaction between sex and MSI in this patient group was noticeable (p = 0.053) and was included as a relevant factor in multivariable analyses. In conclusion, our results show an effect of sex on OS in gastric/gastro-esophageal cancer specifically for patients treated with neoadjuvant CTx. The superior survival of women with MSI-H tumors after neoadjuvant CTx implies that combined consideration of these factors could contribute to an individualized treatment of the patients.
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spelling pubmed-79586002021-03-16 Sexual Difference Matters: Females with High Microsatellite Instability Show Increased Survival after Neoadjuvant Chemotherapy in Gastric Cancer Kohlruss, Meike Ott, Katja Grosser, Bianca Jesinghaus, Moritz Slotta-Huspenina, Julia Novotny, Alexander Hapfelmeier, Alexander Schmidt, Thomas Gaida, Matthias M. Weichert, Wilko Keller, Gisela Cancers (Basel) Article SIMPLE SUMMARY: Here we report a sex- and age-specific analysis of 717 patients with gastric/gastro-esophageal adenocarcinomas treated with or without neoadjuvant chemotherapy (CTx) regarding overall survival (OS) and response to CTx. The analysis was also performed in molecular subtypes determined previously. Females demonstrated a significantly increased OS particularly in the group of patients treated with neoadjuvant CTx. Specifically in this patient group and taken into account the molecular subtypes, females with high microsatellite instability (MSI-H) showed the best survival followed by the male MSI-H, the female microsatellite stable (MSS) group and the male MSS group. Thus, we show an effect of sex on OS in gastric/gastro-esophageal cancer in particular for patients treated with neoadjuvant CTx. The superior survival of women with MSI-H tumors among the CTx patients implies that the combined consideration of these factors could contribute to an individualized treatment of the patients. ABSTRACT: We aimed to investigate patients with gastric/gastro-esophageal adenocarcinomas for sex- and age-specific differences regarding overall survival (OS) and response to neoadjuvant chemotherapy (CTx) under consideration of tumor specific molecular subtypes. Overall, 717 patients were analyzed, including 426 patients treated with and 291 treated without neoadjuvant CTx. Microsatellite instability (MSI) and Epstein-Barr virus positivity (EBV+) were determined previously. Females demonstrated a significantly increased OS (p = 0.035), particularly in the subgroup treated with CTx (p = 0.054). No significant differences regarding age were found. In the molecular subgroups, no sex-related differences were observed in the non-CTx group. However in the CTx group, females with MSI-high (H) tumors showed the best OS (p = 0.043), followed by the male MSI-H (p = 0.198) and female MSS (p = 0.114) compared to the male MSS group as reference. The interaction between sex and MSI in this patient group was noticeable (p = 0.053) and was included as a relevant factor in multivariable analyses. In conclusion, our results show an effect of sex on OS in gastric/gastro-esophageal cancer specifically for patients treated with neoadjuvant CTx. The superior survival of women with MSI-H tumors after neoadjuvant CTx implies that combined consideration of these factors could contribute to an individualized treatment of the patients. MDPI 2021-03-02 /pmc/articles/PMC7958600/ /pubmed/33801374 http://dx.doi.org/10.3390/cancers13051048 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kohlruss, Meike
Ott, Katja
Grosser, Bianca
Jesinghaus, Moritz
Slotta-Huspenina, Julia
Novotny, Alexander
Hapfelmeier, Alexander
Schmidt, Thomas
Gaida, Matthias M.
Weichert, Wilko
Keller, Gisela
Sexual Difference Matters: Females with High Microsatellite Instability Show Increased Survival after Neoadjuvant Chemotherapy in Gastric Cancer
title Sexual Difference Matters: Females with High Microsatellite Instability Show Increased Survival after Neoadjuvant Chemotherapy in Gastric Cancer
title_full Sexual Difference Matters: Females with High Microsatellite Instability Show Increased Survival after Neoadjuvant Chemotherapy in Gastric Cancer
title_fullStr Sexual Difference Matters: Females with High Microsatellite Instability Show Increased Survival after Neoadjuvant Chemotherapy in Gastric Cancer
title_full_unstemmed Sexual Difference Matters: Females with High Microsatellite Instability Show Increased Survival after Neoadjuvant Chemotherapy in Gastric Cancer
title_short Sexual Difference Matters: Females with High Microsatellite Instability Show Increased Survival after Neoadjuvant Chemotherapy in Gastric Cancer
title_sort sexual difference matters: females with high microsatellite instability show increased survival after neoadjuvant chemotherapy in gastric cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958600/
https://www.ncbi.nlm.nih.gov/pubmed/33801374
http://dx.doi.org/10.3390/cancers13051048
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