Casabella, Amanda M.

OBJECTIVE The goal of microsurgical resection of vestibular schwannoma (VS) is gross-total resection (GTR) to provide oncological cure. However, a popular strategy is to halt the resection if the surgical team feels the risk of cranial nerve injury is imminent, achieving a maximally safe subtotal resection (STR) instead. The tumor remnant can then be treated with stereotactic radiosurgery (SRS) once the patient has recovered from the immediate postoperative period, or it can be followed with serial imaging and treated with SRS in a delayed fashion if residual tumor growth is seen. In this study, the authors evaluated the efficacy of this multimodality approach, particularly the influence of timing and dose of SRS on radiological tumor control, need for salvage treatment, and cranial nerve function. METHODS VS patients treated with initial microsurgery and subsequent radiosurgery were retrospectively included from two tertiary treatment centers and dichotomized depending on whether SRS was given upfront (defined as before 12 months) or later. Radiological tumor control was defined as less than 20% tumor volume expansion and oncological tumor control as an absence of salvage treatment. Facial and cochlear nerve functions were assessed after surgery, at the time of SRS, and at last follow-up. Finally, a systematic literature review was conducted according to PRISMA guidelines. RESULTS A total of 110 VS patients underwent SRS following microsurgical resection, with a mean preradiosurgical tumor volume of 2.2 cm3 (SD 2.5 cm3) and mean post-SRS follow-up time of 5.8 years (SD 4.1 years). The overall radiological tumor control and oncological tumor control were 77.3% and 90.9%, respectively. Thirty-five patients (31.8%) received upfront SRS, while 75 patients (68.2%) were observed for a minimum of 12 months prior to SRS. The timing of SRS did not influence the radiological tumor control (p = 0.869), the oncological tumor control (p = 0.560), or facial nerve (p = 0.413) or cochlear nerve (p = 0.954) function. An escalated marginal dose (> 12 Gy) was associated with greater tumor shrinkage (p = 0.020) and superior radiological tumor control (p = 0.020), but it did not influence the risk of salvage treatment (p = 0.904) or facial (p = 0.351) or cochlear (p = 0.601) nerve deterioration. CONCLUSIONS Delayed SRS after close observation of residuals following STR is a safe alternative to upfront SRS regarding tumor control and cranial nerve preservation in selected patients.

Abstract Glioblastoma multiforme (GBM) is the most aggressive CNS neoplasm with a mere 15 month progression-free survival following current standards-of-care. Furthermore, conventional therapies have been effective, in part, by inducing a senescent-like phenotype in at least a proportion of glioma, as well as within the tumor-adjacent, healthy brain cells. Through an N-glyco-capture large-scale screening method, we were able to identify 25 genes exclusively overexpressed on glioma cell surfaces. Of those 25 targets, CD38 was an attractive target due to pre-existing FDA approved therapeutics. Recent studies have shown, however, that senescent cells, such as those induced via chemo- and radiotherapies, secrete a pro-inflammatory array of cytokines, known collectively as senescence associated secretory phenotype (SASP), that are capable of increasing CD38 expression in monocytes. CD38 functions as an ectoenzyme to convert extracellular NAD+ to nicotinamide (required for glioma cell salvage pathway NAD+ synthesis) and ADPR/cADPR (a cellular proliferation signal). To examine the effects of radiation on human glioma tissue, we performed reverse cyclase assays (RCA) on paired primary and recurrent human glioma tissue samples and found an increase in CD38 activity in post-irradiated tissues (recurrent glioma) compared to pre-irradiated (primary glioma). Through proliferation assays, we also found an increase in glioma cell growth following treatment with cADPR compared to untreated. Our results demonstrate that CD38 activity is tumorgenic, and furthermore that conventional chemo- and radiotherapies increase this CD38 activity. This indicates that treating CD38 with previously FDA approved therapeutics may provide hope for increasing progression free survival in our GBM patient population, and moreover emphasize the importance of leveraging novel large scale screening methods for identifying additional opportunities for treatment.

