Impact of tumor-treating fields on the survival of Japanese patients with newly diagnosed glioblastoma: A multicenter, retrospective cohort study

doi:10.1093/noajnl/vdae176

. 2024 Nov 28;6(1):vdae176.

doi: 10.1093/noajnl/vdae176. eCollection 2024 Jan-Dec.

Impact of tumor-treating fields on the survival of Japanese patients with newly diagnosed glioblastoma: A multicenter, retrospective cohort study

Masayuki Kanamori¹, Shunsuke Tsuzuki², Ichiyo Shibahara³, Kuniaki Saito⁴, Yoshiteru Shimoda¹, Kazuhiro Tanaka⁵, Shigeru Yamaguchi⁶, Manabu Natsumeda⁷, Tomoo Matsutani⁸, Mitsuto Hanihara⁹, Mitsutoshi Nakada¹⁰, Jun-Ichiro Kuroda¹¹, Masahide Matsuda¹², Koji Yoshimoto¹³, Ushio Yonezawa¹⁴, Yukihiko Sonoda¹⁵, Koji Takano¹⁶, Hajime Yonezawa¹⁷, Yoshihiro Otani¹⁸, Yukiko Nakahara¹⁹, Masashi Uchida²⁰, Masahiro Nonaka²¹, Yohei Mineharu²², Yohei Kitamura²³, Shinji Yamashita²⁴, Takahiro Yamauchi²⁵, Yohei Miyake²⁶, Shoichi Deguchi²⁷, Takaaki Beppu²⁸, Kaoru Tamura²⁹, Shinichiro Koizumi³⁰, Yuichi Hirose³¹, Kenichiro Asano³², Ryo Hiruta³³, Manabu Kinoshita³⁴, Keisuke Miyake³⁵, Noriyuki Nakayama³⁶, Akihiro Inoue³⁷, Takahiro Ono³⁸, Takahiro Sasaki³⁹, Yukinori Akiyama⁴⁰, Shinjiro Fukami⁴¹, Atsuo Yoshino⁴², Yu Kawanishi⁴³, Taku Asanome⁴⁴, Takuhiro Yamaguchi⁴⁵, Masamichi Takahashi⁴⁶, Fumiyuki Yamasaki¹⁴, Yoshiki Arakawa²², Yoshitaka Narita⁴⁶

