Bendok, Bernard R.

Abstract INTRODUCTION Leptomeningeal disease (LMD) is an aggressive, late-stage complication of systemic cancers that maintains a poor prognosis with an average survival of 3-6 months. Ommaya reservoirs (OR) are an accessible alternative to serial lumbar punctures for the delivery of intrathecal chemotherapy in the treatment of LMD. However, widespread use of OR has been limited by reports of complications, limited physicians trained in their use, and the stigma of brain surgery. Here, we assess survival and complication rates for patients who received intrathecal chemotherapy through OR for LMD treatment. METHODS After IRB approval, chart review of patients who received at least one administration of intrathecal chemotherapy through OR for LMD treatment between 2017- 2020 at Mayo Clinic in Phoenix, Arizona was conducted. Charts were reviewed for demographics, treatment type, complications, and outcomes. RESULTS A total of 10 patients were included. The median overall survival from date of first OR injection was 110.5 days (95% CI: 64 – not estimable). The median time to progression from the first injection was 55.5 days (95% CI: 45 – 753). A total of 82 OR injections were conducted for an average of approximately 8 injections per patient. Two patients (20%) experienced mild adverse events – grade 2 or lower by Common Terminology Criteria for Adverse Events with a single injection. The majority of injections involved no adverse events with the overall risk of any complication at 2.4%. None of the patients experienced infection, a commonly reported complication of OR use. CONCLUSIONS Our results support the inclusion of intrathecal chemotherapy via OR into the treatment paradigm in patients with leptomeningeal malignancies. This approach is feasible, safe, and median survival is comparable with data reported in published series. The overall complication rate in patients receiving intrathecal chemotherapy through OR is very low including the risk of infection.

Moyamoya angiopathy is a rare cerebral vasculopathy characterized by a progressive stenosis of the terminal portion of the internal carotid arteries and the development of abnormal collateral vessels. Children with moyamoya angiopathy become symptomatic because of cerebral ischemic complications, and many patients eventually need revascularization. In most pediatric patients with this disease, the etiology is likely genetic. We aim to report clinical characteristics of a single-center cohort of pediatric patients with moyamoya. We performed a retrospective chart review of patients <18 years with angiographically confirmed moyamoya disease evaluated at our institution. An in-house text search tool, Advanced Cohort Explorer, was used to filter electronic medical records for patients with a diagnosis of moyamoya angiopathy from January 1999 to December 2018. The inclusion criteria were age <18 years at the time of onset of disease and a diagnosis confirmed at Mayo clinic. Fifty-one patients met the inclusion criteria. Fifty-five percent of our cohort were male, and the median age was 9 years. Three patients had a family history of moyamoya disease. Approximately half of our patients had bilateral disease. Sixteen patients had a genetic or chromosomal diagnosis (Down syndrome and NF1 being most common). Congenital anomalies like heart defects and renal dysplasia were also noted. This study is unique in that it was a large study on pediatric patients with moyamoya angiopathy. It also highlights the importance of considering genetic syndromes as an underlying cause when moyamoya angiopathy starts early in life.

Abstract BACKGROUND For optimizing high-grade glioma resection, 5-aminolevulinic acid is a reliable tool. However, its efficacy in low-grade glioma resection remains unclear. OBJECTIVE To study the role of 5-aminolevulinic acid in low-grade glioma resection and assess positive fluorescence rates and the effect on the extent of resection. METHODS A systematic review of PubMed, Google Scholar, and Cochrane was performed from the date of inception to February 1, 2019. Studies that correlated 5-aminolevulinic acid fluorescence with low-grade glioma in the setting of operative resection were selected. Studies with biopsy only were excluded. Positive fluorescence rates were calculated. The quality index of the selected papers was provided. No patient information was used, so Institutional Review Board approval and patient consent were not required. RESULTS A total of 12 articles met the selection criteria with 244 histologically confirmed low-grade glioma patients who underwent microsurgical resection. All patients received 20 mg/kg body weight of 5-aminolevulinic acid. Only 60 patients (n = 60/244; 24.5%) demonstrated visual intraoperative 5-aminolevulinic acid fluorescence. The extent of resection was reported in 4 studies; however, the data combined low- and high-grade tumors. Only 2 studies reported on tumor location. Only 3 studies reported on clinical outcomes. The Zeiss OPMI Pentero microscope was most commonly used across all studies. The average quality index was 14.58 (range: 10-17), which correlated with an overall good quality. CONCLUSION There is an overall low correlation between 5-aminolevulinic acid fluorescence and low-grade glioma. Advances in visualization technology and using standardized fluorescence quantification methods may further improve the visualization and reliability of 5-aminolevulinic acid fluorescence in low-grade glioma resection.

Abstract Background : Sex is recognized as a significant determinant of outcome among glioblastoma patients, but the relative prognostic importance of glioblastoma features has not been thoroughly explored for sex differences. Methods : Combining multi-modal MR images, biomathematical models, and patient clinical information, this investigation assesses which pretreatment variables have a sex-specific impact on the survival of glioblastoma patients (299 males and 195 females). Results : Among males, tumor (T1Gd) radius was a predictor of overall survival (HR=1.027, p=0.044). Among females, higher tumor cell net invasion rate was a significant detriment to overall survival (HR=1.011, p<0.001). Female extreme survivors had significantly smaller tumors (T1Gd) (p=0.010 t-test), but tumor size was not correlated with female overall survival (p=0.955 CPH). Both male and female extreme survivors had significantly lower tumor cell net proliferation rates than other patients (M p=0.004, F p=0.001, t-test). Additionally, extent of resection, tumor laterality, and IDH1 mutation status were also found to have sex-specific effects on overall survival. Conclusion : Despite similar distributions of the MR imaging parameters between males and females, there was a sex-specific difference in how these parameters related to outcomes.

Abstract Background: Sex is recognized as a significant determinant of outcome among glioblastoma patients, but the relative prognostic importance of glioblastoma features has not been thoroughly explored for sex differences. Methods: Combining multi-modal MR images, biomathematical models, and patient clinical information, this investigation assesses which pretreatment variables have a sex-specific impact on the survival of glioblastoma patients (299 males and 195 females). Results: Among males, tumor (T1Gd) radius was a predictor of overall survival (HR=1.027, p=0.044). Among females, higher tumor cell net invasion rate was a significant detriment to overall survival (HR=1.011, p<0.001). Female extreme survivors had significantly smaller tumors (T1Gd) (p=0.010 t-test), but tumor size was not correlated with female overall survival (p=0.955 CPH). Both male and female extreme survivors had significantly lower tumor cell net proliferation rates than other patients (M p=0.004, F p=0.001, t-test). Additionally, extent of resection, tumor laterality, and IDH1 mutation status were also found to have sex-specific effects on overall survival. Conclusion: Despite similar distributions of the MR imaging parameters between males and females, there was a sex-specific difference in how these parameters related to outcomes.