Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:The management of World Health Organization (WHO) grade 2 meningiomas is complicated by their diverse clinical behaviors. Stereotactic radiosurgery (SRS) can be an effective management option. Literature on SRS dose selection is limited but suggests that a higher dose is better for tumor control. We characterize the predictors of post-SRS outcomes that can help guide planning and management. METHODS:We reviewed a cohort of consecutive patients with pathologically-proven WHO grade 2 meningiomas who underwent SRS at a single institution between 2011 and 2023. RESULTS:Ninety-nine patients (median age 62 years) underwent SRS, 11 of whom received hypofractionated SRS in 5 fractions. Twenty-two patients had received previous irradiation. The median follow-up was 49 months. The median overall survival was 119 months (95% CI 92-NA) with estimated 5- and 10-year survival of 83% and 27%, respectively. The median progression-free survival (PFS) was 40 months (95% CI 32-62), with 3- and 5-year rates at 54% and 35%, respectively. The median locomarginal PFS was 63 months (95% CI 51.8-NA) with 3- and 5-year rates at 65% and 52%. Nine (9%) patients experienced adverse events, 2 Common Terminology Criteria for Adverse Events grade 3 and 7 grade 2, consisting of worsening neurologic deficit from edema. In the single-session cohort, Ki-67 significantly predicted both overall survival and intracranial PFS. Tumors with Ki-67 >10% had 2.17 times the risk of locomarginal progression compared with Ki-67 ≤10% (P = .018) adjusting for covariates. Sex, prescription dose, tumor volume, and location also predicted tumor control. In tumors with Ki-67 >10%, margin dose ≥14 Gy was associated with significantly better tumor control but not for tumors with Ki-67 ≤10%. CONCLUSION/CONCLUSIONS:The management of WHO grade 2 meningiomas requires a multimodality approach. This study demonstrates the value of a targeted SRS approach in patients with limited disease and further establishes predictive biomarkers that can guide planning through a personalized approach.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Stereotactic radiosurgery (SRS) is effective for patients with medically refractory trigeminal neuralgia with a 75%-90% response rate. Consideration of the integral dose (ID) to the target nerve within the 50% isodose line was reported to help select prescription doses to maximize effectiveness and minimize bothersome numbness. The objective of this study was to externally validate the ID as a predictor of outcomes after SRS. METHODS:We reviewed the outcomes and parameters of 94 consecutive patients of type 1 trigeminal neuralgia who had SRS for the first time where nerve ID was calculated. 70% of the prescription doses were 80 Gy, with 28% at 85 Gy, and 2% at 70 Gy. RESULTS:The median follow-up time was 14.4 months. A total of 85 (90%) patients reported significant pain relief (Barrow Neurological Institute I-III) after initial SRS. The median pain recurrence-free survival was 82 months (95% CI 41.1-NA), and estimates at 1, 3, and 5 years were 80.5%, 65.5%, and 55.9%, respectively. The ID was not significantly associated with initial pain relief, or affect the risk of pain recurrence or sensory dysfunction after SRS using the Cox proportional hazards model. A nerve mean dose ≥65 Gy was associated with a reduced risk of pain recurrence on multivariate analysis (hazard ratio 0.408, P = .039). Twenty (21%) patients experienced sensory dysfunction after SRS with 3 (3%) requiring further medications, which was not correlated with the prescription dose or brainstem maximum dose. CONCLUSION/CONCLUSIONS:The ID did not predict recurrence-free survival or sensory dysfunction. Our observations suggest improved nerve coverage by the most powerful area of the isocenter, for instance, by targeting a narrower segment if feasible, could result in more durable pain relief. Further studies to validate these findings are needed.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Hydrocephalus after Gamma Knife® stereotactic radiosurgery (SRS) for vestibular schwannomas is a rare but manageable occurrence. Most series report post-SRS communicating hydrocephalus in about 1% of patients, thought to be related to a release of proteinaceous substances into the cerebrospinal fluid. While larger tumor size and older patient age have been associated with post-SRS hydrocephalus, the influence of baseline ventricular anatomy on hydrocephalus risk remains poorly defined. METHODS:A single-institution retrospective cohort study examining patients who developed symptomatic communicating hydrocephalus after undergoing Gamma Knife® SRS for unilateral vestibular schwannomas from 2011 to 2021 was performed. Patients with prior hydrocephalus and cerebrospinal fluid diversion or prior surgical resection were excluded. Baseline