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Purpose To develop, externally test, and evaluate clinical acceptability of a deep learning pediatric brain tumor segmentation model using stepwise transfer learning. Materials and Methods In this retrospective study, the authors leveraged two T2-weighted MRI datasets (May 2001 through December 2015) from a national brain tumor consortium ( n = 184; median age, 7 years [range, 1-23 years]; 94 male patients) and a pediatric cancer center ( n = 100; median age, 8 years [range, 1-19 years]; 47 male patients) to develop and evaluate deep learning neural networks for pediatric low-grade glioma segmentation using a stepwise transfer learning approach to maximize performance in a limited data scenario. The best model was externally tested on an independent test set and subjected to randomized blinded evaluation by three clinicians, wherein they assessed clinical acceptability of expert- and artificial intelligence (AI)-generated segmentations via 10-point Likert scales and Turing tests. Results The best AI model used in-domain stepwise transfer learning (median Dice score coefficient, 0.88 [IQR, 0.72-0.91] vs 0.812 [IQR, 0.56-0.89] for baseline model; P = .049). With external testing, the AI model yielded excellent accuracy using reference standards from three clinical experts (median Dice similarity coefficients: expert 1, 0.83 [IQR, 0.75-0.90]; expert 2, 0.81 [IQR, 0.70-0.89]; expert 3, 0.81 [IQR, 0.68-0.88]; mean accuracy, 0.82). For clinical benchmarking ( n = 100 scans), experts rated AI-based segmentations higher on average compared with other experts (median Likert score, 9 [IQR, 7-9] vs 7 [IQR 7-9]) and rated more AI segmentations as clinically acceptable (80.2% vs 65.4%). Experts correctly predicted the origin of AI segmentations in an average of 26.0% of cases. Conclusion Stepwise transfer learning enabled expert-level automated pediatric brain tumor autosegmentation and volumetric measurement with a high level of clinical acceptability. Keywords: Stepwise Transfer Learning, Pediatric Brain Tumors, MRI Segmentation, Deep Learning Supplemental material is available for this article . © RSNA, 2024.

Background: Clinical predictors of local recurrence following radiation among patients with brain metastases (BrM) provide limited explanatory power. We developed a DNA-based signature of radiotherapeutic efficacy among patients with BrM to better characterize recurrence risk., Methods: We identified 570 patients with 1487 BrM managed with whole-brain (WBRT) or stereotactic radiation therapy at Brigham and Women's Hospital/Dana-Farber Cancer Institute (2013-2020) for whom next-generation sequencing panel data (OncoPanel) were available. Fine/Gray's competing risks regression was utilized to compare local recurrence on a per-metastasis level among patients with versus without somatic alterations of likely biological significance across 84 genes. Genes with a q-value ≤ 0.10 were utilized to develop a "Brain-Radiation Prediction Score" ("Brain-RPS")., Results: Genomic alterations in 11 (ATM, MYCL, PALB2, FAS, PRDM1, PAX5, CDKN1B, EZH2, NBN, DIS3, and MDM4) and 2 genes (FBXW7 and AURKA) were associated with decreased or increased risk of local recurrence, respectively (q-value ≤ 0.10). Weighted scores corresponding to the strength of association with local failure for each gene were summed to calculate a patient-level RPS. On multivariable Fine/Gray's competing risks regression, RPS [1.66 (1.44-1.91, P < .001)], metastasis-associated edema [1.60 (1.16-2.21), P = .004], baseline size [1.02 (1.01-1.03), P < .001] and receipt of WBRT without local therapy [4.04 (2.49-6.58), P < .001] were independent predictors of local failure., Conclusions: We developed a genomic score to quantify local recurrence risk following brain-directed radiation. To the best of our knowledge, this represents the first study to systematically correlate DNA-based alterations