Intracranial Metastatic Disease Research Articles

Impact of SUSAN Denoising and ComBat Harmonization on Machine Learning Model Performance for Malignant Brain Neoplasms.

Feature variability in radiomics studies due to technical and magnet strength parameters is well known and may be addressed through various pre-processing methods. However, very few studies have evaluated downstream impact of variable pre-processing on model classification performance in a multi-class setting. We sought to evaluate the impact of SUSAN denoising and ComBat harmonization on model classification performance. A total of 493 cases (410 internal and 83 external dataset) of glioblastoma (GB), intracranial metastatic disease (IMD) and primary CNS lymphoma (PCNSL) underwent semi-automated 3D-segmentation post baseline image processing (BIP) consisting of resampling, realignment, co-registration, skull stripping and image normalization. Post BIP, two sets were generated, one with and another without SUSAN denoising (SD). Radiomics features were extracted from both datasets and batch corrected to produce four datasets: (a) BIP, (b) BIP with SD, (c) BIP with ComBat and (d) BIP with both SD and ComBat harmonization. Performance was then summarized for models using a combination of six feature selection techniques and six machine learning models across four mask-sequence combinations with features derived from one-three (multi-parametric) MRI sequences. Most top performing models on the external test set used BIP+SD derived features. Overall, use of SD and ComBat harmonization led to a slight but generally consistent improvement in model performance on the external test set. The use of image pre-processing steps such as SD and ComBat harmonization may be more useful in a multiinstitutional setting and improve model generalizability. Models derived from only T1-CE images showed comparable performance to models derived from multiparametric MRI.

Early Experience With Biologically Effective Dose-Comparable Short-Course Whole Brain Radiation Therapy for Metastatic Intracranial Disease.

For inpatients with metastatic intracranial disease burden exceeding established guidelines for stereotactic radiosurgery (SRS), the standard of care involves whole brain radiation therapy (WBRT), typically administered as a 2-week course of treatment with biologically effective dose (BED) of 60Gy. However, shorter course WBRT provides theoretical advantages in quality of life and decreasing systemic therapy delay. This retrospective study evaluates our early experience with BED-comparable short-course WBRT (23Gy in 5 fractions; BED=58.3Gy) for metastatic intracranial disease. Over a recent 2-month timeframe, 3 inpatients with intracranial disease burden exceeding SRS guidelines were administered BED-comparable short-course WBRT. Due to the high intracranial disease burden, 23Gy was chosen over 20Gy for 5-fraction WBRT due to the desire to optimally mimic the durability of the classic 30Gy in 10 fraction treatment regimen. The mean age at treatment was 65.7 years, the mean Karnofsky Performance Status (KPS) was 60, and the mean number of intracranial metastases was 20.3. The mean duration between inpatient Radiation Oncology consultation and the start of WBRT (following CT radiation therapy simulation) was 6.7 days. All patients completed WBRT no later than 2 weeks from the initial inpatient consultation. For inpatients with intracranial metastatic disease burden exceeding established SRS guidelines, BED-comparable short-course WBRT administered to 23Gy in 5 fractions (4.6Gy/fraction) is safe and efficacious. Given previous literature indicating that nearly half of the patients prescribed traditional 2-week WBRT die without completing treatment, BED-comparable WBRT represents an attractive and promising WBRT alternative in this patient population.

A Population-Based Analysis of Brain Metastasis Burden and Management in 8705 Small Cell Lung Cancer Patients

INTRODUCTION: Patients with small cell lung cancer (SCLC) have historically been characterised by poor overall survival (OS) and high risk for intracranial metastatic disease (IMD), but large-scale real-world evidence on clinical presentation and treatment in this population is lacking. These patients traditionally receive whole brain radiation therapy (WBRT) for IMD, however, a recent systematic review has indicated that OS following stereotactic radiosurgery (SRS) may be non-inferior compared with WBRT. METHODS: We included all patients diagnosed with SCLC between April 2007 and March 2018 identified through a provincial health administrative database. Information on patient and treatment characteristics, incidence and time to IMD, and OS from time of SCLC diagnosis were collected and analyzed using R. RESULTS: A total of 8705 patients were included. Median age was 68 years (range 18-103). Most patients presented with extensive disease (n = 5625) and were diagnosed after 2011 (n = 5768). Patients who received chemotherapy (n = 5563) had significantly longer OS than those who did not (median 10.64 vs 1.58 mo, HR 0.36, 95% CI 0.34-0.37). 6662 patients received brain imaging at the time of primary diagnosis (CT: 5126, MRI: 1536), and 88% of patients surviving longer than 6 mo received more than one follow-up brain scan. 31% developed IMD (synchronous: 1175, asynchronous: 1511) with median intracranial progression-free survival of 5.65 mo. Median OS of patients with IMD was 9.76 mo, 29 and 1300 received SRS and WBRT as first treatment for their IMD, respectively. OS was in favour of SRS over WBRT (median 20.47 vs 8.74 mo, HR 0.57, 95% CI 0.39-0.84), which remained significant in multivariate analysis (p < 0.001). CONCLUSIONS: OS for patients with SCLC remains poor and many patients present with IMD. Some patients with SCLC may benefit from SRS treatment.