tumor volume, third ventricle width, and Evans Index (EI)-maximum width of the frontal horns of the lateral ventricles/maximum internal diameter of the skull-were measured on axial postcontrast T1-weighted magnetic resonance imaging. RESULTS:A total of 378 patients met the inclusion criteria; 14 patients (3.7%) developed symptomatic communicating hydrocephalus and 10 patients (2.6%) underwent shunt placement and 4 patients (1.1%) were observed with milder symptoms. The median age of patients who developed hydrocephalus was 69 years (IQR, 67-72) and for patients younger than age 65 years, the risk was 1%. For tumor volumes <1 cm3, the risk of requiring shunting was 1.2%. The odds of developing symptomatic hydrocephalus were 5.0 and 7.7 times higher in association with a baseline EI > 0.28 (P = .024) and tumor volume >3 cm3 (P = .007), respectively, in multivariate analysis. Fourth ventricle distortion on pre-SRS imaging was significantly associated with hydrocephalus incidence (P < .001). CONCLUSION/CONCLUSIONS:Patients with vestibular schwannoma with higher baseline EI, larger tumor volumes, and fourth ventricle deformation are at increased odds of developing post-SRS hydrocephalus. These patients should be counseled regarding risk of hydrocephalus and carefully monitored after SRS.

PURPOSE/OBJECTIVE:Although ongoing studies are assessing the efficacy of new systemic therapies for patients with triple negative breast cancer (TNBC), the overwhelming majority have excluded patients with brain metastases (BM). Therefore, we aim to characterize systemic therapies and outcomes in a cohort of patients with TNBC and BM managed with stereotactic radiosurgery (SRS) and delineate predictors of increased survival. METHODS:We used our prospective patient registry to evaluate data from 2012 to 2023. We included patients who received SRS for TNBC-BM. A competing risk analysis was conducted to assess local and distant control. RESULTS:Forty-three patients with 262 tumors were included. The median overall survival (OS) was 16 months (95% CI 13-19 months). Predictors of increased OS after initial SRS include Breast GPA score > 1 (p < 0.001) and use of immunotherapy such as pembrolizumab (p = 0.011). The median time on immunotherapy was 8 months (IQR 4.4, 11.2). The median time to new CNS lesions after the first SRS treatment was 17 months (95% CI 12-22). The cumulative rate for development of new CNS metastases after initial SRS at 6 months, 1 year, and 2 years was 23%, 40%, and 70%, respectively. Thirty patients (70%) underwent multiple SRS treatments, with a median time of 5 months (95% CI 0.59-9.4 months) for the appearance of new CNS metastases after second SRS treatment. CONCLUSIONS:TNBC patients with BM can achieve longer survival than might have been previously anticipated with median survival now surpassing one year. The use of immunotherapy is associated with increased median OS of 23 months.

BACKGROUND AND OBJECTIVES/OBJECTIVE:To study the clinical, imaging, and survival outcomes in patients with motor cortex brain metastases treated with stereotactic radiosurgery (SRS). METHODS:Imaging and clinical data were obtained from our prospective patient registry. Tumor volumes were obtained from serial imaging data. RESULTS:The outcomes of 208 patients with metastases involving the motor cortex who underwent SRS between 2012 and 2021 were analyzed. A total of 279 metastases (0.01 cm3-12.18 cm3, mean 0.74 cm3) were irradiated. The SRS margin dose varied from 10 to 20 Gy (mean 16.9 Gy). The overall tumor control rate was 97.8%. Perilesional edema was noted in 69 (25%) tumors at presentation. Adverse radiation effects (ARE) were noted in 6% of all tumors but were symptomatic in only 1.4%. Median time to appearance of symptomatic ARE was 8 months. Edema without ARE was observed in 13%. New focal seizures were noted in 5 patients (2%) and new generalized seizures in 1 patient (0.3%). Thirty-six patients (17%) presented with motor deficits. At final follow-up, 32 (85%) were improved or unchanged, 13 (41%) had a normal examination, 10 (31%) had mild deficits, and 9 (28%) still had moderate deficits. New remote brain metastases were found in 31% of patients at a median of 8 months. After treatment, the Karnofsky performance score distribution of the population showed an overall right shift and a median survival of 10 months. Patients with incidentally found brain metastases had significantly better survival than those presenting with deficits (median 13 vs 9 months) (P = .048). Absence of a neurological deficit, recursive partitioning analysis Class I and II, and dose >18 Gy were each associated with a significant survival advantage. CONCLUSION/CONCLUSIONS:SRS for motor cortex metastases is safe in most patients and effective in providing tumor control. Patients treated before neurological deficits develop show better outcomes.

