Management Of Brain Metastases Research Articles

Abstract PS14-08: Clinical factors and association with treatment modalities in patients with breast cancer and brain metastases who develop leptomeningeal disease

Abstract BACKGROUNDImprovements in systemic therapies have led to significantly improved survival in patients with breast cancer and have created a challenge with regards to management of brain metastases (BM) and leptomeningeal disease (LMD). LMD is a highly aggressive condition, resulting in rapid neurological decline and a short survival of weeks to months. The purpose of this study is to identify clinical factors that can predict for LMD when a patient is diagnosed with BM, and to assess outcomes with various treatment modalities.METHODSA retrospective analysis was conducted using a clinical database at a single institution and included 178 patients with breast cancer and treated BM between 2007-2020. Demographic, clinical, radiographic, and dosimetric data were collected. LMD was diagnosed by cytology or neuroimaging. Chi-square and t-test were used.RESULTSOut of 178 patients with breast cancer and treated BM, 41 (23%) developed LMD. Median age for the study cohort was 51.3 +-13.4 years; those with LMD was 47.9 +-12.3 (p=0.057) years. One of the 178 patients was a male and all 41 with LMD were females. There were 58.5% Caucasian women in the LMD group followed by African-American being 24.4% (p=0.31). Characteristics like number of brain lesions (p=0.57), median size of the largest brain lesion (p=0.70), hemorrhagic/cystic lesions (p=0.68), systemic disease being progressive in 42.6%, stable in 19.3% and 26.1% with no evidence of systemic disease at the time of diagnosis of BM (p=0.34) did not pose a higher risk in developing LMD. For 29% patients the brain lesions were supratentorial, 23.7% were infratentorial and 47.4% patients had both and had a higher risk for LMD (p=0.025). Patients with liver (p=0.45) and bone (p=0.48) lesions did not have higher risk for LMD which was seen in those without lung metastases (p=0.03). In the LMD group, 39% had HR+, 31.7% HER2+, and 41.4% had triple negative breast cancer (TNBC). The higher incidence of HR+ patients could be attributed to the fact that the more aggressive HER2+ and TNBC patients may have not gotten treatment for their BM as they pursued comfort care status. In the LMD group, 13.1% received prior stereotactic radiation, 39.5% whole brain radiation, 10.5% had surgery alone and 36.8% had surgery with pre/post-op radiation. Patients who had any surgery did not have a higher risk for LMD (p=0.26). Surgery did not pose a higher risk for local recurrence, seen in 28% patients (p=0.42) and occurrence of BM at another site, seen in 36.5% patients (p=0.16). CONCLUSIONSAmong breast cancer patients with brain metastases those who develop LMD tend to be younger, with higher risk in Caucasians and African-American women; however, this was not statistically significant. The number, size, hemorrhagic/cystic character of brain lesions did not pose a higher risk whereas occurrence of synchronous lesions in supratentorial and infratentorial locations increased risk of LMD. There was no statistically significant difference in the rates of LMD, local recurrence, CNS recurrence at another site with surgery and/or radiation. EthnicityBrain metastases (N=178)LMD group (N=41) (p=0.31)Caucasian58.4%58.5%Hispanic12.4%4.9%African-American19.1%24.2%Others10.1%12.2% Clinical characteristicsBrain metastasesLMD groupP valueNumber of brain lesions (Median interquartile range)3 (1-8)2.5 (1-9)P=0.57Median size of the largest brain lesion (cm)2.4 1.42.53 1.69p=0.70Hemorrhagic lesions223P=0.68Cystic lesions163 Citation Format: Akshjot Puri, Charisma Mylavarapu, Jiagiong Xu, Tejal A Patel, Bin S Teh, Ivo Tremont-Lukats, Jenny C Chang, Polly Niravath. Clinical factors and association with treatment modalities in patients with breast cancer and brain metastases who develop leptomeningeal disease [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-08.

Prognostic Value of 5-ALA Fluorescence, Tumor Cell Infiltration and Angiogenesis in the Peritumoral Brain Tissue of Brain Metastases.

