Abstract
BackgroundSex is recognized as a significant determinant of outcome among glioblastoma patients, but the relative prognostic importance of glioblastoma features has not been thoroughly explored for sex differences.MethodsCombining multi-modal MR images, biomathematical models, and patient clinical information, this investigation assesses which pretreatment variables have a sex-specific impact on the survival of glioblastoma patients (299 males and 195 females).ResultsAmong males, tumor (T1Gd) radius was a predictor of overall survival (HR = 1.027, p = 0.044). Among females, higher tumor cell net invasion rate was a significant detriment to overall survival (HR = 1.011, p < 0.001). Female extreme survivors had significantly smaller tumors (T1Gd) (p = 0.010 t-test), but tumor size was not correlated with female overall survival (p = 0.955 CPH). Both male and female extreme survivors had significantly lower tumor cell net proliferation rates than other patients (M p = 0.004, F p = 0.001, t-test).ConclusionDespite similar distributions of the MR imaging parameters between males and females, there was a sex-specific difference in how these parameters related to outcomes.
Highlights
Sex is recognized as a significant determinant of outcome among glioblastoma patients, but the relative prognostic importance of glioblastoma features has not been thoroughly explored for sex differences
We tested whether these variables and additional categorical variables, including tumor laterality, extent of resection (EOR), isocitrate dehydrogenase 1 (IDH1) mutation status, and O(6)-methylguanine-DNA methyltransferase promoter (MGMT) methylation status, significantly impacted the overall survival of male and female patients
Both when EOR was included in multivariate Cox-Proportional Hazards models (CPH) analysis (Supplement 14) and when only Stupp protocol patients were considered (Supplement 15B), PIHNA D was still an independent predictor of survival for females. It was not significant in the CPH multivariate analysis, it is notable that males had a significant positive association between overall survival and PI D/ρ in univariate analysis (Table 4). This suggests that more nodular tumors at time of diagnosis are associated with worse prognosis for males, which is contrary to the finding that more diffusely invasive tumors are associated with worse prognosis for females
Summary
Sex is recognized as a significant determinant of outcome among glioblastoma patients, but the relative prognostic importance of glioblastoma features has not been thoroughly explored for sex differences. According to Ostrom et al [4], only 35% of patients survive more than 1 year and 4.7% of patients survive more than 5 years after diagnosis Factors such as age at diagnosis, Karnofsky performance score (KPS), extent of Whitmire et al BMC Cancer (2020) 20:447 of the duration of overall survival has clinical value and identifies areas for future research. By using variables derived from patient clinical information and routinely-obtained, noninvasive MR images, we can establish predictors of survival duration that can be readily assessed in a pre-tx setting. Knowing whether these factors affect males and females in the same way will contribute to guiding research efforts towards best-practice, individualized patient care. Throughout the analysis, males and females were tested separately as distinct population groups and their results were compared, allowing us to identify sexspecific impactors of survival outcome among GBM patients
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