Sex-specific impact of patterns of imageable tumor growth on survival of primary glioblastoma patients

Author:

Whitmire Paula,Rickertsen Cassandra R.,Hawkins-Daarud Andrea,Carrasco Eduardo,Lorence Julia,De Leon Gustavo,Curtin Lee,Bayless Spencer,Clark-Swanson Kamala,Peeri Noah C.,Corpuz Christina,Lewis-de los Angeles Christine Paula,Bendok Bernard R.,Gonzalez-Cuyar Luis,Vora Sujay,Mrugala Maciej,Hu Leland S.,Wang Lei,Porter Alyx,Kumthekar Priya,Johnston Sandra K.,Egan Kathleen M.,Gatenby Robert,Canoll Peter,Rubin Joshua B.,Swanson Kristin R.

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. Pretreatment MR images of 494 glioblastoma patients (299 males and 195 females) were segmented to quantify tumor volumes. Cox proportional hazard (CPH) models and Student’s t-tests were used to assess which variables were associated with survival outcomes.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). Additionally, extent of resection, tumor laterality, and IDH1 mutation status were also found to have sex-specific effects on overall survival.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, which emphasizes the importance of considering sex as a biological factor when determining patient prognosis and treatment approach.

Publisher

Cold Spring Harbor Laboratory

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