NF2 mutation associated with accelerated time to recurrence for older patients with atypical meningiomas.

PURPOSE: Meningiomas occur more frequently in older adults, with the incidence rates increasing from 5.8/100,000 for adults 35-44 years old to 55.2/100,000 for those 85+. Due to the increased risk of surgical management in older adults, there is a need to characterize the risk factors for aggressive disease course to inform management decisions in this population. We therefore sought to determine age-stratified relationships between tumour genomics and recurrence after resection of atypical meningiomas. METHODS: We identified 137 primary and recurrent Grade 2 meningiomas from our existing meningioma genomic sequencing database. We examined the differential distribution of genomic alterations in those older than 65 compared to younger. We then performed an age stratified survival analysis to model recurrence for a mutation identified as differentially present. RESULTS: In our cohort of 137 patients with grade 2 meningiomas, alterations in NF2 were present at a higher rate in older adults compared to younger (37.8% in < 65 vs. 55.3% in > 65; recurrence adjusted p-value =0.04). There was no association between the presence of NF2 and recurrence in the whole cohort. In the age-stratified model for those less than 65 years old, there was again no relationship. For patients in the older age stratum, there is a relationship between NF2 and worsened recurrence outcomes (HR = 3.64 (1.125 - 11.811); p = 0.031). CONCLUSIONS: We found that mutations in NF2 were more common in older adults. Further, the presence of mutant NF2 was associated with an increased risk of recurrence in older adults.

Association of mutations in DNA polymerase epsilon with increased CD8+ cell infiltration and prolonged progression-free survival in patients with meningiomas.

OBJECTIVE: Prior studies have demonstrated a relationship between underlying tumor genetics and lymphocyte infiltration in meningiomas. In this study, the authors aimed to further characterize the relationship between meningioma genomics, CD4+ and CD8+ T-cell infiltration, and oncological outcomes of meningiomas. Understanding specific characteristics of the inflammatory infiltration could have implications for treatment and prognostication. METHODS: Immunohistochemically stained meningioma slides were reviewed to assess the CD4+ and CD8+ cell infiltration burden. The relationship between immune cell infiltration and tumor genomics was then assessed using an adjusted ANOVA model. For a specific gene identified by the ANOVA, the relationship between that mutation and tumor recurrence was assessed using Cox regression. RESULTS: In immunohistochemically stained samples from a subcohort of 25 patients, the mean number of CD4+ cells was 42.2/400× field and the mean number of CD8+ cells was 69.8/400× field. Elevated CD8+ cell infiltration was found to be associated with the presence of a mutation in the gene encoding for DNA polymerase epsilon, POLE (51.6 cells/hpf in wild-type tumors vs 95.9 cells/hpf in mutant tumors; p = 0.0199). In a retrospective cohort of 173 patients, the presence of any mutation in POLE was found to be associated with a 46% reduction in hazard of progression (HR 0.54, 95% CI 0.311-0.952; p = 0.033). The most frequent mutation was a near-C-terminal nonsense mutation. CONCLUSIONS: A potential association was found between mutant POLE and both an increase in CD8+ cell infiltration and progression-free survival. The predominant mutation was found outside of the known exonuclease hot spot; however, it was still associated with a slight increase in mutational burden, CD8+ cell infiltration, and progression-free survival. Alterations in gene expression, resulting from alterations in POLE, may yield an increased presentation of neoantigens, and, thus, greater CD8+ cell-mediated apoptosis of neoplastic cells. These findings have suggested the utility of checkpoint inhibitors in the treatment of POLE-mutant meningiomas.

Evaluating Adult Idiopathic Scoliosis as an Independent Risk Factor for Critical Illness in SARS-CoV-2 Infection.

BACKGROUND: Thoracic spinal deformities may reduce chest wall compliance, leading to respiratory complications. The first SARS-CoV-2 (L-variant) strain caused critical respiratory illness, especially in vulnerable patients. This study investigates the association between scoliosis and SARS-CoV-2 (COVID-19) disease course severity. METHODS: Clinical data of 129 patients treated between March 2020 to June 2021 who received a positive COVID-19 polymerase chain reaction result from Mount Sinai and had a scoliosis ICD-10 code (M41.0-M41.9) was retrospectively analyzed. Degree of coronal plane scoliosis on imaging was confirmed by 2 independent measurers and grouped into no scoliosis (Cobb angle <10°), mild (10°-24°), moderate (25°-39°), and severe (>40°) cohorts. Baseline characteristics were compared, and a multivariable logistic regression controlling for clinically significant comorbidities examined the significance of scoliosis as an independent risk factor for hospitalization, intensive care unit (ICU) admission, acute respiratory distress syndrome (ARDS), mechanical ventilation, and mortality. RESULTS: The no (n = 42), mild (n = 14), moderate (n = 44), and severe scoliosis (n = 29) cohorts differed significantly only in age (P = 0.026). The percentage of patients hospitalized (P = 0.59), admitted to the ICU (P = 0.33), developing ARDS (P = 0.77), requiring mechanical ventilation (P = 1.0), or who expired (P = 0.77) did not significantly differ between cohorts. The scoliosis cohorts did not have a significantly higher likelihood of hospital admission (mild P = 0.19, moderate P = 0.67, severe P = 0.98), ICU admission (P = 0.97, P = 0.94, P = 0.22), ARDS (P = 0.87, P = 0.74, P = 0.94), mechanical ventilation (P = 0.73, P = 0.69, P = 0.70), or mortality (P = 0.74, P = 0.87, P = 0.66) than the no scoliosis cohort. CONCLUSIONS: Scoliosis was not an independent risk factor for critical COVID-19 illness. No trends indicated any consistent effect of degree of scoliosis on increased adverse outcome likelihood.

