Concurrent TTFields (200 kHz) With Chemoradiation for Patients With Newly Diagnosed Glioblastoma May Increase the Rate of Pseudoprogression: Analysis of a Pilot Clinical Trial

Abstract

Standard of care for glioblastoma includes concurrent chemoradiation and maintenance temozolomide with tumor treating fields (TTFields). Data suggest that TTFields, may reversibly affect the blood-brain-barrier (BBB), with a maximum effect at 100 KHz. We suspect this may increase the rate of pseudoprogression (PsP) in patients who received concurrent chemoradiation with TTFields (200 kHz) in our pilot clinical trial. We report the rates of PsP among consecutive patients enrolled on our clinical trial of trimodality therapy to inform this hypothesis.The current analysis included all patients enrolled on the single arm pilot study of concurrent TTFields with chemoradiation (clinicaltrials.gov Identifier: NCT03477110). Adult patients (age ≥ 18 years) with newly diagnosed glioblastoma and a KPS of ≥ 60 were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions), standard concurrent temozolomide (75 mg/m2 daily), and TTFields (200 kHz). Radiation treatment was delivered through TTFields arrays. The rate of PsP was assessed based on the first MRI following completion of trimodality therapy. PsP was defined as radiographic progression of enhancing lesions within 3 months of completion of chemoradiation without clinical decline and remained stable or improved on subsequent imaging. PsP was defined based upon the radiology report and multidisciplinary tumor board discussion. If subsequent imaging demonstrated worsening progression or the patient deteriorated clinically this was classified as true progression.A total of 30 patients were enrolled on the trial and 29 had evaluable imaging. Twenty were male, and ten were female, with a median age of 58 years (range 19 to 77 years). Median KPS was 90 (range 70 to 100). Median follow-up was 8.9 months (range 1.6 to 21.4 months). Twenty (66.7%) patients had an unmethylated MGMT promotor and ten (33.3%) patients had a methylated promoter. Median time from surgery to radiation was 34 days (26 to 49 days). Median time from completion of ChemoRT + TTFields to first follow-up MRI was 25 days (1 to 40 days). In the entire cohort, 16 of 29 patients (55%) had findings consistent with PsP. The rate of PsP among patients with a methylated MGMT promotor was 40% (4 of 10), 63% (12 of 19) among patients with an unmethylated MGMT promotor.Among patients receiving concurrent TTFields with chemoradiation treatment, 55% of patients demonstrated findings consistent with PsP. Although limited by the small sample size, the incidence of PsP may be greater than historical reports, especially in patients without MGMT promoter methylation. Further data are needed to verify if TTFields (200 kHz) disrupts the BBB and if this can lead to increased rates of PsP among larger cohorts.J. Taylor: None. R.C. Miller: None. A. Ali: None. V. Bar-Ad: None. N. Martinez: None. J. Glass: None. I. Alnahhas: None. D.W. Andrews: None. K. Judy: None. C. Farrell: None. H. Liu: None. W. Shi: Independent Contractor; Wenyin Shi. Research Grant; Novocure, Brainlab, Regeneron. Consultant; Varian, Brainlab, Zai lab.