Treatment of Pediatric Low-Grade Gliomas.

PURPOSE OF REVIEW: Pediatric low-grade gliomas and glioneuronal tumors (pLGG) account for approximately 30% of pediatric CNS neoplasms, encompassing a heterogeneous group of tumors of primarily glial or mixed neuronal-glial histology. This article reviews the treatment of pLGG with emphasis on an individualized approach incorporating multidisciplinary input from surgery, radiation oncology, neuroradiology, neuropathology, and pediatric oncology to carefully weigh the risks and benefits of specific interventions against tumor-related morbidity. Complete surgical resection can be curative for cerebellar and hemispheric lesions, while use of radiotherapy is restricted to older patients or those refractory to medical therapy. Chemotherapy remains the preferred first-line therapy for adjuvant treatment of the majority of recurrent or progressive pLGG. RECENT FINDINGS: Technologic advances offer the potential to limit volume of normal brain exposed to low doses of radiation when treating pLGG with either conformal photon or proton RT. Recent neurosurgical techniques such as laser interstitial thermal therapy offer a "dual" diagnostic and therapeutic treatment modality for pLGG in specific surgically inaccessible anatomical locations. The emergence of novel molecular diagnostic tools has enabled scientific discoveries elucidating driver alterations in mitogen-activated protein kinase (MAPK) pathway components and enhanced our understanding of the natural history (oncogenic senescence). Molecular characterization strongly supplements the clinical risk stratification (age, extent of resection, histological grade) to improve diagnostic precision and accuracy, prognostication, and can lead to the identification of patients who stand to benefit from precision medicine treatment approaches. The success of molecular targeted therapy (BRAF inhibitors and/or MEK inhibitors) in the recurrent setting has led to a gradual and yet significant paradigm shift in the treatment of pLGG. Ongoing randomized trials comparing targeted therapy to standard of care chemotherapy are anticipated to further inform the approach to upfront management of pLGG patients.

Fourth ventricular subarachnoid stent for Chiari malformation type I-associated persistent syringomyelia.

OBJECTIVE: Syringomyelia (syrinx) associated with Chiari malformation type I (CM-I) is commonly managed with posterior fossa decompression, which can lead to resolution in most cases. A persistent syrinx postdecompression is therefore uncommon and challenging to address. In the setting of radiographically adequate decompression with persistent syrinx, the authors prefer placing fourth ventricular subarachnoid stents that span the craniocervical junction particularly when intraoperative observation reveals arachnoid plane scarring. The objective of this study was to evaluate the safety and efficacy of a fourth ventricle stent for CM-I-associated persistent syringomyelia, assess dynamic changes in syrinx dimensions, and report stent-reduction durability, clinical outcomes, and procedure-associated complications. METHODS: The authors performed a single-institution, retrospective review of patients who underwent fourth ventricular subarachnoid stent placement for persistent CM-I-associated syringomyelia following a prior posterior fossa decompression. The authors' institutional Chiari database contains 600 cases with 149 decompressions for CM-I-associated syringomyelia, of which 13 met criteria for inclusion. Data on patient demographics, clinical presentation and outcomes, and MRI findings were collected. The maximal syrinx diameter was estimated by calculating the area of an elliptical cross-section in the largest axial plane from preoperative, immediately postoperative, and late postoperative T2-weighted MR images. RESULTS: All 13 patients experienced a significant decrease in mean syrinx area from the preoperative to the late postoperative MRI (mean syrinx diameter 114.1 ± 81.8 mm2 vs 24.5 ± 23.8 mm2, p < 0.001). The mean time until late postoperative MRI was 19.7 months (range 2.0-70.7 months). The syrinx area reduced on average by 75.0% ± 23.9% at the time of the last postoperative scan. Syrinx resolution was variable, with 4 patients (30.8%) achieving near-complete resolution (> 90%, grade III reduction), 7 patients (50%) having 50%-90% reduction (grade II), and 2 patients (14.3%) having < 50% decrease (grade I). One patient experienced catheter migration into the left brachium pontis with an associated cyst at the tip of the catheter that decreased in size on follow-up imaging. CONCLUSIONS: Placement of fourth ventricular subarachnoid stents spanning the craniocervical junction in patients with persistent CM-I-associated syringomyelia after posterior fossa decompression is a safe therapeutic option and significantly reduced the mean syrinx area, with a greater reductive effect seen over longer follow-up periods.

