Overall survival in patients with recurrent glioblastomas with combination chemotherapy and tumor treating fields (TTF).
Authors: Nahm Joshua , Sinha Mousumi , Schumann Eva Highberg , Vu Mia , Hsu Sigmund H. , Zhu Jay-Jiguang 
Published: June 2023

e14057

Background: Glioblastoma (GBM) is the most common malignant primary brain tumor with an annual incidence of 3.19 per 100,000 and a very poor prognosis. The median overall survival (OS) is 14.6 to 23 months for clinical trial participants and 11 months for the real-world population. Most GBM recurs in 6 to 9 months and the median OS since recurrence is 3 to 9 months. Despite advancements in clinical trials, there is no uniform standard of care (SOC) for recurrent GBM. We investigated a combination therapy of TTF with temozolomide, bevacizumab, and irinotecan (TBI) chemotherapy at GBM recurrence that improves OS of GBM patients with manageable and reversible side effects. Methods: Retrospective review of medical records of adult GBM patients treated at our institution between 2011 and 2021 showed 500 eligible patients. The primary outcomes were OS and SAE. Statistical analyses utilized the Kaplan-Meier estimate and log-rank tests. Data was compared with published GBM studies. Severe adverse events (SAE) were collected and analyzed by the Common Terminology Criteria for Adverse Events Version 5.0. Results: The 500 patients were separated into three groups based on treatment received at GBM recurrence: TBI+TTF (N = 49), TBI (N = 51) and physician’s choice group (PCG) (N = 400). Median age at diagnosis was 60 (range: 18-87). The median OS from diagnosis was 21, 24.5 and 13 months for TBI+TTF, TBI and PCG, respectively. Among the IDH-1 wild type GBM patients, the median OS was 20, 24 and 13 months for TBI+TTF (N = 42), TBI (N = 47), and PCG (N = 352), respectively. Both demonstrated statistically significant differences among the three groups (HR 0.51, 95% CI 0.33-0.78, p = 0.002) (all patients) and (HR 0.54, 95% CI 0.33-0.90, p = 0.017) (IDH-1 wide type GBM). Other contributing factors that may improve OS include a team of brain tumor treating physicians working together for timely identification of GBM at recurrence and implementation of best treatment accordingly, with combination of modalities, such as stereotactic radiosurgery, salvage radiation, laser ablation, or craniotomy followed by chemotherapy and TTF. Among those that were reviewed, the SAE from TBI-TTF, TBI and PCG groups are grade 3 lymphopenia, (51.0% vs 41.2% vs 31.1%), grade 3 hypertension (26.5% vs. 21.6% vs. 13.1%), and grade 3 leukopenia (10.2% vs. 9.8% vs. 13.1%). An updated SAE count and MGMT promoter methylation survival analyses will be presented at the conference. Conclusions: Compared with published results and PCG, the data suggests that both TBI+TTF and TBI regimens increase OS of GBM patients with manageable and reversible side effects. Optimization of GBM treatments through a collaborative teamwork with all surgical, radiation, and chemotherapy modalities may also contribute to the increased OS. Further research of larger sample sizes and prospective clinical trials are warranted to evaluate the two treatment regimens.