||Nobuhiro Hata, Masahiro Mizoguchi, Daisuke Kuga, Ryusuke Hatae, Yuhei Sangatsuda, Yojiro Akagi, Koji Yoshimoto, Koji Iihara, First-line bevacizumab contributes to survival improvement in glioblastoma patients complementary to temozolomide, 16th ASNO meeting,, 2019.09, Introduction: First-line bevacizumab (BEV) is now available as a treatment option for glioblastoma patients with severe clinical conditions in Japan. However, the survival benefits remain controversial. To elucidate these potential survival benefits, we retrospectively analyzed survival in glioblastoma patients receiving BEV.
Methods: We analyzed survival in 120 patients with IDH-wild type glioblastoma treated from 2002 to 2018. Overall survival (OS) was assessed in three subgroups (pre-temozolomide [TMZ], TMZ, and TMZ-BEV), and the correlations of prognostic factors with survival were evaluated.
Results: An improvement in survival was observed after BEV approval (median OS in the pre-TMZ, TMZ, and TMZ-BEV eras: (14.6, 14.9, and 22.1 months, respectively). A Cox proportional hazards model identified extent of resection and MGMT methylation status as significant prognostic factors in the TMZ era; however, these factors were not significant in the TMZ-BEV era. In subgroup analyses, patients with MGMT methylation had improved OS after TMZ introduction (pre-TMZ vs TMZ, 18.5 vs 28.1 months; P = 0.13), and those without MGMT methylation had increased OS after BEV approval (TMZ vs TMZ-BEV, 12.2 vs 16.7 months; P = 0.04). Conclusions: Our findings imply that optional first-line administration of BEV can overcome the impact of conventional risk factors and prolong survival complementary to TMZ. The patient subgroups benefitting from TMZ and BEV did not seem not overlap, and stratification based on risk factors, including MGMT methylation status, might be effective for selecting patients in whom BEV should be preferentially used as a first-line therapy..
||Hata N, Mizoguchi M, Akagi Y, Suzuki SO, Kuga D, Amemiya T, Hatae R, Yoshimoto K, Iwaki T, Iihara K., The correlation between 1p19q and TERT promoter mutation status in IDH-mutant gliomas, 36th Annual Meeting of the Japan Society of Brain Tumor Pathology, 2018.09, (Background) The revised WHO 2016 classification established the consensus that the diagnosis of oligodendrogliomas should be confirmed by IDH mutation and 1p19q codeletion. As these tumors are known to harbor TERT promoter mutation also, TERT status seems to be useful as a surrogate marker for 1p19q. Herein, we aim to verify this theory by analyzing the correlation between 1p19q and TERT status. (Methods) IDH and TERT status were determined by Sanger sequencing. 1p19q codeletion was confirmed by LOH on total arms using multiple microsatellite markers. We reviewed our case series of 70 gliomas with IDH mutation whose 1p19q and TERT status were examined. (Results) Whereas 65 out of 70 showed the consistency of 1p19q and TERT status, the remaining 5 were 1p19q non-codel/TERT mutant. In these 5 cases, 3 showed consistent clinical, radiographic and pathological features of oligodendroglioma. In contrast, the pathological diagnoses of the remaining 2 were anaplastic astrocytoma and glioblastoma, both of which also showed astrocytic molecular findings. (Conclusion) This study seems to support the theory that, in general, TERT mutation can be used as an effective surrogate marker of 1p19q for IDH mutant gliomas. Although, there were a few exceptional cases, thereby, we need further efforts to elucidate the correlation between 1p19q and TERT status..
||Nobuhiro Hata, Koji Yoshimoto, Ryusuke Hatae, Daisuke Kuga, Yojiro Akagi, Yuhei Sangatsuda, Takeo Amemiya, Tadahisa Shono, Masahiro Mizoguchi, Koji Iihara, Add-on bevacizumab can prevent early clinical deterioration and prolong survival in newly diagnosed partially resected glioblastoma patients with a poor performance status, ASNO, 2017.10, Purpose: The rationality of using Bevacizumab (BEV) for newly-diagnosed glioblastomas (nd-GBMs) remains controversial. The purpose of this study was to analyze the outcomes of this treatment.
Methods: The outcomes of 69 nd-GBM patients treated after 2006 were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Since add-on BEV therapy was only used for partially resected GBMs (pr-GBMs) after its approval in 2013, the patients were subdivided into three treatment groups: Type I, partial removal with TMZ/BEV and concurrent radiotherapy (CCRT); Type II, partial removal with TMZ and CCRT; and Type III, gross total removal with TMZ and CCRT.
Results: The PFS rate of Type I patients was significantly higher than that of Type II patients (P = 0.014), but comparable to that of Type III patients. Differences in OS rates between Type I and Type II patients were less apparent (P = 0.075), although the median OS of Type I patients was approximately 8 months higher than that of Type II patients (17.4 vs 9.8 months, respectively). The clinical deterioration rate during initial treatment was significantly (P = 0.024) lower in Type I than in Type II patients (7.7 vs 47.4%, respectively). Differences in OS rates between Type I and Type II patients with a poor performance status (PS) were significant (P = 0.017).
Conclusions: Our findings suggest that add-on BEV can prevent early clinical deterioration of pr-GBM patients and contribute to a prolonged survival, especially for those with a poor PS..