Simple SummaryIn a recent study, we observed 5-ALA fluorescence not only in brain metastases (BM) but also in the peritumoral brain tissue. However, the histopathological correlate of visible 5-ALA fluorescence in the peritumoral brain tissue is not fully understood. Therefore, we safely collected and analyzed tissue samples from fluorescing and non-fluorescing peritumoral brain tissue. Surprisingly, 5-ALA fluorescence in the peritumoral brain tissue did not correlate with tumor cell infiltration but did show a significant relation with angiogenesis. Moreover, the presence of angiogenesis significantly correlated with shorter time to local progression/recurrence and one-year survival. Consequently, angiogenesis in the peritumoral brain tissue might be a novel prognostic marker in BM. This represents the first study in the literature describing the prognostic impact of angiogenesis in fluorescent peritumoral brain tissue of BM, which might support individualized perioperative treatment concepts in the future.Complete resection is an indispensable treatment option in the management of brain metastases (BM). 5-aminolevulinic acid (5-ALA) fluorescence is used for improved intraoperative visualization of tumor tissue in gliomas and was recently observed in BM. We investigated the potential of 5-ALA fluorescence to visualize the infiltrative growth of BM in the peritumoral brain tissue and its histopathological correlate. Patients with BM resection after 5-ALA administration and collection of tissue samples from peritumoral brain tissue were included. Each tissue sample was histopathologically investigated for tumor cell infiltration and angiogenesis. Altogether, 88 samples were collected from the peritumoral brain tissue in 58 BM of 55 patients. Visible 5-ALA fluorescence was found in 61 (69%) of the samples, tumor infiltration in 19 (22%) and angiogenesis in 13 (15%) of samples. Angiogenesis showed a significant correlation with presence of fluorescence (p = 0.008). Moreover, angiogenesis was related to visible 5-ALA fluorescence and showed an association with patient prognosis since it was significantly correlated to shorter time to local progression/recurrence (p = 0.001) and lower one-year survival (p = 0.031). Consequently, angiogenesis in the peritumoral brain tissue of BM might be a novel prognostic marker for individualized perioperative treatment concepts in the future.

Post-operative management of brain metastases: GRADE-based clinical practice recommendations on behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

To perform a systematic review of the current level of evidence on post-operative management following brain metastasectomy (namely: adjuvant stereotactic radiosurgery, whole brain radiotherapy or observation), and to propose a GRADE-based dedicated recommendation to inform Radiation Oncologists' clinical practice. A panel of expert Radiation Oncologists from the Italian Association of Radiotherapy and Clinical Oncology had defined the search question per the PICO methodology. Electronic databases were independently screened; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was adopted. The individual and pooled hazard ratios with 95% confidence intervals (CI), as well as the pooled risk ratio (RR) were calculated using a fixed- or random-effects model. Eight full-texts were retrieved: six retrospective studies and two randomized clinical trials. Outcomes of benefit and damage were analyzed for SRS + observation (PICO A) and SRS + WBRT. SRS allowed for increased rates of local control when compared to both observation and WBRT, while evidence was less conclusive for distant brain control, leptomeningeal disease control and overall survival. In the SRS, the incidence of severe radionecrosis was higher as compared to WBRT, despite neurocognitive deterioration rates were lower. Overall, SRS seems to favorably compare with observation and whole brain RT, despite the level of evidence for the recommendation was low and very low, respectively. Despite low level of evidence, the panel concluded that the risk/benefit ratio probably favors adjuvant SRS as compared to the observation and whole brain RT as adjuvant treatments following brain metastasectomy (5 votes/5 participants, 100% attendance).

18F]FET PET Uptake Indicates High Tumor and Low Necrosis Content in Brain Metastasis.

