{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T17:02:53Z","timestamp":1793638973239,"version":"4.5.1"},"reference-count":43,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T00:00:00Z","timestamp":1617840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20hk0102069h0001"],"award-info":[{"award-number":["20hk0102069h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurology International"],"abstract":"<jats:p>Tumor-treating fields (TTFields) are alternating electric fields applied continuously to the brain by attaching two-pair arrays on the scalp. Although TTFields therapy has demonstrated efficacy against supratentorial glioblastoma (GBM) in adults, its safety and efficacy in children have not been confirmed. Despite differences in the genetic etiology of the adult and pediatric forms of GBM, both have certain clinical behaviors in common, allowing us to test TTFields therapy in pediatric GBM. Recently, several, pediatric case-series using TTFields therapy have been published, and a few, prospective, pediatric studies are ongoing. Because GBMs are extremely rare in pediatric patients, where they comprise a wide variety of genetic subtypes, these pediatric studies are feasibility studies targeting various types of malignant brain tumor. Although they are important for confirming the safety and feasibility of TTFields therapy in the pediatric population, confirming its efficacy against each type of pediatric brain tumor, including the GBM, is difficult. Our clinical research team, therefore, planned an investigator-initiated clinical trial targeting pediatric supratentorial GBMs (as in adults) with the aim of expanding regulatory approval of TTFields therapy for pediatric GBM treatment based on safety and exploratory efficacy data in combination with the accumulated evidence on adult GBMs.<\/jats:p>","DOI":"10.3390\/neurolint13020015","type":"journal-article","created":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T21:27:44Z","timestamp":1617917264000},"page":"151-165","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Tumor-Treating Fields Therapy for Pediatric Brain Tumors"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0036-7748","authenticated-orcid":false,"given":"Atsushi","family":"Makimoto","sequence":"first","affiliation":[{"name":"Department of Hematology\/Oncology, Tokyo Metropolitan Children\u2019s Medical Center, 2-8-29, Musashidai, Fuchu, Tokyo 183-8561, Japan"},{"name":"Clinical Research Support Center, Tokyo Metropolitan Children\u2019s Medical Center, 2-8-29, Musashidai, Fuchu, Tokyo 183-8561, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Nishikawa","sequence":"additional","affiliation":[{"name":"Department of Neuro-Oncology\/Neurosurgery, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka, Saitama 350-1298, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keita","family":"Terashima","sequence":"additional","affiliation":[{"name":"Department of Neuro-Oncology, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo 157-8535, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9098-9291","authenticated-orcid":false,"given":"Jun","family":"Kurihara","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Saitama Children\u2019s Medical Center, 1-2, Shin-toshin, Chuo-ku, Saitama 330-8777, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Fujisaki","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology, Osaka City General Hospital, 2-13-22, Miyakojima-hondori, Miyakojima-ku, Osaka 534-0021, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Ihara","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Tokyo Metropolitan Children\u2019s Medical Center, 2-8-29, Musashidai, Fuchu, Tokyo 183-8561, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1437-0374","authenticated-orcid":false,"given":"Yoshihiko","family":"Morikawa","sequence":"additional","affiliation":[{"name":"Clinical Research Support Center, Tokyo Metropolitan Children\u2019s Medical Center, 2-8-29, Musashidai, Fuchu, Tokyo 183-8561, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Yuza","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, Tokyo Metropolitan Children\u2019s Medical Center, 2-8-29, Musashidai, Fuchu, Tokyo 183-8561, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/neuonc\/noaa200","article-title":"CBTRUS Statistical Report: Primary brain and other central nervous system tumors diagnosed in the United States in 2013\u20132017","volume":"22","author":"Ostrom","year":"2020","journal-title":"Neuro Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.ejca.2014.12.014","article-title":"Glioblastoma in England: 2007\u20132011","volume":"51","author":"Brodbelt","year":"2015","journal-title":"Eur. J. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/S1470-2045(09)70025-7","article-title":"European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups; National Cancer Institute of Canada Clinical Trials Group. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial","volume":"10","author":"Stupp","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.1001\/jama.2017.18718","article-title":"Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: A randomized clinical trial","volume":"318","author":"Stupp","year":"2017","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1093\/neuonc\/noq191","article-title":"Temozolomide in the treatment of high-grade gliomas in children: A report from the Children\u2019s Oncology Group","volume":"13","author":"Cohen","year":"2011","journal-title":"Neuro Oncol."