AI-based classification of three common malignant tumors in neuro-oncology: A multi-institutional comparison of machine learning and deep learning methods

PurposeTo determine if machine learning (ML) or deep learning (DL) pipelines perform better in AI-based three-class classification of glioblastoma (GBM), intracranial metastatic disease (IMD) and primary CNS lymphoma (PCNSL). MethodologyRetrospective analysis included 502 cases for training (208 GBM, 67 PCNSL and 227 IMD), with external validation on 86 cases (27:27:32). Multiparametric MRI images (T1W, T2W, FLAIR, DWI and T1-CE) were co-registered, resampled, denoised and intensity normalized, followed by semiautomatic 3D segmentation of the enhancing tumor (ET) and peritumoral region (PTR). Model performance was assessed using several ML pipelines and 3D-convolutional neural networks (3D-CNN) using sequence specific masks, as well as combination of masks. All pipelines were trained and evaluated with 5-fold nested cross-validation on internal data followed by external validation using multi-class AUC. ResultsTwo ML models achieved similar performance on test set, one using T2-ET and T2-PTR masks (AUC: 0.885, 95% CI: [0.816, 0.935] and another using T1-CE-ET and FLAIR-PTR mask (AUC: 0.878, CI: [0.804, 0.930]). The best performing DL models achieved an AUC of 0.854, (CI [0.774, 0.914]) on external data using T1-CE-ET and T2-PTR masks, followed by model derived from T1-CE-ET, ADC-ET and FLAIR-PTR masks (AUC: 0.851, CI [0.772, 0.909]). ConclusionBoth ML and DL derived pipelines achieved similar performance. T1-CE mask was used in three of the top four overall models. Additionally, all four models had some mask derived from PTR, either T2WI or FLAIR.

Brain metastasis burden and management in small cell lung cancer: An analysis of 8705 patients.

8596 Background: Patients with small cell lung cancer (SCLC) have historically been characterised by poor overall survival (OS) and high risk for intracranial metastatic disease (IMD), but large-scale real-world evidence on clinical presentation and treatment in this population is lacking. These patients traditionally receive whole brain radiation therapy (WBRT) for IMD, however, a recent systematic review has indicated that OS following stereotactic radiosurgery (SRS) may be non-inferior compared with WBRT. We aim to describe the clinical characteristics and outcomes of patients with SCLC and IMD in Ontario, Canada. Methods: We included all patients diagnosed with SCLC between April 2007 and March 2018 identified through a provincial health administrative database. Information on patient and treatment characteristics, incidence and time to IMD, and OS from time of SCLC diagnosis were collected and analyzed using R. Results: A total of 8705 patients were included. Median age was 68 years (range 18-103). Most patients presented with extensive disease (n = 5625) and were diagnosed after 2011 (n = 5768). Patients who received chemotherapy (n = 5563) had significantly longer OS than those who did not (median 10.64 vs 1.58 months (mo), hazard ratio (HR) 0.36, 95% confidence interval (CI) 0.34-0.37). 6662 patients received brain imaging at the time of primary diagnosis (CT: 5126, MRI: 1536), and 88% of patients surviving longer than 6 mo received more than one follow-up brain scan. 31% developed IMD (synchronous: 1175, asynchronous: 1511) with median intracranial progression-free survival of 5.65 mo. Median OS of patients with IMD was 9.76 mo, 29 and 1300 received SRS and WBRT as first treatment for their IMD, respectively. OS was in favour of SRS over WBRT (median 20.47 vs 8.74 mo, HR 0.57, 95% CI 0.39-0.84), which remained significant in multivariate analysis (p < 0.001). Conclusions: OS for patients with SCLC remains poor, and many patients present with IMD. With careful selection, patients with SCLC may benefit from SRS treatment.

