Objective
To evaluate the patterns of care in elderly glioblastoma (GBM) patients from a large population‐based registry.
Methods
We identified a cohort of GBM patients 65 years or older from ...Surveillance, Epidemiology, and End Results cancer registry data linked with Medicare claims between 1994 and 2002. We assessed the impact of demographic characteristics and comorbidities on the probability of undergoing surgical resection, radiotherapy (RT), and chemotherapy within 3 months of diagnosis using multivariate logistic regression.
Results
A total of 4,137 patients with GBM were included, with a median overall survival of 4 months. Sixty‐one percent of patients underwent resection at diagnosis; 65% received RT and 10% received chemotherapy within 3 months of diagnosis. In a multivariate regression analysis, age was the most significant predictor of resection, RT, or chemotherapy. Black race (odds ratio OR, 0.64; p = 0.008) was associated with lower rates of surgical resection. Factors associated with decreased likelihood of receiving RT included unmarried marital status (OR, 0.64; p < 0.0001) and more comorbidities (OR, 0.55; p < 0.0001). Factors associated with decreased likelihood of receiving chemotherapy included unmarried marital status (OR, 0.59; p = 0.0002) and more comorbidities (OR, 0.56; p = 0.02).
Interpretation
Survival of elderly GBM patients was poor in this population‐based study. Age, marital status, and comorbidities influenced the probability of receiving RT or chemotherapy in this cohort. Ann Neurol 2008;64:628–634
Antiangiogenic therapies are known to cause high radiographic response rates due to reduction in vascular permeability resulting in a lower degree of contrast extravasation. In this study, we ...investigate the prognostic ability for model-derived parameters describing enhancing tumor volumetric dynamics to predict survival in recurrent glioblastoma treated with antiangiogenic therapy.
N = 276 patients in two phase II trials were used as training data, including bevacizumab ± irinotecan (NCT00345163) and cabozantinib (NCT00704288), and N = 74 patients in the bevacizumab arm of a phase III trial (NCT02511405) were used for validation. Enhancing volumes were estimated using T1 subtraction maps, and a biexponential model was used to estimate regrowth (g) and regression (d) rates, time to tumor regrowth (TTG), and the depth of response (DpR). Response characteristics were compared to diffusion MR phenotypes previously shown to predict survival.
Optimized thresholds occurred at g = 0.07 months-1 (phase II: HR = 0.2579, P = 5 × 10-20; phase III: HR = 0.2197, P = 5 × 10-5); d = 0.11 months-1 (HR = 0.3365, P < 0.0001; HR = 0.3675, P = 0.0113); TTG = 3.8 months (HR = 0.2702, P = 6 × 10-17; HR = 0.2061, P = 2 × 10-5); and DpR = 11.3% (HR = 0.6326, P = 0.0028; HR = 0.4785, P = 0.0206). Multivariable Cox regression controlling for age and baseline tumor volume confirmed these factors as significant predictors of survival. Patients with a favorable pretreatment diffusion MRI phenotype had a significantly longer TTG and slower regrowth.
Recurrent glioblastoma patients with a large, durable radiographic response to antiangiogenic agents have significantly longer survival. This information is useful for interpreting activity of antiangiogenic agents in recurrent glioblastoma.
The objective of this phase II single-arm study was to evaluate the efficacy and safety of pazopanib, a multi-targeted tyrosine kinase inhibitor, against vascular endothelial growth factor receptor ...(VEGFR)-1, -2, and -3, platelet-derived growth factor receptor- and - , and c-Kit, in recurrent glioblastoma. Patients with ≤2 relapses and no prior anti-VEGF/VEGFR therapy were treated with pazopanib 800 mg daily on 4-week cycles without planned interruptions. Brain magnetic resonance imaging and clinical reassessment were made every 8 weeks. The primary endpoint was efficacy as measured by 6-month progression-free survival (PFS6). Thirty-five GBM patients with a median age of 53 years and median Karnofsky performance scale of 90 were accrued. Grade 3/4 toxicities included leukopenia (n = 1), lymphopenia (n = 2), thrombocytopenia (n = 1), ALT elevation (n = 3), AST elevation (n = 1), CNS hemorrhage (n = 1), fatigue (n = 1), and thrombotic/embolic events (n = 3); 8 patients required dose reduction. Two patients had a partial radiographic response by standard bidimensional measurements, whereas 9 patients (6 at the 8-week point and 3 only within the first month of treatment) had decreased contrast enhancement, vasogenic edema, and mass effect but <50% reduction in tumor. The median PFS was 12 weeks (95% confidence interval CI: 8-14 weeks) and only 1 patient had a PFS time ≥6 months (PFS6 = 3%). Thirty patients (86%) had died and median survival was 35 weeks (95% CI: 24-47 weeks). Pazopanib was reasonably well tolerated with a spectrum of toxicities similar to other anti-VEGF/VEGFR agents. Single-agent pazopanib did not prolong PFS in this patient population but showed in situ biological activity as demonstrated by radiographic responses. ClinicalTrials.gov identifier: NCT00459381.
Glioblastoma (GBM) is the most common malignant primary brain tumor, and approximately 50% of cases occur in patients aged > or =65 years. However, to the authors' knowledge, there is no accepted ...standard treatment for elderly GBM patients, and specific prognostic factors in the elderly GBM population have not been systematically studied to date.