Utilization of Palliative Care Services Among Patients With Malignant Brain Tumors: An Analysis of the National Inpatient Sample (2016-2019).

BACKGROUND: Recent advances in treatment of malignant brain tumors have improved outcomes. However, patients continue to experience significant disability. Palliative care helps patients with advanced illnesses improve their quality of life. There is a paucity of clinical studies examining palliative care usage among patients with malignant brain tumors. OBJECTIVE: To assess if there were any patterns in palliative care utilization among patients hospitalized with malignant brain tumors. METHODS: A retrospective cohort representing hospitalizations for malignant brain tumors was created from The National Inpatient Sample (2016-2019). Palliative care utilization was identified by ICD-10 code. Univariable and multivariable logistic regression models, accounting for the sample design, were built to evaluate the demographic variables associated with palliative care consultation in all patients and fatal hospitalizations. RESULTS: 375 010 patients admitted with a malignant brain tumor were included in this study. Over the whole cohort, 15.0% of patients used palliative care. In fatal hospitalizations, Black and Hispanic patients had 28% lower odds of receiving a palliative care consultation compared with White patients (odds ratio for both = 0.72; P = .02). For fatal hospitalizations, patients insured privately were 34% more likely to use palliative care services compared with patients insured with Medicare (odds ratio = 1.34, P = .006). CONCLUSION: Palliative care is underutilized among all patients with malignant brain tumors. Within this population, disparities in utilization are exacerbated by sociodemographic factors. Prospective studies investigating utilization disparities across race and insurance status are necessary to improve access to palliative care services for this population.

ARID1A mutation associated with recurrence and shorter progression-free survival in atypical meningiomas.

PURPOSE: The oncologic outcomes for atypical meningiomas can be poor. Generally, patients that have had a prior recurrence have a substantially elevated risk of a future recurrence. Additionally, certain tumor genomic profiles have been shown as markers of poor prognosis. We sought to characterize the genomic differences between primary and recurrent tumors as well as assess if those differences had implications on recurrence. METHODS: We identified primary and recurrent gross totally resected WHO grade II meningiomas with > 30 days of post-surgical follow-up at our institution. For genes with a prevalence of > 5% in the cohort, we compared the mutational prevalence in primary and recurrent tumors. For a gene of interest, we assessed the time to radiographic recurrence using adjusted cox-regression. RESULTS: We identified 88 meningiomas (77 primary, 16 recurrent) with a median follow-up of 5.33 years. Mutations in ARID1A found in association with recurrent tumors (7/16 recurrent tumors vs 5/72 primary tumors, p < 0.001). In the whole cohort, mutations in ARID1A were not associated with alterations in time to recurrence after adjusting for recurrence status (p = 0.713). When restricted to primary tumors, ARID1A is associated with a 625% increase in the hazard of recurrence (HR = 7.26 [1.42-37.0]; p = 0.017). CONCLUSION: We demonstrate mutations in ARID1A, a chromatin remodeling gene, in a higher prevalence in recurrent tumors. We further demonstrate that when mutations in ARID1A are present in primary atypical meningiomas, these tumors tend to have worse prognosis. Further prospective study may validate ARID1A as a prognostic marker.

Association between tumor mutations and meningioma recurrence in Grade I/II disease.

BACKGROUND: Meningiomas are common intracranial tumors with variable prognoses not entirely captured by commonly used classification schemes. We sought to determine the relationship between meningioma mutations and oncologic outcomes using a targeted next-generation sequencing panel. MATERIALS AND METHODS: We identified 184 grade I and II meningiomas with both >90 days of post-surgical follow-up and linked targeted next-generation sequencing. For mutated genes in greater than 5% of the sample, we computed progression-free survival Cox-regression models stratified by gene. We then built a multi-gene model by including all gene predictors with a p-value of less than 0.20. Starting with that model, we performed backward selection to identify the most predictive factors. RESULTS: ATM (HR = 4.448; 95% CI: 1.517-13.046), CREBBP (HR = 2.727; 95% CI = 1.163-6.396), and POLE (HR = 0.544; HR = 0.311-0.952) were significantly associated with alterations in disease progression after adjusting for clinical and pathologic factors. In the multi-gene model, only POLE remained a significant predictor of recurrence after adjusting for the same clinical covariates. Backwards selection identified recurrence status, resection extent, and mutations in ATM (HR = 7.333; 95% CI = 2.318-23.195) and POLE (HR = 0.413; 95% CI = 0.229-0.743) as predictive of recurrence. CONCLUSIONS: Mutations in ATM and CREBBP were associated with accelerated meningioma recurrence, and mutations in POLE were protective of recurrence. Each mutation has potential implications for treatment. The effect of these mutations on oncologic outcomes and as potential targets for intervention warrants future study.