The role of immune checkpoint inhibitors in patients with intracranial metastatic disease.

Intracranial metastatic disease (IMD) complicates the course of nearly 2-4% of patients with systemic cancer. The prevalence of IMD has been increasing over the past few decades. Historically, definitive treatment for brain metastases (BM) has been limited to radiation therapy or surgical resection. Chemotherapies have not typically proven valuable in the treatment of IMD, with the exception of highly chemotherapy-sensitive lesions. Recent data have supported a role for systemic targeted therapies and immune checkpoint inhibitors (ICIs) in the treatment of select patients with IMD. There remains, however, a clear clinical need for further investigation to delineate the role of ICIs in patients with BM. In this review, we outline and describe recent and current efforts to identify the efficacy of ICI therapy in patients with IMD.

358P Intracranial metastatic disease (IMD) burden and management of patients with small cell lung cancer (SCLC): A population-based analysis of 8705 patients

Patients with SCLC have historically been characterised by poor overall survival (OS) and high risk for IMD, but large-scale real-world evidence on clinical presentation and treatment in this population is lacking. These patients traditionally receive whole brain radiation therapy (WBRT) for IMD, however, a recent systematic review has indicated that OS following stereotactic radiosurgery (SRS) may be non-inferior compared with WBRT. We aim to describe the clinical characteristics and outcomes of patients with SCLC and IMD in Ontario, Canada.

Stereotactic radiosurgery and local control of brain metastases from triple-negative breast cancer.

Stereotactic radiosurgery (SRS) is an effective treatment for intracranial metastatic disease, but its role in triple-negative breast cancer requires further study. Herein, the authors report overall survival (OS) and local tumor control in a multiinstitutional cohort with triple-negative breast cancer metastases treated with SRS. Patients treated from 2010 to 2019 at 9 institutions were included in this retrospective study if they had biopsy-proven triple-negative breast cancer with intracranial metastatic lesions treated with SRS. Patients were excluded if they had undergone prior SRS, whole-brain radiation therapy, or resection of the metastatic lesions. A retrospective chart review was conducted to determine OS, local control, and treatment efficacy. Sixty-eight patients with 315 treated lesions were assessed. Patients had a median Karnofsky Performance Status of 80 (IQR 70-90) and age of 57 years (IQR 48-67 years). Most treated patients had 5 or fewer intracranial lesions, with 34% of patients having a single lesion. Treated lesions were small, having a median volume owf 0.11 cm3 (IQR 0.03-0.60 cm3). Patients were treated with a median margin dose of 18 Gy (IQR 18-20 Gy) to the median 71% isodose line (IQR 50%-84%). Overall, patients had a 1-year OS of 43% and 2-year OS of 20%. Most patients (88%) were followed until death, by which time local tumor progression had occurred in only 7% of cases. Furthermore, 76% of the lesions demonstrated regression. Tumor volume was correlated with local tumor progression (p = 0.012). SRS was very well tolerated, and only 3 patients (5%) developed symptomatic radiation necrosis. SRS is a safe and efficacious treatment for well-selected patients with triple-negative breast cancer, especially for those with a favorable performance status and small- to moderate-volume metastatic lesions.

Factors associated with progression and mortality among patients undergoing stereotactic radiosurgery for intracranial metastasis: results from a national real-world registry.

