Clinical trial NCT03940196: Effect of Tumor Treating Fields (TTFields, 200 kHz) Concomitant With Weekly Paclitaxel for the Treatment of Recurrent Ovarian Cancer (ENGOT-ov50 / GOG-3029 / INNOVATE-3)
Official title: ENGOT-ov50 / GOG-3029 / INNOVATE-3: Pivotal, Randomized, Open-label Study of Tumor Treating Fields (TTFields, 200kHz) Concomitant With Weekly Paclitaxel for the Treatment of Recurrent Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ovarian Cancer
Keywords: Platinum Resistant Ovarian Cancer
TTFields
Paclitaxel
Minimal toxicity
TTF
Tumor Treating Fields
Novocure
Lead sponsor: NovoCure Ltd.
Sponsor class: INDUSTRY
First posted: 2019-05-07
Enrollment: 540
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is a prospective, randomized controlled phase III trial aimed to test the efficacy and safety of Tumor Treating Fields (TTFields) concomitant with weekly paclitaxel for the treatment of recurrent ovarian cancer . The device is an experimental, portable, battery operated device for chronic administration of alternating electric fields (termed TTFields or TTF) to the region of the malignant tumor, by means of surface, insulated electrode arrays.

Detailed description: PAST PRE-CLINICAL AND CLINICAL EXPERIENCE:

The effect of the electric fields (TTFields, TTF) has demonstrated significant activity in in vitro and in vivo ovarian carcinoma pre-clinical models both as a single modality treatment and in combination with chemotherapies. TTFields have been demonstrated to act synergistically with taxanes and have been shown to be additive when combined with other chemotherapies. In addition, TTFields have shown to inhibit metastatic spread of malignant melanoma in in vivo experiment.

In a pilot study, 31 patients with recurrent platinum-resistant ovarian carcinoma received paclitaxel together with TTFields (200 kHz) applied to the abdomen/pelvis until disease progression. The combination was well tolerated and the only device-related adverse event was contact dermatitis.

In addition, a phase III trial of Optune® (200 kHz) as monotherapy compared to active chemotherapy in recurrent glioblastoma patients showed TTFields to be equivalent to active chemotherapy in extending survival, associated with minimal toxicity, good quality of life, and activity within the brain (14% response rate). Finally, a phase III trial of Optune® combined with maintenance temozolomide compared to maintenance temozolomide alone has shown that combined therapy led to a significant improvement in both progression free survival and overall survival in patients with newly diagnosed glioblastoma without the addition of high grade toxicity and without decline in quality of life.

DESCRIPTION OF THE TRIAL:

All patients included in this trial are patients with platinum-resistant ovarian carcinoma. In addition, all patients must meet all eligibility criteria.

Eligible patients will be randomly assigned to one of two groups:

1. Patients receive TTFields at 200 kHz to the abdomen and pelvis using the NovoTTF-100L(O) System together with weekly paclitaxel.
2. Patients receive weekly paclitaxel alone.

Patients will be randomized at a 1:1 ratio. Baseline tests will be performed in patients enrolled in both arms. If assigned to the NovoTTF-100L(O) group, the patients will be treated continuously with the device until progression in the abdomen/pelvis. On both arms, patients who have progression outside the abdomen/pelvis will switch to a second line treatment according to local practice.

SCIENTIFIC BACKGROUND:

Electric fields exert forces on electric charges similar to the way a magnet exerts forces on metallic particles within a magnetic field. These forces cause movement and rotation of electrically charged biological building blocks, much like the alignment of metallic particles seen along the lines of force radiating outwards from a magnet.

Electric fields can also cause muscles to twitch and if strong enough may heat tissues. TTFields are alternating electric fields of low intensity. This means that they change their direction repetitively many times a second. Since they change direction very rapidly (200 thousand times a second), they do not cause muscles to twitch, nor do they have any effects on other electrically activated tissues in the body (brain, nerves and heart). Since the intensities of TTFields in the body are very low, they do not cause heating.

