Outcomes Of Brain Metastases Research Articles

Outcomes of Brain Metastasis from Lung Cancer

Background/Objectives: Little information has been published on patients diagnosed with brain metastasis secondary to lung cancer. Correlating outcome patterns (hospice care, lost to follow-up, death before hospice care or treatment) and specific characteristics of treated and untreated patients may identify subsets of patients who may benefit from treatment. Methods: We evaluated data from the Kentucky Cancer Registry and identified 284 cases who were diagnosed with brain metastasis secondary to non-small cell lung cancer (NSCLC) between 1 August 2016, and 31 December 2019. We evaluated type and timing of treatment received, as well as focused on those patients who did not receive treatment. For those patients who did not receive treatment, various characteristics that may have impacted their decision or ability to undergo follow-up were also evaluated. This included social history, disease burden, as well as oncology treatment timelines. Lastly, due to the high smoking rate in Kentucky, we conducted an analysis of patient tobacco use. Results: Our results show that 61 cases (21.8%) never received treatment for lung cancer with brain metastasis. Further analysis of the non-treated cases demonstrated that 19 cases (31.1%) never met with an oncology team while in the hospital or after discharge; 14 of the 61 cases (23.0%) were too sick to receive treatment and died prior to having the option of treatment; and 47 of the 61 cases (77.0%) may have had the option of treatment but declined. Conclusions: Historically, patients with brain metastases have faced poor prognoses and limited treatment options. However, advancements in systemic chemoimmunotherapy and targeted therapies have introduced new treatment possibilities, offering improved symptom control and the potential for prolonged survival. This analysis is crucial for identifying potential barriers to care, optimizing resource allocation, and guiding future research.

MTAS-01 UPDATES ON BRAIN METASTASIS MANAGEMENT AND OUTCOMES IN LMICS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract BACKGROUND Brain Metastases (BM) occur in the natural course of malignant tumors and cause a high rate of morbidity and mortality. The approaches to their management have changed considerably over the past decade. We aimed to give an update regarding the current means of diagnosis, management, and the outcomes of brain metastases in LMIC. METHODS We searched PubMed, ScienceDirect, Medline, Embase, Global Index Medicus, African Journals Online, and Google Scholar for studies reporting data on Brain metastasis diagnosis, management, and outcomes in LMICs from inception to October 23rd, 2022. The systematic review was conducted using the PRISMA principles. RESULTS A total of 7916 unique studies were identified, of which, 48 were included. The most studied (21, 43.75%) and common cause of metastases was lung tumors (1602, 51.43%). A subtotal resection (STR) was archived in the majority of reported cases in the frequency of 56.2% (n = 1751), gross total resection (GTR) in 37.5% (n = 1169) of cases, while only biopsy was possible in 6.3% (n = 195). The reported adjuvant treatments were radiotherapy 39.9% (n = 1036), radiosurgery 22.5% (n = 585), and radiosurgery + radiotherapy 37.5% (N = 974). Management of the primary tumor was reported in 13 (27.08%) studies. Half (24, 50%) of the studies reported the overall survival time to be 4-52 months. CONCLUSION Lung, breast, and GI tumors were the most common primary tumors for the MB. Whole-brain radiotherapy is the most common management method in LMICs.

