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: clinicaltrials.gov Identifier: NCT00916409.

Clinical Neuro Oncology Research Program Department of Internal Medicine Methodist Hospital Houston Texas

Clinical Neuro Oncology Research Program Department of Internal Medicine University of Kentucky Medical Center Lexington

Department of Medical Oncology Centre Hospitalier Universitaire Vaudois Lausanne Switzerland

Department of Medical Oncology Cross Cancer Institute Edmonton California

Department of Neuro oncology Hospices Civils de Lyon University Claude Bernard Lyon Lyon France

Department of Neurology 2 Salpêtrière University Hospital Assistance Public Hôpitaux de Paris L'Université Pierre et Marie Curie University Paris 6 University Paris France

Department of Neurology Haaglanden Medical Center The Hague The Netherlands

Department of Neurology Hospital Universitari Bellvitge Barcelona Spain

Department of Neurology Leiden University Medical Center Leiden The Netherlands

Department of Neurology University of Zurich Zurich Switzerland

Department of Neurosurgery Geisinger Medical Center Danville Pennsylvania

Department of Neurosurgery Lahey Clinic Burlington Massachusetts

Department of Neurosurgery Na Homolce Hospital Prague Czech Republic

Department of Neurosurgery Rabin Medical Center Sackler School of Medicine Tel Aviv University Tel Aviv Israel

Department of Neurosurgery Seoul National University Bundang Hospital Seoul National University College of Medicine Bundang Korea

Department of Neurosurgery Tel Aviv Medical Center Tel Aviv University Tel Aviv Israel

Department of Neurosurgery University of Southern California Los Angeles

Neurosurgery and Spine Association Maine Medical Center Scarborough Maine

Northwestern Brain Tumor Institute Northwestern University Feinberg School of Medicine Chicago Illinois

Research and Development Novocure Haifa Switzerland

Robert H Lurie Comprehensive Cancer Center Northwestern University Feinberg School of Medicine Chicago Illinois

JAMA Oncol. 2018 Apr 1;4(4):504-505. doi: 10.1001/jamaoncol.2017.5062. PubMed

See more in PubMed

Adamson C, Kanu OO, Mehta AI, et al. . Glioblastoma multiforme: a review of where we have been and where we are going. Expert Opin Investig Drugs. 2009;18(8):1061-1083. PubMed

Ohgaki H. Epidemiology of brain tumors. Methods Mol Biol. 2009;472:323-342. PubMed

Henriksson R, Asklund T, Poulsen HS. Impact of therapy on quality of life, neurocognitive function and their correlates in glioblastoma multiforme: a review. J Neurooncol. 2011;104(3):639-646. PubMed PMC

Osoba D, Aaronson NK, Muller M, et al. . Effect of neurological dysfunction on health-related quality of life in patients with high-grade glioma. J Neurooncol. 1997;34(3):263-278. PubMed

Taphoorn MJ, Klein M. Cognitive deficits in adult patients with brain tumours. Lancet Neurol. 2004;3(3):159-168. PubMed

Taphoorn MJ, Sizoo EM, Bottomley A. Review on quality of life issues in patients with primary brain tumors. Oncologist. 2010;15(6):618-626. PubMed PMC

Corn BW, Wang M, Fox S, et al. . Health related quality of life and cognitive status in patients with glioblastoma multiforme receiving escalating doses of conformal three dimensional radiation on RTOG 98-03. J Neurooncol. 2009;95(2):247-257. PubMed PMC

Chiu L, Chiu N, Zeng L, et al. . Quality of life in patients with primary and metastatic brain cancer as reported in the literature using the EORTC QLQ-BN20 and QLQ-C30. Expert Rev Pharmacoecon Outcomes Res. 2012;12(6):831-837. PubMed

Archibald YM, Lunn D, Ruttan LA, et al. . Cognitive functioning in long-term survivors of high-grade glioma. J Neurosurg. 1994;80(2):247-253. PubMed

Meyers CA, Rock EP, Fine HA. Refining endpoints in brain tumor clinical trials. J Neurooncol. 2012;108(2):227-230. PubMed

