After radiosurgery or surgery of a limited number of brain metastases, adjuvant WBRT reduces intracranial relapses and neurologic deaths but fails to improve the duration of functional independence and overall survival.

No abstract

This study shows that adjuvant WBRT after surgery or radiosurgery of a limited number of brain metastases from solid tumors may negatively impact some aspects of HRQOL, even if these effects are transitory. Consequently, observation with close monitoring with magnetic resonance imaging (as done in the EORTC trial) is not detrimental for HRQOL.

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.