Investigating the Effects of Tumor Treating Fields and Genetic Mutations in Patients With Glioblastoma
Andy Wang1, Knarik Arkun2
1Department of Neurology, 2Department of Pathology and Laboratory Medicine, Tufts
Objective:
Here, we evaluate the efficacy of Optune treatment on survival, as well as perform extensive genetic sequencing on a subset of these patients to examine genetic associations with survival.
Background:
Patients with glioblastomas (GBMs) typically expire within 12-18 months after diagnosis. Optune is a wearable device that has been emerging as a treatment modality.
Design/Methods:
Patient data was collected between 2011 to 2021 from electronic health records at a single tertiary care medical center, which included age at diagnosis, presenting concern, presence/absence of seizures, tumor location, extent of surgical resection, steroid use, Karnofsky performance scale (KPS), time to progression, survival, and treatment modalities. Optune efficacy was measured via survival comparisons between patients treated with or without Optune. Foundation One sequencing was performed on most patient’s tumor samples. Survival time and genetic mutations were analyzed using a univariate Cox regression model to determine hazard ratios (HRs).
Results:

All patients were treated with the Stupp protocol, and those treated with Optune (n=25) were diagnosed at an average age of 62.3 years with an average KPS of 73.33, while patients treated without Optune (n=32) were diagnosed at an average age of 64.5 years old with an average KPS of 72.16. Overall survival after diagnosis was 23.7 months with Optune, and 14.4 months without Optune, though the study is not sufficiently powered to establish statistical significance. A subset of 54 patients also underwent genetic sequencing of 324 oncogenic gene mutations. IDH1 and ATRX were associated with prolonged survival (HR<1), whereas PDGFRA, CDKN2A/B, NF1, PTEN, KDR, and TERT mutations were associated with worse overall survival (HR>1).

Conclusions:
We assess the efficacy of Optune treatment and establish genetic markers of long-term survival in glioblastoma patients. Patients treated with Optune survive for an additional 9.3 months, and key genes were identified to have differential effects on survival.
10.1212/WNL.0000000000204203