Genetic analysis in patients with newly diagnosed glioblastomas treated with interferon-beta plus temozolomide in comparison with temozolomide alone.

Autor: Natsume A; Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Japan. anatsume@med.nagoya-u.ac.jp., Aoki K; Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Japan., Ohka F; Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Japan., Maeda S; Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Japan., Hirano M; Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Japan., Adilijiang A; Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Japan., Motomura K; Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Japan., Sumi M; Radiation Oncology Department, Cancer Institute Hospital, Tokyo, Japan., Nishikawa R; Department of Neuro-Oncology/Neurosurgery, Saitama Medical University International Medical Center, Saitama, Japan., Narita Y; Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan., Muragaki Y; Department of Neurosurgery, Tokyo Women's Medical University, Tokyo, Japan., Maruyama T; Department of Neurosurgery, Tokyo Women's Medical University, Tokyo, Japan., Ito T; Department of Neurosurgery, Nakamura Memorial Hospital, Sapporo, Japan., Beppu T; Department of Neurosurgery, Iwate Medical University, Iwate, Japan., Nakamura H; Department of Neurosurgery, Kumamoto University Graduate School of Medicine, Kumamoto, Japan., Kayama T; Department of Neurosurgery, Yamagata University Graduate School of Medicine, Yamagata, Japan., Sato S; Department of Neurosurgery, Yamagata University Graduate School of Medicine, Yamagata, Japan., Nagane M; Department of Neurosurgery, Faculty of Medicine, Kyorin University, Tokyo, Japan., Mishima K; Department of Neuro-Oncology/Neurosurgery, Saitama Medical University International Medical Center, Saitama, Japan., Nakasu Y; Department of Neurosurgery, Shizuoka Cancer Center, Shizuoka, Japan., Kurisu K; Department of Neurosurgery, Hiroshima University Hospital, Hiroshima, Japan., Yamasaki F; Department of Neurosurgery, Hiroshima University Hospital, Hiroshima, Japan., Sugiyama K; Department of Clinical Oncology & Neuro-Oncology Program, Hiroshima University Hospital, Hiroshima, Japan., Onishi T; Department of Neurosurgery, Ehime University Graduate School of Medicine, Ehime, Japan., Iwadate Y; Department of Neurological Surgery, Chiba University Graduate School of Medicine, Chiba, Japan., Terasaki M; Department of Neurosurgery, Kurume University Graduate School of Medicine, Kurume, Japan., Kobayashi H; Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan., Matsumura A; Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan., Ishikawa E; Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan., Sasaki H; Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan., Mukasa A; Department of Neurosurgery, The University of Tokyo Hospital, Tokyo, Japan., Matsuo T; Department of Neurosurgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan., Hirano H; Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan., Kumabe T; Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan., Shinoura N; Department of Neurosurgery, Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital, Tokyo, Japan., Hashimoto N; Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan., Aoki T; Department of Neurosurgery, Kitano Hospital, Osaka, Japan., Asai A; Department of Neurosurgery, Kansai Medical University, Osaka, Japan., Abe T; Department of Neurosurgery, Faculty of Medicine, Oita University, Oita, Japan., Yoshino A; Department of Neurological Surgery, Nihon University Graduate School of Medicine, Tokyo, Japan., Arakawa Y; Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan., Asano K; Department of Neurosurgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan., Yoshimoto K; Department of Neurosurgery, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan., Shibui S; Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan., Okuno Y; Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan., Wakabayashi T; Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Jazyk: angličtina
Zdroj: Journal of neuro-oncology [J Neurooncol] 2020 May; Vol. 148 (1), pp. 17-27. Date of Electronic Publication: 2020 May 04.
DOI: 10.1007/s11060-020-03505-9
Abstrakt: Purpose: This study aimed to explore the genetic alterations and to identify good responders in the experimental arm in the tumor samples from newly diagnosed glioblastoma (GBM) patients enrolled in JCOG0911; a randomized phase II trial was conducted to compare the efficacy of interferonβ (IFNβ) plus temozolomide (TMZ) with that of TMZ alone.
Experimental: DESIGN: Of 122 tumors, we performed deep targeted sequencing to determine the somatic mutations, copy number variations, and tumor mutation burden; pyrosequencing for O 6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation; Sanger sequencing for the telomerase reverse transcriptase (TERT) promoter; and microsatellite instability (MSI) testing in 95, 91, 91 and 72 tumors, respectively. We performed a multivariable Cox regression analysis using backward stepwise selection of variables including clinical factors (sex, age, performance status, residual tumor after resection, tumor location) and genetic alterations.
Results: Deep sequencing detected an IDH1 mutation in 13 tumors (14%). The MGMT promoter methylation by quantitative pyrosequencing was observed in 41% of the tumors. A mutation in the TERT promoter was observed in 69% of the tumors. While high tumor mutation burden (> 10 mutations per megabase) was seen in four tumors, none of the tumors displayed MSI-high. The clinical and genetic factors considered as independent favorable prognostic factors were gross total resection (hazard ratio [HR]: 0.49, 95% confidence interval, 0.30-0.81, P = 0.0049) and MGMT promoter methylation (HR: 0.43, 0.21-0.88, P = 0.023). However, tumor location at the temporal lobe (HR: 1.90, 1.22-2.95, P = 0.0046) was an independent unfavorable prognostic factor. No predictive factors specific to the TMZ + IFNβ + Radiotherapy (RT) group were found.
Conclusion: This additional sub-analytical study of JCOG0911 among patients with newly diagnosed GBM showed that tumor location at the temporal lobe, gross total resection, and MGMT promoter methylation were significant prognostic factors, although no factors specific to IFNβ addition were identified.
Databáze: MEDLINE
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