Improved outcomes for triple negative breast cancer brain metastases patients after stereotactic radiosurgery and new systemic approaches.

PURPOSE: 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.

Long-term radiographic and endocrinological outcomes of stereotactic radiosurgery for recurrent or residual nonfunctioning pituitary adenomas.

OBJECTIVE: Stereotactic radiosurgery (SRS) is used for the treatment of residual/recurrent nonfunctional pituitary adenoma (NFPA). The aim of this study was to evaluate the factors related to long-term tumor control and delayed endocrinopathies following SRS. METHODS: This retrospective, multicenter study included patients with recurrent/residual NFPA treated with single-fraction SRS; they were then divided into two arms. The first arm included patients with at least 5 years of radiographic follow-up and all patients with local tumor progression. The second arm included patients with at least 5 years of endocrinological follow-up and all patients who developed endocrinopathy. Study endpoints were tumor control and new or worsening hypopituitarism after SRS and were analyzed using Cox regression and Kaplan-Meier methodology. RESULTS: There were 360 patients in the tumor control arm (median age 52.7 [IQR 42.9-61] years, 193 [53.6%] males) and 351 patients in the hypopituitarism arm (median age 52.5 [IQR 43-61] years, 186 [53.0%] males). The median follow-up in the tumor control evaluation group was 7.95 (IQR 5.7-10.5) years. Tumor control rates at 5, 8, 10, and 15 years were 93% (95% CI 90%-95%), 87% (95% CI 83%-91%), 86% (95% CI 82%-90%), and 69% (95% CI 59%-81%), respectively. The median follow-up in the endocrinopathy evaluation group was 8 (IQR 5.9-10.7) years. Pituitary function preservation rates at 5, 8, 10, and 15 years were 83% (95% CI 80%-87%), 81% (95% CI 77%-85%), 78% (95% CI 74%-83%), and 71% (95% CI 63%-79%), respectively. A margin dose > 15 Gy (HR 0.8, 95% CI 0.7-0.9; p < 0.001) and a delay from last resection to SRS > 1 year (HR 0.9, 95% CI 0.7-0.9; p = 0.04) were significant factors related to tumor control in multivariable analysis. A maximum dose to the pituitary stalk ≤ 10 Gy (HR 1.1, 95% CI 1.09-1.2; p < 0.001) was associated with pituitary function preservation. New visual deficits after SRS occurred in 7 (1.94%) patients in the tumor control group and 8 (2.3%) patients in the endocrinopathy group. Other new cranial nerve deficits post-SRS occurred in 4 of 160 patients with data in the tumor control group and 3 of 140 patients with data in the endocrinopathy group. CONCLUSIONS: SRS affords favorable and durable tumor control for the vast majority of NFPAs. Post-SRS hypopituitarism occurs in a minority of patients, but this risk increases with time and warrants long-term follow-up.

Upfront stereotactic radiosurgery versus adjuvant radiosurgery for parasagittal and parafalcine meningiomas: a systematic review and meta-analysis.

Parafalcine and parasagittal (PFPS) are common locations for meningiomas. Surgical resection for these tumors, the first-line treatment, poses challenges due to their proximity to critical structures. This systematic review investigates the use of stereotactic radiosurgery (SRS) as a treatment for PFPS meningiomas, aiming to elucidate its safety and efficacy. The review adhered to PRISMA guidelines. Searches were conducted on MEDLINE, Embase, and Cochrane. Inclusion criteria involved studies on SRS for PFPS meningiomas, reporting procedure outcomes and complications. Tumors were presumed or confirmed to be WHO grade 1. Data was systematically extracted. Meta-analysis was performed where applicable. The review included data from eight studies, 821 patients with 878 lesions. Tumor control was achieved in greater than 80% of cases. Adverse radiation effects were reported in 7.3% of them. Recurrence and further surgical approach were observed in 17.1% and 9.2% of cases, respectively. Symptom improvement was noted in 33.2% of patients. Edema occurred in approximately 25.1% of patients. A subgroup of 283 patients had upfront SRS, achieving tumor control in approximately 97% of such cases. SRS is a safe and effective treatment for PFPS meningiomas, both as an adjuvant therapy and as an upfront treatment for often smaller tumors. Post-SRS edema can typically be managed medically and usually does not require further surgical intervention. Further studies should provide more specific data on PFPS meningiomas. The use of single and hypofractionated SRS for larger volume PFPS meningiomas should be more explored to better define the risks and benefits.