Affiliations

¹ Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
² Department of Neurosurgery, Tokyo Women's Medical University, Tokyo, Japan.
³ Department of Neurosurgery, Kitasato University School of Medicine, Sagamihara, Japan.
⁴ Department of Neurosurgery, Kyorin University Facility of Medicine, Tokyo, Japan.
⁵ Department of Neurosurgery, Kobe University Graduate School of Medicine, Kobe, Japan.
⁶ Department of Neurosurgery, Faculty of Medicine, Hokkaido University, Sapporo, Japan.
⁷ Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Japan.
⁸ Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
⁹ Department of Neurosurgery, University of Yamanashi, Yamanashi, Japan.
¹⁰ Department of Neurosurgery, Kanazawa University, Kanazawa, Japan.
¹¹ Department of Neurosurgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
¹² Department of Neurosurgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
¹³ Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
¹⁴ Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
¹⁵ Department of Neurosurgery, Faculty of Medicine, Yamagata University, Yamagata, Japan.
¹⁶ Department of Neurosurgery, Osaka International Cancer Institute, Osaka, Japan.
¹⁷ Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
¹⁸ Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
¹⁹ Department of Neurosurgery, Faculty of Medicine, Saga University, Saga, Japan.
²⁰ Department of Neurosurgery, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
²¹ Department of Neurosurgery, Kansai Medical University, Hirakata, Japan.
²² Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
²³ Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan.
²⁴ Division of Neurosurgery, Department of Clinical Neuroscience, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
²⁵ Division of Medicine, Department of Neurosurgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
²⁶ Department of Neurosurgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
²⁷ Division of Neurosurgery, Shizuoka Cancer Center, Nagaizumi, Japan.
²⁸ Department of Neurosurgery, Iwate Medical University, Shiwa, Japan.
²⁹ Department of Neurosurgery, Tokyo Medical and Dental University, Tokyo, Japan.
³⁰ Department of Neurosurgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
³¹ Department of Neurosurgery, Fujita Health University, Toyoake, Japan.
³² Department of Neurosurgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
³³ Department of Neurosurgery, Fukushima Medical University, Fukushima, Japan.
³⁴ Department of Neurosurgery, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
³⁵ Department of Neurological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan.
³⁶ Department of Neurosurgery, Graduate School of Medicine, Gifu University, Gifu, Japan.
³⁷ Department of Neurosurgery, Ehime University School of Medicine, Toon, Japan.
³⁸ Department of Neurosurgery, Akita University Graduate School of Medicine, Akita, Japan.
³⁹ Department of Neurological Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan.
⁴⁰ Department of Neurosurgery, Sapporo Medical University, Sapporo, Japan.
⁴¹ Department of Neurosurgery, Tokyo Medical University, Tokyo, Japan.
⁴² Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan.
⁴³ Department of Neurosurgery, Kochi Medical School, Kochi University, Kochi, Japan.
⁴⁴ Department of Neurosurgery, Brain Tumor Center, Nakamura Memorial Hospital, Sapporo, Japan.
⁴⁵ Division of Biostatistics, Tohoku University Graduate School of Medicine, Sendai, Japan.
⁴⁶ Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan.

PMID: 39659832
PMCID: PMC11629686
DOI: 10.1093/noajnl/vdae176

Impact of tumor-treating fields on the survival of Japanese patients with newly diagnosed glioblastoma: A multicenter, retrospective cohort study

Masayuki Kanamori et al. Neurooncol Adv. 2024.

. 2024 Nov 28;6(1):vdae176.

doi: 10.1093/noajnl/vdae176. eCollection 2024 Jan-Dec.

Authors

Affiliations

¹ Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
² Department of Neurosurgery, Tokyo Women's Medical University, Tokyo, Japan.
³ Department of Neurosurgery, Kitasato University School of Medicine, Sagamihara, Japan.
⁴ Department of Neurosurgery, Kyorin University Facility of Medicine, Tokyo, Japan.
⁵ Department of Neurosurgery, Kobe University Graduate School of Medicine, Kobe, Japan.
⁶ Department of Neurosurgery, Faculty of Medicine, Hokkaido University, Sapporo, Japan.
⁷ Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Japan.
⁸ Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
⁹ Department of Neurosurgery, University of Yamanashi, Yamanashi, Japan.
¹⁰ Department of Neurosurgery, Kanazawa University, Kanazawa, Japan.
¹¹ Department of Neurosurgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
¹² Department of Neurosurgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
¹³ Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
¹⁴ Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
¹⁵ Department of Neurosurgery, Faculty of Medicine, Yamagata University, Yamagata, Japan.
¹⁶ Department of Neurosurgery, Osaka International Cancer Institute, Osaka, Japan.
¹⁷ Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
¹⁸ Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
¹⁹ Department of Neurosurgery, Faculty of Medicine, Saga University, Saga, Japan.
²⁰ Department of Neurosurgery, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
²¹ Department of Neurosurgery, Kansai Medical University, Hirakata, Japan.
²² Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
²³ Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan.
²⁴ Division of Neurosurgery, Department of Clinical Neuroscience, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
²⁵ Division of Medicine, Department of Neurosurgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
²⁶ Department of Neurosurgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
²⁷ Division of Neurosurgery, Shizuoka Cancer Center, Nagaizumi, Japan.
²⁸ Department of Neurosurgery, Iwate Medical University, Shiwa, Japan.
²⁹ Department of Neurosurgery, Tokyo Medical and Dental University, Tokyo, Japan.
³⁰ Department of Neurosurgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
³¹ Department of Neurosurgery, Fujita Health University, Toyoake, Japan.
³² Department of Neurosurgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
³³ Department of Neurosurgery, Fukushima Medical University, Fukushima, Japan.
³⁴ Department of Neurosurgery, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
³⁵ Department of Neurological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan.
³⁶ Department of Neurosurgery, Graduate School of Medicine, Gifu University, Gifu, Japan.
³⁷ Department of Neurosurgery, Ehime University School of Medicine, Toon, Japan.
³⁸ Department of Neurosurgery, Akita University Graduate School of Medicine, Akita, Japan.
³⁹ Department of Neurological Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan.
⁴⁰ Department of Neurosurgery, Sapporo Medical University, Sapporo, Japan.
⁴¹ Department of Neurosurgery, Tokyo Medical University, Tokyo, Japan.
⁴² Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan.
⁴³ Department of Neurosurgery, Kochi Medical School, Kochi University, Kochi, Japan.
⁴⁴ Department of Neurosurgery, Brain Tumor Center, Nakamura Memorial Hospital, Sapporo, Japan.
⁴⁵ Division of Biostatistics, Tohoku University Graduate School of Medicine, Sendai, Japan.
⁴⁶ Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan.