Simple SummaryVarious types of cancers can lead to brain metastasis. Treatment strategies have improved substantially in the past decade, leading to longer survival in many cases, but also to new diagnostic challenges. Being able to locate those parts of a lesion suspicious for brain metastasis that contain the highest concentrations of viable tumor cells can be crucial, e.g., to obtain a precise diagnosis via targeted biopsies or to differentiate recurring tumor from dead tissue after treatment. Positron emission tomography (PET) imaging has the potential to provide this kind of information. However, studies relating PET findings to actual tissue properties are sparse. The aim of this study was to investigate the association of PET imaging with microscopic tissue properties in samples obtained neurosurgically from brain metastases. Our findings can improve the planning and yield of biopsies from brain metastases, and they may inform future studies aimed at improving the discrimination of recurring from dead tumor in treated brain metastases using PET.Amino acid positron emission tomography (PET) has been employed in the management of brain metastases. Yet, histopathological correlates of PET findings remain poorly understood. We investigated the relationship of O-(2-[18F]Fluoroethyl)-L-tyrosine ([18F]FET) PET, magnetic resonance imaging (MRI), and histology in brain metastases. Fifteen patients undergoing brain metastasis resection were included prospectively. Using intraoperative navigation, 39 targeted biopsies were obtained from parts of the metastases that were either PET-positive or negative and MRI-positive or negative. Tumor and necrosis content, proliferation index, lymphocyte infiltration, and vascularization were determined histopathologically. [18F]FET PET had higher specificity than MRI (66% vs. 56%) and increased sensitivity for tumor from 73% to 93% when combined with MRI. Tumor content per sample increased with PET uptake (rs = 0.3, p = 0.045), whereas necrosis content decreased (rs = −0.4, p = 0.014). PET-positive samples had more tumor (median: 75%; interquartile range: 10–97%; p = 0.016) than PET-negative samples. The other investigated histological properties were not correlated with [18F]FET PET intensity. Tumors were heterogeneous at the levels of imaging and histology. [18F]FET PET can be a valuable tool in the management of brain metastases. In biopsies, one should aim for PET hotspots to increase the chance for retrieval of samples with high tumor cell concentrations. Multiple biopsies should be performed to account for intra-tumor heterogeneity. PET could be useful for differentiating treatment-related changes (e.g., radiation necrosis) from tumor recurrence.

Management of brain metastases from lung cancer in the era of immunotherapy: a review of the literature.

The brain is one of the most frequent sites of metastases in lung cancer patients, whose prognosis is related to the histological, biomolecular and clinical features of the disease. Over the years, the survival hasimproved significantly with the introduction of immune checkpoint inhibitors (ICIs), but there are limited data concerning their efficacy in patients with brain metastases. The aim of this review is to describe the biological mechanisms supporting the use of immunotherapy for brain metastases and the outcomes experienced by lung cancer patients with brain involvement enrolled in Phase III registration trials of ICIs. We also reviewretrospective data on ICIs alone or combined with brain radiotherapy, and indicate future directions for preclinical and clinical research.

SURG-04. SALVAGE RESECTION OF RECURRENT PREVIOUSLY-IRRADIATED BRAIN METASTASES: CLINICAL AND RADIOGRAPHIC OUTCOMES

Abstract BACKGROUND The management of brain metastasis (BrM) recurrence after stereotactic body radiotherapy (SBRT) poses a clinical challenge. The efficacy of salvage resection is undefined, and the role of adjuvant resection cavity reirradiation is unclear given the compounded risk of radiation injury. METHODS Retrospective analysis of previously-irradiated BrM that underwent resection between March 2003 and February 2020 at Memorial Sloan Kettering Cancer Center was performed. Only cases with histopathologic evidence of viable malignancy were included, and specimens were classified by the gross proportion of viable tumor versus treatment effect. Clinical and radiographic parameters were collected. Post-operative recurrence and radiation necrosis were based on RANO-BM criteria and distinguished by histopathologic, radiographic and clinical characteristics. Equivocal cases were adjudicated by a blinded neuroradiologist. RESULTS One-hundred fifty-five resected recurrent BrM following SBRT in 135 patients were evaluated. Seventeen received additional prior whole-brain radiation. Metastases derived from non-small-cell lung (36.8%), melanoma (27.1%), breast (21.3%), renal (3.9%), colorectal (1.9%) and other (9.0%) primary malignancies. Forty-eight (31.0%) had only microscopic malignant disease with extensive necrosis, 44 (28.4%) had mixed or unspecified tumor with treatment effect, and 63 (40.6%) were reported as purely viable tumor by histopathologic report. Thirty-nine (25.2%) post-operative cavities underwent adjuvant reirradiation within 60 days. At 6 and 12 months, local tumor recurrence occurred in 31.6% (95% CI: 24.4%-39.1%) and 40.4% (95% CI: 32.5%-48.2%), respectively, with a proportion of these lesions displaying mixed tumor plus treatment effect. Median overall survival was 13.4 months (95% CI: 10.5-17.7) from salvage resection. CONCLUSIONS Salvage of previously-irradiated BrM remains challenging. This represents the largest known series correlating salvage resection and histopathologically-confirmed viable recurrent BrM with long-term outcomes. Tumor recurrence risk remains high at one year. Further exploration will stratify local progression and radiation necrosis rates by features including extent of resection, degree of viable tumor and adjuvant reirradiation use.