with radiotherapeutic outcomes in BrM. If validated, Brain-RPS has potential to facilitate clinical trials aimed at genome-based personalization of radiation in BrM., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Leptomeningeal disease (LMD) is a relatively uncommon manifestation of advanced cancer. Patients with LMD carry a poor prognosis and often decline rapidly, complicating inclusion in clinical trials. Identification of LMD subsets of greater incidence and more favorable prognosis might facilitate dedicated clinical trials in the future. We hypothesized that patients with breast cancer may represent such a population and sought to assess the relative incidence and prognosis of LMD secondary to breast vs. non-breast primaries., Methods: We identified 2411 patients with intracranial metastases secondary to breast (N = 501) and non-breast (N = 1910) primaries at Brigham and Women's Hospital/Dana-Farber Cancer Institute between 1996 and 2020, of whom 112 presented with and an additional 161 subsequently developed LMD. A log-rank test and Cox modeling were used to compare outcomes in patients with breast vs. non-breast primaries., Results: Among patients with newly diagnosed intracranial disease, the incidence proportion of concurrent LMD was 11.4% vs. 2.9% among patients with breast vs. non-breast primaries (P < .001). Development of LMD among initially LMD-naïve patients was also more common among patients with breast vs. non-breast primaries (HR = 1.49 [1.05-2.11], P = .03). Patients with LMD secondary to breast vs. non-breast primaries displayed lower all-cause mortality (HR 0.70 [0.52-0.93], P = .01; median survival: 5.2 vs. 2.4 months, respectively), with a greater numerical difference observed in patients with LMD at intracranial involvement (7.4 vs. 2.6 months, respectively)., Conclusions: Patients with breast cancer and LMD may represent an ideal population for clinical trials given the higher incidence and potentially more favorable prognosis seen in this population., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Neurologic death is the most serious consequence of intracranial disease among patients with brain metastases. Identifying patients with brain metastases at increased risk of neurologic death can improve care and guide further research. We sought to delineate factors predictive of neurologic death among patients with brain metastases., Methods: We identified 1218 patients with newly diagnosed brain metastases managed at Brigham and Women's Hospital/Dana-Farber Cancer Institute from 2008-2015. Factors predictive of neurologic death were assessed via univariable and multivariable Fine and Gray competing risks regression., Results: On multivariable analysis, neurologic death was associated with number of brain metastases (hazard ratio [HR] 1.01 per 1 metastasis increase, 95% confidence interval [CI] 1.01-1.02, P < 0.001) and 3 primary tumor sites (reference=non-small cell lung cancer): melanoma (HR 4.67, 95% CI 3.27-6.68, P < 0.001), small cell lung cancer (HR 2.33, 95% CI 1.47-3.68, P < 0.001), and gastrointestinal cancer (HR 2.21, 95% CI 1.28-3.82, P = 0.005). Conversely, a reduction in neurologic death was found in patients with good Karnofsky performance status (90-100 vs. 30-80, HR 0.67, 95% CI 0.48-0.95, P = 0.03) and progressive extracranial metastases at diagnosis of intracranial disease (HR 0.50, 95% CI 0.38-0.67, P = 0.001). Among patients with breast primaries, HER2+ patients displayed increased neurologic death relative to the reference of HR+/HER2- (univariable analysis only: HR 2.41, 95% CI 1.00-5.84, P = 0.05)., Conclusions: Patients with melanoma, small cell lung cancer, gastrointestinal cancer, and HER2+ breast cancer primaries, as well as greater intracranial versus extracranial disease burden, harbor significant risk of neurologic death. Future research investigating novel intracranial approaches should focus on these