Characteristics and outcomes of elderly patients with diffuse gliomas: a multi-institutional cohort study by Kansai Molecular Diagnosis Network for CNS Tumors

Abstract

IntroductionThis study investigates the current state of clinical practice and molecular analysis for elderly patients with diffuse gliomas and aims to elucidate treatment outcomes and prognostic factors of patients with glioblastomas.MethodsWe collected elderly cases (≥ 70 years) diagnosed with primary diffuse gliomas and enrolled in Kansai Molecular Diagnosis Network for CNS Tumors. Clinical and pathological characteristics were analyzed retrospectively. Various factors were evaluated in univariate and multivariate models to examine their effects on overall survival.ResultsIncluded in the study were 140 elderly patients (WHO grade II: 7, III: 19, IV: 114), median age was 75 years. Sixty-seven patients (47.9%) had preoperative Karnofsky Performance Status score of ≥ 80. All patients underwent resection (gross-total: 20.0%, subtotal: 14.3%, partial: 39.3%, biopsy: 26.4%). Ninety-six of the patients (68.6%) received adjuvant treatment consisting of radiotherapy (RT) with temozolomide (TMZ). Seventy-eight of the patients (75.0%) received radiation dose of ≥ 50 Gy. MGMT promoter was methylated in 68 tumors (48.6%), IDH1/2 was wild-type in 129 tumors (92.1%), and TERT promoter was mutated in 78 of 128 tumors (60.9%). Median progression-free and overall survival of grade IV cases was 8.2 and 13.6 months, respectively. Higher age (≥ 80 years) and TERT promoter mutated were associated with shorter survival. Resection and adjuvant RT + TMZ were identified as independent factors for good prognosis.ConclusionsThis community-based study reveals characteristics and outcomes of elderly glioma patients in a real-world setting. Elderly patients have several potential factors for poor prognosis, but resection followed by RT + TMZ could lengthen duration of survival.Electronic supplementary materialThe online version of this article (10.1007/s11060-018-2957-7) contains supplementary material, which is available to authorized users.

The interaction between TERT promoter mutation and MGMT promoter methylation on overall survival of glioma patients: a meta-analysis

“…Finally, a total of nine studies were included for meta-analyses comprising of 2819 glioma patients ( Fig. 1) [16,[25][26][27][28][29][30][31][32]. The baseline characteristics of these studies were presented in Table 1.…”

“…There have been robust efforts to decipher the molecular biomarkers of glioma and their prognostic significance as well as apply these findings to clinical practice, particularly in choosing appropriate candidates for initial chemotherapy [13,30,[33][34][35][36][37]. TERT promoter mutation and MGMT methylation status are among the most important markers.…”

TERT promoter mutation associated with multifocal phenotype and poor prognosis in patients with IDH wild-type glioblastoma

“…The isocitrate dehydrogenase1/2 ( IDH1/2 ), H3F3A , HIST1H3B , TP53 , BRAF , and TERT p genes were amplified via polymerase chain reaction (PCR), and sequencing was conducted as previously described. 18 , 19 In the MGMT promoter methylation analysis, we performed methylation-specific PCR or quantitative methylation-specific PCR following the bisulfite modification of tumor DNA. 19 To assess copy number alterations (CNAs), we performed Multiplex Ligation-dependent Probe Amplification (MLPA) using the SALSA MLPA KIT P105 (version D2), in accordance with the manufacturer’s protocol (MRC Holland).…”

“… 18 , 19 In the MGMT promoter methylation analysis, we performed methylation-specific PCR or quantitative methylation-specific PCR following the bisulfite modification of tumor DNA. 19 To assess copy number alterations (CNAs), we performed Multiplex Ligation-dependent Probe Amplification (MLPA) using the SALSA MLPA KIT P105 (version D2), in accordance with the manufacturer’s protocol (MRC Holland). 20 The P105 kit is designed to detect CNAs typically found in gliomas and includes probes against the PDGFRA , EGFR , CDKN2A , PTEN , TP53 , CDK4 , MDM2 , and NFKBIA genes.…”

The interaction between TERT promoter mutation and MGMT promoter methylation on overall survival of glioma patients: a meta-analysis

“…There have been robust efforts to decipher the molecular biomarkers of glioma and their prognostic signi cance as well as apply these ndings to clinical practice, particularly in choosing appropriate candidates for initial chemotherapy [30,[33][34][35][36][37][38]. TERT promoter mutation and MGMT methylation status are among the most important markers.…”