Histology of high-grade glioma samples resected using 5-ALA fluorescent headlight and loupe combination.

PURPOSE: 5-Aminolevulinic acid (5-ALA) fluorescence-guided resection of high-grade gliomas (HGG) increases the extent of resection (EOR) and progression-free survival. The headlamp/loupe combination has been introduced as a method of performing fluorescent-guided surgery. This study aims to understand the correlation between fluorescent intensity and histology and between residual fluorescence and radiographic EOR utilizing the headlamp/loupe device. METHODS: Intraoperative samples resected using the headlamp/loupe device from 14 patients were labeled as PINK, VAGUE, or NEGATIVE depending on the degree of fluorescence. Histological assessment of microvascular proliferation, necrosis, and cell density was performed, and samples were classified as histologically consistent with glioblastoma (GBM), high-grade infiltrating glioma (HGIG), IG, or non-diagnostic (NDX). The presence of intraoperative residual fluorescence was compared to EOR on post-operative MRI. RESULTS: There was a significant difference in cell density comparing PINK, VAGUE, and NEGATIVE specimens (ANOVA, p < 0.00001). The PPV of PINK for GBM or HGIG was 88.4% (38/43). The NPV of NEGATIVE for IG or NDX was 74.4% (29/39). The relationship between the degree of fluorescence determination and histological results was significant (X2 (6 degrees of freedom, N = 101) = 42.57, p < 0.00001). The PPV of intraoperative GTR for post-operative GTR on MRI was 100%, while the NPV of intraoperative STR for post-operative STR on MRI was 60%. CONCLUSION: The headlamp/loupe device provides information about histology, cell density, and necrosis with similar PPV for tumor to the operative microscope. Safe complete resection of florescence has a PPV of 100% for radiographic GTR and should be the goal of surgery.

Familial colloid cysts: not a chance occurrence.

PURPOSE: Colloid cysts are rare, benign brain tumors of the third ventricle with an estimated population prevalence of 1 in 5800. Sudden deterioration and death secondary to obstructive hydrocephalus are well-described presentations in patients with a colloid cyst. Although historically conceptualized as driven by sporadic genetic events, a growing body of literature supports the possibility of an inherited predisposition. METHODS: A prospective registry of patients with colloid cysts was maintained between 1996 and 2021. Data pertaining to a family history of colloid cyst was collected retrospectively; self-reporting was validated in each case by medical record or imaging review. Frequency of patients with a documented first-degree family member with a colloid cyst based on self-reporting was calculated. The rate of familial co-occurrence within our series was then compared to a systematic literature review and aggregation of familial case studies, as well as population-based prevalence rates of sporadic colloid cysts. RESULTS: Thirteen cases with affected first-degree relatives were identified in our series. Of the entire cohort, 19/26 were symptomatic from the lesion (73%), 12/26 (46.2%) underwent resection, and 2/26 (7.7%) had sudden death from presumed obstructive hydrocephalus. The majority of transmission patterns were between mother and child (9/13). Compared with the estimated prevalence of colloid cysts, our FCC rate of 13 cases in 383 (3.4%) estimates a greater-than-chance rate of co-occurrence. CONCLUSION: Systematic screening for FCCs may facilitate early recognition and treatment of indolent cysts, thereby preventing the rapid deterioration that can occur with an unrecognized third ventricular tumor. Furthermore, identifying a transmission pattern may yield more insight into the molecular and genetic underpinnings of colloid cysts.

Salvage resection plus cesium-131 brachytherapy durably controls post-SRS recurrent brain metastases.

