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Background Bevacizumab (BEV) received accelerated FDA approval in 2009 for the treatment of recurrent glioblastoma (rGBM). Unfortunately, prospective randomized controlled phase 3 studies (AVAglio and Radiation Therapy Oncology Group 0825 in newly diagnosed, European Organisation for Research and Treatment of Cancer 26101 in rGBM) failed to show an overall survival benefit with BEV added to standard therapy. In light of these data, we aimed to capture current utilization patterns and perceived value of BEV in the treatment of GBM among experts in the field. Methods An online questionnaire comprising 14 multiple choice questions was sent out in spring 2017 to 207 oncologists/neuro-oncologists treating patients with GBM at all National Cancer Institute–designated cancer centers in the United States. Results Sixty-two of 207 (30%) invitees responded (by training, 70% neuro-oncologists, 20% medical oncologists, 10% pediatric oncologists/neuro-oncologists). Participants reported use of BEV most frequently in rGBM for control of edema (85% of respondents) and/or when no other treatment options were available (68%). BEV is rarely used in newly diagnosed GBM (<5% of cases by 78% respondents and in 5% to 10% cases by 15% respondents). Sixty-six percent of participants indicated that they thought BEV improved symptoms, 30% that it improved symptoms and survival, 3% that it had no benefit in GBM patients. Conclusion In this cross-sectional online survey we found that among neuro-oncology experts in the United States in 2017, BEV is predominantly utilized in select patients with rGBM, and is only rarely used in a small subgroup of patients with newly diagnosed GBM for control of edema. The low response rate may have introduced a nonresponse bias. [ABSTRACT FROM AUTHOR]

Background Pneumocystis jirovecii pneumonia (PJP) is a known complication in patients with high-grade gliomas (HGGs) who are treated with radiation and chemotherapy. PJP prophylaxis is commonly recommended, but there are currently no clear guidelines regarding duration of treatment and choice of drugs. This study aimed to assess current practice patterns of PJP prophylaxis among neuro-oncologists. Methods An online survey of 14 multiple choice questions was sent to 207 neuro-oncologists and medical oncologists treating brain cancers at all National Cancer Institute-designated cancer centers in the United States. Recipients were identified via a search of the cancer centers' websites. Results Sixty-one invited experts completed the survey (response rate 29%; of these, 72% were neuro-oncologists, 18% were medical oncologists, and 10% were pediatric neuro- or medical oncologists). Seventy percent of respondents stated that they routinely prescribe PJP prophylaxis, while 7% do not provide prophylaxis. Eighty-one percent of respondents use absolute lymphocyte count (ALC) to assess lymphopenia and 13% also monitor CD4 lymphocyte counts during prophylaxis. The most commonly used first-line agent is trimethoprim-sulfamethoxazole (88% of respondents), followed by pentamidine (6%). Discontinuation of PJP prophylaxis is determined by the following: count recovery (33% by ALC; 18% by CD4 lymphocyte counts), radiation completion (23%), and chemotherapy completion (7%). Glucose-6-phosphate dehydrogenase levels were routinely checked by only 13% of respondents. Conclusions PJP prophylaxis is commonly used in HGG patients, but there are large variations in practice patterns, including the duration of prophylaxis. As consideration for PJP prophylaxis affects all patients with HGG, standardization of prophylaxis should be formally addressed. [ABSTRACT FROM AUTHOR]

Purpose: Cancer patients at Johns Hopkins undergo insurance clearance to verify coverage for enrollment to interventional clinical trials. We sought to explore the impact of insurance clearance on disparities in access to cancer clinical trials at this urban comprehensive cancer center., Experimental Design: We evaluated the frequency of insurance-based denial of access to cancer clinical trials over a 5-year period after initiation of a formal insurance clearance process. We used a case-control design to compare demographic and clinical parameters of patients denied or approved for clinical trials participation by their insurance company in a 3-year interval., Results: From July 2003 to July 2008, insurance requests for clinical trial participation were submitted on 4,617 consented cancer patients at Johns Hopkins. A total of 628 patients (13.6%) with health insurance were denied therapeutic trial enrollment owing to lack of insurance coverage for participation. A total of 254 patients denied enrollment from 2005 to 2007 were selected for further analysis. Two-hundred sixty randomly selected patients approved for clinical trial participation served as controls. Patients approved were on average older (59.2 versus 54.9 years) than patients denied (P = 0.0001). Residents of Pennsylvania, which lacks a state law mandating cancer clinical trial coverage for residents, were overrepresented among the denied patients (P = 0.0009). No statistically significant variance in the likelihood of insurance denial was found on the basis of sex, race, stage of disease, or presence of comorbidities., Conclusions: Denial of access to therapeutic clinical trials, even among insured patients, is a significant barrier to clinical cancer research. This barrier spans racial, ethnic, and gender categories., (©2010 AACR.)