PMID: 39659832
PMCID: PMC11629686
DOI: 10.1093/noajnl/vdae176

Abstract

Background: The EF-14 clinical trial demonstrated the safety and efficacy of tumor-treating fields (TTFields) for newly diagnosed glioblastoma. This study aimed to clarify the current status, safety, and efficacy of TTFields in Japanese patients who meet the EF-14 inclusion criteria.

Methods: This was a multicenter retrospective cohort study. Background, treatment, and outcome data of patients who satisfied the inclusion criteria of the EF-14 trial were collected from 45 institutions across Japan. The rate, determinants, and current status of TTField use, including its safety and efficacy in terms of progression and survival, were retrospectively investigated. This study was conducted in accordance with the STROBE checklist.

Results: Among the 607 patients enrolled, 70 were excluded due to progressive disease during radiation and temozolomide therapy, age > 80 years old, and Karnofsky Performance Status score of <70. Among the remaining 537 patients, 210 (39%) underwent TTField treatment. Multivariate analysis revealed younger age and spouse as a caregiver as significant factors for TTField use. The compliance rate of TTField use exceeded 75% in 60% of patients, with a median TTField usage duration of 11 months. Skin disorders requiring medical treatment occurred in 56% of patients. Multivariate Cox proportional hazards analysis in the whole series and propensity score-matched analysis revealed that TTField use was not a prognostic factor for progression-free survival (PFS) or overall survival (OS).

Conclusions: TTField use did not have a substantial effect on either PFS or OS in Japanese patients with glioblastoma, despite compliance rates comparable to those observed in the EF-14.

Keywords: Asian population; determinant of use; glioblastoma; survival; tumor-treating fields.

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Conflict of interest statement

M.Ka. received honoraria from Novocure and Eisai and research funding from Eisai. K.S. received honoraria from Novocure and Eisai and research funding from Eisai and Nippon Kayaku. S.Y. received honoraria from Novocure. M.N. received honoraria from Novocure and Eisai. T.M. received honoraria from Novocure and Eisai. M.N. received honoraria from Novocure, Eisai, and Nippon Kayaku and research funding from Eisai and MSD. K.Y. received honoraria from Novocure. H.Y. received honoraria from Novocure and Eisai. Y.Nakahara received honoraria from Novocure and Eisai. Y.H. received honoraria from Novocure and Eisai and research funding from Eisai. M.Ki. received honoraria from Novocure and Eisai. A.Y. received research funding from Eisai. Y.K. received honoraria from Novocure and Eisai. M.T. received research funding for clinical trial from Eisai. Y.A. received honoraria from Novocure, Eisai, and Nippon Kayaku. Y.Narita received honoraria from Novocure and Eisai and research funding from Eisai. All remaining authors have declared no conflicts of interest.