BACKGROUND: Salvage of recurrent previously irradiated brain metastases (rBrM) is a significant challenge. Resection without adjuvant re-irradiation is associated with a high local failure rate, while reirradiation only partially reduces failure but is associated with greater radiation necrosis risk. Salvage resection plus Cs131 brachytherapy may offer dosimetric and biologic advantages including improved local control versus observation, with reduced normal brain dose versus re-irradiation, however data are limited. METHODS: A prospective registry of consecutive patients with post-stereotactic radiosurgery (SRS) rBrM undergoing resection plus implantation of collagen-matrix embedded Cs131 seeds (GammaTile, GT Medical Technologies) prescribed to 60 Gy at 5 mm from the cavity was analyzed. RESULTS: Twenty patients underwent 24 operations with Cs131 implantation in 25 tumor cavities. Median maximum preoperative diameter was 3.0 cm (range 1.1-6.3). Gross- or near-total resection was achieved in 80% of lesions. A median of 16 Cs131 seeds (range 6-30), with a median air-kerma strength of 3.5 U/seed were implanted. There was one postoperative wound dehiscence. With median follow-up of 1.6 years for survivors, two tumors recurred (one in-field, one marginal) resulting in 8.4% 1-year progression incidence (95%CI = 0.0-19.9). Radiographic seed settling was identified in 7/25 cavities (28%) 1.9-11.7 months post-implantation, with 1 case of distant migration (4%), without clinical sequelae. There were 8 cases of radiation necrosis, of which 4 were symptomatic. CONCLUSIONS: With > 1.5 years of follow-up, intraoperative brachytherapy with commercially available Cs131 implants was associated with favorable local control and toxicity profiles. Weak correlation between preoperative tumor geometry and implanted tiles highlights a need to optimize planning criteria.

Barriers to Pursuing a Career in Surgery: An Institutional Survey of Harvard Medical School Students.

OBJECTIVE: This study aimed to elucidate current medical student perceptions on barriers to a career in surgery, with a particular focus on gender-specific differences. SUMMARY BACKGROUND DATA: Although gender parity in medical school composition has been reached, women continue to be underrepresented in the field of surgery. METHODS: An anonymous, single-institution, internet-based survey conducted at Harvard Medical School. RESULTS: Approximately 720 medical students were surveyed and 261 completed the questionnaire (36.3%; 58.6% women, 41% men, 0.4% transgender). Overall, there was no significant gender difference in intention to pursue surgery (27% of men, 22% of women; P = 0.38). Sixty-nine percent of all students and 75% of those pursuing surgery reported verbal discouragement from pursuing a surgical career. Women were significantly more likely to perceive that the verbal discouragement was based on gender (P < 0.0001), age (P < 0.0001), and family aspirations (P = 0.043) compared to men. Surgical work hours and time for outside interests were the greatest deterrents for both genders. Significantly more women reported concerns about time to date or marry (P = 0.042), time to spend with family (P = 0.015), finding time during residency to have a child (P < 0.0001), taking maternity/paternity leave during residency (P < 0.0001), and being too old after residency to have a child (P < 0.0001). CONCLUSIONS: Both men and women reported high rates of verbal discouragement, but more women perceived that the discouragement was gender-based. Concerns about marriage and childbearing/rearing significantly deterred more women than men. Family aspirations were also a significant factor for men to choose an alternative career path. Additional support within the surgical field is needed to mitigate these concerns and support trainees in both their career and familial aspirations.

Impact of the COVID-19 pandemic on neuro-oncology outcomes.

INTRODUCTION: The Coronavirus disease 2019 (COVID-19) pandemic has uprooted healthcare systems worldwide, disrupting care and increasing dependence on alternative forms of health care delivery. It is yet to be determined how the pandemic affected neuro-oncology patient outcomes, given that the majority of even "elective" neurosurgical oncology procedures are time-sensitive. This study quantifies changes in neuro-oncological care during the height of the pandemic and investigates patient outcomes in 2020 compared to a historical control. METHODS: We performed a retrospective review of patients with malignant brain tumor diagnoses who were seen at our institution between March 13 and May 1 of 2020 and 2019. Alterations in care, including shift from in-person to telehealth, delays in evaluation and intervention, and treatment modifications were evaluated. These variables were analyzed with respect to brain tumor control and mortality. RESULTS: 112 patients from 2020 to 166 patients from 2019 were included. There was no significant difference in outcomes between the cohorts, despite significantly more treatment delays (p = 0.0160) and use of telehealth (p < 0.0001) in 2020. Patients in 2020 who utilized telehealth visits had significantly more stable tumor control than those who had office visits (p = 0.0124), consistent with appropriate use of in-person visits for patients with progression. CONCLUSIONS: Our study showed that use of telehealth and selective alterations in neuro-oncological care during the COVID-19 pandemic did not lead to adverse patient outcomes. This suggests that adaptive physician-led changes were successful and may inform management during the ongoing pandemic, especially with the emergence of the Delta variant.