Abstract INTRODUCTION Laser Interstitial Thermal Therapy (LITT) is a novel treatment modality that has been used for an array of intracranial pathology. In the current manuscript, we sought to conduct a systematic review and meta-analysis to summarize all available literature to date, on outcomes of patients with recurrent GBM (r-GBM) undergoing LITT, pooling together quantitatively the overall survival and progression-free survival data. METHODS A comprehensive literature search was performed to retrieve all studies investigating overall survival, post-procedure survival, and progression-free survival outcomes of patients with r-GBM undergoing LITT. All statistics were pooled together by the meta-analysis of the mean using a weighted random-effects (RE) or fixed-effect (FE) model. RESULTS Eleven studies were included in the final cohort, representing a total of 134 patients with rGBM. The pooled mean age of the cohort at the time of recurrence diagnosis was found to be 56.7 ± 4.56 while 41% of the cohort were females. For the delivery of LITT, two studies utilized neodymium-yttrium aluminum-garnet laser (Neodp-YAG Laser), three studies utilized the Visualase system, five studies utilized the Neuroblate system, and one study used both the Neuroblate and the Visualase system. A total of eight studies with 107 patients had available data for overall median survival. The pooled overall survival was found to be 18.6 months (95%CI 16.2-21.1). A total of six studies with 93 patients had available data for post-LITT survival. The pooled post-LITT survival was found to be 10.1 months (95%CI 8.8-11.6). A total of eight studies with 119 patients had available data for progression-free survival. The pooled progression-free survival was found to be 6 months (95%CI 5.3-6.7). CONCLUSION LITT is a novel minimally invasive procedure which, when used with optimal adjuvant therapy, may confer survival benefit for patients with r-GBM.

OBJECTIVESphenoorbital meningioma (SOM) is a unique skull base tumor, characterized by infiltrative involvement and hyperostosis primarily of the lesser wing of sphenoid bone, with frequent involvement of the orbital compartment. SOM often manifests with proptosis and visual impairment. Surgical technique and outcome are highly variable among studies reported in the literature. The authors present a single-surgeon experience with SOM.METHODSA retrospective review of a prospectively maintained institutional database was performed. A blinded imaging review by 2 study team members was completed to confirm SOM, after which chart review was carried out to capture demographics and outcomes. All statistical testing was completed using JMP Pro version 14.1.0, with significance defined as p < 0.05.RESULTSForty-seven patients who underwent surgery between 2000 and 2017 were included. The median age at surgery was 47 years (range 36–70 years), 81% of patients were female, and the median follow-up was 43 months (range 0–175 months). All operations were performed via a frontotemporal craniotomy, orbitooptic osteotomy, and anterior clinoidectomy, with extensive resection of all involved bone and soft tissue. Preoperatively, proptosis was noted in 44 patients, 98% of whom improved. Twenty-eight patients (60%) had visual deficits before surgery, 21 (75%) of whom improved during follow-up. Visual field defect other than a central scotoma was the only prognostic factor for improvement in vision on multivariate analysis (p = 0.0062). Nine patients (19%) had recurrence or progression during follow-up.CONCLUSIONSSOM is a unique skull base tumor that needs careful planning to optimize outcome. Aggressive removal of involved bone and periorbita is crucial, and proptosis and visual field defect other than a central scotoma can improve after surgery.

Abstract Flow diverters have drastically changed the landscape of intracranial aneurysm treatment and are now considered first-line therapy for select lesions. Their mechanism of action relies on intrinsic alteration in hemodynamic parameters, both at the parent artery and within the aneurysm sac. Moreover, the device struts act as a nidus for endothelial cell growth across the aneurysm neck ultimately leading to aneurysm exclusion from the circulation. In silico computational analyses and investigations in preclinical animal models have provided valuable insights into the underlying biological basis for flow diverter therapy. Here, we review the present understanding pertaining to flow diverter biology and mechanisms of action, focusing on stent design, induction of intra-aneurysmal thrombosis, endothelialization, and alterations in hemodynamics.