Simultaneous Parkinsonism and Dementia as Initial Presentation of Intracranial Dural Arteriovenous Fistulas: A Systematic Review.

BACKGROUND: Intracranial dural arteriovenous fistulas (IDAVFs) are abnormal vascular connections between dural arteries and various venous structures within the brain. IDAVFs, rarely present with parkinsonism and dementia concurrently, making this a unique and underexplored clinical scenario. To the best of our knowledge, this is the first systematic review to comprehensively analyze cases of IDAVFs manifesting as both parkinsonism and dementia. METHODS: We assessed databases from inception to September 18, 2023. We identified studies describing patients with IDAVFs initially presenting with dementia or parkinsonism. Inclusion criteria encompassed case reports and case series, while excluding review articles, guidelines, technical notes, comments, conference abstracts, and editorials. RESULTS: The systematic search resulted in the initial screening of 383 studies, with 33 articles meeting the inclusion criteria. Among these, 29 were case reports, often describing 3 or fewer patients. From the remaining 4 case series, data pertinent to patients presenting both parkinsonism and dementia were selectively extracted, yielding a total study population of 43 patients. The anatomical distribution of IDAVFs within this cohort was diverse, with the transverse and sigmoid sinuses being the most common locations. Although most of these patients received endovascular therapy, a few underwent microsurgical occlusion or combined surgical and endovascular treatment. CONCLUSIONS: IDAVFs presenting with both parkinsonism and dementia represent a rare clinical entity. This systematic review provides valuable insights into the clinical characteristics, treatment options, and outcomes for such cases. However, additional research involving larger cohorts is essential to better comprehend the underlying mechanisms and establish standardized therapeutic guidelines.

Long-term Survival From Breast Cancer Brain Metastases in the Era of Modern Systemic Therapies.

BACKGROUND AND OBJECTIVES: 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: 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.

Impact of Multiple Sclerosis Subtypes on Pain Management in Patients With Trigeminal Neuralgia After Stereotactic Radiosurgery: An International Multicenter Analysis.

BACKGROUND AND OBJECTIVES: Trigeminal neuralgia affects approximately 2% of patients with multiple sclerosis (MS) and often shows higher rates of pain recurrence after treatment. Previous studies on the effectiveness of stereotactic radiosurgery (SRS) for trigeminal neuralgia did not consider the different MS subtypes, including remitting relapsing (RRMS), primary progressive (PPMS), and secondary progressive (SPMS). Our objective was to investigate how MS subtypes are related to pain control (PC) rates after SRS. METHODS: We conducted a retrospective multicenter analysis of prospectively collected databases. Pain status was assessed using the Barrow National Institute Pain Intensity Scales. Time to recurrence was estimated through the Kaplan-Meier method and compared groups using log-rank tests. Logistic regression was used to calculate the odds ratio (OR). RESULTS: Two hundred and fifty-eight patients, 135 (52.4%) RRMS, 30 (11.6%) PPMS, and 93 (36%) SPMS, were included from 14 institutions. In total, 84.6% of patients achieved initial pain relief, with a median time of 1 month; 78.7% had some degree of pain recurrence with a median time of 10.2 months for RRMS, 8 months for PPMS, 8.1 months for SPMS (P = .424). Achieving Barrow National Institute-I after SRS was a predictor for longer periods without recurrence (P = .028). Analyzing PC at the last available follow-up and comparing with RRMS, PPMS was less likely to have PC (OR = 0.389; 95% CI 0.153-0.986; P = .047) and SPMS was more likely (OR = 2.0; 95% CI 0.967-4.136; P = .062). A subgroup of 149 patients did not have other procedures apart from SRS. The median times to recurrence in this group were 11.1, 9.8, and 19.6 months for RRMS, PPMS, and SPMS, respectively (log-rank, P = .045). CONCLUSION: This study is the first to investigate the relationship between MS subtypes and PC after SRS, and our results provide preliminary evidence that subtypes may influence pain outcomes, with PPMS posing the greatest challenge to pain management.

Stereotactic radiosurgery for non-functioning pituitary tumor: a multicenter study of new pituitary hormone deficiency.