Immune profiling of pituitary tumors reveals variations in immune infiltration and checkpoint molecule expression.

PURPOSE: Pituitary tumors are the second most common primary brain tumors. Functional tumors demonstrate increased PD-L1 expression, but expression of other checkpoint regulators has not been characterized. We sought to characterize the immune microenvironment of human pituitary tumors to identify new treatment opportunities. METHODS: 72 pituitary tumors were evaluated for expression of the immune regulatory markers programmed death ligand 1 (PD-L1), programmed death ligand 2 (PD-L2), V-domain Ig suppressor of T cell activation (VISTA), lymphocyte activation gene 3 (LAG3) and tumor necrosis factor receptor superfamily member 4 (OX40) by immunohistochemistry (IHC). Lymphocyte infiltration, macrophage infiltration, and angiogenesis were analyzed using IHC. Expression of pituitary tumor initiating cell marker CD15 and mismatch repair proteins MutS protein homolog 2 (MSH2) and MutS protein homolog 6 (MSH6) was also assessed. RESULTS: Pituitary tumors were infiltrated by macrophages and T cells, and they expressed varying levels of PD-L1, PD-L2, VISTA, LAG3, and OX40. Functional tumors and tumors with high expression of tumor stem cell markers had higher immune cell infiltration and greater expression of immunosuppressive checkpoint regulators. Increased PD-L1 and LAG3 and reduced VISTA were observed in primary tumors compared to recurrent tumors. CONCLUSION: Immune cell infiltration and checkpoint regulator expression vary depending on functional status and presence of pituitary tumor initiating cells. Functional tumors may have a particularly immunosuppressive microenvironment. Further studies of immune checkpoint blockade of pituitary tumors, particularly functional tumors, are warranted, though combination therapy may be required.

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.

Leptomeningeal dissemination in pediatric brain tumors.

Leptomeningeal disease (LMD) in pediatric brain tumors (PBTs) is a poorly understood and categorized phenomenon. LMD incidence rates, as well as diagnosis, treatment, and screening practices, vary greatly depending on the primary tumor pathology. While LMD is encountered most frequently in medulloblastoma, reports of LMD have been described across a wide variety of PBT pathologies. LMD may be diagnosed simultaneously with the primary tumor, at time of recurrence, or as primary LMD without a primary intraparenchymal lesion. Dissemination and seeding of the cerebrospinal fluid (CSF) involves a modified invasion-metastasis cascade and is often the result of direct deposition of tumor cells into the CSF. Cells develop select environmental advantages to survive the harsh, nutrient poor and turbulent environment of the CSF and leptomeninges. Improved understanding of the molecular mechanisms that underlie LMD, along with improved diagnostic and treatment approaches, will help the prognosis of children affected by primary brain tumors.

Olfactory groove meningiomas: supraorbital keyhole versus orbitofrontal, frontotemporal, or bifrontal approaches.

OBJECTIVE: Olfactory groove meningiomas (OGMs) often require surgical removal. The introduction of recent keyhole approaches raises the question of whether these tumors may be better treated through a smaller cranial opening. One such approach, the supraorbital keyhole craniotomy, has never been compared with more traditional open transcranial approaches with regard to outcome. In this study, the authors compared clinical, radiographic, and functional quality of life (QOL) outcomes between the keyhole supraorbital approach (SOA) and traditional transcranial approach (TTA) for OGMs. They sought to examine the potential advantages and disadvantages of open/TTA versus keyhole SOA for the resection of OGMs in a relatively case-matched series of patients. METHODS: A retrospective, single-institution review of 57 patients undergoing a keyhole SOA or larger traditional transcranial (frontotemporal, pterional, or bifrontal) craniotomy for newly diagnosed OGMs between 2005 and 2023 was performed. Extent of resection, olfaction, length of stay (LOS), radiographic volumetric assessment of postoperative vasogenic and cytotoxic edema, and QOL (using the Anterior Skull Base Questionnaire) were assessed. RESULTS: Thirty-two SOA and 25 TTA patients were included. The mean EOR was not significantly different by approach (TTA: 99.1% vs SOA: 98.4%, p = 0.91). Olfaction was preserved or improved at similar rates (TTA: 47% vs SOA: 43%, p = 0.99). The mean LOS was significantly shorter for SOA patients (4.1 ± 2.8 days) than for TTA patients (9.4 ± 11.2 days) (p = 0.002). The authors found an association between an increase in postoperative FLAIR cerebral edema and TTA (p = 0.031). QOL as assessed by the ASQB at last follow-up did not differ significantly between groups (p = 0.74). CONCLUSIONS: The keyhole SOA was associated with a statistically significant decrease in LOS and less postoperative edema relative to traditional open approaches.

Outcomes Following Early Postoperative Adjuvant Radiosurgery for Brain Metastases.

Importance: Adjuvant stereotactic radiosurgery (SRS) enhances the local control of resected brain metastases (BrM). However, the risks of local failure (LF) and potential for posttreatment adverse radiation effects (PTRE) after early postoperative adjuvant SRS have not yet been established. Objective: To evaluate whether adjuvant SRS delivered within a median of 14 days after surgery is associated with improved LF without a concomitant increase in PTRE. Design, Setting, and Participants: This prospective cohort study examines a clinical workflow (RapidRT) that was implemented from 2019 to 2022 to deliver SRS to surgical patients within a median of 14 days, ensuring all patients were treated within 30 days postoperatively. This prospective cohort was compared with a historical cohort (StanRT) of patients with BrM resected between 2013 and 2019 to assess the association of the RapidRT workflow with LF and PTRE. The 2 cohorts were combined to identify optimal SRS timing, with a median follow-up of 3.3 years for survivors. Exposure: Timing of adjuvant SRS (14, 21, and 30 days postoperatively). Main Outcomes and Measures: LF and PTRE, according to modified Response Assessment in Neuro-Oncology Brain Metastases criteria. Results: There were 438 patients (265 [60.5%] female patients; 23 [5.3%] Asian, 27 [6.2%] Black, and 364 [83.1%] White patients) with a mean (SD) age of 62 (13) years; 377 were in the StanRT cohort and 61 in the RapidRT cohort. LF and PTRE rates at 1 year were not significantly different between RapidRT and StanRT cohorts. Timing of SRS was associated with radiographic PTRE. Patients receiving radiation within 14 days had the highest 1-year PTRE rate (18.08%; 95% CI, 8.31%-30.86%), and patients receiving radiation between 22 and 30 days had the lowest 1-year PTRE rate (4.10%; 95% CI, 1.52%-8.73%; P = .03). LF rates were highest for patients receiving radiation more than 30 days from surgery (10.65%; 95% CI, 6.90%-15.32%) but comparable for patients receiving radiation within 14 days, between 15 and 21 days, and between 22 and 30 days (≤14 days: 5.12%; 95% CI, 0.86%-15.60%; 15 to ≤21 days: 3.21%; 95% CI, 0.59%-9.99%; 22 to ≤30 days: 6.58%; 95% CI, 3.06%-11.94%; P = .20). Conclusions and Relevance: In this cohort study of adjuvant SRS timing following surgical resection of BrM, the optimal timing for adjuvant SRS appears to be within 22 to 30 days following surgery. The findings of this study suggest that this timing allows for a balanced approach that minimizes the risks associated with LF and PTRE.

Interns Without Subinternships.

