Molecular Markers Impacting Survival in Patients Receiving Concurrent Chemoradiation and Tumor-Treating Fields (TTF) in Patients with Newly Diagnosed Glioblastoma: Secondary Analysis of SPARE Trial

Abstract

<h3>Purpose/Objective(s)</h3> SPARE trial (Scalp-sparing radiation with concurrent temozolomide and tumor treating fields; NCT03477110) is a single-arm pilot study that demonstrated the safety and feasibility of concurrent TTF with chemoradiation for newly diagnosed GBM. The current study is a secondary analysis evaluating the impact of molecular markers (PTEN, TP53, EGFR, and TERT) on overall survival (OS) and progression-free survival (PFS) of the patients in the trial. <h3>Materials/Methods</h3> This is a secondary analysis of SPARE trial. Molecular markers of histologically-confirmed, IDH-wildtype GBM patients age ≥ 18 years old with a KPS ≥ 60 who received concurrent chemoradiation and TTF followed by maintenance TMZ + TTF were evaluated. Molecular profile was evaluated with next-generation sequencing. Interaction of mutations in PTEN, TP53, EGFR, and TERT with TTF on OS and PFS was evaluated using a multivariable backward model. <h3>Results</h3> A total of 30 patients were enrolled in the SPARE trial, and 1 patient with IDH-mutant was excluded from the current analysis. All patients underwent concurrent TTF and chemoradiation. The median age is 58 (range; 19-77). The median KPS was 90 (range; 70-100). 9 patients (31.0%) have methylated MGMT promotor. 14 patients (48.3%) are found to have PTEN mutation, 9 patients (31.0%) with EGFR, 7 (24.1%) with TP53 mutation, and 23 patients (79.3%) with TERT mutated. MGMT methylation remained statistically significant for an increased OS (p=0.032; HR 7.18). TERT also had a statistically significant OS benefit (p=0.012; HR 7.60). MGMT and TERT also showed significant improvement in PFS. However, neither EGFR, TP53, nor PTEN showed any association of PFS or OS for patients who received concurrent TTF and chemoradiation treatment. <h3>Conclusion</h3> In this secondary analysis, patients with MGMT methylation showed better PFS and OS as expected. Neither EGRF, TP53, or PTEN mutation showed any association of PFS or OS. However, patients with TERT mutant showed improved OS with concurrent TTF with chemoradiation. A TERT mutation may be a new molecular biomarker in the described treatment approach. Due to the small sample size, further validation studies should be conducted.