SP-0145: For the motion -consider brain metastases management as a whole

SP-0145: For the motion -consider brain metastases management as a whole

Management of Brain Metastases from Small Cell Lung Cancer using SRS

Management of Brain Metastases from Small Cell Lung Cancer using SRS

Role of Gamma Knife Radiosurgery in Small Cell Lung Cancer: A Multi-Institutional Retrospective Study of the International Radiosurgery Research Foundation (IRRF).

Despite a high incidence of brain metastases in patients with small-cell lung cancer (SCLC), limited data exist on the use of stereotactic radiosurgery (SRS), specifically Gamma Knife™ radiosurgery (Elekta AB), for SCLC brain metastases. To provide a detailed analysis of SCLC patients treated with SRS, focusing on local failure, distant brain failure, and overall survival (OS). A multi-institutional retrospective review was performed on 293 patients undergoing SRS for SCLC brain metastases at 10 medical centers from 1991 to 2017. Data collection was performed according to individual institutional review boards, and analyses were performed using binary logistic regression, Cox-proportional hazard models, Kaplan-Meier survival analysis, and competing risks analysis. Two hundred thirty-two (79%) patients received SRS as salvage following prior whole-brain irradiation (WBRT) or prophylactic cranial irradiation, with a median marginal dose of 18 Gy. At median follow-up after SRS of 6.4 and 18.0 mo for surviving patients, the 1-yr local failure, distant brain failure, and OS were 31%, 49%, and 28%. The interval between WBRT and SRS was predictive of improved OS for patients receiving SRS more than 1 yr after initial treatment (21%, <1 yr vs 36%, >1 yr, P=.01). On multivariate analysis, older age was the only significant predictor for OS (hazard ratio 1.63, 95% CI 1.16-2.29, P=.005). SRS plays an important role in the management of brain metastases from SCLC, especially in salvage therapy following WBRT. Ongoing prospective trials will better assess the value of radiosurgery in the primary management of SCLC brain metastases and potentially challenge the standard application of WBRT in SCLC patients.

Isolated Central Nervous System Metastasis From Neuroendocrine Carcinoma of the Cervix Without Pulmonary Metastasis

Neuroendocrine carcinoma of the cervix (NECC) accounts for 2% of all cervical cancers. Brain metastasis is rare, with few cases described in the literature, and is usually associated with preceding pulmonary metastasis. We describe an additional case of isolated brain metastasis without pulmonary metastasis from NECC and reflect on unique management.A 37-year-old woman with a history of NECC presented with severe headache post-total hysterectomy with pelvic lymph node dissection. The computed tomography (CT) scan demonstrated obstructive hydrocephalus with several intra-axial lesions located in the pineal region, left cerebellar hemisphere, and left frontal operculum. A right frontal ventriculostomy was initially placed to relieve the hydrocephalus. CSF was sent for cytology but was unrevealing. Due to the degree of brainstem compression and the need to obtain a pathologic diagnosis, a posterior fossa craniotomy for the removal of the lesion was performed. Histopathology demonstrated small blue cell tumors positive for neuroendocrine markers consistent with neuroendocrine carcinoma of the cervix. Resection of additional metastasis was not recommended. An endoscopic third ventriculostomy (ETV) was then performed in order to remove the ventriculostomy with success. The patient was then referred to radiation oncology and received whole-brain radiotherapy (WBRT) for a total of 30 Grays (3000 cGy) over 10 fractions. Interval imaging demonstrated complete resolution of the pineal and left frontal lesions. The patient was symptom-free for approximately three months. She then presented with paraplegia consistent with follow-up imaging of her neuraxis, demonstrating drop metastasis in her cervical, thoracic, and lumbar spine. Spinal radiation was given with partial recovery in upper extremity function, however, lower extremity function did not recover. The patient was then transferred to palliative care.There are no guidelines on NECC brain metastasis management. Brain metastasis is associated with reduced longevity. NECC has a propensity for early dissemination and treatment failure. ETV is preferred over ventriculoperitoneal shunting in cases with obstructive hydrocephalus, as it may reduce the risk of tumor seeding. Retrospectively, our patient may have benefitted from upfront craniospinal radiation.