The finding made by Novocure was that finely tuned alternating fields of very low intensity, now termed TTFields (Tumor Treating Fields), cause a significant slowing in the growth of cancer cells. Due to the unique geometric shape of cancer cells when they are multiplying, TTFields cause electrically-charged cellular components of these cells to change their location within the dividing cell, disrupting their normal function and ultimately leading to cell death. In addition, cancer cells also contain miniature building blocks which act as tiny motors in moving essential parts of the cells from place to place. TTFields interfere with the normal orientation of these tiny motors related to other cellular components since they are electrically-charged as well. As a result of these two effects, tumor cell division is slowed, results in cellular death or reverses after continuous exposure to TTFields.

Other cells in the body (normal healthy tissues) are affected much less than cancer cells since they multiply at a much slower rate if at all. In addition TTFields can be directed to a certain part of the body, leaving sensitive areas out of their reach. Finally, the frequency of TTFields applied to each type of cancer is specific and may not damage normally dividing cells in healthy tissues.

In conclusion, TTFields could potentially become treatment for ovarian cancer with very few side effects.

Eligibility criteria: Inclusion Criteria:

1. 18 years of age and older
2. Epithelial histology of ovarian/primary peritoneal or fallopian tube carcinoma at the time of diagnosis
3. Life expectancy of ≥ 12 weeks
4. Maximum two prior lines of systemic therapy following diagnosis of platinum-resistance
5. Maximum total of 5 prior lines of systemic therapy
6. Amenable to receive weekly paclitaxel and able to operate the NovoTTF-100L(O) System
7. ECOG 0-1
8. Evaluable (measurable or non-measurable) disease in the abdominal/pelvic region per RECIST V1.
9. Signed informed consent form for the study protocol

Exclusion Criteria:

1. Primary platinum-refractory disease (progression per RECIST V1.1 during or within 1 month after first line therapy), while secondary platinum-refractory disease is allowed
2. Prior disease progression on a weekly paclitaxel for recurrent disease
3. Brain metastasis or leptomeningeal spread of the tumor
4. Albumin level \<25 gram/liter (subjects should not receive total parenteral nutrition or albumin within 2 weeks of the test)
5. CTCAE V5.0 Grade 3 or higher peripheral neuropathy
6. Implantable electrical medical devices
7. Known allergies to medical adhesives or hydrogel
8. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to paclitaxel or drugs similar or related to paclitaxel, except for cases that were able to undergo desensitization per investigator
9. Prior malignancies treated primarily or for recurrence within 2 years prior to inclusion in this study, except for completely resected non-melanomatous skin carcinoma, or successfully treated in situ carcinoma of the skin, breast or cervix of the uterus
10. Serious co-morbidities
11. Concurrent anti-tumor therapy beyond weekly paclitaxel, excluding hormonal therapy for breast cancer
12. Concurrent active treatment in another clinical trial. However prior participation in clinical trials is allowed as well as participation during survival follow-up
13. Pregnancy or breast-feeding (female patients with reproductive potential and their partners must accept to use effective contraception throughout the entire study period and for 3 months after the end of treatment). All patients who are capable of becoming pregnant must take a pregnancy test which is negative within 72 hours before beginning treatment. The definition of effective contraception is left up to the decision of the investigator
14. Admitted to an institution by administrative or court order

