Impact of alternating electric fields therapy for newly diagnosed WHO grade 4 astrocytoma on patient survival: a real-world propensity-score adjusted prospective multicenter study

Abstract Purpose Alternating electric fields (AEF) therapy in addition to temozolomide chemoradiotherapy (TMZ CRT) is increasingly being recommended as first-line treatment for patients with newly-diagnosed WHO grade 4 astrocytoma. However, few have validated this treatment with real-world evidence. Methods Consecutive adult patients with newly-diagnosed WHO grade 4 astrocytoma treated with adjuvant TMZ CRT across all neuro-oncology centers in Hong Kong were reviewed. Identified from a territory-wide prospective glioma registry, propensity-score matching (1:2) was performed to match patients that either received TMZ CRT with AEF or TMZ CRT alone. Matching was according to age, Karnofsky performance status, IDH-1 mutation, p MGMT methylation and extent of resection. The primary endpoint was overall survival (OS). Secondary endpoints were the incidence of AEF-associated adverse effects and mean monthly treatment compliance. Results 141 patients were reviewed, of whom 47 patients received AEF with TMZ CRT and 94 had CRT alone. Multivariate Cox proportional hazards analysis revealed that patients with p MGMT- methylated tumors (mOS: 30.8 months vs. 16.7 months [95% CI: 1.9–4.7] and those that received AEF (mOS: 22.8 vs. 14.3 months [95% CI: 1.9–4.7]) had longer OS. AEF therapy patients had a mOS benefit of 8.5 months. The mean monthly treatment compliance was 74 ± 12%. A compliance threshold of 60% conferred a survival benefit of 4.1 months (mOS: 21.5 months vs. 17.4 months [95% CI: 0.10–0.96]). The only identified AEF-associated adverse reaction was scalp dermatitis that occured in 77% (36/47) of patients. Conclusion This post-approval study offers real-world evidence in support of the use of AEF therapy as first-line treatment.