Which elderly newly diagnosed glioblastoma patients can benefit from radiotherapy and temozolomide? A PERNO prospective study

Abstract

The role of temozolomide concurrent with and adjuvant to radiotherapy (RT/TMZ) in elderly patients with glioblastoma (GBM) remains unclear. We evaluated the outcome of patients >70 years in the context of the Project of Emilia-Romagna Region in Neuro-Oncology (PERNO), the first Italian prospective observational population-based study in neuro-oncology. For this analysis the criteria for selecting patients enrolled in the PERNO study were: age >70 years; PS 0-3; histologically confirmed GBM; postoperative radiotherapy (RT) after surgery with or without concomitant temozolomide (TMZ) or postsurgical TMZ alone. Between January 2009 and December 2010, 76 GBM elderly patients were identified in the prospective PERNO study. Twenty-three patients did not receive any treatment after surgery, and 53 patients received postsurgical treatments (25 patients received RT alone and 28 patients RT/TMZ). Median survival was 11.1 months (95 % CI 8.8-13.5), adding temozolomide concomitant and adjuvant to radiotherapy it was 11.6 months (95 % CI 8.6-14.6), and 9.3 months (95 % CI 8.1-10.6) in patients treated with RT alone (P = 0.164). However, patients with MGMT methylated treated with RT/TMZ obtained a better survival (17.2 months, 95 % CI 11.5-22.9) (P = 0.042). No difference in terms of survival were observed if patients with MGMT unmethylated tumor received RT alone, or RT/TMZ or, in MGMT methylated tumor, if patients received radiotherapy alone. In elderly patients RT/TMZ represent a widely used approach but it is effective with methylated MGMT tumors only.

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.…”

“…While the positive prognosis role of MGMT methylation in patients treated with TMZ has been observed in many studies [9,36,[53][54][55][56], there were still con icting results regarding the prognostic value of this genetic marker in GBM patients [34,57]. It raises the question that there might be other factors affecting the responsiveness to TMZ besides MGMT methylation status.…”

Hypofractionated radiotherapy and concomitant temozolomide for high-grade glial tumors in elderly patients

“…The median age at prognosis is approximately 65 years (3), and age is a poor prognostic factor. The main therapy for HGG is surgical removal; however, because of comorbidities, elderly patients are often suboptimally treated (4). After surgery, RT becomes the mainstay treatment for GB.…”

Patterns of care and predictors of adjuvant therapies in elderly patients with glioblastoma: An analysis of the National Cancer Data Base

“…4,5 Elderly patients have frequently been excluded from clinical trials, 6 and those studies that do examine this population have demonstrated suboptimal survival outcomes. Chemotherapy (CT) alone, 8,9 radiotherapy (RT) alone, 10 and combined-modality therapy using CT and RT (CRT), 11,12 have all produced improved outcomes in select elderly patients. Chemotherapy (CT) alone, 8,9 radiotherapy (RT) alone, 10 and combined-modality therapy using CT and RT (CRT), 11,12 have all produced improved outcomes in select elderly patients.…”

“…4,5,7 Determining the ideal adjuvant treatment for elderly patients is further complicated by multiple treatment options. Chemotherapy (CT) alone, 8,9 radiotherapy (RT) alone, 10 and combined-modality therapy using CT and RT (CRT), 11,12 have all produced improved outcomes in select elderly patients. Age is just 1 of many factors clinicians may consider when choosing therapy for patients with GBM.…”