Primary outcomes:
measure: Overall survival
timeFrame: 4 years
Secondary outcomes:
measure: Progression-free survival
timeFrame: 4 years
measure: Objective response rate
timeFrame: 4 years
measure: Next progression-free survival
timeFrame: 4 years
measure: Time to undisputable deterioration in health-related quality of life (HRQoL)
timeFrame: 4 years
measure: Time to first and second subsequent treatment
timeFrame: 4 years
measure: Quality of life using the EORTC QLQ C30 questionnaire with the ovarian cancer symptom OV28 module.
timeFrame: 4 years
measure: Severity and frequency of adverse events
timeFrame: 4 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Oncology- Biltmore Cancer Center
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology
state: Arizona
city: La Jolla
country: United States
facility: University of California
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center- Pacific Campus
state: California
city: Sylmar
country: United States
facility: Olive View - UCLA Medical Center
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Boulder
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Colorado Springs
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Lakewood
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Littleton
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Longmont
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Parker
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Pueblo
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Thornton
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Fort Lauderdale
country: United States
facility: Broward Health Medical Center
state: Florida
city: Orlando
country: United States
facility: AdventHealth Cancer Institute
state: Florida
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Chicago
country: United States
facility: Rush University Cancer Center - Chicago and Innovation
state: Illinois
city: Des Moines
country: United States
facility: Des Moines Oncology Research Association
state: Iowa
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Silver Spring
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Burlington
country: United States
facility: Lahey Hospital & Medical Center
state: Massachusetts
city: Saint Paul
country: United States
facility: Minnesota Oncology Hematology, PA
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis
state: Missouri
city: Omaha
country: United States
facility: Methodist Estabrook Cancer Center
state: Nebraska
city: Las Vegas
country: United States
facility: Women's Cancer Center of Nevada
state: Nevada
city: Reno
country: United States
facility: Center of Hope at Renown Medical Center
state: Nevada
city: Camden
country: United States
facility: MD Anderson Cancer Center at Cooper
state: New Jersey
city: Paramus
country: United States
facility: The Valley Hospital
state: New Jersey
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Centerville
country: United States
facility: Miami Valley Hospital South
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Portland
country: United States
facility: Northwest Cancer Specialists, PC
state: Oregon
city: Pittsburgh
country: United States
facility: West Penn OB/GYN
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center
state: Pennsylvania
city: Willow Grove
country: United States
facility: Abington Hospital- Asplundh Cancer Pavilion
state: Pennsylvania
city: Providence
country: United States
facility: Women & Infants Hospital of Rhode Island
state: Rhode Island
city: Sioux Falls
country: United States
facility: Sanford Gynecologic Oncology Clinic
state: South Dakota
city: Austin
country: United States
facility: Texas Oncology Austin-Balcones
state: Texas
city: Austin
country: United States
facility: Texas Oncology Austin-Midtown
state: Texas
city: Austin
country: United States
facility: Texas Oncology Austin-North Austin
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology-Fort Worth
state: Texas
city: Houston
country: United States
facility: The University of Texas Medical School at Houston
state: Texas
city: McAllen
country: United States
facility: Texas Oncology-McAllen
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology San Antonio Medical Center
state: Texas
city: Sugar Land
country: United States
facility: Texas Oncology - Sugar Land
state: Texas
city: The Woodlands
country: United States
facility: Texas Oncology
state: Texas
city: Tyler
country: United States
facility: Texas Oncology-Tyler
state: Texas
city: Webster
country: United States
facility: Texas Oncology-Deke Slayton Cancer Center