Role of Hospital Connectedness in Brain Metastasis Outcomes

Although patients with brain metastases receive interdisciplinary and multi-institutional care, the association between neuro-oncologic care networks and patient outcomes remains unknown. As patients often interact with multiple facilities, quantifying this association across a network of hospitals is critical to capture the complexity of the health care journey for patients with brain metastases. To evaluate how statewide health care network metrics are associated with inpatient mortality and hospital length of stay (LOS) for patients with brain metastases. This multicenter, statewide cohort study used data from the 2018 to 2019 Healthcare Cost and Utilization Project State Inpatient and Emergency Department Databases. Primary analyses were completed by August 2023. Participants included adults with a brain metastases receiving care in Massachusetts. All inpatient and emergency department visits mapped for patients following the first diagnosis of brain metastasis. Inpatient mortality and hospital LOS were the main outcomes assessed. Hospital interdependence in brain metastases care was calculated using a connectedness score (weighted degree: weighted sum of ties to other care facilities). The association between hospital connectedness and clinical outcomes was analyzed using mixed-effects logistic and linear regression models, adjusting for hospital-level features. In this cohort study, 4679 patients with brain metastases were identified with inpatient or ED encounters in Massachusetts (from 2018 to 2019). The median (IQR) age was 64 (57-73) years, and 2559 (55%) were female. There was interdependence in brain metastases care, with 993 patients (21%) visiting 2 or more unique hospitals. Highly connected hospitals were heterogeneous, with many being small and one-half lacking subspecialty neuro-oncologic care or teaching status. Increased hospital connectedness was significantly associated with improved inpatient mortality for patients with brain metastases, with the lowest connectedness quartile associated with more than double the risk of mortality compared with the highest quartile (odds ratio, 2.34; 95% CI, 1.33-4.11; P = .003). A stepwise increase in inpatient mortality risk was observed as hospital connectedness decreased, independently of hospital volume. Furthermore, intermediate hospital connectedness was associated with increased hospital LOS (coefficient, 1.08; 95% CI, 0.17-1.95; P = .006). This study found that hospital-to-hospital interconnectedness was significantly associated with improved clinical outcomes for patients with brain metastases. The salience of network metrics highlights their potential role alongside other patient-level and hospital-level variables to evaluate and improve oncology care delivery.

Impact of cyclin dependent kinase 4/6 inhibitors on breast cancer brain metastasis outcomes

BackgroundCyclin dependent kinase 4/6 inhibitors (CDK4/6i) are recommended 1st line treatments in HR+HER2- metastatic breast cancer. However, the impact of prior CDK4/6i on the natural history of brain metastases (BM) is not well described. Materials and methodsWe reviewed retrospective data for 363 patients with HR+HER2- BM who received a CDK4/6i (CDK-Y) between 1 Jan 2015 to 31 July 2021 and 299 patients with HR+HER2- BM who did not receive a CDK4/6i (CDK-N) between 1 Jan 2010 to 31 Dec 2014.CNS PFS and OS were assessed in patients who received CDK4/6i after BM. OS from the time of BM development was assessed between patients who received CDK4/6i before BM and the CDK-N cohort ResultsIn the CDK-Y cohort of 363 patients, 203 (56 %) received a CDK4/6i before BM, 133 (37 %) received a CDK4/6i only after BM and 27 (7 %) received a CDK4/6i both before and after BM.Median CNS PFS was 21.4 months for patients receiving a CDK4/6i only after BM and 9.4 months for patients who received CDK4/6i both before and after BM (p = 0.006). Median OS was 24.9 months for patients receiving a CDK4/6i only after BM and 12.1 months for patients who received CDK4/6i both before and after BM (p = 0.0098). Median OS from time of BM development for patients receiving a CDK4/6i before BM versus the CDK-N cohort was 4.3 months and 7.7 months respectively (p = 0.0082). ConclusionsCDK4/6i exposure prior to BM may lead to development of resistance mechanisms which in turn reduces CNS PFS and OS upon rechallenging with a CDK4/6i after BM development. This motivates investigation of biomarkers for patient selection.

Treatment outcomes of brain metastasis from primary renal cell carcinoma in United States: A National Cancer Database analysis.

