Search Results (41)

Background: Burkitt lymphoma is a rare, aggressive B-cell neoplasm with frequent central nervous system (CNS) involvement, treated with intensive multidrug regimens associated with rituximab. The aim of this study was to assess the efficacy, safety, and feasibility of the LMB protocol in adults with BL in a real-world setting. Methods: We included 55 patients with BL diagnosis according to the 2008 WHO classification, treated with LMB protocol associated with rituximab. Low-risk patients (no bone marrow or CNS involvement) were treated in the group B arm, while high-risk patients were placed in group C, which was further stratified by age and CNS infiltration. Results: Thirty-four patients (62%) were treated in group B and 21 patients (38%) were treated in group C, with a median age of 34 years (16–77). Extranodal infiltration was present in 71% patients, including 11 (20%) with CNS involvement. After a median follow up time of 7 years, the complete remission rate was 85%, and progression-free and overall survival at 3 years were 79% and 84%, respectively. Patients with CNS infiltration had an inferior survival rate (55% at 3 years). Grade 3–4 toxicities were frequent, mainly hematologic, infectious, and mucosal. Treatment required substantial supportive care, including 1604 transfusions and 4696 days of hospitalization. Patients over 60 years had poorer outcomes and higher toxicity. Conclusions: The LMB protocol demonstrated high survival rates in adult BL, although at the cost of significant toxicity and considerable health care resource utilization. Outcomes remained suboptimal in patients with CNS involvement despite treatment intensification. Full article

Background/Objectives: Astrocytoma, IDH-mutant, CNS WHO grade 3, is a diffuse glioma with poor prognosis, molecularly defined by IDH mutations and frequently co-occurring TP53 and ATRX alterations. This study aimed to delineate the genomic landscape and identify clinically relevant molecular features of astrocytoma, IDH-mutant, CNS WHO grade 3 using this resource. Methods: Patients in the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (AACR Project GENIE) database were selected based on histological diagnosis of “anaplastic astrocytoma”, confirmed IDH1/2 mutation, and exclusion of CDKN2A/B homozygous deletions. We analyzed frequencies of somatic mutations, copy number alterations (CNAs), structural variants (SVs), assessed co-occurrence/exclusivity patterns, and explored associations with available demographic and limited survival data. Results: The most common somatic mutations were in IDH1 (98.0%), TP53 (94.8%), and ATRX (55.2%). The observed ATRX mutation frequency was lower than some historical reports (e.g., ~86%). Other recurrent alterations included phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) (6.9%), Notch receptor 1 (NOTCH1) (6.9%), and platelet-derived growth factor receptor alpha (PDGFRA) (mutations 4.3%; CNAs also observed). Conclusions: This study provides a comprehensive genomic characterization of astrocytoma, IDH-mutant, CNS WHO grade 3 using the AACR GENIE database, confirming core mutational signatures while also highlighting potential variations in alteration frequencies, such as for ATRX. The findings establish a valuable real-world genomic benchmark for this tumor type, while promoting the need for continued data integration with robust clinical outcomes to identify actionable prognostic and therapeutic targets. Full article

Background/Objectives: Recurrent meningiomas remain difficult to manage due to the absence of effective systemic therapies and comparatively high treatment failure rates, particularly in high-grade tumors. Stereotactic radiosurgery (SRS) offers a minimally-invasive and precise option, particularly for tumors in surgically complex locations. However, the risks associated with re-irradiation, and recent changes in the WHO classification of CNS tumors highlight the need for more personalized and strategic treatment approaches. This systematic review evaluates the safety, efficacy, and clinical considerations for use of SRS for recurrent meningiomas. Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature search was conducted using the PubMed, Scopus, and Web of Science databases for studies reporting outcomes of SRS in recurrent, pathologically confirmed intracranial meningiomas. Studies were excluded if they were commentaries, reviews, case reports with fewer than three cases, or had inaccessible full text. The quality and risk of bias of the included studies were assessed using the modified Newcastle-Ottawa Scale. Data on patient and tumor characteristics, SRS treatment parameters, clinical outcomes, adverse effects, and statistical analysis results were extracted. Results: Sixteen studies were included. For WHO Grade I tumors, 3- to 5-year progression-free survival (PFS) ranged from 85% to 100%. Grade II meningiomas demonstrated more variable outcomes, with 3-year PFS ranging from 23% to 100%. Grade III tumors had consistently poorer outcomes, with reported 1-year and 2-year PFS rates as low as 0% and 46%, respectively. SRS performed after surgery alone was associated with superior outcomes, with local control rates of 79% to 100% and 5-year PFS ranging from 40.4% to 91%. In contrast, tumors previously treated with radiotherapy, with or without surgery, showed substantially poorer outcomes, with 3- to 5-year PFS ranging from 26% to 41% and local control rates as low as 31%. Among patients with prior radiotherapy, outcomes were particularly poor in Grade II and III recurrent tumors. Toxicity rates ranged from 3.7% to 37%, and were generally higher for patients with prior radiation. Predictors of worse PFS included prior radiation, older age, and Grade III histology. Conclusions: SRS may represent a reasonable salvage option for carefully selected patients with recurrent meningioma, particularly following surgery alone. Outcomes were notably worse in high-grade recurrent meningiomas following prior radiotherapy, emphasizing the prognostic significance of both histological grade and treatment history. Notably, the lack of molecular and genetic data in most existing studies represents a key limitation in the current literature. Future prospective studies incorporating molecular profiling may improve risk stratification and support more personalized treatment strategies. Full article

