{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T02:29:33Z","timestamp":1783391373578,"version":"3.54.6"},"reference-count":38,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"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":"crossref","award":["20hk0102069h0001"],"award-info":[{"award-number":["20hk0102069h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["21hk0102069h0002"],"award-info":[{"award-number":["21hk0102069h0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["22hk0102069h0003"],"award-info":[{"award-number":["22hk0102069h0003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["23hk0102069h0004"],"award-info":[{"award-number":["23hk0102069h0004"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["24hk0102069h0005"],"award-info":[{"award-number":["24hk0102069h0005"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background\/Objectives: Although Tumor-Treating Fields (TTFields) therapy is an established treatment modality for adult glioblastoma, clinical data on its efficacy in pediatric brain tumors are extremely scarce. The present study aimed to evaluate the safety of TTFields therapy for pediatric diffuse high-grade glioma (HGG) and to conduct an exploratory analysis of its efficacy. Methods: A prespecified, interim analysis was performed to determine whether the study should be continued on the basis of safety and feasibility data on the first three patients. The target population was children aged 5 to 17 years with newly diagnosed, supratentorial HGG or its first recurrence following frontline therapy. After completion of initial, local treatment for the tumor (surgical removal and\/or radiotherapy), all patients received TTFields therapy using OptuneTM for 28 days per course for up to 26 courses until disease progression. Results: The interim analysis, which was completed in October 2022, included three female patients aged 14, 17, and 9 years. All had a histological grade 4 tumor, two of which were radiation-induced, secondary HGG. No serious, treatment-related toxicities or device-related issues were observed. All three patients were able to continue using the device for 75% or more of the time in accordance with the protocol, suggesting that the treatment was feasible. The MRI findings of two patients indicated that the treatment has a potential antitumor effect. Based on these results, the study was resumed and is currently being continued at multiple centers. Conclusions: The initial results of the prespecified, interim analysis demonstrated that TTFields therapy was safe and feasible for children with HGG. This study was funded by the Japan Agency for Medical Research and Development (AMED) and was registered with the Japan Registry of Clinical Trials (jRCTs032200423).<\/jats:p>","DOI":"10.3390\/children13010084","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T08:42:58Z","timestamp":1767688978000},"page":"84","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Safety and Efficacy of Tumor-Treating Fields (TTFields) Therapy for Pediatric High-Grade Glioma: Results of a Prespecified Interim Analysis of the First Three Cases"],"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 Transfusion and Laboratory Medicine, Tokyo Metropolitan Children\u2019s Medical Center, 2-8-29, Musashidai, Fuchu, Tokyo 183-8561, Japan"},{"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":"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\/0000-0001-5617-8068","authenticated-orcid":false,"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":"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"}]},{"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, Saitama 330-8777, 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"}]},{"given":"Jun-ichi","family":"Adachi","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8652-5742","authenticated-orcid":false,"given":"Mikako","family":"Enokizono","sequence":"additional","affiliation":[{"name":"Department of Radiology, Tokyo Metropolitan Children\u2019s Medical Center, 2-8-29, Musashidai, Fuchu, Tokyo 183-8561, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2989-0900","authenticated-orcid":false,"given":"Naoko","family":"Mori","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"}]},{"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":[[2026,1,6]]},"reference":[{"key":"ref_1","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 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