Abstract
Simple SummaryHere 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.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.
Highlights
Gastric cancer is one of the most common tumors and is still the third leading cause of cancer-related death worldwide [1]
Subgroup analysis stratified by sex and age (< and ≥55 years) revealed that women with non-intestinal-type tumors were significantly younger than women with intestinal type tumors (p = 0.027) (Table S2)
We showed a significant association of p53 mutations with the male sex and patients with mutated p53 and a Microsatellite instability (MSI)-H tumor showed a worse survival when treated with neoadjuvant CTx [47]
Summary
Gastric cancer is one of the most common tumors and is still the third leading cause of cancer-related death worldwide [1]. The availability of markers indicating response to specific treatments is still limited. Patient’s sex is a simple, defined, often underestimated and costfree feature, which is suggested to be a modulator of treatment response and toxicity [6]. Sex-specific differences are clearly evident in clinical routine. The incidence of this tumor is sex-dependent with male dominance [7]. Gastric cancer of men is more frequently of the intestinal subtype, whereas female sex is associated with the diffuse
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