Sex-specific impact of patterns of imageable tumor growth on survival of primary glioblastoma patients
Cassandra R Rickertsen,
Andrea J Hawkins-Daarud,
Gustavo De Leon,
Noah C Peeri,
Christine Paula Lewis-de los Angeles,
Bernard R Bendok,
Leland S Hu,
Sandra K Johnston,
Kathleen M Egan,
Robert A. Gatenby,
Joshua B. Rubin,
Kristin R Swanson
Posted 18 May 2018
bioRxiv DOI: 10.1101/325464
Posted 18 May 2018
Purpose: Patient sex is recognized as a significant determinant of outcome but the relative prognostic importance of molecular, imaging, and other clinical features of GBM has not yet been thoroughly explored for male versus female patients. Combining multi-modal MR images and patient clinical information, this investigation assesses which pretreatment MRI-based and clinical variables impact sex-specific survivorship in glioblastoma patients. Methods: We considered the multi-modal MRI and clinical data of 494 patients newly diagnosed with primary glioblastoma (299 males and 195 females). Patient MR images (T1Gd, T2, and T2-FLAIR) were segmented to quantify imageable tumor volumes for each MR sequence. Cox proportional hazard (CPH) models and Students t-tests were used to assess which variables were significantly associated with survival outcomes. We used machine learning algorithms to develop pruned decision trees to integrate the impact of these variables on patient survival. Results: Among males, tumor (T1Gd) radius was a significant 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 significantly correlated with female overall survival (p=0.955 CPH). Both male and female extreme survivors had significantly lower tumor cell net proliferation rates than patients in other survival groups (M p=0.004, F p=0.001, t-test). Age at diagnosis was a significant predictive factor for overall survival length for both males and females (M HR= 1.030, F HR=1.022). Additional variables like extent of resection, tumor laterality, and IDH1 mutation status were also found to have sex-specific effects on overall survival. Conclusion: The results indicated that some variables, like the tumor cell diffuse invasion rate and tumor size, had sex-specific implications for survival, while other variables, such as age at diagnosis and tumor cell proliferation rate, impacted both sexes in the same way. Despite similar distributions of the MR imaging parameters between males and females, there was a sex-specific difference in how these parameters related to outcomes. The sex differences in the predictive value of these and other variables emphasizes the importance of considering sex as a biological factor when determining patient prognosis and treatment approach.
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