Objective: Central neurocytomas (CNs), classified as CNS (central nervous system) grade 2 tumors, are exceptionally rare tumors, accounting for approximately 0.1–0.5% of all intracranial neoplasms, and are typically characterized by a benign clinical course and frequent association with hydrocephalus. This study aims to present a comprehensive analysis of surgical and adjuvant therapies for CN. Methods: The study comprised all patients who underwent microsurgical tumor removal in our center over the past decade (2013–2023). Clinical manifestations, surgical and adjuvant therapy approaches, MRI and histological findings, clinical outcomes, and recurrence-free survival were evaluated. Results: A total of eleven patients (six men, mean age of 28.0 years; five women, mean age of 53.6 years) underwent surgical treatment. Intraventricular tumors were the most common (72.7%, n = 8). The predominant presenting symptoms were headache and visual disturbances. All tumors exhibited contrast enhancement on MRI. Hydrocephalus was present in five patients. The Ki67 proliferation index ranged from 2% to 10%, with nine patients exhibiting Ki67 > 3%. The median recurrence-free survival was 38.0 months (IQR: 25.0–53.0). The most severe postoperative complications included aphasia, hemiparesis, and memory impairment, resulting in a postoperative Karnofsky Performance Status (KPS) below 70% in five patients. Follow-up assessments showed significant symptomatic improvement in all affected patients. Conclusions: Gross total resection is the recommended first-line therapy with favorable neurological outcomes and for atypical CN as well. Adjuvant radiotherapy should be reserved for tumor progression and recurrence. The role of adjuvant chemotherapy remains unclear, but it may be an option for CN with a high proliferation index. Full article

Background/Objectives: This study evaluates intratumoral susceptibility signals (ITSS) as imaging markers for glioma grade prediction and their association with molecular and histopathologic features, in the context of the fifth edition of the World Health Organization Classification of Tumors of the Central Nervous System (WHO CNS5). Methods: We retrospectively analyzed patients with adult diffuse gliomas who underwent pretreatment magnetic resonance imaging. ITSS were semiquantitatively graded by two radiologists: grade 0 (no signal), grade 1 (1–5), grade 2 (6–10), and grade 3 (≥11). Relative cerebral blood volume (rCBV) and tumor volume were also obtained. Histopathologic features included tumor grade, Ki-67, mitotic count, necrosis, microvascular proliferation, and molecular alterations (isocitrate dehydrogenase [IDH], 1p/19q, cyclin-dependent kinase inhibitors 2A and 2B [CDKN2A/B], and p53). Regression models predicted tumor grade (low: 1–2, high: 3–4) using ITSS, tumor volume, and rCBV. ROC curves and diagnostic performance metrics were analyzed. Results: 99 patients were included. ITSS grading correlated with rCBV, tumor volume, mitotic count, Ki-67, and tumor grade (p < 0.001). ITSS grades 0–1 were associated with oligodendrogliomas and astrocytomas (p < 0.001), IDH mutations (p < 0.001), and 1p/19q co-deletions (p = 0.01). ITSS grades 2–3 were linked to glioblastomas (p < 0.001), necrosis (p < 0.001), microvascular proliferation (p < 0.001), and CDKN2A/B homozygous deletions (p = 0.02). Models combining ITSS with rCBV and volume showed AUC of 0.94 and 0.96 (p < 0.001), outperforming univariate models. Conclusions: Semiquantitative ITSS grading correlates with key histopathologic and molecular glioma features. Combined with perfusion and volumetric parameters, ITSS enhance non-invasive glioma grading, in alignment with WHO CNS5. Full article