populations., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Prognostic estimates for patients with brain metastases (BM) stem from younger, healthier patients enrolled in clinical trials or databases from academic centers. We characterized population-level prognosis in elderly patients with BM., Methods: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified 9882 patients ≥65 years old with BM secondary to lung, breast, skin, kidney, esophageal, colorectal, and ovarian primaries between 2014 and 2016. Survival was assessed by primary site and evaluated with Cox regression., Results: In total, 2765 versus 7117 patients were diagnosed with BM at primary cancer diagnosis (synchronous BM, median survival = 2.9 mo) versus thereafter (metachronous BM, median survival = 3.4 mo), respectively. Median survival for all primary sites was ≤4 months, except ovarian cancer (7.5 mo). Patients with non-small-cell lung cancer (NSCLC) receiving epidermal growth factor receptor (EGFR)- or anaplastic lymphoma kinase (ALK)-based therapy for synchronous BM displayed notably better median survival at 12.5 and 20.1 months, respectively, versus 2.8 months exhibited by other patients with NSCLC; survival estimates in melanoma patients based on receipt of BRAF/MEK therapy versus not were 6.7 and 2.8 months, respectively. On multivariable regression, older age, greater comorbidity, and type of managing hospital were associated with poorer survival; female sex, higher median household income, and use of brain-directed stereotactic radiation, neurosurgical resection, or systemic therapy (versus brain-directed non-stereotactic radiation) were associated with improved survival (all P < 0.05)., Conclusions: Elderly patients with BM have a poorer prognosis than suggested by prior algorithms. If prognosis is driven by systemic and not intracranial disease, brain-directed therapy with potential for significant toxicity should be utilized cautiously., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Prior literature has suggested synergy between immune checkpoint therapy (ICT) and radiotherapy (RT) for the treatment of brain metastases (BrM), but to the authors' knowledge the optimal timing of therapy to maximize this synergy is unclear., Methods: A total of 199 patients with melanoma and non-small cell lung cancer with BrM received ICT and RT between 2007 and 2016 at the study institution. To reduce selection biases, individual metastases were included only if they were treated with RT within 90 days of ICT. Concurrent treatment was defined as RT delivered on the same day as or in between doses of an ICT course; all other treatment was considered to be nonconcurrent. Multivariable Cox proportional hazards models were used to assess time to response and local disease recurrence on a per-metastasis basis, using a sandwich estimator to account for intrapatient correlation., Results: The final cohort included 110 patients with 340 BrM, with 102 BrM treated concurrently and 238 BrM treated nonconcurrently. Response rates were higher with the use of concurrent treatment (70% vs 47%; P < .001), with correspondingly lower rates of progressive disease (5% vs 26%; P < .001). On multivariable analysis, concurrent treatment was found to be associated with improved time to response (hazard ratio, 1.76; 95% CI, 1.18-2.63 [P = .006]) and decreased local recurrence (hazard ratio, 0.42; 95% CI, 0.23-0.78 [P = .006]). This effect appeared to be greater for melanoma than for non-small cell lung cancer, although interaction tests were not statistically significant. Only 1 of 103 metastases which had a complete response later developed disease progression., Conclusions: Concurrent RT and ICT may improve response rates and decrease local recurrence of brain metastases compared with treatment that was nonconcurrent but delivered within 90 days. Further study of this combination in prospective, randomized trials is warranted., (© 2020 American Cancer Society.)