Stereotactic radiosurgery (SRS) has been increasingly employed in recent years to treat intracranial metastatic lesions. However, there is still a need for optimization of treatment paradigms to provide better local control and prevent progressive intracranial disease. In the current study, the authors utilized a national collaborative registry to investigate the outcomes of patients with intracranial metastatic disease who underwent SRS and to determine factors associated with lesion treatment response, overall progression, and mortality. The NeuroPoint Alliance SRS registry was queried for all patients with intracranial metastatic lesions undergoing single- or multifraction SRS at participating institutions between 2016 and 2020. The main outcomes of interest included lesion response (lesion-level analysis), progression using Response Assessment for Neuro-Oncology criteria, and mortality (patient-level analysis). Kaplan-Meier analysis was used to report time to progression and overall survival, and multivariable Cox proportional hazards analysis was used to investigate factors associated with lesion response, progression, and mortality. A total of 501 patients (1447 intracranial metastatic lesions) who underwent SRS and had available follow-up were included in the current analyses. The most common primary tumor was lung cancer (49.5%, n = 248), followed by breast (15.4%, n = 77) and melanoma (12.2%, n = 61). Most patients had a single lesion (44.9%, n = 225), 29.3% (n = 147) had 2 or 3 lesions, and 25.7% (n = 129) had > 3 lesions. The mean sum of baseline measurements of the lesions according to Response Evaluation Criteria in Solid Tumors (RECIST) was 35.54 mm (SD 25.94). At follow-up, 671 lesions (46.4%) had a complete response, 631 (43.6%) had a partial response (≥ 30% decrease in longest diameter) or were stable (< 30% decrease but < 20% increase), and 145 (10%) showed progression (> 20% increase in longest diameter). On multivariable Cox proportional hazards analysis, melanoma-associated lesions (HR 0.48, 95% CI 0.34-0.67; p < 0.001) and larger lesion size (HR 0.94, 95% CI 0.93-0.96; p < 0.001) showed lower odds of lesion regression, while a higher biologically effective dose was associated with higher odds (HR 1.001, 95% CI 1.0001-1.00023; p < 0.001). A total of 237 patients (47.3%) had overall progression (local failure or intracranial progressive disease), with a median time to progression of 10.03 months after the index SRS. Factors found to be associated with increased hazards of progression included male sex (HR 1.48, 95% CI 1.108-1.99; p = 0.008), while administration of immunotherapy (before or after SRS) was found to be associated with lower hazards of overall progression (HR 0.62, 95% CI 0.460-0.85; p = 0.003). A total of 121 patients (23.95%) died during the follow-up period, with a median survival of 19.4 months from the time of initial SRS. A higher recursive partitioning analysis score (HR 21.3485, 95% CI 1.53202-3.6285; p < 0.001) was found to be associated with higher hazards of mortality, while single-fraction treatment compared with hypofractionated treatment (HR 0.082, 95% CI 0.011-0.61; p = 0.015), administration of immunotherapy (HR 0.385, 95% CI 0.233-0.64; p < 0.001), and presence of single compared with > 3 lesions (HR 0.427, 95% CI 0.187-0.98; p = 0.044) were found to be associated with lower risk of mortality. The comparability of results between this study and those of previously published clinical trials affirms the value of multicenter databases with real-world data collected without predetermined research purpose.

Analysis of Rates of Brain Metastases and Association With Breast Cancer Subtypes in Ontario, Canada

Approximately 1 in 7 patients with metastatic breast cancer (MBC) will receive radiotherapy for brain metastases (BRM). Significant differences in cumulative incidence of BRM by breast cancer subtype may inform future BRM screening protocols. To describe cumulative incidence of BRM among patients with de novo MBC. In this population-based cohort study, population health administrative databases in Ontario, Canada, held at the ICES were used to identify patients diagnosed with de novo MBC between 2009 and 2018. Given that a code for BRM does not exist within ICES, we analyzed the incidence of radiotherapy for BRM. The median (IQR) follow-up was 19.3 (6.2-39.5) months. A total of 100 747 patients with a new diagnosis of breast cancer between January 2009 and December 2018 were identified. Of these patients, 17 955 were excluded because they had previous or subsequent malignant neoplasms, 583 were excluded because they were younger than 18 years, 974 were excluded because there was an invalid Ontario Health Insurance Plan number or a date of death on or before the index date. Among 81 235 remaining patients, 3916 were identified as having de novo MBC. Treatment with radiotherapy for breast cancer BRM. Cumulative incidence of radiotherapy for BRM accounting for the competing risk of death, and time from MBC diagnosis to brain radiotherapy. Kaplan-Meier analyses were performed for time-to-event end points. Logistic regression was used to account for confounding variables. Among 3916 patients with MBC, 1215 (31.0%) had HR-positive/ERBB2 (formerly HER2)-negative cancer, 310 (7.9%) had ERBB2-positive/HR-positive cancer, 200 (5.1%) had ERBB2-positive/HR-negative cancer, 258 (6.6%) had TNBC, and the remaining 1933 patients (49.4%) had an unknown breast cancer subtype. The median (IQR) age at diagnosis was 63 (52-75). A total of 549 (14.0%) underwent stereotactic radiosurgery or whole brain radiotherapy for breast cancer BRM. Cumulative incidence of BRM was higher among patients with ERBB2-positive/HR-negative breast cancer (34.7%), ERBB2-positive/HR-positive breast cancer (28.1%), and triple-negative breast cancer (21.9%) compared to those with HR-positive/ERBB2-negative breast cancer (12.1%). The median (IQR) time from MBC diagnosis to brain radiotherapy ranged from 7.5 (2.3-17.4) months for patients with TNBC to 19.8 (12.2-35.1) months for those with ERBB2-positive/HR-positive breast cancer. Incidence and time to development of BRM vary significantly by breast cancer subtype. A better understanding of the biology of intracranial metastatic disease may help inform potential screening programs or preventative interventions.