Meningiomas account for approximately 40% of all primary brain tumors, of which 1.5% are classified as grade 3. Whilst meningiomas are discovered on imaging with high-grade meningiomas being associated with certain imaging features, the final diagnosis is based on histopathology in combination with molecular markers. According to the latest World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS), grade 3 should be assigned based on criteria for anaplastic meningiomas, which comprise malignant cytomorphology (anaplasia) that resembles carcinoma, high-grade sarcoma or melanoma; elevated mitotic activity; a TERT promoter mutation and/or a homozygous CDKN2A and/or CDKN2B deletion. Surgery remains the mainstay treatment modality for grade 3 meningiomas, followed by radiotherapy. Limited data are available on the effect of stereotactic radiosurgery and systemic therapy for grade 3 meningiomas; however, studies are underway. Despite optimal treatment, the estimated recurrence rate ranges between 50% and 95% with a 5-year survival rate of 66% and a 10-year estimated survival rate of 14% to 24%. Full article

This study aims to determine the extent to which coating composition and workpiece properties impact machinability and tool selection when turning Compacted Graphite Iron (CGI) under extreme roughing conditions. Two CGI workpieces, differing in pearlite content and graphite nodularity, were machined at a cutting speed of 180 m/min, feed rate of 0.18 mm/rev, and depth of cut of 3 mm. To assess the impact of tool properties across a wide range of commercially available tools, four diverse multilayered cemented carbide tools were evaluated: Tool A and Tool B with a thin AlTiSiN PVD coating, Tool C with a thick Al₂O₃-TiCN CVD coating, and Tool D with a thin Al₂O₃-TiC PVD coating. The machinability of CGI and wear mechanisms were analyzed using pre-cutting characterization, in-process optical microscopy, and post-test SEM analysis. The results revealed that CGI microstructural variations only affected tool life for Tool A, with a 110% increase in tool life between machining CGI Grade B and Grade A, but that the effects were negligible for all other tools. Tool C had a 250% and 70% longer tool life compared to the next best performance (Tool A) for CGI Grade A and CGI Grade B, respectively. With its thick CVD-coating, Tool C consistently outperformed the others due to its superior protection of the flank face and cutting edge under high-stress conditions. The cutting-induced stresses played a more significant role in the tool wear process than minor differences in workpiece microstructure or tool properties, and a thick CVD coating was most effective in addressing the tool wear effects for the extreme roughing conditions. However, differences in tool life for Tool A showed that tool behavior cannot be predicted based on a single system parameter, even for extreme conditions. Instead, tool properties, workpiece properties, cutting conditions, and their interactions should be considered collectively to evaluate the extent that an individual parameter impacts machinability. This research demonstrates that a comprehensive approach such as this can allow for more effective tool selection and thus lead to significant cost savings and more efficient manufacturing operations. Full article

Background/Objectives: Anaplastic oligodendrogliomas (AOs) are central nervous system (CNS) World Health Organization (WHO) grade 3 gliomas characterized by isocitrate dehydrogenase (IDH) mutation (m)IDH and 1p/19q codeletion. AOs are typically treated with surgery and chemoradiation. However, chemoradiation can cause detrimental late neurocognitive morbidities and an accelerated disease course. The recently regulatory-approved vorasidenib, a brain-penetrating oral inhibitor of IDH1/2, has altered the treatment paradigm for recurrent/residual non-enhancing surgically resected CNS WHO grade 2 mIDH gliomas. Though vorasidenib can delay the time to chemoradiation for grade 2 gliomas, the implications for vorasidenib in non-grade 2 mIDH gliomas are not well understood. Results: We present a case of a 71-year-old male with a grade 3 non-enhancing oligodendroglioma successfully treated with vorasidenib with an 11% reduction in residual tumor volume. Vorasidenib was well tolerated in our patient with a mild elevation in his liver transaminases that resolved following a brief interruption in treatment. Conclusions: Our case suggests that vorasidenib may impart therapeutic benefits in this setting. This case illustrates the need for further investigation into these less commonly addressed scenarios and treatment strategies that extend beyond current guidelines. Full article