Purpose: Novel agents are currently combined with radiation and temozolomide (RT + TMZ) in newly diagnosed glioblastoma using overall survival as the primary end point. Results of these phase II studies are typically compared with the phase III European Organization for Research and Treatment of Cancer (EORTC) survival data that resulted in RT + TMZ becoming standard therapy., Experimental Design: The New Approaches to Brain Tumor Therapy (NABTT) Consortium assigned 365 patients with glioblastoma to four single-cohort studies with similar eligibility criteria. Patients received RT + TMZ with talampanel (n = 72), poly-ICLC (n = 97), or cilengitide (n = 112) or RT + TMZ alone with monitoring of CD4 counts (n = 84). Overall survival of those ages 18 to 70 years with glioblastoma was compared with published EORTC data., Results: NABTT and EORTC patients had comparable performance status and debulking surgery. Median, 12-month, and 24-month survival rates for the EORTC patients (n = 287) and the comparable NABTT patients receiving RT + TMZ and novel agents (n = 244) are 14.6 versus 19.6 months, 61% versus 81%, and 27% versus 37%, respectively. This represents a 37% reduction in odds of death (P < 0.0001) through 2 years of follow-up. NABTT and EORTC patients receiving only RT + TMZ had similar survival., Conclusions: Newly diagnosed glioblastoma treated recently with RT + TMZ and talampanel, poly-ICLC, or cilengitide had significantly longer survival than similar patients treated with only RT + TMZ accrued internationally from 2000 to 2002. These differences could result from the novel agents or changing patterns of care. Until the reasons for these different survival rates are clarified, comparisons of outcomes from phase II studies with published RT + TMZ survival data should be interpreted with caution.

Purpose: Recent data suggest that the glutamatergic system is important in the proliferation and migration of glioblastoma. Talampanel is a well-tolerated, oral alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor blocker that could be beneficial in this disease., Patients and Methods: This trial was designed to estimate overall survival in adults with newly diagnosed glioblastoma treated with talampanel in addition to standard radiation (RT) and temozolomide (TMZ). A secondary purpose was to evaluate talampanel toxicity in this setting. Talampanel was initiated with RT + TMZ and discontinued for toxicity or disease progression. Survival was compared with historical controls., Results: Seventy-two patients were enrolled from December 2005 to July 2006. Their median age was 60 years (range, 37 to 85 years, with 17% > 70 years), median Karnofsky performance score was 90 (range, 70 to 100), and 77% had a debulking procedure. With a median follow-up time of 18 months, 55 patients (76%) have died, yielding a median survival time of 18.3 months (95% CI, 14.6 to 22.5 months). When the 60 patients who were 18 to 70 years old were compared with the European Organisation for Research and Treatment of Cancer (EORTC) RT + TMZ data, the median survival (20.3 v 14.6 months, respectively) and percentage of patients surviving at 24 months (41.7% v 26.5%, respectively; P = .02) seemed superior. The percentage of patients methylated at O(6)-methylguanine-DNA methyltransferase was lower than on the EORTC study (29% v 43%, respectively). Talampanel was well tolerated and did not increase the known hematologic or nonhematologic toxicities of TMZ., Conclusion: Talampanel can be added to RT + TMZ without significant additional toxicity. The encouraging survival results in methylated and unmethylated patients suggest that blocking AMPA receptors may be a useful strategy in newly diagnosed glioblastoma.

Purpose: Hyperglycemia has been associated with poor outcomes in many disease states. This retrospective study assessed the association between hyperglycemia and survival in patients with newly diagnosed glioblastoma multiforme (GBM). PATIENTS AND METHODS; Between 1999 and 2004, before the standard use of temozolomide, 191 patients were accrued onto New Approaches to Brain Tumor Therapy CNS Consortium trials with similar eligibility criteria. Time-weighted mean glucose and mean glucocorticoid dose were calculated for each patient using all values collected regularly in follow-up. The primary outcome was survival., Results: Mean glucose levels ranged between 65 and 459 mg/dL. These were divided into quartiles: quartile one (< 94 mg/dL), quartile two (94 to 109 mg/dL), quartile three (110 to 137 mg/dL), and quartile four (> 137 mg/dL). Median survival times for patients in quartiles one, two, three, and four were 14.5, 11.6, 11.6, and 9.1 months, respectively. The association between higher mean glucose and shorter survival persisted after adjustment for mean daily glucocorticoid dose, age, and baseline Karnofsky performance score (KPS). Compared with patients in the lowest mean glucose quartile, those in quartile two (adjusted hazard ratio [HR], 1.29; 95% CI, 0.85 to 1.96), quartile three (adjusted HR, 1.35; 95% CI, 0.89 to 2.06), and quartile four (adjusted HR, 1.57; 95% CI, 1.02 to 2.40) were at progressively higher risk of dying (P = .041 for trend)., Conclusion: In these patients with newly diagnosed GBM and good baseline KPS, hyperglycemia was associated with shorter survival, after controlling for glucocorticoid dose and other confounders. The effect of intensive management of glucocorticoid-related hyperglycemia on survival deserves additional study in patients with GBM.