A Propensity-Matched Study to Evaluate PTEN and TP53 Mutations as Predictive Biomarkers of Survival in Newly Diagnosed IDH-Wildtype Glioblastoma after Tumor Treating Fields

Abstract

<h3>Purpose/Objective(s)</h3> The addition of tumor treating fields (TTF) to adjuvant temozolomide (TMZ) for newly diagnosed glioblastoma (GBM) has been shown to improve overall survival (OS) and progression-free survival (PFS). PTEN and TP53 mutations have been shown to increase response to TTF in recurrent GBM and preclinical GBM models, respectively. However, no effect modification has been shown for these makers in newly diagnosed GBM patients. This study aims to leverage a large, multi-institutional cohort to evaluate whether PTEN or TP53 mutation can predict survival in newly diagnosed GBM patients receiving adjuvant TTF. <h3>Materials/Methods</h3> Histologically-confirmed, supratentorial, and nonmetastatic IDH-wildtype GBM patients aged ≥ 18 yrs with KPS ≥ 60 who received chemoradiation and adjuvant TMZ ± TTF at 3 cancer centers were retrospectively reviewed. RT included long and short-course regimens. TTF patients were compared to patients without TTF using 1:1 propensity-score matching (PSM) based on age, sex, MGMT promotor methylation status, KPS, extent of resection, and RT course. PTEN and TP53 status were assessed using next generation sequencing of tumor specimens. Interaction of PTEN or TP53 with TTF for OS and PFS was evaluated using Cox regression and are presented as hazard ratios (HR) with 95% confidence intervals. Median OS (months) was calculated using the Kaplan Meier method. <h3>Results</h3> From 10/2015 to 1/2021, 245 patients met inclusion criteria, including 87 (36%) who received adjuvant TTF. After PSM (n = 174), no significant difference in any covariate was noted between TTF and no TTF arms with standardized mean differences < 0.2 signifying a good match. The cohort had 40% PTENmutant and 25% TP53mutant cases. Neither TTF use nor PTEN or TP53 mutation were significantly associated with OS or PFS. There was also no significant interaction of PTEN or TP53 with TTF for OS or PFS (Table 1). Among PTENmutant cases, TTF use resulted in similar OS (21.5 months [95% CI: 17.0 – 26.0]) compared to chemoradiotherapy without TTF (20.5 months [95% CI: 15.1 – 26.0]). Among TP53mutant cases, TTF use was also associated with similar OS (24.7 months [95% CI: 15.9 - 33.4]) compared to chemoradiotherapy without TTF (17.9 months [95% CI: 12.6 – 23.1]). <h3>Conclusion</h3> In this propensity-matched study, PTEN and TP53 mutations were not predictive of survival for GBM patients receiving adjuvant TTF. However, adjuvant TTF was also not associated with improved survival, which may be due to unaccounted selection bias or TTF device compliance.