Background: Trastuzumab deruxtecan (TDXd) is an antibody–drug conjugate that has demonstrated impressive activity in randomized controlled clinical trials in the context of patients with HER2-amplified and HER2-low metastatic breast cancer. We aimed to review the activity and adverse event profile of TDXd in heavily pretreated breast cancer patients in real practice. Methods: We describe a single-center retrospective case series of metastatic breast cancer patients who were treated with TDXd. The outcomes of interest were the overall response rate, overall survival, progression-free survival and grade 4–5 adverse events. Objective responses and PFS were assessed in accordance with RECIST 1.1 criteria. Results: We identified 38 patients treated with TDXd. Of these, 15 patients had classically defined HER2-positive (HER2+) breast cancer, 4 of whom had active central nervous system (CNS) metastases. A total of 23 patients had HER2-low breast cancer, 2 of whom had active CNS disease. Of the 33 patients evaluable for response, 21 (63%) patients had a response to treatment, including three (9%) complete responses. Outcomes were similar between patients with a HER2+ and HER2-low status, as well as in patients with or without CNS metastases. No patients experienced grade 4 or 5 toxicities, and four of thirty-eight patients (10.5%) experienced pneumonitis (two patients with grade 3 pneumonitis, one patient with grade 2 and one patient with grade 1), resulting in TDXd discontinuation for three patients (with steroid administration in two patients). Conclusions: TDXd demonstrates impressive activity with manageable adverse event profiles in this heavily pretreated population that includes patients with active CNS metastases. Full article

Background: Homozygous cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) loss is one of the parameters that support the designation of meningiomas as Central Nervous System (CNS) WHO grade 3 tumors. Evaluation of CDKN2A/B by sequencing or Fluorescence in situ hybridization (FISH) is costly and not always readily accessible. An immunohistochemistry (IHC)-based marker for the evaluation of CDKN2A/B loss would provide faster results at a lower cost. Methods: This retrospective study included patients diagnosed with meningioma at our institution between 2016 and 2019. Archival tumor tissue was used for analysis. MTAP immunohistochemistry (IHC) was performed at various dilutions (1:1200, 1:400, 1:200, 1:100) using two different antibodies, and p16 IHC was conducted simultaneously. These analyses were carried out at two different institutions. To determine the sensitivity and specificity of MTAP and p16 as surrogate markers for CDKN2A/B loss, CDKN2A FISH was utilized as the gold standard. Results: Overall, 46/49 tumors showed strong MTAP staining (94%) at institution 1, and 44/49 (90%) showed either faint positive or positive results at institution 2. One grade 3 meningioma that demonstrated homozygous CDKN2A loss by FISH also showed loss of MTAP expression by IHC. One grade 2 meningioma showed regional CDKN2A loss by FISH and variable MTAP expression under different IHC conditions. MTAP expression evaluation was superior at a dilution of 1:100 with the Abnova Anti-MTAP Monoclonal antibody. Conclusions: P16 expression was variable and did not correlate with either MTAP expression or CDKN2A FISH results. MTAP IHC is a promising surrogate marker for the evaluation of CDKN2A status in meningiomas. Full article

Background and Objectives: Microsurgical resection with intraoperative neuromonitoring is the gold standard for acoustic neurinomas (ANs) which are classified as T3 or T4 tumors according to the Hannover Classification. Microscope-based augmented reality (AR) can be beneficial in cerebellopontine angle and lateral skull base surgery, since these are small areas packed with anatomical structures and the use of this technology enables automatic 3D building of a model without the need for a surgeon to mentally perform this task of transferring 2D images seen on the microscope into imaginary 3D images, which then reduces the possibility of error and provides better orientation in the operative field. Materials and Methods: All patients who underwent surgery for resection of ANs in our department were included in this study. Clinical outcomes in terms of postoperative neurological deficits and complications were evaluated, as well as neuroradiological outcomes for tumor remnants and recurrence. Results: A total of 43 consecutive patients (25 female, median age 60.5 ± 16 years) who underwent resection of ANs via retrosigmoid osteoclastic craniotomy with the use of intraoperative neuromonitoring (22 right-sided, 14 giant tumors, 10 cystic, 7 with hydrocephalus) by a single surgeon were included in this study, with a median follow up of 41.2 ± 32.2 months. A total of 18 patients underwent subtotal resection, 1 patient partial resection and 24 patients gross total resection. A total of 27 patients underwent resection in sitting position and the rest in semi-sitting position. Out of 37 patients who had no facial nerve deficit prior to surgery, 19 patients were intact following surgery, 7 patients had House Brackmann (HB) Grade II paresis, 3 patients HB III, 7 patients HB IV and 1 patient HB V. Wound healing deficit with cerebrospinal fluid (CSF) leak occurred in 8 patients (18.6%). Operative time was 317.3 ± 99 min. One patient which had recurrence and one further patient with partial resection underwent radiotherapy following surgery. A total of 16 patients (37.2%) underwent resection using fiducial-based navigation and microscope-based AR, all in sitting position. Segmented objects of interest in AR were the sigmoid and transverse sinus, tumor outline, cranial nerves (CN) VII, VIII and V, petrous vein, cochlea and semicircular canals and brain stem. Operative time and clinical outcome did not differ between the AR and the non-AR group. However, use of AR improved orientation in the operative field for craniotomy planning and microsurgical resection by identification of important neurovascular structures. Conclusions: The single-center experience of resection of ANs showed a high rate of gross total (GTR) and subtotal resection (STR) with low recurrence. Use of AR improves intraoperative orientation and facilitates craniotomy planning and AN resection through early improved identification of important anatomical relations to structures of the inner auditory canal, venous sinuses, petrous vein, brain stem and the course of cranial nerves. Full article