The Role of Stereotactic Radiosurgery in the Management of Brain Metastases From a Health-Economic Perspective: A Systematic Review.

Stereotactic radiosurgery (SRS) is an effective option in the management of brain metastases, offering improved overall survival to whole-brain radiation therapy (WBRT). However, given the need for active surveillance and the possibility of repeated interventions for local/distant brain recurrences, the balance between clinical benefit and economic impact must be evaluated. To conduct a systematic review of health-economic analyses of SRS for brain metastases, compared with other existing intervention options, to determine the cost-effectiveness of this treatment across different clinical scenarios. The MEDLINE, EMBASE, Cochrane, CRD, and EconLit databases were searched for health-economic analyses, according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, using terms relevant to brain metastases and radiation-based therapies. Simple cost analysis studies were excluded. Quality analysis was based on BMJ Consolidated Health Economics Reporting Standards (CHEERS) checklist. Eleven eligible studies were identified. For lesions with limited mass effect, SRS was more cost-effective than surgical resection (6 studies). In patients with Karnofsky performance scale (KPS)>70 and good predicted survival, SRS was cost-effective compared to WBRT (7 studies); WBRT became cost-effective with poor performance status or low anticipated life span. Following SRS, routine magnetic resonance imaging surveillance saved $1326/patient compared to symptomatic imaging due to reduced surgical salvage and hospital stay (1 study). Based on our findings, SRS is cost-effective in the management of brain metastases, particularly in high-functioning patients with longer expected survival. However, before an optimal care pathway can be proposed, emerging factors such as tumor molecular subtype, diagnosis-specific graded prognostic assessment, neuroprognostic score, tailored surveillance imaging, and patient utilities need to be studied in greater detail.

Management of brain metastases according to molecular subtypes.

The incidence of brain metastases has markedly increased in the past 20 years owing to progress in the treatment of malignant solid tumours, earlier diagnosis by MRI and an ageing population. Although local therapies remain the mainstay of treatment for many patients with brain metastases, a growing number of systemic options are now available and/or are under active investigation. HER2-targeted therapies (lapatinib, neratinib, tucatinib and trastuzumab emtansine), alone or in combination, yield a number of intracranial responses in patients with HER2-positive breast cancer brain metastases. New inhibitors are being investigated in brain metastases from ER-positive or triple-negative breast cancer. Several generations of EGFR and ALK inhibitors have shown activity on brain metastases from EGFR and ALK mutant non-small-cell lung cancer. Immune-checkpoint inhibitors (ICIs) hold promise in patients with non-small-cell lung cancer without druggable mutations and in patients with triple-negative breast cancer. The survival of patients with brain metastases from melanoma has substantially improved after the advent of BRAF inhibitors and ICIs (ipilimumab, nivolumab and pembrolizumab). The combination of targeted agents or ICIs with stereotactic radiosurgery could further improve the response rates and survival but the risk of radiation necrosis should be monitored. Advanced neuroimaging and liquid biopsy will hopefully improve response evaluation.

Commentary: The Role of Stereotactic Radiosurgery in the Management of Brain Metastases From a Health-Economic Perspective: A Systematic Review.

Haider, Sameah A MBA, MD; Shank, Christopher D MD, MBA; Walters, Beverly C MD, MSc, FRCSC Author Information

Patterns of palliative care consultation among patients with brain metastasis: an opportunity for radiation oncologists to facilitate earlier referral

Early palliative care (PC) physician involvement alongside standard oncologic care has been recommended by the American Society of Clinical Oncology (ASCO) guidelines for all advanced cancer patients, although adherence to these guidelines is variable. Radiation oncologists (ROs) could help facilitate early PC referral for patients treated with palliative radiation, particularly those with brain metastasis (BRM), and the aim of this study was to evaluate the circumstances of PC referral at our institution to better understand the multidisciplinary approaches to facilitate it. Patients diagnosed with BRM from non-small cell lung cancer (NSCLC) from 2012 to 2018 whose primary RO and MO were at our institution were reviewed. Overall survival and time to PC consultation from the first oncologic visit following BRM diagnosis was determined using the KaplanMeier method. Mann-Whitney U and Chi-Squared assessed for predictive factors for shorter time to PC consultation. For these factors, the overall survival, rate of PC consultation, and PC setting was used to determine utilization of early PC. Among 103 eligible patients, only 48% underwent a PC consultation in their lifetime, with the initial evaluation being as an outpatient for 37%, and within 1 month of death for 35%. Median survival from BRM diagnosis was 9.0 months. The median time from oncologic appointment to PC referral was 2.8 months, and from initial PC consultation to death was 1.6 months. Only more recent BRM diagnosis (2016-2018 vs. 2012-2015) was associated with shorter time to PC consultation (1.0 vs. 5.6 months, P=0.013), increased PC consult rate (60% vs. 42%, P=0.105), and increased outpatient PC consultation (56% vs. 26%, P=0.037). The majority of patients did not undergo early PC consultation, though utilization has improved over time. As ROs are commonly involved in BRM management, they may be in a position to proactively support early PC consultations in this patient population.