BACKGROUND: Stereotactic radiosurgery (SRS) is used to treat recurrent or residual nonfunctioning pituitary neuroendocrine tumors (NFPA). The objective of the study was to assess imaging and development of new pituitary hormone deficiency. METHODS: Patients treated with single-session SRS for a NFPA were included in this retrospective, multicenter study. Tumor control and new pituitary dysfunction were evaluated using Cox analysis and Kaplan-Meier curves. RESULTS: 869 patients (male 476 [54.8%], median age at SRS 52.5 years [Interquartile range (IQR):18.9]) were treated using a median margin dose of 14Gy (IQR:4) for a median tumor volume of 3.4 cc (IQR: 4.3). With a median radiological follow-up of 3.7 years (IQR: 4.8), volumetric tumor reduction occurred in 451 patients (51.9%), stability in 364 (41.9%) and 54 patients (6.2%) showed tumor progression.The probability of tumor control was 95.5% (95% Confidence Interval [CI]: 93.8-97.3) and 88.8% (95%CI: 85.2-92.5) at 5 and 10 years, respectively. A margin dose >14 Gy was associated with tumor control (Hazard Ratio HR:0.33 [95%CI:0.18-0.60], p<0.001).The probability of new hypopituitarism was 9.9% (95% CI: 7.3-12.5) and 15.3% (95% CI:11-19.4) at 5 and 10 years, respectively.A maximum point dose >10 Gy in the pituitary stalk was associated with new pituitary hormone deficiency (HR:3.47, 95% CI:1.95-6.19). The cumulative probability of new cortisol, thyroid, gonadotroph and growth hormone deficiency was 8% (95% CI:3.9-11.9), 8.3% (95% CI:3.9-12.5), 3.5% (95% CI:1.7-5.2), and 4.7% (95% CI:1.9-7.4), respectively at 10 years. CONCLUSION: SRS provides long-term tumor control with a 15.3% risk of hypopituitarism at 10 years.

EGFR-mutated non-small lung cancer brain metastases and radiosurgery outcomes with a focus on leptomeningeal disease.

PURPOSE: Patients with EGFR-mutated NSCLC represent a unique subset of lung cancer patients with distinct clinical and molecular characteristics. Previous studies have shown a higher incidence of brain metastases (BM) in this subgroup of patients, and neurologic death has been reported to be as high as 40% and correlates with leptomeningeal disease (LMD). METHODS: Between 2012 and 2021, a retrospective review of our prospective registry identified 606 patients with BM from NSCLC, with 170 patients having an EGFR mutation. Demographic, clinical, radiographic, and treatment characteristics were correlated to the incidence of LMD and survival. RESULTS: LMD was identified in 22.3% of patients (n = 38) at a median follow-up of 19 (2-98) months from initial SRS. Multivariate regression analysis showed targeted therapy and a cumulative number of metastases as significant predictors of LMD (p = 0.034, HR = 0.44), (p = .04, HR = 1.02). The median survival time after SRS of the 170 patients was 24 months (CI 95% 19.1-28.1). In a multivariate Cox regression analysis, RPA, exon 19 deletion, and osimertinib treatment were significant predictors of overall survival. The cumulative incidence of neurological death at 2 and 4 years post initial stereotactic radiosurgery (SRS) was 8% and 11%, respectively, and correlated with LMD. CONCLUSION: The study shows that current-generation targeted therapy for EGFR-mutated NSCLC patients may prevent the development and progression of LMD, leading to improved survival outcomes. Nevertheless, LMD is associated with poor outcomes and neurologic death, making innovative strategies to treat LMD essential.

Unusual Intraventricular Bullet Migration During Operation: A Case Report on Treatment Strategies.

Gunshot head injuries are increasingly prevalent in the urban setting and carry complex technical and clinical decision-making challenges to practicing neurosurgeons. Here, we present a unique case of a patient who suffered a gunshot injury and presented to the emergency department with an intraventricular bullet lodgment without significant neurological deficits. The patient was rushed to the operating room to remove the bullet after neuroimaging demonstrated its migration inside the ventricular system. The patient showed a favorable outcome postoperatively. This case report highlights the importance of prompt diagnosis and tailored management strategies in cases of intraventricular bullet lodgment.

Quantitative Analysis of Parenchymal Effects and Flow of Large Arteriovenous Malformations Managed With Stereotactic Radiosurgery.

BACKGROUND AND OBJECTIVES: 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: 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.

Translation and cultural validation of the Revised Illness Perception Questionnaire for Healthcare Professionals for Brazilian Portuguese.