Background: Pediatric patients with metastatic and/or recurrent solid tumors have poor survival outcomes despite standard-of-care systemic therapy. Stereotactic ablative radiation therapy (SABR) may improve tumor control. We report the outcomes with the use of SABR in our pediatric solid tumor population. Methods: This was a single-institutional study in patients < 30 years treated with SABR. The primary endpoint was local control (LC), while the secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. The survival analysis was performed using Kaplan–Meier estimates in R v4.2.3. Results: In total, 48 patients receiving 135 SABR courses were included. The median age was 15.6 years (interquartile range, IQR 14–23 y) and the median follow-up was 18.1 months (IQR: 7.7–29.1). The median SABR dose was 30 Gy (IQR 25–35 Gy). The most common primary histologies were Ewing sarcoma (25%), rhabdomyosarcoma (17%), osteosarcoma (13%), and central nervous system (CNS) gliomas (13%). Furthermore, 57% of patients had oligometastatic disease (≤5 lesions) at the time of SABR. The one-year LC, PFS, and OS rates were 94%, 22%, and 70%, respectively. No grade 4 or higher toxicities were observed, while the rates of any grade 1, 2, and 3 toxicities were 11.8%, 3.7%, and 4.4%, respectively. Patients with oligometastatic disease, lung, or brain metastases and those who underwent surgery for a metastatic site had a significantly longer PFS. LC at 1-year was significantly higher for patients with a sarcoma histology (95.7% vs. 86.5%, p = 0.01) and for those who received a biological equivalent dose (BED10) > 48 Gy (100% vs. 91.2%, p = 0.001). Conclusions: SABR is well tolerated in pediatric patients with 1-year local failure and OS rates of <10% and 70%, respectively. Future studies evaluating SABR in combination with systemic therapy are needed to address progression outside of the irradiated field. Full article

(1) Background: The combination of CAR-T with ASCT has been observed to enhance the efficacy of CAR-T cell therapy. However, the impact of this combination on adverse reactions is still uncertain. (2) Methods: Between January 2019 and February 2023, 292 patients diagnosed with r/r B-cell lymphoma received either CAR-T therapy alone or in combination with ASCT at our institution. We evaluated the incidence of CRS and CRES and utilized a logistic regression model to identify factors contributing to severe CRS (grade 3–4) and CRES (grade 3–4). (3) Results: The overall incidence of CRS and CRES was 78.9% and 8.2% in 147 patients receiving CAR-T alone, and 95.9% and 15.2% in 145 patients receiving CAR-T combined with ASCT, respectively. The incidence of overall CRS (p < 0.0001) and mild CRS (grade 1–2) (p = 0.021) was elevated in the ASCT combined with CAR-T group. No significant difference was observed in severe CRS and CRES between the groups. Among the 26 cases of lymphoma involving the central nervous system (CNS), 96.2% (25/26) developed CRS (15.4% grade 3–4), and 34.6% (9/26) manifested CRES (7.7% grade 3–4). Female patients had a lower incidence of severe CRS but a higher incidence of severe CRES. Lymphomas with CNS involvement demonstrated a higher risk of CRES compared to those without central involvement. (4) Conclusions: The combination of ASCT with CAR-T demonstrated a preferable option in r/r B-cell lymphoma without an increased incidence of severe CRS and CRES. Full article

