title: Response patterns of recurrent glioblastomas treated with tumor-treating fields.
abstract: Glioblastoma multiforme (GBM) is the most common form of primary malignant brain cancer. Median overall survival (OS) for newly diagnosed patients is only about 12 to 18 months. GBM tumors invariably recur, and there is no widely recognized and effective standard treatment for recurrent GBM. NovoTTF Therapy is a novel and US Food and Drug Administration (FDA)-approved antimitotic treatment for recurrent GBM with potential benefits compared with other options. Recurrent GBM patients from two prior trials with demonstrated radiologic tumor response to single-agent NovoTTF Therapy were analyzed to better characterize tumor response patterns and evaluate the associations between response, compliance, and OS. In addition, a compartmental tumor growth model was developed and evaluated for its ability to predict GBM response to tumor-treating fields (TTFields). The overall response rate across both trials was 15% (4% complete responses): 14% in the phase III trial (14/120) and 20% (2/10) in a pilot study. Tumor responses to NovoTTF Therapy developed slowly (median time to response, 5.2 months) but were durable (median duration, 12.9 months). Response duration was highly correlated with OS (r(2) = .92, P<.0001), and median OS for responders was 24.8 months. Seven of 16 responders exhibited initial tumor growth on magnetic resonance imaging. Compliance appeared to be linked with both improved response and survival. The tumor growth model predicted tumor arrest and shrinkage only after several weeks of continuous NovoTTF Therapy, consistent with the observed clinical findings of initial transient tumor growth in some patients. NovoTTF Therapy is a novel antimitotic treatment for recurrent GBM associated with slowly developing but durable tumor responses in approximately 15% of patients. Some responders exhibit initial tumor growth before shrinkage, indicating treatment should not be terminated prior to allowing for the full effect of NovoTTF Therapy to be realized. OS is longer in responders than in nonresponders. High daily compliance rates may be associated with increased likelihood of an objective response and are predictive of improved survival.
authors.affiliation: Department of Radiology, Na Homolce Hospital, Prague, Czech Republic; Department of Neurology, Charles University in Prague, 1st Medical Faculty, Prague, Czech Republic. Electronic address: josef.vymazal@homolka.cz.
authors.forename: Josef
authors.initials: J
authors.lastname: Vymazal
authors.affiliation: Brain Tumor Center and Neuro-Oncology Unit, Beth Israel Deaconess Medical Center, Boston, MA. Electronic address: ewong@bidmc.harvard.edu.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Wong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D017326:Clinical Trials, Phase III as Topic; D003131:Combined Modality Therapy; D004599:Electric Stimulation Therapy; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D010865:Pilot Projects; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult