Acta Neuropathologica Communications (Jul 2024)

Neuroradiological, genetic and clinical characteristics of histone H3 K27-mutant diffuse midline gliomas in the Kansai Molecular Diagnosis Network for CNS Tumors (Kansai Network): multicenter retrospective cohort

  • Nobuhide Hayashi,
  • Junya Fukai,
  • Hirokazu Nakatogawa,
  • Hiroshi Kawaji,
  • Ema Yoshioka,
  • Yoshinori Kodama,
  • Kosuke Nakajo,
  • Takehiro Uda,
  • Kentaro Naito,
  • Noriyuki Kijima,
  • Yoshiko Okita,
  • Naoki Kagawa,
  • Yoshinobu Takahashi,
  • Naoya Hashimoto,
  • Hideyuki Arita,
  • Koji Takano,
  • Daisuke Sakamoto,
  • Tomoko Iida,
  • Yoshiki Arakawa,
  • Takeshi Kawauchi,
  • Yukihiko Sonoda,
  • Yuta Mitobe,
  • Kenichi Ishibashi,
  • Masahide Matsuda,
  • Takamune Achiha,
  • Takahiro Tomita,
  • Masahiro Nonaka,
  • Keijiro Hara,
  • Noriyoshi Takebe,
  • Takashi Tsuzuki,
  • Yoshikazu Nakajima,
  • Shiro Ohue,
  • Nobuyuki Nakajima,
  • Akira Watanabe,
  • Akihiro Inoue,
  • Masao Umegaki,
  • Daisuke Kanematsu,
  • Asako Katsuma,
  • Miho Sumida,
  • Tomoko Shofuda,
  • Masayuki Mano,
  • Manabu Kinoshita,
  • Kanji Mori,
  • Naoyuki Nakao,
  • Yonehiro Kanemura

DOI
https://doi.org/10.1186/s40478-024-01808-w
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 17

Abstract

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Abstract This study aims to elucidate the clinical and molecular characteristics, treatment outcomes and prognostic factors of patients with histone H3 K27-mutant diffuse midline glioma. We retrospectively analyzed 93 patients with diffuse midline glioma (47 thalamus, 24 brainstem, 12 spinal cord and 10 other midline locations) treated at 24 affiliated hospitals in the Kansai Molecular Diagnosis Network for CNS Tumors. Considering the term “midline” areas, which had been confused in previous reports, we classified four midline locations based on previous reports and anatomical findings. Clinical and molecular characteristics of the study cohort included: age 4–78 years, female sex (41%), lower-grade histology (56%), preoperative Karnofsky performance status (KPS) scores ≥ 80 (49%), resection (36%), adjuvant radiation plus chemotherapy (83%), temozolomide therapy (76%), bevacizumab therapy (42%), HIST1H3B p.K27M mutation (2%), TERT promoter mutation (3%), MGMT promoter methylation (9%), BRAF p.V600E mutation (1%), FGFR1 mutation (14%) and EGFR mutation (3%). Median progression-free and overall survival time was 9.9 ± 1.0 (7.9–11.9, 95% CI) and 16.6 ± 1.4 (13.9–19.3, 95% CI) months, respectively. Female sex, preoperative KPS score ≥ 80, adjuvant radiation + temozolomide and radiation ≥ 50 Gy were associated with favorable prognosis. Female sex and preoperative KPS score ≥ 80 were identified as independent good prognostic factors. This study demonstrated the current state of clinical practice for patients with diffuse midline glioma and molecular analyses of diffuse midline glioma in real-world settings. Further investigation in a larger population would contribute to better understanding of the pathology of diffuse midline glioma.

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