BACKGROUND: Multiple sclerosis progression and disability can be rated differently by healthcare professionals. Therefore, how physicians perceive the disease can impact treatment decisions. There are no previous studies on this matter. OBJECTIVE: To translate and transculturally validate the Revised Illness Perception Questionnaire for Healthcare Professionals (IPQ-R HP), for use in Brazilian Portuguese. METHODS: The process used to validate the IPQ-R HP was based on the steps presented in the guide proposed by Dorcas Beaton. The final version of the IPQ-R HP had 38 questions, divided into seven different dimensions to assess the patient's disease. Also, two clinical cases that were representative of real-life patients with multiple sclerosis (MS) were assembled to consider the two main profiles of the disease. We applied the questionnaire to neurologists at the Federal University of São Paulo (UNIFESP) to assess their perception of MS. These doctors also answered a brief survey to establish the profile of the interviewees. For statistical analysis, we used Bayesian CFA models and kappa statistics. CONCLUSIONS: The kappa statistics showed a general agreement of 0.4. For the Bayesian CFAs with seven-factor correlation solution, we had a poor fit for case 1 with a 95% confidence interval ranging from -52.893 to 273.797 and a PPP of 0.107. Regarding case 2, the model did not converge even after 50,000 iterations, which indicated that the specified model (i.e. seven-factor correlation solution) for case 2 was inadmissible. Thus, the IPQ-R HP questionnaire in Brazilian Portuguese has not been validated.

Translation and cultural validation of the Revised Illness Perception Questionnaire for Healthcare Professionals for Brazilian Portuguese / Tradução e validação cultural do Questionário de Percepção de Doença Revisado para Profissionais de Saúde em português brasileiro

ABSTRACT Background: Multiple sclerosis progression and disability can be rated differently by healthcare professionals. Therefore, how physicians perceive the disease can impact treatment decisions. There are no previous studies on this matter. Objective: To translate and transculturally validate the Revised Illness Perception Questionnaire for Healthcare Professionals (IPQ-R HP), for use in Brazilian Portuguese. Methods: The process used to validate the IPQ-R HP was based on the steps presented in the guide proposed by Dorcas Beaton. The final version of the IPQ-R HP had 38 questions, divided into seven different dimensions to assess the patient's disease. Also, two clinical cases that were representative of real-life patients with multiple sclerosis (MS) were assembled to consider the two main profiles of the disease. We applied the questionnaire to neurologists at the Federal University of São Paulo (UNIFESP) to assess their perception of MS. These doctors also answered a brief survey to establish the profile of the interviewees. For statistical analysis, we used Bayesian CFA models and kappa statistics. Conclusions: The kappa statistics showed a general agreement of 0.4. For the Bayesian CFAs with seven-factor correlation solution, we had a poor fit for case 1 with a 95% confidence interval ranging from -52.893 to 273.797 and a PPP of 0.107. Regarding case 2, the model did not converge even after 50,000 iterations, which indicated that the specified model (i.e. seven-factor correlation solution) for case 2 was inadmissible. Thus, the IPQ-R HP questionnaire in Brazilian Portuguese has not been validated.

RESUMO Antecedentes: A progressão da esclerose múltipla e a incapacidade podem ser avaliadas de formas diferentes por médicos. Portanto, a forma como estes percebem a doença pode afetar as decisões de tratamento. Não há estudos anteriores sobre o assunto. Procuramos traduzir e validar o Revised Illness Perception Questionnaire-Revised Healthcare Professionals (IPQ-R HP). Objetivos: Validação transcultural da versão IPQ-R HP para português. Métodos: O processo de validação do IPQ-R HP foi baseado nas etapas apresentadas no guia proposto por Dorcas Beaton. A versão final do IPQ-R HP continha 38 questões, divididas em sete dimensões diferentes para avaliar a doença do paciente. Além disso, dois casos clínicos representativos de esclerose múltipla (EM) foram criados para contemplar os dois perfis principais da doença. Aplicamos o questionário a neurologistas da UNIFESP para avaliar sua percepção sobre a EM, além de uma pesquisa para estabelecer o perfil dos entrevistados. Para a análise estatística, usamos modelos CFA Bayesianos e estatísticas kappa. Conclusões: A estatística kappa mostrou concordância geral de 0,4. Para os CFAs bayesianos com solução de sete fatores correlacionados, tivemos um ajuste ruim para o caso 1 com um intervalo de confiança de 95% variando de -52,893 a 273,797 e o PPP de 0,107. Em relação ao Caso 2, o modelo não convergiu mesmo após 50000 iterações, indicando que o modelo especificado (ou seja, solução de sete fatores correlacionados) para o caso 2 é inadmissível. Assim, o questionário IPQ-R HP em português não é validado.