Surgical interns who have completed medical school in the era of Covid-19 will not have the same experience gained through the traditional multi-month fourth-year surgical subinternships. During subinternships, medical students learn relevant anatomic and radiographic features of surgical pathologies, hone technical skills, and gain exposure to surgical consults and procedures. This lack of intensive exposure will have this cohort starting at a lower comfort and knowledge level compared to years prior. Residency programs, especially subspeciality programs, should review and utilize national resources to facilitate the transition to intern year, such as the American College of Surgeons Entering Resident Readiness Assessment and American College of Surgeons/ Association of Program Directors in Surgery/Association for Surgical Education Resident Prep Curriculum. We recommend the use of a specialty-tailored intern boot-camp and longitudinal curriculum that focuses on learning procedural skills and surgical conditions, anatomy, pathology, clinical examination, radiographic findings, surgical approach, and postoperative complications. These steps will help address knowledge gaps and promote intern readiness in this cohort of individuals.

Challenges in the Diagnosis and Management of Low-Grade Gliomas.

Low-grade gliomas are clinically challenging entities. Patients with these tumors tend to be relatively young at presentation, and lesions are often incidental findings or are identified because the patient presents with a seizure. Rapidly emerging and evolving molecular classifications of gliomas have influenced treatment paradigms. Importantly, low-grade gliomas can be classified on the basis of IDH mutation status, whereby low-grade astrocytomas harbor the IDH mutation, while oligodendrogliomas are defined by both IDH mutant status and 1p/19q co-deletion. Given the importance of molecular classification for diagnosis, treatment planning, and prognostication, tissue samples are necessary for proper management. Literature supports improved overall survival and outcomes with increased extent of resection for low-grade glioma. Awake craniotomies and resection of insular low-grade gliomas both have been demonstrated as safe and improve outcomes for patients with lesions located in eloquent areas. Given the younger age at diagnosis of these lesions compared with higher-grade gliomas, fertility, fertility preservation, and potential malignant transformation should be discussed with patients of childbearing age.

Acromegaly: Medical and Surgical Considerations.

Acromegaly results from excessive secretion of insulinlike growth factor-1 and growth hormone, which most commonly occurs because of pituitary somatotrophinoma. Diagnostic features of acromegaly include elevated insulinlike growth factor-1 and growth hormone; lesion on brain MRI; and clinically dysmorphic features, such as soft tissue swelling, jaw prognathism, and acral overgrowth. Transsphenoidal resection is the primary therapy for individuals with acromegaly, even in the cases where gross total resection is not possible because of parasellar extension and cavernous sinus involvement. For recurrent or persistent disease after resection, systemic medications and stereotactic radiosurgery are used.

Innovations in the Diagnosis and Surgical Management of Low-Grade Gliomas.

Low-grade gliomas are a broad category of tumors that can manifest at different stages of life. As a group, their prognosis has historically been considered to be favorable, and surgery is a mainstay of treatment. Advances in the molecular characterization of individual lesions has led to newer classification systems, a better understanding of the biological behavior of different neoplasms, and the identification of previously unrecognized entities. New prospective genetic and molecular data will help delineate better treatment paradigms and will continue to change the taxonomy of central nervous system tumors in the coming years. Advances in the field of radiomics will help predict the molecular profile of a particular tumor through noninvasive testing. Similarly, more precise methods of intraoperative tumor tissue analysis will aid surgical planning. Improved surgical outcomes propelled by novel surgical techniques and intraoperative adjuncts and emerging forms of medical treatment in the field of immunotherapy have enriched the management of these lesions. We review the contemporary management and innovations in the treatment of low-grade gliomas.

Novel approaches to the management of patients with 5-15 brain metastases: a narrative review.

BACKGROUND AND OBJECTIVE: The management of metastatic disease has been greatly influenced by molecular-based tumor classification and associated therapeutic targets, leading to a significant improvement in survival in many cases. This improvement, in both progression free survival and overall survival, has led to an increased incidence of brain metastases (BM) in a population with systemically well controlled disease or patients with promising therapeutic options available. Within this review, we discuss the paradigm of treatment for 5 to 15 BM, and how the treatment has evolved away from short-term palliation towards providing long term intracranial control. METHODS: A review of literature pertaining to treatment of multiple BM was performed. We searched in PubMed to identify literature on treatment of multiple brain metastases. Only English literature published until February 1st, 2022 was reviewed. KEY CONTENT AND FINDINGS: The management of 5-15 BM include multi-modality treatment pathways that are tailored towards each individual's primary cancer and burden of disease. Surgical resection of a dominant metastasis is still reserved for large symptomatic lesions, and is combined with post-operative local disease control. Overall, there is a shift away from whole brain radiation therapy (WBRT) due to side effect profile towards stereotactic radiosurgery (SRS). However, advances in WBRT continue to be studied, as well as the use of immunotherapy, targetable mutations, and synergistic effects between SRS and targeted therapies. CONCLUSIONS: The use of SRS to treat 5 to 15 BM is an increasingly acceptable and well-regarded practice, along with a combinatorial approach taking into account systemic options during all treatment timepoints.

