Molecular evolution of a glioblastoma controlled with tumor treating fields and concomitant temozolomide

Abstract

Tumor Treating Field (TTFields) therapy has demonstrated efficacy in a Phase 3 study of newly diagnosed glioblastoma (GB) following radiation (RT) and temozolomide (TMZ). We report the appearance of an isolated satellite anterior temporal lobe lesion, 2 months post primary RT/TMZ directed at the primary GB (MGMT methylated) parietal lobe lesion and one adjuvant cycle of TMZ and TTFields. The mean RT dose delivered to the temporal lobe lesion was negligible, i.e., 4.53 ± 0.95 Gy. Mapping of the generated TTFields demonstrated that both lesions were encompassed by a field intensity in a therapeutic range. The temporal lobe lesion remained under the control of TTFields up to 12 months, at which point progression on a T1 contrast MRI resulted in surgery and a definitive diagnosis of GB without MGMT methylation. The primary parietal lobe at this time was in remission. Molecular sequencing on the GB tissue from multiple time points demonstrates clonal evolution of the cancer over time and in response to treatment.