The Memorial Sloan-Kettering Cancer Center institutional database was used to identify patients with histologically confirmed GBM who were aged > or =65 years at the time of diagnosis.
Three hundred ninety-four GBM patients with a median age of 71.9 years (59% of whom were men) were included. Approximately 18% of patients underwent biopsy, whereas 82% underwent tumor resection; 81% received radiotherapy (RT), and 43% received adjuvant chemotherapy. The median overall survival was 8.6 months; at the time of last follow-up, 90% of patients had died, and the median follow-up of the 39 surviving patients was 12 months. In a multivariate analysis, younger age, better Karnofsky performance status (KPS), single tumor, and surgical resection were found to be independent predictors of survival. Comparing 103 patients who received adjuvant chemotherapy with 48 who were only followed after RT, there was a 55% decrease in the risk of death (hazards ratio, 0.45; 95% confidence interval, 0.30-0.66 P < .0001) after adjusting for age, KPS, extent of surgical resection, and number of lesions.
Similar to studies in younger GBM patients, advancing age, KPS, and extent of tumor resection were found to be independent prognostic factors in the current study. Although survival is inferior in older GBM patients, age alone should not disqualify patients from aggressive therapy with surgical resection, RT, and chemotherapy.
Patients with (a) recurrent malignant glioma (MG): glioblastoma (GBM) or recurrent anaplastic glioma (AG), and (b) nonprogressive (NP) GBM following radiation therapy (RT) were eligible. Primary ...objective for recurrent MG was progression-free survival at 6 months (PFS-6) and overall survival at 12 months for NP GBM post-RT. Secondary objectives for recurrent MGs were response, survival, assessment of toxicity, and pharmacokinetics (PKs). Treatment with enzyme-inducing antiepileptic drugs was not allowed. Patients received 150 mg/day erlotinib. Patients requiring surgery were treated 7 days prior to tumor removal for PK analysis and effects of erlotinib on epidermal growth factor receptor (EGFR) and intracellular signaling pathways. Ninety-six patients were evaluable (53 recurrent MG and 43 NP GBM); 5 patients were not evaluable for response. PFS-6 in recurrent GBM was 3% with a median PFS of 2 months; PFS-6 in recurrent AG was 27% with a median PFS of 2 months. Twelve-month survival was 57% in NP GBMs post-RT. Primary toxicity was dermatologic. The tissue-to-plasma ratio normalized to nanograms per gram dry weight for erlotinib and OSI-420 ranged from 25% to 44% and 30% to 59%, respectively, for pretreated surgical patients. No effect on EGFR or intratumoral signaling was seen. Patients with NP GBM post-RT who developed rash in cycle 1 had improved survival (P < .001). Single-agent activity of erlotinib is minimal for recurrent MGs and marginally beneficial following RT for NP GBM patients. Development of rash in cycle 1 correlates with survival in patients with NP GBM after RT.
We initiated a prospective multicenter phase II trial using rituximab and temozolomide in immunocompetent patients with progressive or recurrent primary central nervous system lymphoma (PCNSL) based ...on activity observed in retrospective studies. Treatment consisted of an induction phase with rituximab (750 mg/m2) on days 1, 8, 15 and 22 and temozolomide (150 mg/m2) days 1-7 and 15-21, followed by six cycles of consolidation temozolomide (150-200 mg/m2 × 5/28 days), followed by maintenance with methylprednisolone (1 g IV every 28 days) until progression. Sixteen patients were enrolled, and a complete response was seen in 2/14 (14%) evaluable patients. The median progression-free survival was 7 weeks and median overall survival was not reached (median follow-up: 37 months). Treatment was well tolerated, but due to slow accrual and preliminary analysis suggesting futility, the trial was closed early. Given the overall modest activity, this regimen should be reserved for patients who are not candidates for other, more aggressive salvage treatments.
Brain metastases are the most common intracranial tumor in adults. The incidence of metastases is thought to be rising due to better detection and treatment of systemic malignancy. More widespread ...use and improved quality of MRI may lead to early detection of brain metastases. Available evidence suggests that survival is longer and quality of life improved if brain metastases are treated aggressively. This article reviews current therapeutic management used for brain metastases. To select the appropriate therapy, the physician must consider the extent of the systemic disease, primary histology, and patient age and performance status, as well as the number, size, and location of the brain metastases. Available treatment options include whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), surgery, and chemotherapy. Multidisciplinary approaches such as the combination of WBRT with SRS or surgery have shown superior results in terms of survival time, neurocognitive function, and quality of life. The utility and optimal use of chemotherapy and radiosensitizing agents is less clear. It is hoped that further advances and multidisciplinary approaches currently under study will result in improved patient outcomes.
The authors report eight patients with primary dural lymphoma (PDL). All patients had extra-axial masses on MRI that diffusely enhanced after gadolinium. Pathology revealed low-grade non-Hodgkin ...lymphoma (marginal zone lymphoma of MALT mucosa-associated lymphoid tissue type) in all patients. All patients underwent radiation therapy, and three received chemotherapy. Complete response was achieved in 100% of patients, but three developed systemic relapse.
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