Stereotactic radiosurgery versus whole brain radiotherapy in patients with intracranial metastatic disease and small-cell lung cancer: a systematic review and meta-analysis.

Patients with small-cell lung cancer (SCLC) are at high risk for intracranial metastatic disease (IMD). Although stereotactic radiosurgery (SRS) has supplanted whole brain radiotherapy (WBRT) as first-line treatment for IMD in most solid cancers, WBRT remains first-line treatment for IMD in patients with SCLC. We aimed to evaluate the efficacy of SRS in comparison with WBRT and assess treatment outcomes following SRS. In this systematic review and meta-analysis, we searched MEDLINE, Embase, CENTRAL, and grey literature sources for controlled trials and cohort studies published in English reporting on SRS for IMD treatment in patients with SCLC from inception to March 23, 2022. Studies were excluded that did not report on SRS for IMD secondary to SCLC. Summary data were extracted. The primary outcome was overall survival, presented as pooled hazard ratios (HR) through random-effects meta-analysis for studies comparing SRS with WBRT with or without SRS boost, and as medians for single-arm SRS studies. This study is registered with the Open Science Framework, DOI 10.17605/OSF.IO/8M4HC, and PROSPERO, CRD42021258197. Of 3823 identified records, 31 were eligible for inclusion; seven were included in the meta-analysis. Overall survival following SRS was longer than following WBRT with or without SRS boost (HR 0·85; 95% CI 0·75-0·97; n=7 studies; n=18 130 patients), or WBRT alone (0·77; 0·72-0·83; n=7 studies; n=16 961 patients), but not WBRT plus SRS boost (1·17, 0·78-1·75; n=4 studies; n=1167 patients). Using single-arm studies, pooled median overall survival from SRS was 8·99 months (95% CI 7·86-10·16; n=14 studies; n=1682 patients). Between-study heterogeneity was considerable when pooled among all comparative studies (I2=71·9%). These results suggest survival outcomes are equitable following treatment with SRS compared with WBRT in patients with SCLC and IMD. Future prospective studies should focus on tumour burden and differences in local and distant intracranial progression between WBRT-treated and SRS-treated patients with SCLC. None.

Brain metastases in the setting of stable extracranial disease: A systematic review and meta-analysis.

2022 Background: Intracranial metastatic disease (IMD) is a life-altering complication for many patients with cancer. Improvements in systemic therapies have transformed the epidemiology of IMD, with some patients presenting with IMD in the context of stable extracranial disease (IMD-SECD). Among patients with metastases in other sites with similarly stable systemic disease, surgical resection and targeted therapy can result in long-term disease control and extended overall survival (OS), yet little is known about the clinical outcomes for patients with IMD-SECD. Methods: We searched MEDLINE, EMBASE, CENTRAL, and grey literature sources up to June 21, 2021 for studies reporting brain metastasis (BrM) with controlled extracranial disease (ECD) as well as IMD-SECD secondary to any primary cancer (criteria: presence of BrM and ≤2 extracranial metastatic sites, with no prior second-line chemotherapy and second-line brain-directed therapy). In studies comparing IMD-SECD and IMD patients, hazard ratios (HR) for OS and intracranial progression-free survival (iPFS) were pooled using random-effects meta-analysis, while medians for OS were estimated from single-arm IMD-SECD studies based on distribution-free summary survival curves. Results: Of 1067 records identified, 68 studies involving 5325 patients with IMD-SECD were included. Patients with IMD-SECD had prolonged OS (HR 1.93; 95% CI, 1.44-2.59; n = 10 studies; n = 877 patients) and iPFS (HR 1.59; 95% CI 1.31-1.92; n = 4 studies; n = 673 patients) compared with IMD patients. Subgroup analysis of patients with BrM and controlled versus uncontrolled ECD found prolonged OS with controlled ECD (HR 2.46; 95% CI, 1.36-4.44; n = 4 studies; n = 135 patients). Pooled median OS for all IMD-SECD patients was 20.85 months (mo) (95% CI, 16.35-25.98; n = 27 studies; n = 2159 patients). Stratification by primary cancer type showed median OS 20.18 mo (95% CI, 10.43-38.20; n = 2 studies; n = 109 patients) and 27.46 mo (95% CI, 18.27-49.66; n = 13 studies; n = 497 patients) for patients with IMD-SECD secondary to breast cancer and non-small cell lung cancer, respectively. Conclusions: Patients with IMD-SECD demonstrate prolonged OS and iPFS compared with patients with IMD, who may have more extensive systemic disease. Our results suggest that patients with IMD-SECD may represent a distinct subpopulation of patients with IMD with a uniquely favourable prognosis. It is possible that aggressive and timely treatment may significantly prolong survival for these patients. Future prospective trials should aim to investigate the efficacy of current treatment regimens in patients with IMD-SECD to further clarify optimal treatment pathways in this unique population of patients.

