The Impact of T2/FLAIR Evaluation per RANO Criteria on Response Assessment of Recurrent Glioblastoma Patients Treated with Bevacizumab.

PURPOSE: The RANO criteria have not been assessed using outcome data from prospective trials. We examined the radiologic data of patients with recurrent glioblastoma from the randomized phase II trial (AVF3708g) to determine the effect of including T2/FLAIR evaluation as per RANO criteria on measurements of objective response rates (ORRs) and progression-free survival (PFS) compared with assessment based on contrast enhancement (Macdonald criteria). EXPERIMENTAL DESIGN: The ORRs and median PFS were determined using the RANO criteria and compared with those obtained using the Macdonald criteria. Landmark analyses were performed at 2, 4, and 6 months, and Cox proportional hazard models were used to determine the associations between OR and progression with subsequent survival. RESULTS: The ORRs were 0.331 [95% confidence interval (CI), 0.260-0.409] and 0.393 (95% CI, 0.317-0.472) by RANO and Macdonald criteria, respectively (P < 0.0001). The median PFS was 4.6 months (95% CI, 4.1-5.5) using RANO criteria, compared with 6.4 months (95% CI, 5.5-7.1) as determined by Macdonald criteria (P = 0.01). At 2-, 4-, and 6-month landmarks, both OR status and PFS determined by either RANO or Macdonald criteria were predictive of overall survival [OS; hazard ratios for 4-month landmark (OR HR = 1.93, P = 0.0012; PFS HR, 4.23, P < 0.0001)]. CONCLUSIONS: The inclusion of T2/FLAIR assessment resulted in statistically significant differences in median PFS and ORRs compared with assessment of solely enhancing tumor (Macdonald criteria), although OR and PFS determined by both RANO and Macdonald criteria correlated with OS.

Exploring primary brain tumor patient and caregiver needs and preferences in brief educational and support opportunities.

PURPOSE: A primary brain tumor patient and caregiver survey was completed to investigate interest in brief support opportunities, focused on education, memory training, and healthy coping, during a routine clinical visit and at 3-month follow-up. METHODS: Patients with primary brain tumors receiving care in the Radiation Oncology Department at Mayo Clinic Rochester and their caregivers were recruited to complete the survey between June 2008 and September 2009. RESULTS: Both patients and their caregivers expressed greatest interest in education about brain tumors and cognitive effects of treatment. Interest in support opportunities targeting education, memory training, or healthy coping was low to modest. Bimodal distributions were found for almost all the support opportunities, revealing subgroups of patients and caregivers with high interest in such sessions. Overall, ratings of interest did not differ over time. CONCLUSIONS: Patients with primary brain tumors and their caregivers expressed most interest in education about their disease and potential cognitive effects of treatment. It appears that subgroups of patients and caregivers have very high interest in brief support opportunities. Identifying these subgroups of patients and families will allow targeted interventions focused on their needs and make the best use of limited resources.

Quality assessment metrics for whole genome gene expression profiling of paraffin embedded samples.

BACKGROUND: Formalin fixed, paraffin embedded tissues are most commonly used for routine pathology analysis and for long term tissue preservation in the clinical setting. Many institutions have large archives of Formalin fixed, paraffin embedded tissues that provide a unique opportunity for understanding genomic signatures of disease. However, genome-wide expression profiling of Formalin fixed, paraffin embedded samples have been challenging due to RNA degradation. Because of the significant heterogeneity in tissue quality, normalization and analysis of these data presents particular challenges. The distribution of intensity values from archival tissues are inherently noisy and skewed due to differential sample degradation raising two primary concerns; whether a highly skewed array will unduly influence initial normalization of the data and whether outlier arrays can be reliably identified. FINDINGS: Two simple extensions of common regression diagnostic measures are introduced that measure the stress an array undergoes during normalization and how much a given array deviates from the remaining arrays post-normalization. These metrics are applied to a study involving 1618 formalin-fixed, paraffin-embedded HER2-positive breast cancer samples from the N9831 adjuvant trial processed with Illumina's cDNA-mediated Annealing Selection extension and Ligation assay. CONCLUSION: Proper assessment of array quality within a research study is crucial for controlling unwanted variability in the data. The metrics proposed in this paper have direct biological interpretations and can be used to identify arrays that should either be removed from analysis all together or down-weighted to reduce their influence in downstream analyses.