Influence of Treatment With Tumor-Treating Fields on Health-Related Quality of Life of Patients With Newly Diagnosed Glioblastoma: A Secondary Analysis of a Randomized Clinical Trial

JAMA Oncol. 2018 Apr 1;4(4):495-504. doi: 10.1001/jamaoncol.2017.5082.


Importance: Tumor-treating fields (TTFields) therapy improves both progression-free and overall survival in patients with glioblastoma. There is a need to assess the influence of TTFields on patients' health-related quality of life (HRQoL).

Objective: To examine the association of TTFields therapy with progression-free survival and HRQoL among patients with glioblastoma.

Design, setting, and participants: This secondary analysis of EF-14, a phase 3 randomized clinical trial, compares TTFields and temozolomide or temozolomide alone in 695 patients with glioblastoma after completion of radiochemotherapy. Patients with glioblastoma were randomized 2:1 to combined treatment with TTFields and temozolomide or temozolomide alone. The study was conducted from July 2009 until November 2014, and patients were followed up through December 2016.

Interventions: Temozolomide, 150 to 200 mg/m2/d, was given for 5 days during each 28-day cycle. TTFields were delivered continuously via 4 transducer arrays placed on the shaved scalp of patients and were connected to a portable medical device.

Main outcomes and measures: Primary study end point was progression-free survival; HRQoL was a predefined secondary end point, measured with questionnaires at baseline and every 3 months thereafter. Mean changes from baseline scores were evaluated, as well as scores over time. Deterioration-free survival and time to deterioration were assessed for each of 9 preselected scales and items.

Results: Of the 695 patients in the study, 639 (91.9%) completed the baseline HRQoL questionnaire. Of these patients, 437 (68.4%) were men; mean (SD) age, 54.8 (11.5) years. Health-related quality of life did not differ significantly between treatment arms except for itchy skin. Deterioration-free survival was significantly longer with TTFields for global health (4.8 vs 3.3 months; P < .01); physical (5.1 vs 3.7 months; P < .01) and emotional functioning (5.3 vs 3.9 months; P < .01); pain (5.6 vs 3.6 months; P < .01); and leg weakness (5.6 vs 3.9 months; P < .01), likely related to improved progression-free survival. Time to deterioration, reflecting the influence of treatment, did not differ significantly except for itchy skin (TTFields worse; 8.2 vs 14.4 months; P < .001) and pain (TTFields improved; 13.4 vs 12.1 months; P < .01). Role, social, and physical functioning were not affected by TTFields.

Conclusions and relevance: The addition of TTFields to standard treatment with temozolomide for patients with glioblastoma results in improved survival without a negative influence on HRQoL except for more itchy skin, an expected consequence from the transducer arrays.

Trial registration: Identifier: NCT00916409.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Neoplasms / epidemiology
  • Brain Neoplasms / psychology
  • Brain Neoplasms / therapy*
  • Chemoradiotherapy / adverse effects
  • Chemoradiotherapy / methods
  • Combined Modality Therapy
  • Cytoreduction Surgical Procedures / adverse effects
  • Cytoreduction Surgical Procedures / methods
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Glioblastoma / epidemiology
  • Glioblastoma / psychology
  • Glioblastoma / therapy*
  • Health Status
  • Humans
  • Male
  • Middle Aged
  • Neurosurgical Procedures / adverse effects
  • Neurosurgical Procedures / methods
  • Physical Therapy Modalities* / adverse effects
  • Quality of Life*
  • Surveys and Questionnaires
  • Temozolomide / therapeutic use
  • Transcranial Direct Current Stimulation* / adverse effects
  • Transcranial Direct Current Stimulation* / methods
  • Treatment Outcome
  • Young Adult


  • Temozolomide

Associated data