BACKGROUND:There are no effective medical therapies for patients with meningioma who progress beyond surgical and radiotherapeutic interventions. Somatostatin receptor Type 2 (SSTR2) represents a promising treatment target in meningiomas. In this multicenter, single-arm phase II clinical study (NCT03971461), the SSTR2-targeting radiopharmaceutical 177Lu-DOTATATE is evaluated for its feasibility, safety, and therapeutic efficacy in these patients. PATIENTS AND METHODS/METHODS:Adult patients with progressive intracranial meningiomas received 177Lu-DOTATATE at a dose of 7.4 GBq (200 mCi) every eight weeks for four cycles. 68Ga-DOTATATE PET-MRI was performed before and six months after begin of treatment. The primary endpoint was progression-free survival (PFS) at 6 months (PFS-6). Secondary endpoints were safety and tolerability, overall survival (OS) at 12 months (OS-12), median PFS, and median OS. RESULTS:Fourteen patients (F=11, M=3) with progressive meningiomas (WHO 1=3, 2=10, 3=1) were enrolled. Median age was 63.1 (range 49.7-78) years. All patients previously underwent tumor resection and at least one course of radiation. Treatment with 177Lu-DOTATATE was well tolerated. Seven patients (50%) achieved PFS-6. Best radiographic response by modified Macdonald criteria was stable disease (SD) in all seven patients. A >25% reduction in 68Ga-DOTATATE (PET) was observed in five meningiomas and two patients. In one lesion, this corresponded to >50% reduction in bidirectional tumor measurements (MRI). CONCLUSIONS:Treatment with 177Lu-DOTATATE was well tolerated. The predefined PFS-6 threshold was met in this interim analysis, thereby allowing this multicenter clinical trial to continue enrollment. 68Ga-DOTATATE PET may be a useful imaging biomarker to assess therapeutic outcome in patients with meningioma.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Median survival for all patients with breast cancer with brain metastases (BCBMs) has increased in the era of targeted therapy (TT) and with improved local control of intracranial tumors using stereotactic radiosurgery (SRS) and surgical resection. However, detailed characterization of the patients with long-term survival in the past 5 years remains sparse. The aim of this article is to characterize patients with BCBM who achieved long-term survival and identify factors associated with the uniquely better outcomes and to find predictors of mortality for patients with BCBM. METHODS:We reviewed 190 patients with breast cancer with 931 brain tumors receiving SRS who were followed at our institution with prospective data collection between 2012 and 2022. We analyzed clinical, molecular, and imaging data to assess relationship to outcomes and tumor control. RESULTS:The median overall survival from initial SRS and from breast cancer diagnosis was 25 months (95% CI 19-31 months) and 130 months (95% CI 100-160 months), respectively. Sixteen patients (17%) achieved long-term survival (survival ≥5 years from SRS), 9 of whom are still alive. Predictors of long-term survival included HER2+ status ( P = .041) and treatment with TT ( P = .046). A limited number of patients (11%) died of central nervous system (CNS) causes. A predictor of CNS-related death was the development of leptomeningeal disease after SRS ( P = .025), whereas predictors of non-CNS death included extracranial metastases at first SRS ( P = .017), triple-negative breast cancer ( P = .002), a Karnofsky Performance Status of <80 at first SRS ( P = .002), and active systemic disease at last follow-up ( P = .001). Only 13% of patients eventually needed whole brain radiotherapy. Among the long-term survivors, none died of CNS progression. CONCLUSION/CONCLUSIONS:Patients with BCBM can achieve long-term survival. The use of TT and HER2+ disease are associated with long-term survival. The primary cause of death was extracranial disease progression, and none of the patients living ≥5 years died of CNS-related disease.

