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

• Published in: Acta neuropathologica communications Vol. 12; no. 1; pp. 120 - 17
• Main Authors: Hayashi, Nobuhide, Fukai, Junya, Nakatogawa, Hirokazu, Kawaji, Hiroshi, Yoshioka, Ema, Kodama, Yoshinori, Nakajo, Kosuke, Uda, Takehiro, Naito, Kentaro, Kijima, Noriyuki, Okita, Yoshiko, Kagawa, Naoki, Takahashi, Yoshinobu, Hashimoto, Naoya, Arita, Hideyuki, Takano, Koji, Sakamoto, Daisuke, Iida, Tomoko, Arakawa, Yoshiki, Kawauchi, Takeshi, Sonoda, Yukihiko, Mitobe, Yuta, Ishibashi, Kenichi, Matsuda, Masahide, Achiha, Takamune, Tomita, Takahiro, Nonaka, Masahiro, Hara, Keijiro, Takebe, Noriyoshi, Tsuzuki, Takashi, Nakajima, Yoshikazu, Ohue, Shiro, Nakajima, Nobuyuki, Watanabe, Akira, Inoue, Akihiro, Umegaki, Masao, Kanematsu, Daisuke, Katsuma, Asako, Sumida, Miho, Shofuda, Tomoko, Mano, Masayuki, Kinoshita, Manabu, Mori, Kanji, Nakao, Naoyuki, Kanemura, Yonehiro
• Format: Journal Article
• Language: English
• Published: BioMed Central Ltd 27.07.2024; BMC
• Subjects: Brain tumors; Cancer; Care and treatment; Chemotherapy; Clinical characteristic; Development and progression; Diffuse midline glioma; Gene mutations; Genetic research; Gliomas; H3 K27-altered; Methylation; Midline location; Molecular feature; Prognosis; Survival
• ISSN: 2051-5960; 2051-5960
• DOI: 10.1186/s40478-024-01808-w

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 [greater than or equal to] 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 [+ or -] 1.0 (7.9-11.9, 95% CI) and 16.6 [+ or -] 1.4 (13.9-19.3, 95% CI) months, respectively. Female sex, preoperative KPS score [greater than or equal to] 80, adjuvant radiation + temozolomide and radiation [greater than or equal to] 50 Gy were associated with favorable prognosis. Female sex and preoperative KPS score [greater than or equal to] 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. Keywords: Diffuse midline glioma, H3 K27-altered, Midline location, Clinical characteristic, Molecular feature, Survival, Prognostic factor