Background: Brain metastases are associated with considerable morbidity and mortality. Integration of hospice at the end of life offers patients symptom relief and improves quality of life, particularly for elderly patients who are less able to tolerate brain-directed therapy. Population-level investigations of hospice utilization among elderly patients with brain metastases are limited., Methods: Using the Surveillance, Epidemiology and End Results-Medicare database for primary cancer sites that commonly metastasize to the brain, we identified 50 148 patients (aged 66 years and older) diagnosed with brain metastases between 2005 and 2016. We calculated the incidence, timing, and predictors of hospice enrollment using descriptive techniques and multivariable logistic regression. All statistical tests were 2-sided., Results: The incidence of hospice enrollment was 71.4% (95% confidence interval [CI] = 71.0 to 71.9; P < .001), a rate that increased over the study period (P < .001). The odds of enrollment for black (odds ratio [OR] = 0.76, 95% CI = 0.71 to 0.82; P < .001), Hispanic (OR = 0.80, 95% CI = 0.72 to 0.87; P < .001), and Asian patients (OR = 0.52, 95% CI = 0.48 to 0.57; P < .001) were substantially lower than white patients; men were less likely to be enrolled in hospice than women (OR = 0.78, 95% CI = 0.74 to 0.81; P < .001). Among patients enrolled in hospice, 32.6% (95% CI = 32.1 to 33.1; P < .001) were enrolled less than 7 days prior to death, a rate that was stable over the study period., Conclusions: Hospice is used for a majority of elderly patients with brain metastases although a considerable percentage of patients die without hospice services. Many patients enroll in hospice late and, concerningly, statistically significant sociodemographic disparities exist in hospice utilization. Further investigations to facilitate targeted interventions addressing such disparities are warranted., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Brain metastases (BM) cause symptoms that supportive medications can alleviate. We assessed whether racial disparities exist in supportive medication utilization after BM diagnosis., Methods: Medicare-enrolled patients linked with the Surveillance, Epidemiology, and End Results program (SEER) who had diagnoses of BM between 2007 and 2016 were identified. Fourteen supportive medication classes were studied: non-opioid analgesics, opioids, anti-emetics, anti-epileptics, headache-targeting medications, steroids, cognitive aids, antidepressants, anxiolytics, antidelirium/antipsychotic agents, muscle relaxants, psychostimulants, sleep aids, and appetite stimulants. Drug administration ≤30 days following BM diagnosis was compared by race using multivariable logistic regression., Results: Among 17,957 patients, headache aids, antidepressants, and anxiolytics were prescribed less frequently to African Americans (odds ratio [95% CI] = 0.81 [0.73-0.90], P < 0.001; OR = 0.68 [0.57-0.80], P < 0.001; and OR = 0.68 [0.56-0.82], P < 0.001, respectively), Hispanics (OR = 0.83 [0.73-0.94], P = 0.004 OR = 0.78 [0.64-0.97], P = 0.02; and OR = 0.63 [0.49-0.81], P < 0.001, respectively), and Asians (OR = 0.81 [0.72-0.92], P = 0.001, OR = 0.67 [0.53-0.85], P = 0.001, and OR = 0.62 [0.48-0.80], P < 0.001, respectively) compared with non-Hispanic Whites. African Americans also received fewer anti-emetics (OR = 0.75 [0.68-0.83], P < 0.001), steroids (OR = 0.84 [0.76-0.93], P < 0.001), psychostimulants (OR = 0.14 [0.03-0.59], P = 0.007), sleep aids (OR = 0.71 [0.61-0.83], P < 0.001), and appetite stimulants (OR = 0.85 [0.77-0.94], P = 0.002) than Whites. Hispanic patients less frequently received antidelirium/antipsychotic drugs (OR = 0.57 [0.38-0.86], P = 0.008), sleep aids (OR = 0.78 [0.64-0.94, P = 0.01), and appetite stimulants (OR = 0.87 [0.76-0.99], P = 0.04). Asian patients received fewer opioids (OR = 0.86 [0.75-0.99], P = 0.04), anti-emetics (OR = 0.83 [0.73-0.94], P = 0.004), anti-epileptics (OR = 0.83 [0.71-0.97], P = 0.02), steroids (OR = 0.81 [0.72-0.92], P = 0.001), muscle relaxants (OR = 0.60 [0.41-0.89], P = 0.01), and appetite stimulants (OR = 0.87 [0.76-0.99], P = 0.03). No medication class was prescribed significantly less frequently to Whites., Conclusions: Disparities