In elderly patients with glioblastoma, the addition of temozolomide to short-course radiotherapy resulted in longer survival than short-course radiotherapy alone. (Funded by the Canadian Cancer Society Research Institute and others; ClinicalTrials.gov number, NCT00482677 .).

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Background Outcome of low-grade glioma (LGG, WHO grade II) is highly variable reflecting molecular heterogeneity of the disease. We compared two different single modality treatment strategies: standard radiotherapy (RT) versus primary temozolomide (TMZ) chemotherapy with the aim of tailoring treatment and identifying predictive molecular factors. Methods 477 patients (2005 – 2012, median FU 48 months) with a low-grade glioma (astrocytoma, oligoastrocytoma, oligodendroglioma, WHO grade II) with at least one high-risk feature (age > 40 years, progressive disease, tumor > 5 cm or crossing the midline, neurological symptoms (e.g. focal or mental deficits, increased intracranial pressure or intractable seizures)) were, after stratification by chromosome 1p-status, randomized to either conformal RT (50.4 Gy/28 fractions) or dose-dense TMZ (75 mg/m2 daily × 21 days, q28 days, max. 12 cycles). Random treatment allocation was performed online using a minimization technique. A planned analysis was performed after 246 progression events. All analyses are intent to treat. Primary clinical endpoint was progression-free survival (PFS), correlative analyses included molecular markers (1p/19q co-deletion, MGMT methylation status, IDH1+2 mutations). The trial has been registered at the European Trials Registry (EudraCT 2004-002714-11) and at ClinicalTrials.gov (NCT00182819). Findings Four hundred seventy-seven patients were randomized. Severe hematological toxicity occurred in 14% of TMZ-treated patients, infections in 3% of TMZ-treated patients, and 1% of RT-treated patients. Moderate to severe fatigue was recorded in 3% of patients in the RT group and 7% in the TMZ group. At a median follow-up of 48 months (IQR:31–56), median PFS was 39 months (IQR:16–46) in the TMZ arm and 46 months (IQR:19–48) in the RT group (hazard ratio 1.16, 95% CI, 0.9–1.5; p=0.22). Median OS has not been reached. Exploratory analyses identified treatment-dependent variation in outcome of molecular LGG subgroups (n=318). Interpretation There was no significant difference in outcome of the overall patient population treated with either radiotherapy alone or TMZ chemotherapy alone. Further data maturation is needed for overall survival analyses and evaluation of the full predictive impact of the molecular subtypes for individualized treatment choices. Funding Merck & Co, Swiss-Bridge Award 2011, Swiss Cancer League.

PURPOSE To determine the efficacy and toxicity of chemoimmunotherapy followed by either whole-brain radiotherapy (WBRT) or intensive chemotherapy and autologous stem-cell transplantation (ASCT) as a first-line treatment of primary CNS lymphoma (PCNSL). PATIENTS AND METHODS Immunocompetent patients (18 to 60 years of age) with untreated PCNSL were randomly assigned to receive WBRT or ASCT as consolidation treatment after induction chemotherapy consisting of two cycles of R-MBVP (rituximab 375 mg/m2 day (D) 1, methotrexate 3 g/m2 D1; D15, VP16 100 mg/m2 D2, BCNU 100 mg/m2 D3, prednisone 60 mg/kg/d D1-D5) followed by two cycles of R-AraC (rituximab 375 mg/m2 D1, cytarabine 3 g/m2 D1 to D2). Intensive chemotherapy consisted of thiotepa (250 mg/m2/d D9; D8; D7), busulfan (8 mg/kg D6 through D4), and cyclophosphamide (60 mg/kg/d D3; D2). WBRT delivered 40 Gy (2 Gy/fraction). The primary end point was 2-year progression-free survival. Cognitive outcome was the main secondary end point. Analysis was intention to treat in a noncomparative phase II trial. RESULTS Between October 2008 and February 2014, 140 patients were recruited from 23 French centers. Both WBRT and ASCT met the predetermined threshold (among the first 38 patients in each group, at least 24 patients were alive and disease free at 2 years). The 2-year progression-free survival rates were 63% (95% CI, 49% to 81%) and 87% (95% CI, 77% to 98%) in the WBRT and ASCT arms, respectively. Toxicity deaths were recorded in one and five patients after WBRT and ASCT, respectively. Cognitive impairment was observed after WBRT, whereas cognitive functions were preserved or improved after ASCT. CONCLUSION WBRT and ASCT are effective consolidation treatments for patients with PCNSL who are 60 years of age and younger. The efficacy end points tended to favor the ASCT arm. The specific risk of each procedure should be considered.