The role of neoadjuvant denosumab in the treatment of aneurysmal bone cysts: a case series and review of the literature.

OBJECTIVE: Aneurysmal bone cysts (ABCs) are benign cystic lesions most commonly occurring in the long bones of pediatric patients. Spinal ABCs may be difficult to resect given their invasive, locally destructive nature, proximity to critical structures such as the spinal cord, and their intrinsic hypervascularity, for which complete embolization is often constrained by radiculomedullary segmental feeders. Denosumab, a monoclonal antibody that binds the receptor activator of nuclear factor kappa B (NF-κB) ligand, has been utilized in the treatment of ABCs most often as a rescue therapy for recurrent disease. Here, the authors present 3 cases of neoadjuvant denosumab use in surgically unresectable tumors to calcify and devascularize the lesions, allowing for safer, more complete resection. METHODS: This is a single-center, retrospective case series treated at a tertiary care cancer center. The authors present 3 cases of spinal ABC treated with neoadjuvant denosumab. RESULTS: All 3 patients experienced calcification, size reduction, and a significant decrease in the vascularity of their ABCs on denosumab therapy. None of the patients developed new neurological deficits while on denosumab. Subsequently, all underwent resection. One patient continued denosumab during the immediate postoperative period because a subtotal resection had been performed, with stabilization of the residual disease. No complications were associated with denosumab administration. CONCLUSIONS: The use of denosumab in unresectable ABCs can cause calcification and devascularization, making safe resection more likely.

Metastases in the Pineal Region: A Systematic Review of Clinical Features, Management Strategies, and Survival Outcomes.

BACKGROUND: Pineal region metastases are rare but often cause severe neurologic deficits. Surgical resection and chemoradiotherapy can provide therapeutic benefit. We investigated the literature to analyze clinical characteristics, management strategies, and survival of adult patients with pineal region metastases. METHODS: PubMed, Embase, Scopus, and Cochrane were searched following the PRISMA guidelines, including studies reporting clinical outcomes of patients with pineal region metastases. Clinical presentation, management, and survival were reviewed. RESULTS: We included 31 studies comprising 47 patients. Lung cancer (29.8%) and carcinomas of unknown origin (14.9%) were the most frequent primary tumors. In 48.9% of patients, symptomatic pineal metastases preceded primary tumor diagnosis. Headache (67.4%) and confusion (46.5%) were the most common symptoms. Parinaud syndrome (46.5%) and hydrocephalus (87.2%) were noted. Biopsy (65.9%) was preferred over resection (34.1%), and shunting strategies used were endoscopic third ventriculostomy (43.9%) and ventriculoperitoneal (26.8%). Eleven patients (32.3%) received adjuvant chemotherapy and 32 (68%) received radiotherapy. Posttreatment improvement in symptoms (56.6%) and hydrocephalus (80.5%) were noted. In patients who received adjuvant chemotherapy/radiotherapy, significant improvement in posttreatment performance status occurred with both biopsy (P < 0.001) and resection (P = 0.007). No survival differences were reported between surgery and biopsy (P = 0.912) or between complete and partial resection (P = 0.220). Overall survival was neither influenced by surgical approach (P = 0.157) nor by shunting strategy (P = 0.822). Mean follow-up was 8 months and median overall survival 3 months. Only 2 cases (4.8%) of pineal metastasis showed recurrence. CONCLUSIONS: Pineal region metastases carry significant morbidity. Biopsy or surgical resection, combined with adjuvant chemotherapy/radiotherapy and/or shunting, may significantly improve performance status.