Stereotactic radiosurgery (SRS) versus whole brain radiation therapy (WBRT) in patients with small cell lung cancer (SCLC) and intracranial metastatic disease (IMD): A systematic review and meta-analysis.

8570 Background: Patients with SCLC are at high risk for the development of IMD and, subsequently, rapid intracranial progression. SRS has supplanted WBRT as first-line treatment for IMD in most solid cancers, but WBRT remains first-line treatment for IMD in SCLC patients. Data on SRS in SCLC are limited to small retrospective studies. Methods: Studies reporting on SRS in SCLC patients with IMD were collected from EMBASE, MEDLINE, CENTRAL, and grey literature sources (n = 3,732 studies). Random-effects meta-analysis pooled hazard ratios (HR) for overall survival (OS) between SRS and WBRT ± SRS boost, as well as medians for OS in months (mo) and risk rates for intracranial local (LC) and intracranial distant control (DC) in single-arm SRS studies. Results: OS following SRS was non-inferior compared with WBRT ± SRS boost (HR 0.90; 95% confidence interval (95CI), 0.73-1.10; n = 7 studies; n = 18,130 patients), and superior compared with WBRT alone (HR 0.80; 95CI, 0.66-0.96; n = 7 studies; n = 16,961 patients). Pooled median OS from single-arm studies following SRS was 8.99 mo (95CI, 7.86-10.15; n = 14 studies; n = 1,682 patients). Pooled LC and DC estimates following SRS were 81% (95CI, 67%-99%) and 66% (95CI, 50%- 86%), respectively, at 6 mo, and 78% (95CI, 61%-98%) and 58% (95CI, 46%-75%), respectively, at 12 mo. Conclusions: This systematic review and meta-analysis provides evidence that SRS may achieve analogous survival outcomes compared with WBRT in patients with SCLC and IMD, indicating that a subset of SCLC patients may benefit from first-line SRS treatment. Prospective trials should investigate the impact of metastatic burden as well as LC and DC differences between WBRT- and SRS-treated SCLC patients.

Stereotactic radiosurgery for prostate cancer cerebral metastases: an international multicenter study.

As novel therapies improve survival for men with prostate cancer, intracranial metastatic disease has become more common. The purpose of this multicenter study was to evaluate the safety and efficacy of stereotactic radiosurgery (SRS) in the management of intracranial prostate cancer metastases. Demographic data, primary tumor characteristics, SRS treatment parameters, and clinical and imaging follow-up data of patients from nine institutions treated with SRS from July 2005 to June 2020 for cerebral metastases from prostate carcinoma were collected and analyzed. Forty-six patients were treated in 51 SRS procedures for 120 prostate cancer intracranial metastases. At SRS, the mean patient age was 68.04 ± 9.05 years, the mean time interval from prostate cancer diagnosis to SRS was 4.82 ± 4.89 years, and extracranial dissemination was noted in 34 (73.9%) patients. The median patient Karnofsky Performance Scale (KPS) score at SRS was 80, and neurological symptoms attributed to intracranial involvement were present prior to 39 (76%) SRS procedures. Single-fraction SRS was used in 49 procedures. Stereotactic radiotherapy using 6 Gy in five sessions was utilized in 2 procedures. The median margin dose was 18 (range 6-28) Gy, and the median tumor volume was 2.45 (range 0.04-45) ml. At a median radiological follow-up of 6 (range 0-156) months, local progression was seen with 14 lesions. The median survival following SRS was 15.18 months, and the 1-year overall intracranial progression-free survival was 44%. The KPS score at SRS was noted to be associated with improved overall (p = 0.02) and progression-free survival (p = 0.03). Age ≥ 65 years at SRS was associated with decreased overall survival (p = 0.04). There were no serious grade 3-5 toxicities noted. SRS appears to be a safe, well-tolerated, and effective management option for patients with prostate cancer intracranial metastases.