Hottinger AF, Yoon H, DeAngelis LM, Abrey LE. Neurological outcome of long-term glioblastoma survivors. J Neurooncol. 2009;95(3):301-305. PubMed

Stupp R, Mason WP, van den Bent MJ, et al. ; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group . Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987-996. PubMed

Giladi M, Schneiderman RS, Voloshin T, et al. . Mitotic spindle disruption by alternating electric fields leads to improper chromosome segregation and mitotic catastrophe in cancer cells. Sci Rep. 2015;5:18046. PubMed PMC

Kirson ED, Gurvich Z, Schneiderman R, et al. . Disruption of cancer cell replication by alternating electric fields. Cancer Res. 2004;64(9):3288-3295. PubMed

Stupp R, Taillibert S, Kanner AA, et al. . Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA. 2017;318(23):2306-2316. PubMed PMC

Wick W. TTFields: where does all the skepticism come from? Neuro Oncol. 2016;18(3):303-305. PubMed PMC

Cloughesy TF, Lassman AB. NovoTTF: where to go from here? Neuro Oncol. 2017;19(5):605-608. PubMed PMC

Aaronson NK, Ahmedzai S, Bergman B, et al. . The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85(5):365-376. PubMed

Osoba D, Aaronson NK, Muller M, et al. . The development and psychometric validation of a brain cancer quality-of-life questionnaire for use in combination with general cancer-specific questionnaires. Qual Life Res. 1996;5(1):139-150. PubMed

Taphoorn MJ, Claassens L, Aaronson NK, et al. ; EORTC Quality of Life Group, and Brain Cancer, NCIC and Radiotherapy Groups . An international validation study of the EORTC brain cancer module (EORTC QLQ-BN20) for assessing health-related quality of life and symptoms in brain cancer patients. Eur J Cancer. 2010;46(6):1033-1040. PubMed

Fayers P, Aaronson N, Bjordal K, et al. , eds. EORTC QLQ-C30 Scoring Manual. 3rd ed Brussels, Belgium: EORTC Publications; 2001.

Efficace F, Bottomley A, Osoba D, et al. . Beyond the development of health-related quality-of-life (HRQOL) measures: a checklist for evaluating HRQOL outcomes in cancer clinical trials—does HRQOL evaluation in prostate cancer research inform clinical decision making? J Clin Oncol. 2003;21(18):3502-3511. PubMed

Brundage M, Blazeby J, Revicki D, et al. . Patient-reported outcomes in randomized clinical trials: development of ISOQOL reporting standards. Qual Life Res. 2013;22(6):1161-1175. PubMed PMC

Osoba D, Rodrigues G, Myles J, Zee B, Pater J. Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol. 1998;16(1):139-144. PubMed

van de Poll-Franse LV, Mols F, Gundy CM, et al. . Normative data for the EORTC QLQ-C30 and EORTC-sexuality items in the general Dutch population. Eur J Cancer. 2011;47(5):667-675. PubMed

Yung WK, Albright RE, Olson J, et al. . A phase II study of temozolomide vs procarbazine in patients with glioblastoma multiforme at first relapse. Br J Cancer. 2000;83(5):588-593. PubMed PMC

Yavas C, Zorlu F, Ozyigit G, et al. . Health-related quality of life in high-grade glioma patients: a prospective single-center study. Support Care Cancer. 2012;20(10):2315-2325. PubMed

Vordermark D. Avoiding bias in the prospective evaluation of patients with brain metastases. J Clin Oncol. 2007;25(25):4023. PubMed

Walker M, Brown J, Brown K, Gregor A, Whittle IR, Grant R. Practical problems with the collection and interpretation of serial quality of life assessments in patients with malignant glioma. J Neurooncol. 2003;63(2):179-186. PubMed

Taphoorn MJ, Henriksson R, Bottomley A, et al. . Health-related quality of life in a randomized phase iii study of bevacizumab, temozolomide, and radiotherapy in newly diagnosed glioblastoma. J Clin Oncol. 2015;33(19):2166-2175. PubMed

See more in PubMed

ClinicalTrials.gov
NCT00916409