Tumor Primary Site and Histology Subtypes Role in Radiotherapeutic Management of Brain Metastases.

Randomized controlled trials have failed to report any survival advantage for WBRT combined with SRS in the management of brain metastases, despite the enhanced local and distant control in comparison to each treatment alone. Literature review have revealed important role of primary histology of the tumor when dealing with brain metastases. NSCLC responds better to combined approach even when there was only single brain metastasis present while breast cancer has registered better survival with SRS alone probably due to better response of primary tumor to advancement in surgical and chemotherapeutic agents. Furthermore, mutation status (EGFR/ALK) in lung cancer and receptor status (ER/PR/HER2) in breast cancer also exhibit diversity in their response to radiotherapy. Radioresistant tumors like renal cell carcinoma and melanoma brain metastases have achieved better results when treated with SRS alone. Secondly, single brain metastasis may benefit from local and distant brain control achieved with combined treatment. These diverse outcomes suggest a primary histology-based analysis of the radiotherapy regimens (WBRT, SRS, or their combination) would more ideally establish the role of radiotherapy in the management of brain metastases. Molecularly targeted therapeutic and immunotherapeutic agents have revealed synergism with radiation therapy particularly SRS in treating cancer patients with brain metastases. Clinical updates in this regard have also been reviewed.

Disparities in the treatment of brain metastases from breast cancer: Insights from the National Cancer Database.

2037 Background: Breast cancer is the most common malignancy in women accounting for over 300,000 cases per year. Unfortunately, brain metastases are found in a sub-group of patients with breast cancer even at presentation. Management of brain metastases typically includes radiotherapy with conventional whole brain radiation therapy (WBRT) or more focused stereotactic radiosurgery (SRS). We queried the National Cancer Database (NCDB) to analyze the incidence of brain metastases at diagnosis in breast cancer patients, as well as trends in radiation use/technique. Methods: The NCDB was queried for patients who were diagnosed with breast cancer between 2004-2015 and had brain metastasis at presentation (N = 4,491). We excluded patients without brain radiation and inadequate follow up. Odds ratios were calculated to identify factors associated with treatment. Multivariable cox regression was used to determine predictors of survival. Results: Using the eligibility criteria above 1,505 patients were identified in the NCDB. The cohort had a median age of 58 years. A small portion were uninsured (7%) population uninsured and 81% of radiation treatments were delivered in metropolitan areas. Two hundred sixty-one (17.3%) patients received SRS while 1,244 (82.7%) received WBRT. Those patients with private insurance, higher income, metro location, and having care delivered at an academic center were more likely to receive SRS. Conversely, the likelihood of receiving WBRT was significantly higher in those with luminal type cancer, African Americans, the uninsured, and those located in urban areas or treated at a community cancer center. On Cox regression, predictors of worse survival were age &gt; 60 with Hazard Ratio (HR) 1.3 (95% CI 1.17-1.49), a comorbidity score &gt; 2 with HR 1.45 (95% CI 1.1-1.9), and extra cranial metastatic disease with HR 1.33 (95% CI 1.15-1.54). Conclusions: This analysis of the NCDB demonstrates socioeconomic and demographic disparities in the treatment of patients with brain metastases from breast cancer. There is a continued need to reduce these disparities and improve access to care for at-risk populations affected by this highly prevalent malignancy.