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Roanoke
country: United States
facility: Carilion Clinic-Gynecologic Oncology
state: Virginia
city: Tacoma
country: United States
facility: Multicare Institute for Research and Innovation
state: Washington
city: Graz
country: Austria
facility: KH der Barmherzigen Brüder Graz
city: Graz
country: Austria
facility: Univ.-Klinik für Gynäkologie und Geburtshilfe
city: Innsbruck
country: Austria
facility: Univ.-Klinik für Gynäkologie und Geburtshilfe, Innsbruck
city: Salzburg
country: Austria
facility: Landesfrauenklinik Salzburg
city: Bonheiden
country: Belgium
facility: Imelda Ziekenhuis Bonheiden
city: Brussel
country: Belgium
facility: Cliniques Universitaires Saint Luc, Institut Roi Albert II
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi, Oncologie-Hématologie
city: Gent
country: Belgium
facility: AZ Maria Middelares, Clinical Trial Unit Medical Oncology - Integrated Cancer Center Ghent
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: University Hospitals Leuven, Leuven Cancer Institute
city: Mons
country: Belgium
facility: CHU Ambroise Paré
city: Namur
country: Belgium
facility: CHU UCL Namur - Site Ste Elisabeth
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Montréal
country: Canada
facility: Centre Hospitalie
state: Quebec
city: Calgary
country: Canada
facility: Tom Baker Cancer Center
city: Montréal
country: Canada
facility: McGill University Health Centre
city: Montréal
country: Canada
facility: Jewish General Hospital
city: Olomouc
country: Czechia
facility: Onkologická Klinika Fakultní nemocnice Olomouc
city: Ostrava-Poruba
country: Czechia
facility: University Hospital Ostrava
city: Praha 10
country: Czechia
facility: Gynekologicko-porodnická klinika, Fakultní nemocnice Královské Vinohrady
city: Praha 2
country: Czechia
facility: Gynekologicko-porodnická klinika 1. LF UK a VFN
city: České Budějovice
country: Czechia
facility: Gynekologicko-porodnické oddělení - Nemocnice České Budějovice a.s.
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Klinik für Gynäkologie
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
city: Wiesbaden
country: Germany
facility: Horst-Schmidt-Kliniken, Gynecology and Gynecologic, Oncology Department
city: Budapest
country: Hungary
facility: Semmelweis University
city: Budapest
country: Hungary
facility: Nőgyógyászati Osztály, Országos Onkológiai Intézet
city: Debrecen
country: Hungary
facility: Szuleszeti és Nogyogyaszati Klinika
city: Hadera
country: Israel
facility: Hillel Yaffe Medical Center
city: Jerusalem
country: Israel
facility: Saare Zedek Medical Center - Gyneco-Oncology
city: Nahariya
country: Israel
facility: Oncology Institute, Galilee Medical Center
city: Ramat Gan
country: Israel
facility: Gyneco-Oncology Chaim Sheba Medical Center
city: Bologna
country: Italy
facility: Policlinico S. Orsola-Malpighi, SSD Oncologia Medica Addarii
city: Brindisi
country: Italy
facility: Presidio Ospedaliero Antonio Perrino - ASL Brindisi
city: Lecco
country: Italy
facility: ASST Lecco - Ospedale Manzoni, Dipartimento Oncologico
city: Milano
country: Italy
facility: Dipartimento Medicina e Chirurgia, Università Milano-Bicocca, Direttore Programma Ginecologia Oncologica, Istituto Europeo Oncologia
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele, U.O. Ginecologia-Ematologia e TMO
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione Pascale
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Gemelli
city: Torino
country: Italy
facility: University Saint Anna
city: Amsterdam
country: Netherlands
facility: Amsterdam Universitair Medische centra
city: Utrecht
country: Netherlands
facility: University Medical Center Utrech
city: Gdynia
country: Poland
facility: Szpitale Pomorskie Sp. z o.o.
city: Kraków
country: Poland
facility: Oddział Kliniczny Chirurgii Ogólnej i Onkologicznej, Szpital Św. Rafała
city: Lublin
country: Poland
facility: Uniwersytet Medyczny w Lublinie, I Klinika Ginekologii Onkologicznej i Ginekologii
city: Olsztyn
country: Poland
facility: Samodzielny Publiczny Zakład Opieki Zdrowotnej MSWiA z Warmińsko-Mazurskim Centrum Onkologii w Olsztynie, Oddział Kliniczny Onkologii i Immunoonkologii z Ośrodkiem Dziennym Terapii Onkologicznej
city: Poznań
country: Poland
facility: Oddział Ginekologii Onkologicznej Katedry i Kliniki Onkologii Uniwersytetu Medycznego w Poznaniu
city: Szczecin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie, Klinika Ginekologii Operacyjnej i Onkologii Ginekologicznej Dorosłych i Dziewcząt
city: Warsaw
country: Poland