4561 Background: The advent of stereotactic radiosurgery (SRS) in treatment of brain metastasis (BM) has improved both clinical outcomes and survival in patients with BM. Recent studies suggest that immunotherapy presents a promising potential in the treatment of patients with BM. However, data regarding the effectiveness of combining SRS with immunotherapy for BM in metastatic renal cell carcinoma (RCC) remain largely unknown. We aim to delineate the impact of various treatment therapies including combination therapy for treatment of RCCBM. Methods: We queried the National Cancer Database (NCDB) to include patients with BM from mRCC from 2004 to 2020. We divided the patients into groups based on the treatment they received. Resultantly, 5 different treatment groups i.e., WRBT± immunotherapy, SRS± immunotherapy and immunotherapy alone were identified. We excluded patients with unknown treatment status. We analyzed survival outcomes using the Kaplan-Meier analysis and compared the effect of treatment modalities on survival with the log-rank test. Results: The NCDB yielded 6,446 patients diagnosed with BM from mRCC. In eligible cases, the median age was 63 years (range: 19-90+ years), 69.2% were male, 86.8% were White, 7.9% were Black, 41.9% had Medicare as primary payor, 27.7% had annual income >$74,063, 79.3% belonged from metropolitan areas, 39.6% were treated at academic/research program, 68.3% had Charlson-Deyo score of 0, 44.6% had an unknown grade of the primary RCC. 1,705 (43.44%) patients who were given WBRT had a median overall survival (OS) of 5.65 months, 427 (10.88%) patients were treated with SRT + immunotherapy had an OS of 19.0 months, 987 (25.15%) patients who underwent SRT only had an OS of 9.7 months, 431 (10.98%) patients who received immunotherapy only showed an OS of 12.9 months, and 375 (9.55%) patients who underwent WBRT + immunotherapy had an OS of 12.78 months (log-rank p <0.001). Conclusions: This national database analysis reveals that the combination of SRS with immunotherapy significantly increases the OS in RCCBM compared to immunotherapy, WBRT, or combination of WRBT and immunotherapy. Further prospective studies are warranted to confirm these findings. [Table: see text]

Prognostic Implications of Small Cell Lung Cancer Transcriptional Subtyping for CNS Metastases.

Small cell lung cancer (SCLC) often metastasizes to the brain and has poor prognosis. SCLC subtypes distinguished by expressing transcriptional factors ASCL1 or NEUROD1 have been identified. This study investigates the impact of transcription factor-defined SCLC subtype on incidence and outcomes of brain metastases (BMs). Patients with SCLC with ASCL1 (A) and NEUROD1 (N) immunohistochemical expression status were identified and classified: (1) A+/N-, (2) A+/N+, (3) A-/N+, and (4) A-/N-. Cumulative incidence competing risk analyses were used to assess incidence of CNS progression. Cox proportional hazards models were used for multivariable analyses of overall survival (OS) and CNS progression-free survival (CNS-PFS). Of 164 patients, most were either A+/N- or A+/N+ (n = 62, n = 63, respectively). BMs were present at diagnosis in 24 patients (15%). Among them, the 12-month cumulative incidence of subsequent CNS progression was numerically highest for A+/N- (50% [95% CI, 10.5 to 74.7]; P = .47). Among those BM-free at diagnosis, the 12-month cumulative incidence of CNS progression was numerically the highest for A+/N- (16% [95% CI, 7.5 to 27.9]) and A-/N+ (9.1% [95% CI, 0.0 to 34.8]; P = .20). Both subtypes, A+/N- and A-/N+, had worse OS compared with A+/N+ (A+/N-: hazard ratio [HR], 1.62 [95% CI, 1.01 to 2.51]; P < .05; A-/N+: HR, 3.02 [95% CI, 1.35 to 6.76]; P = .007). Excellent response rates (28, 65% CR/PR) across subtypes were seen in patients who had CNS-directed radiotherapy versus systemic therapy alone (9, 36% CR/PR). To our knowledge, this report is the first to investigate CNS-specific outcomes based on transcription factor subtypes in patients with SCLC. BM-free patients at diagnosis with A+/N- or A-/N+ subtypes had worse outcomes compared with those with transcriptional factor coexpression. Further investigation into the mechanisms and implications of SCLC subtyping on CNS-specific outcomes is warranted to ultimately guide personalized care.