in supportive medication prescription for non-White/Hispanic groups with BM exist; improved provider communication and engagement with at-risk patients is needed., Key Points: 1. Patients with BM commonly experience neurologic symptoms.2. Supportive medications improve quality of life among patients with BM.3. Non-White patients with BM receive fewer supportive medications than White patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Whole brain radiation therapy (WBRT) remains an important component of treatment for patients with multiple brain metastases (BrM) but is associated with significant neurotoxicity and memory impairment. Although RTOG 0614 demonstrated that administration of memantine to patients receiving WBRT may reduce radiation-associated cognitive decline, prior literature has suggested that radiation oncologists are hesitant to prescribe memantine. We sought to assess the frequency of memantine prescription in patients managed with non-stereotactic, brain-directed radiation for BrM., Methods: Patients > 65 years old with newly diagnosed BrM between 2007 and 2016 receiving non-stereotactic, brain-directed radiation (including WBRT) were identified using the SEER-Medicare database. Receipt of memantine with non-stereotactic, brain-directed radiation was defined as any Part D claim for memantine 30 days before or after initiation of non-stereotactic, brain-directed radiation. Clinical and demographic variables among patients who did and did not receive memantine were compared., Results: Between 2007 and 2016, we identified 6220 patients with BrM receiving non-stereotactic, brain-directed radiation. Only 2.20% of patients (n = 137) received memantine with radiation. Rates were 1.10% versus 5.14% in the period preceding (2007-2013) and following (2014-2016) the publication of RTOG 0614, respectively. Overall utilization of memantine remained low across several clinical, demographic, and prognostic variables., Conclusion: Despite phase 3 evidence supporting memantine utilization among patients receiving WBRT, our population-based study indicates that rates of memantine prescription are strikingly low, although memantine utilization seems to be increasing since publication of RTOG 0614. Further investigation is needed to identify provider and practice-related barriers preventing incorporation of memantine into management paradigms.

Purpose: Brain metastases from breast cancer are frequently managed with brain-directed radiation but the impact of subtype on intracranial recurrence patterns after radiation has not been well-described. We investigated intracranial recurrence patterns of brain metastases from breast cancer after brain-directed radiation to facilitate subtype-specific management paradigms., Methods: We retrospectively analyzed 349 patients with newly diagnosed brain metastases from breast cancer treated with brain-directed radiation at Brigham and Women's Hospital/Dana-Farber Cancer Institute between 2000 and 2015. Patients were stratified by subtype: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-), HER2+ positive (HER2+), or triple-negative breast cancer (TNBC). A per-metastasis assessment was conducted. Time-to-event analyses were conducted using multivariable Cox regression., Results: Of the 349 patients, 116 had HR+/HER2- subtype, 164 had HER2+ subtype, and 69 harbored TNBC. Relative to HR+/HER2- subtype, local recurrence was greater in HER2+ metastases (HR 3.20, 95% CI 1.78-5.75, p < 0.001), while patients with TNBC demonstrated higher rates of new brain metastases after initial treatment (HR 3.16, 95% CI 1.99-5.02, p < 0.001) and shorter time to salvage whole brain radiation (WBRT) (HR 3.79, 95% CI 1.36-10.56, p = 0.01) and salvage stereotactic radiation (HR 1.86, 95% CI 1.11-3.10, p = 0.02)., Conclusions: We identified a strong association between breast cancer subtype and intracranial recurrence patterns after brain-directed radiation, particularly local progression for HER2+ and distant progression for TNBC patients. If validated, the poorer local control in HER2+ brain metastases may support evaluation of novel local therapy-based approaches, while the increased distant recurrence in TNBC suggests the need for improved systemic therapy and earlier utilization of WBRT.