A 61-year-old patient was diagnosed with a left-sided falx meningioma. Histopathological analysis following extirpation showed a meningothelial meningioma ZNS WHO grade 1 with sparse mitoses. Over the course of 12 years, the patient received irradiation (54.0 Gy), peptide radio-receptor therapy (¹⁷⁷Lu-DOMITATE) and targeted therapy (mTOR inhibitor). Follow-up imaging revealed an increased size of the residual tumor. Due to increased liver function parameters, imaging of the liver was performed, showing widespread space-occupying lesions with atypical appearance. Biopsy revealed metastasis of the meningioma, now with 2.7 mitoses/mm², necrosis and homozygous CDKN2A/B deletion, corresponding to an anaplastic CNS meningioma WHO grade 3. A second small meningioma on the left petroclival side has been consistent in size over 12 years. Metastatic meningiomas pose a pertinent clinical challenge due to poor prognosis. The lung, bone, liver and cervical lymph nodes are the most common sites of extracranial metastasis. According to the World Health Organization criteria, the most important predictive factor for recurrence and metastasis is the tumor grade. Full article

Background: Breast cancer is the second most common cause of brain metastases (BM). Despite increasing incidence of BM in older women, there are limited data on the optimal management of BM in this age group. In this study, we assessed the survival outcomes and treatment patterns of older breast cancer patients ≥65 years old with BM compared to younger patients at our institution. Methods: An IRB-approved single-institutional retrospective review of biopsy-proven breast cancer patients with BM treated with 1- to 5-fraction stereotactic radiation therapy (SRS) from 2015 to 2020 was performed. Primary endpoint was intracranial progression-free survival (PFS) defined as the time interval between the end of SRS to the date of the first CNS progression. Secondary endpoints were overall survival (OS) from the end of SRS and radiation treatment patterns. Kaplan–Meier estimates and Cox proportional hazard regression method were used for survival analyses. Results: A total of 112 metastatic breast cancer patients with BMs were included of which 24 were ≥65 years old and 88 were <65 years old. Median age at RT was 72 years (range 65–84) compared to 52 years (31–64) in younger patients. There were significantly higher number of older women with ER/PR positive disease (75% vs. 49%, p = 0.036), while younger patients were more frequently triple negative (32% vs. 12%, p = 0.074) and HER2 positive (42% vs. 29%, p = 0.3). Treatment-related adverse events were similar in both groups. Overall, 14.3% patients had any grade radiation necrosis (RN) (older vs. young: 8.3% vs. 16%, p = 0.5) while 5.4% had grade 3 or higher RN (0% vs. 6.8%, p = 0.7). Median OS after RT was poorer in older patients compared to younger patients (9.5 months vs. 14.5 months, p = 0.037), while intracranial PFS from RT was similar between the two groups (9.7 months vs. 7.1 months, p = 0.580). On univariate analysis, significant predictors of OS were age ≥65 years old (hazard risk, HR = 1.70, p = 0.048), KPS ≤ 80 (HR = 2.24, p < 0.001), HER2 positive disease (HR = 0.46, p < 0.001), isolated CNS metastatic disease (HR = 0.29, p < 0.001), number of brain metastases treated with RT (HR = 1.06, p = 0.028), and fractionated SRS (HR = 0.53, p = 0.013). On multivariable analysis, KPS ≤ 80, HER2 negativity and higher number of brain metastases predicted for poorer survival, while age was not a significant factor for OS after adjusting for other variables. Patients who received systemic therapy after SRS had a significantly improved OS on univariate and multivariable analysis (HR = 0.32, p < 0.001). Number of brain metastases treated was the only factor predictive of worse PFS (HR = 1.06, p = 0.041), which implies a 6% additive risk of progression for every additional metastasis treated. Conclusions: Although older women had poorer OS than younger women, OS was similar after adjusting for KPS, extracranial progression, and systemic therapy; and there was no difference in rates of intracranial PFS, neurological deaths, and LMD in the different age groups. This study suggests that age alone may not play an independent role in treatment-selection and that outcomes for breast cancer patients with BMs and personalized decision-making including other clinical factors should be considered. Future studies are warranted to assess neurocognitive outcomes and other radiation treatment toxicities in older patients. Full article