Brain metastases from renal cell carcinoma: Effects of novel systemic agents on brain metastasis outcomes

ObjectiveThe objective of this study was to examine survival outcomes in 136 patients with renal cell carcinoma with metastases to the brain who were treated with radiation combined with immunotherapy or tyrosine kinase inhibitor compared to those who were treated with radiation therapy alone. MethodsThe Wake Forest Gamma Knife prospective database was searched for all patients with renal cell carcinoma brain metastases. Outcome measurements included overall survival, determined via the Kaplan-Meier Method, and cumulative incidence of local and distant failure, determined using the Fine Gray competing risks analysis with death as a competing risk for the 136 patients included. ResultsOverall survival for the entire population at 6 months, 12 months, and 24 months was 67%, 47% and 30%, respectively. For the TKI (non-immunotherapy-treated) population (n = 37), overall survival was 75%, 61%, and 40% at 6 months, 12 months, and 24 months, respectively. For the immunotherapy-treated population (n = 35), overall survival was 85%, 64%, and 50% at 6 months, 12 months, and 24 months, respectively. Overall survival was significantly increased for patients who received radiation with either immunotherapy or TKI (p < 0.0001). ConclusionPrior series of patients with brain metastases of multiple histologies have demonstrated an improvement in the local efficacy of stereotactic radiosurgery when combined with systemic agents. We found that patients treated with targeted agents and patients treated with immunotherapy demonstrated a trend towards improvement over patients treated in the era prior to the advent of either classes of novel therapies.

The Effect of Non-Overlapping Somatic Mutations in BRAF, NRAS, NF1, or CKIT on the Incidence and Outcome of Brain Metastases during Immune Checkpoint Inhibitor Therapy of Metastatic Melanoma

Previous studies suggested that somatic BRAF and NRAS mutations in metastatic melanoma increase the risk for brain metastases. The risk related to other non-overlapping “driver” mutations is unknown. We performed a retrospective evaluation of the incidence, timing, and outcome of brain metastases in a population of melanoma patients that underwent uniform next-gen sequencing. All patients were treated with initial checkpoint inhibitor therapy. Seventeen of 88 patients (20.0%) developed brain metastases. Eleven patients had brain metastases at diagnosis (12.9%). These were all patients with BRAF V600 or NF1 mutations. Only six patients with NRAS, NF1, KIT, or BRAF mutations (including fusions/internal rearrangements experienced delayed CNS progression following immunotherapy (7.1%)). No “quadruple negative” patient developed brain metastases. Patients with brain metastases at diagnosis had a better outcome than those with delayed intracranial progression. Current predictive markers, (LDH, tumor mutation burden, and PDL1) were poorly correlated with the development of brain metastases. Treatment with immunotherapy appears to reduce the incidence of brain metastases. Next-gen molecular sequencing of tumors in metastatic melanoma patients was useful in identifying genetic subpopulations with an increased or reduced risk of brain metastases. This may allow eventual personalization of screening strategies.

Management and outcomes of brain metastases from pancreatic adenocarcinoma: a pooled analysis and literature review.

Brain metastases (BM) are rare in pancreatic ductal adenocarcinoma (PDAC) and little data exists concerning these patients and their outcomes. We aimed to analyze the management, practices, and outcomes of patients presenting BM from PDAC both in our institution and in all cases reported in the literature. We conducted a retrospective, monocentric analysis using a data mining tool (ConSoRe) to identify all patients diagnosed with PDAC and BM in our comprehensive cancer center (Paoli-Calmettes Institute), from July 1997 to June 2022 (cohort 1). Simultaneously, we reviewed and pooled the case reports and case series of patients with PDAC and BM in the literature (cohort 2). The clinical characteristics of patients in each cohort were described and survival analyses were performed using the Kaplan-Meier method. In cohort 1, 19 patients (0.3%) with PDAC and BM were identified with a median age of 69 years (range: 39-81). Most patients had metastatic disease (74%), including 21% with BM, at diagnosis. Lung metastases were present in 58% of patients. 68% of patients had neurological symptoms and 68% were treated by focal treatment (surgery: 21%, radiotherapy: 42%, Gamma Knife radiosurgery: 5%). In cohort 2, among the 61 PDAC patients with BM described in the literature, 59% had metastatic disease, including 13% with BM at diagnosis. Lung metastases were present in 36% of patient and BM treatments included: surgery (36%), radiotherapy (36%), radiosurgery (3%), or no local treatment (25%). After the pancreatic cancer diagnosis, the median time to develop BM was 7.8 months (range: 0.0-73.9) in cohort 1 and 17.0 months (range: 0.0-64.0) in cohort 2. Median overall survival (OS) in patients of cohort 1 and cohort 2 was 2.9 months (95% CI [1.7,4.0]) and 12.5 months (95% CI [7.5,17.5]), respectively. BM are very uncommon in PDAC and seem to occur more often in younger patients with lung metastases and more indolent disease. BM are associated with poor prognosis and neurosurgery offers the best outcomes and should be considered when feasible.

