Brown, Paul D.

Abstract Background Cognitive function is an important outcome in brain-tumor clinical trials. Cognitive examiners are often needed across multiple sites, many of whom have no prior testing experience. To ensure quality, we looked at examiner errors in administering a commonly used cognitive test battery, determined whether the errors were correctable upon central review, and considered whether the same errors would be detected using onsite electronic data entry. Methods We looked at 500 cognitive exams administered for brain-tumor trials led by the Alliance for Clinical Trials in Oncology (Alliance). Of 2277 tests examined, 32 noncorrectable errors were detected with routine central review (1.4% of tests administered), and thus removed from the database of the respective trial. The invalidation rate for each test was 0.8% for each part of the Hopkins Verbal Learning Test-Revised, 0.8% for Controlled Oral Word Association, 1.8% for Trail Making Test-A and 2.6% for Trail Making Test-B. It was estimated that, with onsite data entry and no central review, 4.9% of the tests entered would have uncorrected errors and 1.3% of entered tests would be frankly invalid but not removed. Conclusions Cognitive test results are useful and robust outcome measures for brain-tumor clinical trials. Error rates are extremely low, and almost all are correctable with central review of scoring, which is easy to accomplish. We caution that many errors could be missed if onsite electronic entry is utilized instead of central review, and it would be important to mitigate the risk of invalid scores being entered. ClinicalTrials.gov identifiers NCT01781468 (Alliance A221101), NCT01372774 (NCCTG N107C), NCT00731731 (NCCTG N0874), and NCT00887146 (NCCTG N0577).

The authors consider the importance of a careful, balanced review of therapeutic options with patients and the current understanding of the therapeutic ratio of whole‐brain radiotherapy in patient populations with widespread intracranial disease. The goal of reviewing these options is to provide an unbiased discussion of the potential benefits and risks of whole‐brain radiotherapy, particularly with regard to cognitive outcomes.

2067 Background: An estimated 2% of the general population has a meningioma (Vernooij et al. 2007), which accounts for about 36% of all primary intracranial tumors (Ostrom et al. 2015). The most established risk factors are older age and female gender. One small study identified gender but no other risk factors with meningioma (Krampla et al 2004). A larger study using the Iowa Women’s Health study data found lower levels of physical activity, greater body mass index (BMI), greater height and uterine fibroids were associated with meningioma (Johnson et al. 2011). We sought to replicate these findings and to identify additional risk factors related to meningioma in a large population-based sample. Methods: Study participants were enrolled in the Mayo Clinic Study of Aging (MCSA), a population-based sample of Olmsted County, Minnesota residents used to study prevalence, incidence, and risk-factors for Mild Cognitive Impairment and dementia and includes a variety of medical factors. Using a text search of radiologists’ notes of 2,402 MCSA individuals, mean age 77±8 years and scanned between 2004-2014.We identified 52 subjects who had at least one meningioma. We estimated the association of selected potential risk factors with presence of meningioma using odds ratios and 95% confidence intervals from logistic regression models adjusted for age and gender, which informed the multivariable models. Results: In the initial models, significant risk factors identified included BMI (as a continuous variable) (OR = 1.06 95%CI 1.01 to 1.12), taking NSAIDS (OR = 2.11, 95%CI 1.13 to 3.95), aspirin (OR = 1.90, 95%CI 1.04 to 3.46), and blood pressure lowering medication (OR = 2.06, 95%CI 1.07 to 3.99). Protective factors included male gender (OR = 0.51, 95%CI 0.29 to 0.90), coronary artery disease (CAD; OR = 0.46, 95%CI 0.22 to 0.97) and higher Beck Anxiety Inventory (BAI) total score (OR = 0.88, 95%CI 0.78 to 0.98). Simultaneous adjustment for these factors in a multivariable model did not attenuate these associations. Conclusions: Findings reveal gender and BMI as risk factors for meningioma. Additionally, certain medications such as NSAIDS and BP lowering medications warrant follow up as potential factors related to development of meningioma.

2057 Background: The optimal role of chemotherapy and radiation (RT) in adult low-grade glioma (LGG, WHO grade 1 & 2) is unclear. We conducted a systematic review and study-level meta-analysis of the literature on overall survival (OS) and progression free survival (PFS) in patients with LGG. Methods: Pubmed was queried with MeSH terms. All comparative studies of adults with newly diagnosed, supratentorial LGG were included. Comparisons of interest were OS and PFS at 2, 5, and 10 years in chemotherapy versus no chemotherapy and early RT versus delayed or no RT. Data were extracted from studies and synthesized with a random effects model. Quality of evidence was determined by American Academy of Neurology criteria and further analysis was performed, separating high quality (class I and II) from low quality (class III and IV) evidence. Numbers needed to treat (NNT) were determined from the risk difference. Results: 1531 articles were screened; 18 studies were included. Chemotherapy was not associated with a significant survival advantage compared to control. However, an analysis of high quality data revealed a survival advantage at 10 years associated with chemotherapy compared to control with NNT 5 (relative risk death chemo vs control 0.69 [0.56-0.86] p = 0.0006). Furthermore, NNT to prevent one progression with chemotherapy at 5 and 10 years was 6 and 3, respectively. Early RT was not associated with an OS advantage compared to control. However, early RT had progression benefit at all time points, with NNT of 10, 6, and 5 at 2, 5, and 10 years. Conclusions: Further study will be needed to confirm the optimal role of chemotherapy and RT. Caution must be used in interpretation as much of the literature consists of low-quality studies. [Table: see text]