18F-FES PET/CT Improves the Detection of Intraorbital Metastases in Estrogen-Receptor-Positive Breast Cancer: Two Representative Cases and Review of the Literature

Orbital metastases are a rare but life-altering complication in cancer. Most commonly seen in breast cancer, metastases to the optic nerves or extraocular muscles can have a devastating impact on visual acuity and quality of life. Hormone receptor status plays a central role in metastatic breast cancer treatment, with endocrine therapy often representing first-line therapy in hormone-receptor-positive cancers. Staging and treatment response evaluation with positron emission tomography (PET) computed tomography (CT) imaging with 18F-fluorodeoxyglucose (18F-FDG) is limited by high physiologic uptake in the intracranial and intraorbital compartments. Thus, traditional staging scans with 18F-FDG PET/CT may under-detect intraorbital and intracranial metastatic disease and inaccurately evaluate active metastatic disease burden. In comparison, 18F-fluoroestradiol (18F-FES) is a novel estrogen-receptor-specific PET radiotracer, which more accurately assesses the intracranial and intraorbital compartments in patients with estrogen-receptor-positive (ER+) cancers than 18F-FDG, due to lack of physiologic background activity in these regions. We present two cases of breast cancer patients with orbital metastases confirmed on MR imaging who underwent PET/CT imaging with 18F-FES and 18F-FDG. Multimodality imaging with 18F-FES PET/CT offers higher detection sensitivity of orbital metastases, compared with traditional 18F-FDG PET/CT imaging, and can improve the assessment of treatment response in patients with estrogen-receptor-positive (ER+) cancers.

Surgical management and outcomes of intracranial metastatic Wilms' tumor in the pediatric population: a case series.

Approximately 1 to 2% of patients with Wilms' tumor (WT), or nephroblastoma, will have metastasis to the brain. Due to the rarity of intracranial metastasis, the clinical characteristics, prognosis, and a standardized treatment approach to this occurrence remain poorly understood. Here we review the surgical management and treatment outcome of WT patients with intracranial metastasis at our institution. A retrospective chart review of patients with WT at the Children's Hospital of Philadelphia was performed from 2007 to 2021. Clinical characteristics, operative details, radiographic studies, pathology, and patient outcomes were collected and analyzed. A total of 3 patients with histologically confirmed intracranial metastatic disease from WT were identified with a mean age of 5.7years (range 3-10years). 2 of the 3 patients were male. The mean time from diagnosis of primary WT to development of central nervous system metastasis was 15.3months. Both supratentorial (n = 3) and infratentorial (n = 1) sites of metastasis were observed. Surgical resection was performed, and gross total resection was achieved in all 3 patients. All cases had favorable histology with no anaplasia and received whole-brain irradiation and chemotherapy. Two of 3 patients had a good neurologic function at postoperative follow-up. One patient died from their disease 4months after resection of the brain metastasis. In WT patients with limited systemic disease burden, the combination of surgery, chemotherapy, and radiotherapy may play a role in enhancing survival when intracranial metastasis is present, despite the perioperative risk associated with surgery.

Intracranial Metastatic Disease: Present Challenges, Future Opportunities.

Intracranial metastatic disease (IMD) is a prevalent complication of cancer that significantly limits patient survival and quality of life. Over the past half-century, our understanding of the epidemiology and pathogenesis of IMD has improved and enabled the development of surveillance and treatment algorithms based on prognostic factors and tumor biomolecular characteristics. In addition to advances in surgical resection and radiation therapy, the treatment of IMD has evolved to include monoclonal antibodies and small molecule antagonists of tumor-promoting proteins or endogenous immune checkpoint inhibitors. Moreover, improvements in the sensitivity and specificity of imaging as well as the development of new serological assays to detect brain metastases promise to revolutionize IMD diagnosis. In this review, we will explore current treatment principles in patients with IMD, including the emerging role of targeted and immunotherapy in select primary cancers, and discuss potential areas for further investigation.

