Sex Difference in Disease-Related Adverse Events Post-Diagnosis of Lung Cancer Brain Metastases in Medicare Individuals ≥ 66 Years of Age

Abstract

Sex differences are evident in adverse events (AEs) related to brain tumors, yet sex differences in AEs specific to brain metastases (BrMs) are underexplored. Lung cancer BrMs dominate among BrM, comprising over half of cases. This study examined sex differences in AEs associated with lung cancer BrMs in individuals aged 66 or older using the SEER-Medicare dataset. Multivariable logistic regression, adjusted for demographic factors and comorbidities, stratified by histological subtype, treatment, age, and year of diagnosis were used to analyze AEs among those with BrMs from primary lung tumors. Year of diagnosis was grouped into prior/post-2013, to account for shifts in treatment paradigms. The results showed nuanced sex-specific AEs. Females diagnosed post-2013 with small-cell, squamous-cell, or other non-small-cell carcinoma BrMs had a higher headache likelihood than males. Males with adenocarcinoma post-2013 were more likely to experience brain herniation. Females aged 76 and older with small-cell BrM exhibited increased vision difficulty risk compared to males of the same age, with no significant difference in other age groups. Males treated for adenocarcinoma faced heightened hemorrhagic stroke risk. This study reveals sex-specific disparities in AEs among older individuals with lung cancer BrMs, varying by histological subtype, age, diagnosis year, and treatment.

Keywords: adverse events; brain metastases; lung cancer; sex differences.

Figure 1

Data selection and exclusion flow chart: the number of individuals selected for the study is summarized.

Figure 2

Male/female odds ratio of adverse events for individuals with small-cell (A), adenocarcinoma (B), squamous-cell carcinoma (C), or other non-small-cell carcinoma (D) BrM OR calculated using multivariable logistic regression model. All groups were adjusted for race, ethnicity, time to BrM after initial cancer diagnosis, Elixhauser score, year of diagnosis, age at BrM diagnosis, surgery, radiation, chemotherapy, targeted therapy, and immunotherapy categories.

Figure 3

Male/female odds ratio of adverse events for individuals with small-cell BrM aged 66–70 (A), 71–75 (B), 76+ (C), adenocarcinoma BrM aged 66–70 (D), 71–75 (E), 76+ (F), squamous-cell carcinoma BrM aged 66–70 (G), 71–75 (H), 76+ (I), or other non-small-cell carcinoma BrM aged 66–70 (J), 71–75 (K), 76+ (L). OR calculated using multivariable logistic regression model. All groups were adjusted for race, ethnicity, time to BrM after initial cancer diagnosis, Elixhauser score, year of diagnosis, surgery, radiation, chemotherapy, targeted therapy, and immunotherapy categories.

Figure 4

Male/female odds ratio of adverse events for individuals with small-cell BrM receiving treatment (A) or no treatment (B), adenocarcinoma BrM receiving treatment (C) or no treatment (D), squamous-cell carcinoma BrM receiving treatment (E) or no treatment (F), or other non-small-cell carcinoma BrM receiving treatment (G) or no treatment (H). OR calculated using multivariable logistic regression model. All groups were adjusted for race, ethnicity, time to BrM after initial cancer diagnosis, Elixhauser score, year of diagnosis, and age at diagnosis. Additionally, the treatment groups were adjusted for surgery, radiation, chemotherapy, targeted therapy, and immunotherapy categories.

Figure 5

Male/female odds ratio of adverse events for individuals with small-cell BrM diagnosed between 2007–2013 (A) and 2014–2017 (B), adenocarcinoma BrM diagnosed between 2007–2013 (C) and 2014–2017 (D), squamous-cell carcinoma BrM diagnosed between 2007–2013 (E) and 2014–2017 (F), or other non-small-cell carcinoma BrM diagnosed between 2007–2013 (G) and 2014–2017 (H). OR calculated using multivariable logistic regression model. All groups were adjusted for race, ethnicity, time to BrM after initial cancer diagnosis, Elixhauser score, age at diagnosis, surgery, radiation, and chemotherapy categories.