Jackson, Christina

Abstract Background DNA methylation profiling can be used to robustly predict postsurgical outcomes and response to radiotherapy (RT) for meningioma patients. To allow for seamless integration of these complementary models into clinical practice, a practical framework is needed. Methods We leveraged a cohort of nearly 2000 surgically-treated meningiomas with DNA methylation profiling and clinical outcomes data. Existing methylation-based prediction models were dichotomized to yield four risk groups: low and high recurrent risk, each with RT sensitive and resistant subgroups. Risk groups were correlated with progression-free survival in the context of existing biomarkers including extent of resection and WHO grade. Results We first demonstrated that all risk groups benefit from gross total resection. All “high-risk, RT sensitive” tumors (n = 306, 15.7%) also benefited from adjuvant RT: after GTR, median PFS increased from 4.68 (4.13-9.48) years to not reached (P = .003); after subtotal resection (STR), from 2.12 (1.59-3.02) to 4.09 (3.41-not reached) years (P = .004). “Low-risk, RT sensitive cases” (n = 1207, 61.8%) also benefited from RT after STR (median PFS 7.39 (6.66-12.8) vs. 16.53 (10.35-not reached) years, P = .03), suggesting that RT be considered in these patients. Neither “low-risk RT resistant” (n = 84, 4.3%) nor “high-risk RT resistant” (n = 356, 18.2%) cases benefited from RT, and the latter group was associated with universally poor outcomes. Conclusions We identify methylation-defined risk groups of meningioma for which additional benefit is gained from adjuvant RT, leading to a clinical decision-making framework for straightforward integration of molecular models into clinical practice.

Abstract Objective Pituitary apoplexy (PA) is a rare condition caused by hemorrhage or infarction of the pituitary gland with associated risk of cranial neuropathies, endocrinopathies, and even death. Human immunodeficiency virus (HIV) has been shown to have some association with pituitary apoplexy, however, large‐scale studies have not been performed. Methods A retrospective cohort study of subjects greater than 18 years of age was performed using the national TriNetX database. The general population was first compared with those undergoing treatment for PA to compare general demographics and incidence of HIV. The PA cohort was then substratified by HIV status and propensity matched by age and sex to evaluate differences in visual outcomes and endocrine metrics. Using the diagnosis of pituitary apoplexy as an index event, the rate of HIV diagnosis at the time of presentation or in the three months following treatment was calculated. Two‐tailed, unpaired t ‐tests were performed. Results A total 2066 patients were identified (902 HIV, 1158 controls). Those with HIV showed an increased rate of pituitary apoplexy (odds ratio [OR]: 19.8) versus healthy adults and were more likely to be younger and male. Among patients treated for pituitary apoplexy, patients with HIV were more likely to have increased thyroid stimulating hormone, reduced T 4 , and increased prolactin compared with healthy controls. There were no significant differences in visual outcomes between HIV positive and control patients. Importantly, 74% of patients did not carry a diagnosis of HIV on presentation but were diagnosed at the time of or in the three months following treatment for pituitary apoplexy. Conclusions Diagnosis and treatment of pituitary apoplexy shows a high rate of concurrent or subsequent diagnosis of HIV. Screening for HIV should be considered in patients undergoing treatment for pituitary apoplexy.