Management Strategies for Large Brain Metastases.

Brain metastases represent the most common intracranial neoplasm and pose a significant disease burden on the individual and the healthcare system. Although whole brain radiation therapy was historically a first line approach, subsequent research and technological advancements have resulted in a larger armamentarium of strategies for treatment of these patients. While chemotherapeutic options remain limited, surgical resection and stereotactic radiosurgery, as well as their combination therapies, have shifted the paradigms for managing intracranial metastatic disease. Ultimately, no single treatment is shown to be consistently effective across patient groups in terms of overall survival, local and distant control, neurocognitive function, and performance status. However, close consideration of patient and tumor characteristics may help delineate more favorable treatment strategies for individual patients. Here the authors present a review of the recent literature surrounding surgery, whole brain radiation therapy, stereotactic radiosurgery, and combination approaches.

Clinical Biomarkers for Early Identification of Patients with Intracranial Metastatic Disease.

Simple SummaryThe development of brain metastases, or intracranial metastatic disease (IMD), is a serious and life-altering complication for many patients with cancer. While there have been substantial advancements in the treatments available for IMD and in our understanding of its pathogenesis, conventional methods remain insufficient to detect IMD at an early stage. In this review, we discuss current research on biomarkers specific to IMD. In particular, we highlight biomarkers that can be easily accessed via the bloodstream or cerebrospinal fluid, including circulating tumor cells and DNA, as well as advanced imaging techniques. The continued development of these assays could enable clinicians to detect IMD prior to the development of IMD-associated symptoms and ultimately improve patient prognosis and survival.Nearly 30% of patients with cancer will develop intracranial metastatic disease (IMD), and more than half of these patients will die within a few months following their diagnosis. In light of the profound effect of IMD on survival and quality of life, there is significant interest in identifying biomarkers that could facilitate the early detection of IMD or identify patients with cancer who are at high IMD risk. In this review, we will highlight early efforts to identify biomarkers of IMD and consider avenues for future investigation.

THER-01. Targeted therapy and intracranial metastatic disease: a population-based retrospective cohort study

BackgroundTargeted therapies have been hypothesized to prolong survival in the management of patients with intracranial metastatic disease (IMD), but, paradoxically, to increase IMD incidence by improving systemic disease control and prolonging survival from the primary tumor. The real-world benefits of targeted therapy in management of patients with IMD are unclear, as clinical trials have excluded patients with IMD and lacked endpoints reporting intracranial outcomes.MethodsThis retrospective cohort study included all patients in Ontario, Canada, diagnosed with IMD from 2005 to 2018 with primary diagnoses of breast cancer, lung or bronchus cancer, or melanoma, and control patients matched by primary disease without IMD. Kaplan-Meier and multivariable Cox regression analyses were performed to compare overall survival (OS) between patient sub-cohorts divided by primary disease and stratified by targeted therapy receipt or IMD status.ResultsPost-IMD targeted therapy was associated with prolonged OS in patients with HER2-positive breast cancer (HR 0.41; 95% CI, 0.33–0.5), EGFR-positive lung cancer (HR 0.28; 95% CI, 0.23–0.34), and BRAF-positive melanoma (HR 0.2; 95% CI, 0.14–0.29), compared to those who did not receive post-IMD targeted therapy. Presence of IMD was associated with shorter OS in patients with metastatic HER2-positive breast cancer (HR 1.8; 95% CI, 1.56–2.08) and metastatic EGFR-positive lung cancer (HR 1.22; 95% CI, 1.08–1.39) but not metastatic BRAF-positive melanoma (HR 1.11; 95% CI, 0.77–1.61), compared to those without IMD.ConclusionsOur findings show that real-world use of targeted therapies was associated with prolonged OS in patients with IMD in the setting of HER2-positive breast cancer, EGFR-positive lung cancer, and BRAF-positive melanoma. Inclusion of patients with IMD in clinical trials and use of endpoints that interrogate IMD will be critical to determine the role of targeted therapies in the management of patients with IMD.