Figures

**Figure 1.**
Patient flow in this retrospective study. GB, glioblastoma; KPS, Karnofsky Performance Status; *One patient was over 80 years old and had a KPS score of <60. A total of 537 patients in the whole series and 330 patients after propensity score matching (PSM) were analyzed. Logistic regression analysis was conducted to identify determinants of TTField usage, while multivariate analysis using the Cox proportional hazards model was performed to estimate the effectiveness of TTFields in the whole series. Kaplan–Meier analysis with the log-rank test was used to estimate the effectiveness of TTFields in the PSM group.

**Figure 2.**
Tumor-treating field (TTField) usage rates according to institution and compliance rates with TTFields. (A) Scattered graph demonstrating the relationship between the total number of patients that met the inclusion criteria during the study period and patients who received TTField treatment at the 45 institutions. (B) Bar graph demonstrating the distribution of the average daily compliance rate with TTFields.

**Figure 3.**
Progression-free survival (A) and overall survival (B) in all patients who received radiation and temozolomide therapy with or without tumor-treating fields (TTFields). The median PFS was 11 and 10 months in TTField users and nonusers, respectively. The median OS was 25 months in both groups. There were no significant differences in PFS and OS between TTField users and nonusers (P = .83 and .57; log-rank test).

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

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

[3] Pallud J, Audureau E, Noel G, et al. Long-term results of carmustine wafer implantation for newly diagnosed glioblastomas: a controlled propensity-matched analysis of a French multicenter cohort. Neuro Oncol. 2015;12(12):201517. - PMC - PubMed

[4] Pallud J, Audureau E, Noel G, et al. Long-term results of carmustine wafer implantation for newly diagnosed glioblastomas: a controlled propensity-matched analysis of a French multicenter cohort. Neuro Oncol. 2015;12(12):201517. - PMC - PubMed

[5] Aoki T, Nishikawa R, Sugiyama K, et al.; NPC-08 study group. NPC-08 study group. A multicenter phase I/II study of the BCNU implant (Gliadel(®) Wafer. Neurol Med Chir (Tokyo). 2014;54(4):290–301. - PMC - PubMed

[6] Aoki T, Nishikawa R, Sugiyama K, et al.; NPC-08 study group. NPC-08 study group. A multicenter phase I/II study of the BCNU implant (Gliadel(®) Wafer. Neurol Med Chir (Tokyo). 2014;54(4):290–301. - PMC - PubMed

[7] Westphal M, Hilt DC, Bortey E, et al. A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel Wafers) in patients with primary malignant glioma. Neuro Oncol. 2003;5(2):79–88. - PMC - PubMed

[8] Westphal M, Hilt DC, Bortey E, et al. A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel Wafers) in patients with primary malignant glioma. Neuro Oncol. 2003;5(2):79–88. - PMC - PubMed

[9] Muragaki Y, Akimoto J, Maruyama T, et al. Phase II clinical study on intraoperative photodynamic therapy with talaporfin sodium and semiconductor laser in patients with malignant brain tumors. J Neurosurg. 2013;119(4):845–852. - PubMed

[10] Muragaki Y, Akimoto J, Maruyama T, et al. Phase II clinical study on intraoperative photodynamic therapy with talaporfin sodium and semiconductor laser in patients with malignant brain tumors. J Neurosurg. 2013;119(4):845–852. - PubMed

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Impact of tumor-treating fields on the survival of Japanese patients with newly diagnosed glioblastoma: A multicenter, retrospective cohort study

Affiliations

Impact of tumor-treating fields on the survival of Japanese patients with newly diagnosed glioblastoma: A multicenter, retrospective cohort study

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