PURPOSE/OBJECTIVE:The expression of PD-L1 in high-grade meningiomas made it a potential target for immunotherapy research in refractory cases. Several prospective studies in this field are still on going. We sought to retrospectively investigate the effects of check-point inhibitors (CI) on meningiomas that had been naïve to either surgical or radiation approaches by following incidental meningiomas found during treatment with CI for various primary metastatic cancers. METHODS:We used the NYU Perlmutter Cancer Center Data Hub to find patients treated by CI for various cancers, who also had serial computerized-tomography (CT) or magnetic-resonance imaging (MRI) reports of intracranial meningiomas. Meningioma volumetric measurements were compared between the beginning and end of the CI treatment period. Patients treated with chemotherapy during this period were excluded. RESULTS:(21 ± 6% from baseline). We did not find significant predictors of tumor volume reduction. CONCLUSION/CONCLUSIONS:Check-point inhibitors may impact the natural history of meningiomas. Additional research is needed to define potential clinical indications and treatment goals.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Stereotactic radiosurgery (SRS) of larger arteriovenous malformations (AVM) is associated with an elevated incidence of adverse radiation effects (ARE). To date, volume-response and dose-response models have been used to predict such effects. To understand radiological outcomes and their hemodynamic effects on the regional brain. METHODS:A retrospective analysis was conducted at our institution using a prospective registry of patients managed between 2014 and 2020. We included patients with AVM with a nidus larger than 5 cc who received either single-session or volume-staged Gamma Knife radiosurgery. AVM volume changes, volumes of parenchymal response, and obliteration were analyzed and correlated with transit times and diameters of feeding arteries and draining veins. RESULTS:Sixteen patients underwent single-session SRS, and 9 patients underwent volume-staged SRS. The average AVM volume was 12.6 cc (5.5-23). The AVM locations were predominantly lobar (80%) and 17 (68%) were in critical locations. The mean margin dose was 17.2 Gy (15-21), and the median V12Gy was 25.5 cc. Fourteen (56%) AVMs had a transit time shorter than 1 second. The median vein-artery ratio (sum diameter of the veins/sum diameter of feeding arteries) was 1.63 (range, 0.60-4.19). Asymptomatic parenchymal effects were detected in 13 (52%) patients and were symptomatic in 4 (16%) patients. The median time to ARE was 12 months (95% CI 7.6-16.4). On univariate analysis, significant predictors of ARE were lower vein-artery ratio (P = .024), longer transit time (P = .05), higher mean dose (P = .028), and higher D95 (P = .036). CONCLUSION/CONCLUSIONS:Transit times and vessel diameters are valuable predictors of the subsequent parenchymal response after SRS. A more quantitative understanding of blood flow is critical for predicting the effects on the regional brain after AVM radiosurgery.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Advances in targeted therapies and wider application of stereotactic radiosurgery (SRS) have redefined outcomes of patients with brain metastases. Under modern treatment paradigms, there remains limited characterization of which aspects of disease drive demise and in what frequencies. This study aims to characterize the primary causes of terminal decline and evaluate differences in underlying intracranial tumor dynamics in patients with metastatic brain cancer. These fundamental details may help guide management, patient counseling, and research priorities. METHODS:Using NYUMets-Brain-the largest, longitudinal, real-world, open data set of patients with brain metastases-patients treated at New York University Langone Health between 2012 and 2021 with SRS were evaluated. A review of electronic health records allowed for the determination of a primary cause of death in patients who died during the study period. Causes were classified in mutually exclusive, but collectively exhaustive, categories. Multilevel models evaluated for differences in dynamics of intracranial tumors, including changes in volume and number. RESULTS:Of 439 patients with end-of-life data, 73.1% died secondary to systemic disease, 10.3% died secondary to central nervous system (CNS) disease, and 16.6% died because of other causes. CNS deaths were driven by acute increases in intracranial pressure (11%), development of focal neurological deficits (18%), treatment-resistant seizures (11%), and global decline driven by increased intracranial tumor burden (60%). Rate of influx of new intracranial tumors was almost twice as high in patients who died compared with those who survived (P < .001), but there was no difference in rates of volume change per intracranial tumor (P = .95). CONCLUSION/CONCLUSIONS:Most patients with brain metastases die secondary to systemic disease progression. For patients who die because of neurological disease, tumor dynamics and cause of death mechanisms indicate that the primary driver of decline for many may be unchecked systemic disease with unrelenting spread of new tumors to the CNS rather than failure of local growth control.