Importance: Neurosurgical resection represents an important management strategy for patients with large, symptomatic brain metastases and increasingly is followed by stereotactic radiation as opposed to whole-brain radiation. Whether neurosurgical resection is associated with tumor spread beyond the resection site and adjuvant stereotactic radiation field remains unknown., Objective: To characterize the association and incidence of pachymeningeal seeding with neurosurgical resection in patients with brain metastases treated with adjuvant stereotactic radiation., Design, Setting, and Participants: Retrospective cohort study of a consecutive sample of patients with newly diagnosed brain metastases managed with neurosurgical resection and stereotactic radiation (n = 318) vs radiation alone (n = 870) between 2001 and 2015., Main Outcomes and Measures: Incidence of pachymeningeal seeding (dural and/or outer arachnoid) and leptomeningeal disease in patients treated with neurosurgical resection and stereotactic radiation vs radiation alone and the risk factors and outcomes associated with pachymeningeal seeding in patients treated with neurosurgical resection followed by stereotactic radiation., Results: In 1188 patients with newly diagnosed brain metastases, 133 men and 185 women (mean [SD] age, 58.9 [11.5] years) underwent neurosurgical resection. Resection was found to be associated with pachymeningeal seeding (36 of 318 patients vs 0 of 870 patients; P < .001) but not leptomeningeal disease (hazard ratio [HR], 1.14; 95% CI, 0.73-1.77; P = .56). In total, 36 (8.4%) of 428 operations were complicated by pachymeningeal seeding, with a higher incidence noted with resection of previously irradiated vs unirradiated metastases (HR, 2.39; 95% CI, 1.25-4.57; P = .008). Patients with pachymeningeal seeding had relatively low rates of subsequent development of new brain metastases and leptomeningeal disease (8 [16%] of 51 and 6 [13%] of 48, respectively). Among patients with pachymeningeal seeding, neurologic death primarily owing to progressive pachymeningeal disease accounted for 26 (72%) of 36 deaths, but when treated with salvage radiation, 49.1% of patients survived 1 year or longer., Conclusions and Relevance: In the era of omission of adjuvant whole-brain radiation after neurosurgical resection, pachymeningeal seeding beyond the stereotactic radiation field represents a notable oncologic event that often proves difficult to salvage. However, in some patients, disease control can be achieved with radiotherapeutic approaches.

Purpose: Brain metastases can be radiographically cystic or solid. Cystic metastases are associated with a greater intracranial disease burden and poorer oncologic outcomes, but the impact of cystic versus solid appearance on local control after radiation remains unknown. We investigated whether cystic versus solid nature is predictive of local control after management with stereotactic or whole brain radiation (WBRT) and whether the radiation modality utilized is an effect modifier., Methods: We identified 859 patients with 2211 newly-diagnosed brain metastases managed with upfront stereotactic radiation or WBRT without preceding resection/aspiration at Brigham and Women's Hospital/Dana-Farber Cancer Institute between 2000 and 2015. Multivariable Cox regression with an interaction term and sandwich covariance matrix was used to quantify local failure., Results: Cystic lesions were more likely to recur than solid ones when managed with stereotactic radiation (HR 2.33, 95% CI 1.32-4.10, p = 0.004) but not WBRT (HR 0.92, 95% CI 0.62-1.36, p = 0.67), p-interaction = 0.007. 1 year local control rates for cystic versus solid metastases treated with stereotactic radiation were 75% versus 88%, respectively; estimates with WBRT were 76% versus 76%, respectively. However, no significant differences were noted between the two cohorts in post-radiation outcomes including all-cause mortality and neurologic death (p > 0.05)., Conclusions: Among patients with brain metastases, stereotactic radiation yields improved local control and less morbidity than WBRT, and consequently for many patients the cystic versus solid designation does not impact treatment selection. However, our results suggest that in patients with a large number of cystic brain metastases, a lower threshold to consider WBRT, as opposed to stereotactic radiation, should be employed. If our results can be confirmed, further investigation into the underlying mechanism(s) would be warranted.

