異型性髄膜腫の診断基準に対する臨床経過の再検討

髄膜腫は最も頻度の多い脳腫瘍で，その多くは手術摘出後に再発が稀な腫瘍であるが，一部ではより高い増殖能を示すものがある．組織学的には異型性髄膜腫に分類されるもので，その頻度は診断基準であるWHO分類の変遷に伴い1993年当初数％であったものが，最近30％程度にまで増加している．しかし，臨床的には髄膜腫全体での再発率や悪性度が高くなっている証拠はない．一つの可能性として異型性髄膜腫と診断される比率が増えたことが考えられる．我々は異型性髄膜腫の組織像を詳細に検討し，臨床経過と併せて検討を行った．対象症例は2009年1月〜2014年7月における64例で，WHO grade Iが37例，異型性髄膜腫が27例であった．異型性髄膜腫は組織像によって，局所での核分裂像を示すⅡa群と，全体的での核分裂像もしくは脳浸潤を伴うⅡb群に分けることが可能であり，Ⅱa群は10例，Ⅱb群は17例であった．臨床像はⅡb群が grade I/Ⅱa群より，高齢(中央値Ⅰ：57，Ⅱa：50，Ⅱb：69歳)で男性に多く，MIB-1 labeling indexがより高値(中央値Ⅰ：3.0，Ⅱa：2.1，Ⅱb：10.3％)であった．追跡期間中にgradeⅠで1 例，Ⅱb群で5例が再発した．Ⅱa群の臨床経過は，grade Iに類似しており，臨床像としてはⅡb群が異型性髄膜腫のような，より再発を認めやすい一群であると考えられる

Bevacizumab beyond Progression for Newly Diagnosed Glioblastoma (BIOMARK): Phase II Safety, Efficacy and Biomarker Study

We evaluated the efficacy and safety of bevacizumab beyond progression (BBP) in Japanese patients with newly diagnosed glioblastoma and explored predictors of response to bevacizumab. This phase II study evaluated a protocol-defined primary therapy by radiotherapy with concurrent and adjuvant temozolomide plus bevacizumab, followed by bevacizumab monotherapy, and secondary therapy (BBP: bevacizumab upon progression). Ninety patients received the protocol-defined primary therapy (BBP group, n = 25). Median overall survival (mOS) and median progression-free survival (mPFS) were 25.0 and 14.9 months, respectively. In the BBP group, in which O6-methylguanine-DNA methyltransferase (MGMT)-unmethylated tumors predominated, mOS and mPFS were 5.8 and 1.9 months from BBP initiation and 16.8 and 11.4 months from the initial diagnosis, respectively. The primary endpoint, the 2-year survival rate of the BBP group, was 27.0% and was unmet. No unexpected adverse events occurred. Expression profiling using RNA sequencing identified that Cluster 2, which was enriched with the genes involved in macrophage or microglia activation, was associated with longer OS and PFS independent of the MGMT methylation status. Cluster 2 was identified as a significantly favorable independent predictor for PFS, along with younger age and methylated MGMT. The novel expression classifier may predict the prognosis of glioblastoma patients treated with bevacizumab

Additional file 2: Table S1. of A combination of TERT promoter mutation and MGMT methylation status predicts clinically relevant subgroups of newly diagnosed glioblastomas

Molecular and clinical characteristics of Cohort 1 (n = 758). Table S2. Molecular and clinical characteristics of GBM cohort (n = 453). Table S3. Univariate and multivariate Cox regression analyses for Group A (IDH mutated-TERT mutated) tumors in Cohort 1 (n = 155). Table S4. Univariate and multivariate Cox regression analyses for Group B (IDH mutated-TERT wild-type) tumors in Cohort 1 (n = 131). Table S5. Univariate and multivariate Cox regression analyses for Group C (IDH wild-type-TERT wild-type) tumors in Cohort 1 (n = 237). Table S6. Univariate and multivariate Cox regression analyses for Group D (IDH wild-type-TERT mutated) tumors in Cohort 1 (n = 235). Table S7. Univariate and multivariate Cox regression analyses for GBM in Cohort 1 (n = 260). Table S8. Univariate and multivariate Cox regression analyses for GBM in Cohort 2 (n = 193). Table S9. Background of combined GBM cohort stratified by TERT and MGMT status (n = 453). Table S10. Survival time and WHO grade in each molecular subgroup of Cohort 1 (n = 758). (XLSX 254 kb

Additional file 3: Figure S1. of A combination of TERT promoter mutation and MGMT methylation status predicts clinically relevant subgroups of newly diagnosed glioblastomas

Distributions of molecular alterations according to histology in Cohort 1. Figure S2. Kaplan-Meier analysis for Group A cases stratified by 1p/19q status. Figure S3. Kaplan-Meier analyses for GBM cases in Cohorts 1 and 2. (PPTX 172 kb