SPARE Trial: Scalp Sparing Radiation With Concurrent Temozolomide and Tumor Treating Fields (200 kHz) for Patients With Newly Diagnosed Glioblastoma

Abstract

Current treatment for patients with newly diagnosed glioblastoma includes concurrent chemoradiation and maintenance temozolomide with Tumor Treating Fields (TTFields, 200 kHz). Preclinical studies suggest TTFields and radiation treatment have synergistic effects. We report our clinical trial evaluating feasibility and tolerability of scalp-sparing radiation with concurrent temozolomide and TTFields.This is a single arm pilot study. Adult patients (age ≥ 18 years) with newly diagnosed glioblastoma with a KPS of ≥ 60 were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions) with temozolomide (75 mg/m2 daily) and TTFields (200 kHz). Maintenance therapy included temozolomide and continuation of TTFields. Radiation treatment was delivered through TTFields arrays. Total scalp was defined as 5 mm thickness from skin surface above the level of the foramen magnum. The scalp was used as an avoidance structure for planning, with the following dose constraints: mean < 20 Gy, 20 cc < 50 Gy, and 30 cc < 40 Gy. The primary endpoint was safety and toxicity of tri-modality treatment within 30 days of completion of chemoradiation treatment.A total of 30 patients were enrolled in the trial. 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 unmethylated MGMT promotor status and ten (33.3%) patients had methylated promoter status. Median time from surgery to radiation was 34 days (26 to 49 days). Scalp dose constraints were achieved for all patients, with the mean dose having a median value of 8.3 Gy (range 4.3 to 14.8 Gy), the D20cc median was 26.1 Gy (range 17.7 to 42.8 Gy), and the D30cc median was 23.5 Gy (range 14.8 to 35.4 Gy). Skin adverse events (AEs; erythema, dermatitis, irritation, folliculitis) were noted in 83.3% of patients, however, these were limited to Grade 1 or 2 events, which resolved spontaneously or with topical medications. No patient had radiation treatment interruption due to skin AEs. Other Grade 1 events included pruritus (33.3%), fatigue (30%), nausea (13.3%), headache (10%), dizziness (6.7%), and cognitive impairment (3.3%). Other Grade 2 events included headache (3.3%). Nineteen patients (63.3%) had progression, with a median PFS of 7.6 months (range 1.6 to 12.7 months). Overall survival was not reached.Concurrent TTFields (200 kHz) with scalp-sparing chemoradiation is feasible treatment option with limited toxicity. Future randomized prospective trials are warranted to define therapeutic advantages of concurrent TTFields with chemoradiation.R.C. Miller: None. A.J. Song: None. A. Ali: None. V. Bar-Ad: None. N. Martinez: None. J. Glass: None. I. Alnahhas: None. D.W. Andrews: None. K. Judy: None. J. Evans: None. C. Farrell: None. M. Werner-Wasik: Advisory Board; ASTRA Zeneca. Stock; Illumina. leading operations of the committee; NRG Oncology. I. Chervoneva: None. M. Ly: None. J.D. Palmer: Research Grant; Varian Medical Systems, The Kroger Company. Consultant; Huron Consulting. Speaker's Bureau; Varian Medical Systems, Depuy Synthes. Advisory Board; Novocure. Member of panel; NCCN.H. Liu: None. W. Shi: Independent Contractor; Wenyin Shi. Research Grant; Novocure, BrainLab, Regeneron. Consultant; Varian, BrainLab, Zai lab.