facility: Szpital Kliniczny im. ks. Anny Mazowieckiej
city: Barcelona
country: Spain
facility: Servicio de Oncología Médica, Hospital Universitario Quirón Dexeus
city: Girona
country: Spain
facility: lnstitut Catala d'Oncologia, Hospital Universitario Dr. Josep Trueta, Servicio de Oncologia,
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra en Madrid
city: Madrid
country: Spain
facility: Hospital MD Anderson Cancer Center
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal, Servicio de Oncologia Médica
city: Madrid
country: Spain
facility: Hospital 12 de Octubre. Servicio Oncología Médica
city: Palma De Mallorca
country: Spain
facility: Fundació Institut d'Investigació Sanitària Illes Balears - IdISBa, Hospital Universitari Son Espases
city: Basel
country: Switzerland
facility: Gynecological Tumor Center, University Hospital Basel
city: Bellinzona
country: Switzerland
facility: IOSI Bellinzona, Oncology Institute of Southern Switzerland, Ospedale San Giovanni
city: Frauenfeld
country: Switzerland
facility: Kantonsspital Frauenfeld - Frauenklinik
city: Zürich
country: Switzerland
facility: UniversitätsSpital Zürich - Klinik für Gynäkologie
Study officials:
affiliation: University Hospitals Leuven, Leuven Cancer Institute
name: Ignace Vergote, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kirson ED, Gurvich Z, Schneiderman R, Dekel E, Itzhaki A, Wasserman Y, Schatzberger R, Palti Y. Disruption of cancer cell replication by alternating electric fields. Cancer Res. 2004 May 1;64(9):3288-95. doi: 10.1158/0008-5472.can-04-0083.
citation: Kirson ED, Dbaly V, Tovarys F, Vymazal J, Soustiel JF, Itzhaki A, Mordechovich D, Steinberg-Shapira S, Gurvich Z, Schneiderman R, Wasserman Y, Salzberg M, Ryffel B, Goldsher D, Dekel E, Palti Y. Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors. Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10152-7. doi: 10.1073/pnas.0702916104. Epub 2007 Jun 5.
citation: Stupp R, Wong ET, Kanner AA, Steinberg D, Engelhard H, Heidecke V, Kirson ED, Taillibert S, Liebermann F, Dbaly V, Ram Z, Villano JL, Rainov N, Weinberg U, Schiff D, Kunschner L, Raizer J, Honnorat J, Sloan A, Malkin M, Landolfi JC, Payer F, Mehdorn M, Weil RJ, Pannullo SC, Westphal M, Smrcka M, Chin L, Kostron H, Hofer S, Bruce J, Cosgrove R, Paleologous N, Palti Y, Gutin PH. NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer. 2012 Sep;48(14):2192-202. doi: 10.1016/j.ejca.2012.04.011. Epub 2012 May 18.
citation: Kirson ED, Giladi M, Gurvich Z, Itzhaki A, Mordechovich D, Schneiderman RS, Wasserman Y, Ryffel B, Goldsher D, Palti Y. Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs. Clin Exp Metastasis. 2009;26(7):633-40. doi: 10.1007/s10585-009-9262-y. Epub 2009 Apr 23.
citation: Giladi M, Schneiderman RS, Voloshin T, Porat Y, Munster M, Blat R, Sherbo S, Bomzon Z, Urman N, Itzhaki A, Cahal S, Shteingauz A, Chaudhry A, Kirson ED, Weinberg U, Palti Y. Mitotic Spindle Disruption by Alternating Electric Fields Leads to Improper Chromosome Segregation and Mitotic Catastrophe in Cancer Cells. Sci Rep. 2015 Dec 11;5:18046. doi: 10.1038/srep18046.
citation: Stupp R, Taillibert S, Kanner AA, Kesari S, Steinberg DM, Toms SA, Taylor LP, Lieberman F, Silvani A, Fink KL, Barnett GH, Zhu JJ, Henson JW, Engelhard HH, Chen TC, Tran DD, Sroubek J, Tran ND, Hottinger AF, Landolfi J, Desai R, Caroli M, Kew Y, Honnorat J, Idbaih A, Kirson ED, Weinberg U, Palti Y, Hegi ME, Ram Z. Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial. JAMA. 2015 Dec 15;314(23):2535-43. doi: 10.1001/jama.2015.16669.
citation: Stupp R, Taillibert S, Kanner A, Read W, Steinberg D, Lhermitte B, Toms S, Idbaih A, Ahluwalia MS, Fink K, Di Meco F, Lieberman F, Zhu JJ, Stragliotto G, Tran D, Brem S, Hottinger A, Kirson ED, Lavy-Shahaf G, Weinberg U, Kim CY, Paek SH, Nicholas G, Bruna J, Hirte H, Weller M, Palti Y, Hegi ME, Ram Z. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA. 2017 Dec 19;318(23):2306-2316. doi: 10.1001/jama.2017.18718.
citation: Vergote I, von Moos R, Manso L, Van Nieuwenhuysen E, Concin N, Sessa C. Tumor Treating Fields in combination with paclitaxel in recurrent ovarian carcinoma: Results of the INNOVATE pilot study. Gynecol Oncol. 2018 Sep;150(3):471-477. doi: 10.1016/j.ygyno.2018.07.018. Epub 2018 Jul 27.
citation: Taphoorn MJB, Dirven L, Kanner AA, Lavy-Shahaf G, Weinberg U, Taillibert S, Toms SA, Honnorat J, Chen TC, Sroubek J, David C, Idbaih A, Easaw JC, Kim CY, Bruna J, Hottinger AF, Kew Y, Roth P, Desai R, Villano JL, Kirson ED, Ram Z, Stupp R. 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.