},{"key":"ref_6","unstructured":"Bronzino, J.D. (1995). Therapeutic applications of low-frequency sinusoidal and pulsed electric and magnetic fields. The Biomedical Engineering Handbook, CRC Press, Inc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1152\/jappl.1966.21.5.1619","article-title":"Stimulation of internal organs by means of externally applied electrodes","volume":"21","author":"Palti","year":"1966","journal-title":"J. Appl. Physiol."},{"key":"ref_8","unstructured":"Bronzino, J.D. (1995). Biologic effects of radiofrequency and microwave fields: In vivo and in vitro experimental results. The Biomedical Engineering Handbook, CRC Press, Inc."},{"key":"ref_9","unstructured":"Bronzino, J.D. (1995). Radiofrequency hyperthermia in cancer therapy. The Biomedical Engineering Handbook, CRC Press, Inc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/S0006-3495(93)81056-7","article-title":"Bioelectrorheological model of the cell. 5. Electrodestruction of cellular membrane in alternating electric field","volume":"65","author":"Pawlowski","year":"1993","journal-title":"Biophys. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3288","DOI":"10.1158\/0008-5472.CAN-04-0083","article-title":"Disruption of cancer cell replication by alternating electric fields","volume":"64","author":"Kirson","year":"2004","journal-title":"Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"65125","DOI":"10.18632\/oncotarget.11372","article-title":"Tumor treating fields inhibit glioblastoma cell migration, invasion and angiogenesis","volume":"7","author":"Kim","year":"2016","journal-title":"Oncotarget"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1038\/s41419-018-1085-9","article-title":"AMPK-dependent autophagy upregulation serves as a survival mechanism in response to Tumor Treating Fields (TTFields)","volume":"9","author":"Shteingauz","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_14","unstructured":"Weinberg, U. (2021, January 25). Novocure\u2019s Tumor Treating Fields: Innovative Brain Cancer Therapy with Survival and Safety Benefits. Nature Outlook, Available online: https:\/\/www.nature.com\/articles\/d42473-018-00156-3."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10152","DOI":"10.1073\/pnas.0702916104","article-title":"Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors","volume":"104","author":"Kirson","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1186\/s12957-015-0722-3","article-title":"NovoTTF\u2122-100A System (Tumor Treating Fields) transducer array layout planning for glioblastoma: A NovoTAL\u2122 system user study","volume":"13","author":"Chaudhry","year":"2015","journal-title":"World J. Surg. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kirson, E.D., Schneiderman, R.S., Dbal\u00fd, V., Tovarys, F., Vymazal, J., Itzhaki, A., Mordechovich, D., Gurvich, Z., Shmueli, E., and Goldsher, D. (2009). Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields (TTFields). BMC Med. Phys., 9.","DOI":"10.1186\/1756-6649-9-1"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1016\/j.ejca.2012.04.011","article-title":"NovoTTF-100A versus physician\u2019s choice chemotherapy in recurrent glioblastoma: A randomised phase III trial of a novel treatment modality","volume":"48","author":"Stupp","year":"2012","journal-title":"Eur. J. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.1001\/jama.2015.16669","article-title":"Maintenance therapy with tumor-treating fields plud temozolomide vs temozolomide alone for glioblastoma: A randomized clinical trial","volume":"314","author":"Stupp","year":"2015","journal-title":"JAMA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1001\/jamaoncol.2017.5082","article-title":"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","volume":"4","author":"Taphoorn","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_21","unstructured":"(2021, January 25). NCCN Guidelines Recommend Optune in Combination with Temozolomide as a Category 1 Treatment for Newly Diagnosed Glioblastoma (20 March 2018). Available online: https:\/\/www.novocure.com\/nccn-guidelines-recommend-novocures-gbm-therapy-in-combination-with-temozolomide-as-a-category-1-treatment-for-newly-diagnosed-glioblastoma\/."},{"key":"ref_22","unstructured":"(2021, January 25). NCCN Guidelines Recommend Tumor Treating Fields as a Standard Treatment Option for Recurrent Glioblastoma (11 May 2015). Available online: https:\/\/www.novocure.com\/nccn-guidelines-recommend-tumor-treating-fields-as-a-standard-treatment-option-for-recurrent-glioblastoma\/."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1093\/neuonc\/now012","article-title":"TTFields: Where does all the skepticism come from?","volume":"18","author":"Wick","year":"2016","journal-title":"Neuro Oncol."},{"key":"ref_24","first-page":"1","article-title":"Current usage of tumor treating fields for glioblastoma","volume":"2","author":"Lassman","year":"2020","journal-title":"Neuro-Oncol. Adv."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1053\/j.seminoncol.2014.09.010","article-title":"Clinical practice experience with NovoTTF-100A\u2122 system for glioblastoma: The Patient Registry Dataset (PRiDe)","volume":"41","author":"Mrugala","year":"2014","journal-title":"Semin. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1093\/neuonc\/now102","article-title":"The cost-effectiveness of tumor-treating fields therapy in patients with newly diagnosed glioblastoma","volume":"18","author":"Lamure","year":"2016","journal-title":"Neuro Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/s11060-019-03197-w","article-title":"Cost-effectiveness of tumor-treating fields added to maintenance temozolomide in patients with glioblastoma: An updated evaluation using a partitioned survival model","volume":"143","author":"Connock","year":"2019","journal-title":"J. Neuro-Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s11060-020-03540-6","article-title":"Global post-marketing safety surveillance of Tumor Treating Fields (TTFields) in patients with high-grade glioma in clinical practice","volume":"148","author":"Shi","year":"2020","journal-title":"J. Neuro-Oncol."},{"key":"ref_29","unstructured":"Louis, D.N., Ohgaki, H., Weistler, O.D., and Cavenee, W.K. (2007). WHO Classification of Tumors of the Central Nervous System, IARC Press. [4th ed.]."},{"key":"ref_30","unstructured":"Louis, D.N., Ohgaki, H., Weistler, O.D., Cavenee, W.K., Ellison, D.W., Figarella-Branger, D., Perry, A., Reifenberger, G., and von Deiming, A. (2016). WHO Classification of Tumors of the Central Nervous System, IARC Press. [revised 4th ed.]."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Branter, J., Estevez-Cebrero, M., Grundy, R., Grundy, R., Basu, S., and Smith, S. (2018, January 15\u201318). Tumour Treating Fields (TTFields) Exhibit efficacy on high-grade paediatric brain tumour cell lines. Neuro-Oncol. 2018, 20 (Suppl. 6), vi207. Proceedings of the Society for Neuro-Oncology Annual Meeting, New Orleans, LA, USA.","DOI":"10.1093\/neuonc\/noy148.861"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2217\/cns-2016-0018","article-title":"First report of tumor treating fields use in combination with bevacizumab in a pediatric patient: A case report","volume":"6","author":"Shen","year":"2017","journal-title":"CNS Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1007\/s00381-017-3431-0","article-title":"Tumor treating fields in pediatric high-grade glioma","volume":"33","author":"Green","year":"2017","journal-title":"Childs Nerv. Syst."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Crawford, J., Dhall, G., Margol, A., Saria, M., and Kesari, S. (2016, January 17\u201320). Clinical experiences of tumor treating fields (TTFields) in pediatric GBM patients. Neuro-Oncol. 2016, 18 (Suppl. 6), vi139. Proceedings of the Society for Neuro-Oncology, Scottsdale, AZ, USA.","DOI":"10.1093\/neuonc\/now212.577"},{"key":"ref_35","unstructured":"U.S. National Library of Medicine, ClinicalTrials.gov (2021, January 25). Feasibility Trial of Optune for Children with Recurrent or Progressive Supratentorial High-Grade glioma and Ependymoma, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03033992."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Goldman, S., Hwang, E., Lai, J.S., Kocak, M., Lulla, R., Dhall, G., Robison, N., Onar-Thomas, A., and Dunkel, I.J. (2018, January 15\u201318). Feasibility trial of TTFields (Tumor Treating Fields) for children with recurrent or progressive supratentorial high grade glioma and ependymoma: A Pediatric Brain Tumor Consortium study (PBTC-048). Neuro-Oncol. 2018, 20 (Suppl. 6), vi201\u2013vi202. Proceedings of the Society for Neuro-Oncology Annual Meeting, New Orleans, LA, USA.","DOI":"10.1093\/neuonc\/noy148.837"},{"key":"ref_37","unstructured":"U.S. National Library of Medicine, ClinicalTrials.gov (2021, January 25). HUMC 1612: Optune NovoTTF-200A System, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03128047."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s11060-020-03406-x","article-title":"Finite element analysis of Tumor Treating Fields in a patient with posterior fossa glioblastoma","volume":"147","author":"Lok","year":"2020","journal-title":"J. Neuro-Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.lungcan.2013.06.025","article-title":"A phase I\/II trial of Tumor Treating Fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer","volume":"81","author":"Pless","year":"2013","journal-title":"Lung Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1016\/S1470-2045(19)30532-7","article-title":"Tumour Treating Fields in combination with pemetrexed and cisplatin or carboplatin as first-line treatment for unresectable malignant pleural mesothelioma (STELLAR): A multicentre, single-arm phase 2 trial","volume":"20","author":"Ceresoli","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.pan.2018.10.004","article-title":"Tumor treating fields in combination with gemcitabine or gemcitabine plus nab-paclitaxel in pancreatic cancer: Results of the PANOVA phase 2 study","volume":"19","author":"Rivera","year":"2019","journal-title":"Pancreatology."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.ygyno.2018.07.018","article-title":"Tumor Treating Fields in combination with paclitaxel in recurrent ovarian carcinoma: Results of the INNOVATE pilot study","volume":"150","author":"Vergote","year":"2018","journal-title":"Gynecol. Oncol."},{"key":"ref_43","unstructured":"Novocure\u00ae (2021, January 25). Our Pipeline. Available online: https:\/\/www.novocure.com\/our-pipeline\/."}],"container-title":["Neurology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2035-8377\/13\/2\/15\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:12:02Z","timestamp":1760364722000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2035-8377\/13\/2\/15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,8]]},"references-count":43,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["neurolint13020015"],"URL":"https:\/\/doi.org\/10.3390\/neurolint13020015","relation":{},"ISSN":["2035-8377"],"issn-type":[{"value":"2035-8377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,8]]}}}