Glioblastoma management in the temozolomide era: have we improved outcome?

Temozolomide (TMZ) during and after radiotherapy (RT) is recommended for patients with newly diagnosed glioblastoma (GBM). We analyzed the adoption of this new standard of care for GBM in an academic cancer centre in Canada and assessed its impact on survival. GBM patients registered with Cancer Care Ontario between 2004 and 2008 were identified. Those ≥ 16 years age, newly diagnosed, treated at our institution, had confirmed pathology and complete records were included. Demographics, treatments, toxicity and outcome were captured. For survival analysis patients were stratified by age, ECOG, and treatment modalities including total cycles of TMZ. Descriptive statistics were used for early progressors and long term survivors. Kaplan-Meier curves, log-rank test and Cox proportional hazards model were used for survival analyses. At a median follow-up of 28 months, we compared our outcome to updated EORTC-NCIC CE 3 results. Of 517 patients 433 were included for analysis. Majority were male (63 %), ECOG 0-1 (66 %), and ≤ 65 years (55 %). 44 % received CRT followed by TMZ, 13 % had CRT only, 30 % had RT only and 13 % had best supportive care. 10 % were early progressors and 9 % survived beyond 2 years. Comparison of our results to NCIC CTG CE.3 study data showed median survival was 15.8 versus 14.6 months, 2 year survival rate for CRT plus TMZ was 35 versus 26 %, and for RT alone 0 versus 10 %, respectively. <50 % of GBM patients complete CRT with TMZ in the real-world setting. Prognosis for most patients with GBM remains dismal particularly if they are not suitable for RT and CRT.

Dexamethasone and enhancing solitary cerebral mass lesions: alterations in perfusion and blood-tumor barrier kinetics shown by magnetic resonance imaging.

OBJECTIVE: Glucocorticoid analogues are often administered to patients with intracranial space-occupying lesions. Clinical response can be dramatic, but the neurophysiological response is not well documented. This study sought to investigate the blood-lesion barrier, blood-brain barrier, and cerebral perfusion characteristics of patients who have undergone such therapy using magnetic resonance imaging. METHODS: Seventeen patients with intracranial mass-enhancing lesions underwent magnetic resonance imaging before and after 3 days of high-dose dexamethasone therapy. Assessments of blood-lesion barrier and blood-brain barrier integrity were based on a dynamic T1-weighted exogenous contrast technique that yielded the normalized maximal change in contrast uptake (T1-uptake). Perfusion was assessed using a dynamic T2*-weighted exogenous contrast technique to yield relative regional cerebral blood volume and first-moment mean transit time. Comparisons were made in T1-uptake, regional cerebral blood volume, and first-moment mean transit time of both enhancing lesion and contralateral normal-appearing white matter (CNAWM) obtained before and after dexamethasone. RESULTS: Significant reduction in T1-uptake was observed (19% decrease, P < 0.005) within enhancing pathological tissue, whereas no significant alteration was detected in CNAWM. Regional cerebral blood volume was significantly reduced in both enhancing tissue (28% decrease, P < 0.005) and in CNAWM (20% decrease, P < 0.001). Bolus first-moment mean transit time significantly increased (2.0 s prolongation, P < 0.05) in CNAWM, whereas there was no significant change (1.4 s prolongation, P > 0.05) within enhancing tissue. CONCLUSION: Glucocorticoid-analogue therapy not only affects the permeability of the blood-lesion barrier and lesion blood volume but also affects blood flow within normal-appearing contralateral parenchyma. There is a need for controls in steroid therapy in magnetic resonance imaging studies, which involve assessments of cerebrovascular function.