Background: Brain metastases commonly manifest in patients with cancer, with ∼20%-50% presenting with 1 intracranial lesion. Among patients with 1, small brain metastasis and controlled or absent extracranial disease, it remains unclear whether aggressive intracranial management using neurosurgical resection plus cavity stereotactic radiosurgery/stereotactic radiotherapy (SRS/SRT) rather than SRS/SRT alone is beneficial. In patients with controlled or absent extracranial disease and 1 brain metastasis ≤2 cm in size, we evaluated the effect of surgery plus SRS/SRT compared with SRS/SRT on oncologic outcomes, including overall survival., Methods: We retrospectively identified 86 patients with controlled or absent extracranial disease and 1 brain metastasis ≤2 cm in size who had been treated from 2000 to 2015 at our institution. We examined differences in the rates of local and distant failure, use of salvage treatment, and other oncologic outcomes, including all-cause mortality., Results: The baseline characteristics were similar between the 2 cohorts. The median follow-up period for the surviving patients was 38 months. On multivariable analysis, surgical resection plus cavity SRS/SRT was associated with a lower risk of all-cause mortality (hazard ratio, 0.44; 95% confidence interval, 0.19-1.00; P = 0.05) compared with SRS/SRT alone. The 1- and 2-year rates of overall survival were 100% and 88% versus 74% and 52% for surgery plus cavity SRS/SRT versus SRS/SRT alone, respectively., Conclusions: Aggressive, local therapy, including neurosurgical resection, might benefit patients with 1 brain metastasis in the context of controlled or absent systemic disease, even if the lesion in question is small. Further studies are needed to evaluate these associations., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Pemetrexed is a folate antimetabolite used in the management of advanced adenocarcinoma of the lung. We sought to assess the impact of pemetrexed on intracranial disease control and radiation-related toxicity among patients with adenocarcinoma of the lung who received stereotactic radiation for brain metastases., Materials/methods: We identified 149 patients with adenocarcinoma of the lung and newly diagnosed brain metastases without a targetable mutation receiving stereotactic radiation. Kaplan-Meier plots and Cox regression were employed to assess whether use of pemetrexed was associated with intracranial disease control and radiation necrosis., Results: Among the entire cohort, 105 patients received pemetrexed while 44 did not. Among patients who were chemotherapy-naïve, use of pemetrexed (n = 43) versus alternative regimens after stereotactic radiation (n = 24) was associated with a reduced likelihood of developing new brain metastases (HR 0.42, 95% CI 0.22-0.79, p = 0.006) and a reduced need for salvage brain-directed radiation therapy (HR 0.36, 95% CI 0.18-0.73, p = 0.005). Pemetrexed use was associated with increased radiographic necrosis. (HR 2.70, 95% CI 1.09-6.70, p = 0.03)., Conclusions: Patients receiving pemetrexed after brain-directed stereotactic radiation appear to benefit from improved intracranial disease control at the possible expense of radiation-related radiographic necrosis. Whether symptomatic radiation injury occurs more frequently in patients receiving pemetrexed requires further study., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Brain metastases are associated with significant morbidity and mortality. Population-level data describing the incidence and prognosis of patients with brain metastases are lacking. The aim of this study was to characterize the incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy using recently released data from the Surveillance, Epidemiology, and End Results (SEER) program., Methods: We identified 1302166 patients with diagnoses of nonhematologic malignancies originating outside of the CNS between 2010 and 2013 and described the incidence proportion and survival of patients with brain metastases., Results: We identified 26430 patients with brain metastases at diagnosis of cancer. Patients with small cell and non-small cell lung cancer displayed the highest rates of identified brain metastases at diagnosis; among patients presenting with metastatic disease, patients with melanoma (28.2%), lung adenocarcinoma (26.8%), non-small cell lung cancer not otherwise specified/other lung cancer (25.6%), small cell lung cancer (23.5%), squamous cell carcinoma of the lung (15.9%), bronchioloalveolar carcinoma (15.5%), and renal cancer (10.8%) had an incidence proportion of identified brain metastases of >10%. Patients with brain metastases secondary to prostate cancer, bronchioloalveolar carcinoma, and breast cancer displayed