Preoperative Radiosurgery in Management of Brain Metastases

Brain metastases (BMs), the most frequent intracranial tumors, are diagnosed in approximately 30% of all adult patients over the span of planned treatment against a broad spectrum of solid cancers. The prognosis of patients presenting with BM is bleak with an expected median OS of only 4-7 months. However, some particular patients’ groups may enjoy longer survival durations with effective systemic and local therapies. At present, the feasible alternatives for active management of BMs typically include the whole-brain radiotherapy (WBRT), surgery, definitive SRS, postoperative SRS, systemic chemotherapy, targeted therapies, and their combination variants. Considering the local treatment, the severe neurotoxic effects of WBRT, and the increased risk for radionecrosis and leptomeningeal dissemination after postoperative SRS and together with the ineligibility of certain patients during the postoperative period prompted the energetic quest of alternative treatment strategies for such patients. In this respect, the novel preoperative SRS (PO-SRS) was proposed to provide at least equivalent local control rates with lesser radionecrosis and leptomeningeal dissemination risk. Respecting the scarcity of related literature, the present review aimed to meticulously detail theplausible rationale and accessible evidence for the novel PO-SRS in the management of patients presenting with BMs.

The rationale and toxicity of combined cranial radiotherapy and immune checkpoint inhibitors in non‐small cell lung cancer

Cranial radiation therapy (CRT) remains to be the foundation stone of the management of brain metastases in non-small cell lung cancer (NSCLC). Nevertheless, the care of NSCLC, recently, has been remarkably reshaped by the immune checkpoint inhibitors (ICIs), such as programmed death protein-1 and programmed death ligand-1 inhibitors, which even showed some efficacy in brain metastases. Furthermore, radiotherapy, traditionally regarded as a therapy via localized cytotoxicity, recently was reported to trigger a systemic immune response, thus probably enhancing the antitumor effect of ICIs. Preliminary datasets confirmed that the combination of these two therapies seemed superior to either monotherapy in NSCLC patients with brain metastases with improved efficacy and comparable toxicity. In this review, we started with discussing the rationale for the combination of CRT and ICIs, then outlined the clinical evidence supporting the high safety of this combined therapy, and finally made a preliminary conclusion on the safety of the combination of CRT and ICIs.

Integration of immuno-oncology with stereotactic radiosurgery in the management of brain metastases.

Brain metastases traditionally carried a poor prognosis with treatment being a combination of surgery, whole-brain radiation therapy, and glucocorticoids; however, this treatment paradigm carried a significant amount of morbidity. In recent years, stereotactic radiosurgery (SRS), which involves the delivery of a highly conformal dose of radiation over a single session, has been shown to be an effective alternative to WBRT with excellent rates of local control and improved quality of life; however, a survival benefit has not been demonstrated. Recent developments have challenged the traditional view of the central nervous system being "immunologically privileged" which has led to a greater focus on treating these patients with systemic therapies. Immune checkpoint inhibitors (ICI) have been shown to improve survival in multiple malignancies. As a result, there has been increased utilization in combining these therapies in this setting. We conducted a literature search of medical databases (e.g. PubMed) for articles involving the use of immune checkpoint inhibitors and stereotactic radiosurgery in managing brain metastases. Published evidence utilizing SRS and ICI is largely limited to single institution and retrospective in nature with the most common histology being melanoma. Combination therapy with SRS and ICI appears to improve survival in patients with brain metastases. The available data are largely retrospective; therefore, ongoing and planned prospective studies are needed to further validate these findings.

Management of brain metastases in breast cancer: a review of current practices and emerging treatments.

Breast cancer brain metastases (BCBM) are becoming an increasingly common diagnosis due to improved systemic control and more routine surveillance imaging. Treatment continues to require a multidisciplinary approach managing systemic and intracranial disease burden. Although, improvements have been made in the diagnosis and management of BCBM, brain metastasis patients continue to pose a challenge for practitioners. In this review, a group of medical oncologists, radiation oncologists, radiologists, breast surgeons, and neurosurgeons specializing in the treatment of breast cancer reviewed the available published literature and compiled a comprehensive review on the current state of BCBM. We discuss the pathogenesis, epidemiology, diagnosis, treatment options (including systemic, surgical, and radiotherapy treatment modalities), and treatment response evaluation for BCBM. Furthermore, we discuss the ongoing prospective trials enrolling BCBM patients and their biologic rationale. BCBM management is an increasing clinical concern. Multidisciplinary management combining the strengths of surgical, systemic, and radiation treatment modalities with prospective trials incorporating knowledge from the basic and translational sciences will ultimately lead to improved clinical outcomes for BCBM patients.