Kaufmann, Timothy

Importance The prognosis for patients with glioblastoma is poor following standard therapy with surgical resection, radiation, temozolomide, and tumor-treating fields. Objectives To evaluate the combination of veliparib and temozolomide in glioblastoma based on preclinical data demonstrating significant chemosensitizing effects of the polyadenosine diphosphate-ribose polymerase 1/2 inhibitor veliparib when combined with temozolomide. Design, Setting, and Participants Patients with newly diagnosed glioblastoma with MGMT promoter hypermethylation who had completed concomitant radiation and temozolomide were enrolled between December 15, 2014, and December 15, 2018, in this Alliance for Clinical Trials in Oncology trial. The data for this analysis were locked on April 21, 2023. Interventions Patients were randomized and treated with standard adjuvant temozolomide (150-200 mg/m 2 orally, days 1-5) combined with either placebo or veliparib (40 mg orally, twice daily, days 1-7) for 6 cycles. Main Outcomes and Measures The primary end point for the phase 3 portion of the trial was overall survival (OS). Results There were 322 patients randomized during the phase 2 accrual period and an additional 125 patients randomized to complete the phase 3 accrual, for a total of 447 patients in the final phase 3 analysis. The median (range) age for patients was 60 (20-85) years and 190 patients (42.5%) were female. The median OS was 24.8 months (90% CI, 22.6-27.7) for the placebo arm and 28.1 months (90% CI, 24.3-33.3) for the veliparib arm ( P = .17). The difference in survival did not meet the prespecified efficacy end point. However, there was a separation of the survival curves that favored the veliparib arm over 24 to 48 months of follow-up. The experimental combination was well tolerated with an acceptable elevation in grade 3 or 4 hematologic toxic effects. Conclusions and Relevance This trial found that adding veliparib to adjuvant temozolomide did not significantly extend OS in patients with newly diagnosed, MGMT -hypermethylated glioblastoma. Trial Registration ClinicalTrials.gov Identifier: NCT02152982

Abstract Brain metastases occur commonly in patients with advanced solid malignancies. Yet, less is known about brain metastases than cancer-related entities of similar incidence. Advances in oncologic care have heightened the importance of intracranial management. Here, in this consensus review supported by the Society for Neuro-Oncology (SNO), we review the landscape of brain metastases with particular attention to management approaches and ongoing efforts with potential to shape future paradigms of care. Each coauthor carried an area of expertise within the field of brain metastases and initially composed, edited, or reviewed their specific subsection of interest. After each subsection was accordingly written, multiple drafts of the manuscript were circulated to the entire list of authors for group discussion and feedback. The hope is that the these consensus guidelines will accelerate progress in the understanding and management of patients with brain metastases, and highlight key areas in need of further exploration that will lead to dedicated trials and other research investigations designed to advance the field.

AbstractBackgroundWith increasing molecular analyses of meningiomas, there is a need to harmonize language used to capture clinical data across centers to ensure that molecular alterations are appropriately linked to clinical variables of interest. Here the International Consortium on Meningiomas presents a set of core and supplemental meningioma-specific common data elements (CDEs) to facilitate comparative and pooled analyses.MethodsThe generation of CDEs followed the 4-phase process similar to other National Institute of Neurological Disorders and Stroke (NINDS) CDE projects: discovery, internal validation, external validation, and distribution.ResultsThe CDEs were organized into patient- and tumor-level modules. In total, 17 core CDEs (10 patient level and 7 tumor level) as well as 14 supplemental CDEs (7 patient level and 7 tumor level) were defined and described. These CDEs are now made publicly available for dissemination and adoption.ConclusionsCDEs provide a framework for discussion in the neuro-oncology community that will facilitate data-sharing for collaborative research projects and aid in developing a common language for comparative and pooled analyses. The meningioma-specific CDEs presented here are intended to be dynamic parameters that evolve with time and The Consortium welcomes international feedback for further refinement and implementation of these CDEs.

Abstract BACKGROUND Degenerative spondylolisthesis is the displacement of one vertebral body over the adjacent one. While standing and flexion-extension X-rays are preferred for determining listhesis, magnetic resonance imaging (MRI) is often utilized to assess the compression of nerve root or spinal cord. OBJECTIVE To investigate the difference in radiographic measurements of spondylolisthesis between X-rays and MRI. METHODS We retrospectively reviewed the records and radiographic images of patients with a confirmed diagnosis of spondylolisthesis undergoing operation in 2016. Primary variable of interest was the degree of slippage as per the Meyerding method. Agreement between the 2 reviewers was assessed using the 2-way intraclass correlation coefficient (ICC) for slippage percentage and Cohen's Kappa for grade. Agreement of Meyerding grade between the 2 imaging techniques was assessed using Cohen's Kappa, while the slip percentage measured for each technique was compared using a Bland-Altman (BA) plot, mean difference (MD), and 1-way ICC. RESULTS A total of 255 cases were analyzed. ICC between the 2 reviewers was found to be 0.75 (95% confidence interval [CI] = 0.64-0.83, P < .001) for X-ray and 0.76 (95% CI = 0.66-0.83, P < .001) for MRI. Agreement between X-ray and MRI for grading of spondylolisthesis was found to be poor (kappa = 0.32, P < .001). BA plot between X-ray and MRI measurements revealed an MD of 4.4% (95% limits of agreement: –10.3% to 19.3%) with 5.16% observations outside the limits of agreement and 1-way ICC of 0.35 showing poor agreement. Conclusion Our results demonstrate the discrepancy of spondylolisthesis grade measurements between weight-bearing X-ray and nonweight-bearing MRI. Careful evaluation of both imaging technique is warranted to determine the final severity of pathology and tailoring of management plan.