Treatment and outcomes of IDH1-mutant gliomas in elderly patients.

OBJECTIVE: Isocitrate dehydrogenase (IDH) mutations in both high- and low-grade gliomas are associated with an increase in survival compared with IDH-wild-type (IDHwt) tumors. A rare and understudied population is elderly individuals, ≥ 65 years of age, who have IDH1-R132H-mutant (IDHmt) gliomas. The objective of this paper was to characterize the institutions' experience with IDHmt gliomas in a patient population ≥ 65 years of age over the last 10 years. METHODS: A retrospective study of individuals ≥ 65 years of age with IDHmt gliomas treated between 2010 and 2020 at Memorial Sloan Kettering was performed. RESULTS: Twenty-five patients ≥ 65 years of age underwent resection or biopsy with a diagnosis of IDHmt glioma (52% WHO grade II, 32% WHO grade III, and 16% WHO grade IV). The most common presenting symptoms were seizure (28%) and motor or sensory deficits (24%). On preoperative MRI, 56% of tumors demonstrated contrast enhancement and 44% had no enhancement. Most patients underwent craniotomy for resection (n = 23, 92%), with subtotal resection achieved in the majority (16/23, 69.6%). Postoperative discharge location included home (64%), acute rehabilitation (16%), subacute rehabilitation (8%), and unknown (12%). Most patients received postoperative chemotherapy (72%) and radiation therapy (68%). The 2- and 5-year survival rates for the overall cohort were 83.1% (95% CI 69.3%-99.7%) and 69.7% (95% CI 53.2%-91.3%), respectively, with gross-total resection or near-total resection, contrast enhancement, and WHO grade significantly associated with survival. From the clinical sequencing data, no significant differences were identified between younger and older IDHmt cohorts. CONCLUSIONS: While IDH mutation in elderly patients may be rare, these patients have favorable survival relative to their IDHwt counterparts. Age at diagnosis should not be used in isolation to suggest a molecular IDHwt status or poor prognosis when guiding patient treatment decisions.

Postradiosurgery cystic degeneration in brain metastases causing delayed and potentially severe sequelae: systematic review and illustrative cases.

BACKGROUND: Cystic postradiation degeneration has previously been described in the literature as a rare but potentially severe complication after central nervous system (CNS) irradiation for vascular malformations. Limited cases have been reported in the setting of brain metastases. OBSERVATIONS: Thirty-six total cases, including three reported here, of cystic postradiation degeneration are identified. Of 35 cases with complete clinical information, 34 (97.25%) of 35 were symptomatic from cystic changes at diagnosis. The average time between initial radiation dose and cyst development was 7.61 years (range 2-31 years). Although most patients were initially treated conservatively with medication, including steroids, 32 (88.9%) of 36 ultimately required surgical intervention. The most common interventions were craniotomy for cyst fenestration or resection (25 of 36; 69.4%) and Ommaya placement (8 of 36). After intervention, clinical improvement was seen in 10 (67%) of 15 cases, with persistent or worsening deficit or death seen in 5 (33%) of 15. Cysts were decompressed or obliterated on postoperative imaging in 20 (83.3%) of 24 cases, and recurrence was seen in 4 (16.7%) of 24. LESSONS: Cystic degeneration is a rare and delayed sequela after radiation for brain metastases. This entity has the potential to cause significant and permanent neurological deficit if not properly recognized and addressed. Durable control can be achieved with a variety of surgical treatments, including cyst fenestration and Ommaya placement.

Meningioma Presenting with Spontaneous Venous Intraparenchymal Hemorrhage.

A 65-year-old woman with a known right-sided, dural-based lesion and metastatic pancreatic neuroendocrine tumor presented with multiple days of progressive lethargy and left-sided weakness culminating with obtundation and dilated pupils. Computed tomography demonstrated an acute right convexity subdural hematoma and a frontotemporal intraparenchymal hemorrhage with 1.3 cm of midline shift, uncal herniation, and an increase in size of now a hemorrhagic dural-based lesion. She underwent emergency hemicraniectomy for evacuation of subdural hematoma and resection of hemorrhagic meningioma with excellent postoperative result including improvement in midline shift and gross total resection of lesion. Pathology was consistent with a World Health Organization grade II meningioma with a chordoid component. She underwent adjuvant stereotactic radiosurgery and cranioplasty and made a full neurologic recovery. Identification of hemorrhagic meningioma as the underlying pathology causing multicompartmental hemorrhage is crucial. We recommend single-stage decompression with extraaxial clot evacuation and resection of the meningioma when feasible.

Investigative needle core biopsies for multi-omics in Glioblastoma.

Glioblastoma (GBM) is a primary brain cancer with an abysmal prognosis and few effective therapies. The ability to investigate the tumor microenvironment before and during treatment would greatly enhance both understanding of disease response and progression, as well as the delivery and impact of therapeutics. Stereotactic biopsies are a routine surgical procedure performed primarily for diagnostic histopathologic purposes. The role of investigative biopsies - tissue sampling for the purpose of understanding tumor microenvironmental responses to treatment using integrated multi-modal molecular analyses ('Multi-omics") has yet to be defined. Secondly, it is unknown whether comparatively small tissue samples from brain biopsies can yield sufficient information with such methods. Here we adapt stereotactic needle core biopsy tissue in two separate patients. In the first patient with recurrent GBM we performed highly resolved multi-omics analysis methods including single cell RNA sequencing, spatial-transcriptomics, metabolomics, proteomics, phosphoproteomics, T-cell clonotype analysis, and MHC Class I immunopeptidomics from biopsy tissue that was obtained from a single procedure. In a second patient we analyzed multi-regional core biopsies to decipher spatial and genomic variance. We also investigated the utility of stereotactic biopsies as a method for generating patient derived xenograft models in a separate patient cohort. Dataset integration across modalities showed good correspondence between spatial modalities, highlighted immune cell associated metabolic pathways and revealed poor correlation between RNA expression and the tumor MHC Class I immunopeptidome. In conclusion, stereotactic needle biopsy cores are of sufficient quality to generate multi-omics data, provide data rich insight into a patient's disease process and tumor immune microenvironment and can be of value in evaluating treatment responses. One sentence summary: Integrative multi-omics analysis of stereotactic needle core biopsies in glioblastoma.