the longest median survival (12.0, 10.0, and 10.0 months, respectively)., Conclusions: In this study we provide generalizable estimates of the incidence and prognosis for patients with brain metastases at diagnosis of a systemic malignancy. These data may allow for appropriate utilization of brain-directed imaging as screening for subpopulations with cancer and have implications for clinical trial design and counseling of patients regarding prognosis., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Importance: Population-based estimates of the incidence and prognosis of brain metastases at diagnosis of breast cancer are lacking., Objective: To characterize the incidence proportions and median survivals of patients with breast cancer and brain metastases at the time of cancer diagnosis., Design, Setting, and Participants: Patients with breast cancer and brain metastases at the time of diagnosis were identified using the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. Data were stratified by subtype, age, sex, and race. Multivariable logistic and Cox regression were performed to identify predictors of the presence of brain metastases at diagnosis and factors associated with all-cause mortality, respectively. For incidence, we identified a population-based sample of 238 726 adult patients diagnosed as having invasive breast cancer between 2010 and 2013 for whom the presence or absence of brain metastases at diagnosis was known. Patients diagnosed at autopsy or with an unknown follow-up were excluded from the survival analysis, leaving 231 684 patients in this cohort., Main Outcomes and Measures: Incidence proportion and median survival of patients with brain metastases and newly diagnosed breast cancer., Results: We identified 968 patients with brain metastases at the time of diagnosis of breast cancer, representing 0.41% of the entire cohort and 7.56% of the subset with metastatic disease to any site. A total of 57 were 18 to 40 years old, 423 were 41 to 60 years old, 425 were 61-80 years old, and 63 were older than 80 years. Ten were male and 958 were female. Incidence proportions were highest among patients with hormone receptor (HR)-negative human epidermal growth factor receptor 2 (HER2)-positive (1.1% among entire cohort, 11.5% among patients with metastatic disease to any distant site) and triple-negative (0.7% among entire cohort, 11.4% among patients with metastatic disease to any distant site) subtypes. Median survival among the entire cohort with brain metastases was 10.0 months. Patients with HR-positive HER2-positive subtype displayed the longest median survival (21.0 months); patients with triple-negative subtype had the shortest median survival (6.0 months)., Conclusions and Relevance: The findings of this study provides population-based estimates of the incidence and prognosis for patients with brain metastases at time of diagnosis of breast cancer. The findings lend support to consideration of screening imaging of the brain for patients with HER2-positive or triple-negative subtypes and extracranial metastases.

Despite a high symptom burden, little is known about the incidence or predictors of hospitalization among glioblastoma patients, including risks during chemoradiation (CRT). We studied 196 consecutive newly diagnosed glioblastoma patients treated at our institution from 2006-2010. Toxicity data were reviewed during and after the CRT phase, defined as the period between diagnosis and 6 weeks after radiotherapy completion. Logistic regression and proportional hazards modeling identified predictors of hospitalization and overall survival (OS). Median age was 59 years (range, 23-90) and 83 % had Karnofsky performance status (KPS) score ≥ 70. Twenty-six percent of patients underwent gross total resection, 77 % received ≥ 59.4 Gy of radiotherapy, and 89 % received concurrent temozolomide. Median OS was 15.6 months (IQR, 8.5-26.8 months). Forty-three percent of patients were hospitalized during the CRT phase; OS was 10.7 vs. 17.8 months for patients who were vs. were not hospitalized, respectively (P < .001). Nearly half of the hospitalizations were due to generalized weakness (17 % of hospitalizations), seizures (16 %), or venous thromboembolism (13 %). On multivariate analysis, age (odds ratio [OR], 1.03; 95 % CI, 1.002-1.060; P = .034) and KPS (OR, 0.95; 95 % CI, 0.93-0.97; P < .001) were associated with risk of hospitalization. Hospitalization during the CRT phase was associated with decreased OS (adjusted hazard ratio, 1.47; 95 % CI, 1.01-2.13; P = .043), after adjustment for known prognostic factors. Hospitalization during the CRT phase is common among glioblastoma patients in the temozolomide era and is associated with shorter overall survival.