Patient-Reported Outcomes in Endoscopic Endonasal Skull Base Surgery.

The functional outcome, quality of life, and patient feedback related to a chosen treatment approach in skull base surgery have become a subject of interest and focused research in recent years. The current advances in endoscopic optical imaging technology and surgical precision have radically lowered the perioperative morbidity associated with skull base surgery. This has pushed toward a higher focus on patient-reported outcomes (PROs). It is now critical to ensure that the offered treatment plan and approach align with the patient's preferences and expectations, in addition to the surgeon's best clinical judgment and experience. PROs represent a view that reflects the patient's own thoughts and perspective on their condition and the management options, without input or interpretations from the surgeon. Having PRO data enables patients the opportunity to learn from the experiences and perspectives of other patients. This input empowers the patient to become an active participant in the decision-making process at different stages of their care. An in-depth PRO evaluation requires specific validated tools and scoring systems, namely the patient-reported outcomes measures (PROM) tools. In this review, we discuss the currently available skull-base-related PROs, the assessment tools used to capture them, and the future trends of this important topic that is in its infancy.

Distant Pituitary Adenoma Spread: A Systematic Review and Report of 2 Cases.

BACKGROUND: Distant spread of pituitary adenoma outside the sellar/suprasellar region is classified as pituitary carcinoma. Cerebrospinal fluid (CSF)-born spread of pituitary adenoma can occur after tumor cell spillage into the CSF space after surgery, irradiation, or apoplexy and is not necessarily related to intrinsic tumor biology. OBJECTIVE: To systematically review the literature and describe the clinical characteristics and treatment strategies of patients with pituitary carcinomas. We further present 2 cases from our institution. METHODS: A single-center retrospective review of patients with pituitary adenoma spread to distant intracranial locations between 2000 and 2020 was performed. Electronic databases were searched from their inception to May 25, 2021, and studies describing patients with pituitary spread to distant locations were included. RESULTS: Of 1210 pituitary adenoma cases reviewed, 2 (0.16%) showed tumor spread to distant locations. We found 134 additional cases (from 108 published articles) resulting in a total of 136 cases (61.9% were male). The time to tumor spread ranged between 0 and 516 months (median: 96 months). The follow-up duration ranged between 0 and 240 months (median: 11.5 months). All but 2 patients (98.5%) underwent surgical resection before adenoma spread. The 2 exceptions included a patient with evidence of an apoplectic event on autopsy and another patient with leptomeningeal pituitary spread but an unclear history of apoplexy. Elevated tumor markers were not linked to poor outcomes. CONCLUSION: Distant spread of pituitary adenoma may occur after surgery, irradiation, or apoplexy. It is not necessarily associated with a malignant clinical course.

Central nervous system tumors and three-dimensional cell biology: Current and future perspectives in modeling.

Central nervous system (CNS) tumors are a variety of distinct neoplasms that present multiple challenges in terms of treatment and prognosis. Glioblastoma, the most common primary tumor in adults, is associated with poor survival and remains one of the least treatable neoplasms. These tumors are highly heterogenous and complex in their nature. Due to this complexity, traditional cell culturing techniques and methods do not provide an ideal recapitulating model for the study of these tumors' behavior in vivo. Two-dimensional models lack the spatial arrangement, the heterogeneity in cell types, and the microenvironment that play a large role in tumor cell behavior and response to treatment. Recently, scientists have turned towards three-dimensional culturing methods, namely spheroids and organoids, as they have been shown to recapitulate tumors in a more faithful manner to their in vivo counterparts. Moreover, tumor-on-a-chip systems have lately been employed in CNS tumor modeling and have shown great potential in both studying the pathophysiology and therapeutic testing. In this review, we will discuss the current available literature on in vitro three-dimensional culturing models in CNS tumors, in addition to presenting their advantages and current limitations. We will also elaborate on the future implications of these models and their benefit in the clinical setting.

Negative pharmacological effect on spine fusion: A narrative review of the literature of evidence-based treatment.

Spine fusion surgery is commonly performed for diverse indications, the most frequent one being degenerative spine diseases. Despite the growing importance of this surgery, there is limited evidence concerning the effects of drugs on the process of spine fusion and healing. While asymptomatic sometimes, nonunion of the spine can have tremendous repercussions on the patients' quality of life and the healthcare system rendering it an "expensive complication". This literature review identifies the role of some perioperative drugs in spine fusion and reveals their potential role in pseudarthrosis of the spine. This review also benefits spine surgeons looking for current evidence-based practices. We reviewed the data related to nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, vancomycin, bisphosphonates, proton pump inhibitors (PPIs), pregabalin, and opioids. From the available experimental and clinical studies, we conclude that bisphosphonates might positively influence the process of spine fusion, while steroids and vancomycin have shown variable effects, and the remaining medications likely disturb healing and union of the spine. We recommend spine surgeons be cautious about the drugs they resort to in the critical perioperative period until further clinical studies prove which drugs are safe to be used.