Predicting stereotactic radiosurgery outcomes with multi-observer qualitative appearance labelling versus MRI radiomics

Qualitative observer-based and quantitative radiomics-based analyses of T1w contrast-enhanced magnetic resonance imaging (T1w-CE MRI) have both been shown to predict the outcomes of brain metastasis (BM) stereotactic radiosurgery (SRS). Comparison of these methods and interpretation of radiomics-based machine learning (ML) models remains limited. To address this need, we collected a dataset of n = 123 BMs from 99 patients including 12 clinical features, 107 pre-treatment T1w-CE MRI radiomic features, and BM post-SRS progression scores. A previously published outcome model using SRS dose prescription and five-way BM qualitative appearance scoring was evaluated. We found high qualitative scoring interobserver variability across five observers that negatively impacted the model’s risk stratification. Radiomics-based ML models trained to replicate the qualitative scoring did so with high accuracy (bootstrap-corrected AUC = 0.84–0.94), but risk stratification using these replicated qualitative scores remained poor. Radiomics-based ML models trained to directly predict post-SRS progression offered enhanced risk stratification (Kaplan–Meier rank-sum p = 0.0003) compared to using qualitative appearance. The qualitative appearance scoring enabled interpretation of the progression radiomics-based ML model, with necrotic BMs and a subset of heterogeneous BMs predicted as being at high-risk of post-SRS progression, in agreement with current radiobiological understanding. Our study’s results show that while radiomics-based SRS outcome models out-perform qualitative appearance analysis, qualitative appearance still provides critical insight into ML model operation.

Outcomes of Brain Metastases with Suspicious Imaging Undergoing Resection to Evaluate for Radionecrosis vs. Tumor Progression

In patients treated with stereotactic radiosurgery (SRS) for brain metastases, radiographic changes on surveillance imaging may result from treatment effect/radionecrosis (RN) or tumor progression. Distinguishing between these processes is critical to appropriate management. We report long-term outcomes for a cohort of patients who demonstrated radiographic progression on serial imaging after initial radiation and ultimately underwent resection to inform further management. A retrospective chart review identified 76 patients with an associated 82 brain lesions between 2009 and 2022 that were initially treated with SRS, then demonstrated suspicious imaging changes developing through at least two scan time points that led to pathologic confirmation of either tumor or RN. We report clinical outcomes and details of further treatments. Of the 82 lesions, 55 (67.1%) were found to be pathologically-confirmed viable tumor and were treated with repeat radiation and 27 (32.9%) were found to be strictly RN and conservatively managed. Over half of the lesions (14/27) ultimately found to be radionecrotic required use of steroids pre-operatively due to neurologic symptoms. Among the 27 that were found to be RN, the most common histology was melanoma (33.3%, n = 9). The most common dose fractionation regimen was 20 Gy in 1 fx (n = 11, 40.7%; range: 16-20 Gy x 1Fx), and the median BED (10) was 50.4 Gy (IQR 41.6 - 50 Gy). None of these lesions required further intervention with median post-surgery follow up of 24.4 months (range 1-104 months). There were 55 instances (in 51 patients) of pathologically-confirmed recurrent/progressive tumor who were consequently treated with repeat radiation with either Cs-131 brachytherapy (12 (21.8%)) or SRS (43 (78.2%)). The most common histology was NSCLC (37.2%, n = 19). The most common fractionation for repeat irradiation with SRS was 8 Gy x 3 fx (n = 15, 27.3%), followed by 5 Gy x 5 fx (n = 10, 18.2%), and 4 Gy x 5 fx (n = 8, 14.6%). Four individuals each had two lesions that were re-irradiated for local recurrence. Among patients treated with re-irradiation, the median follow-up to local failure was 15.2 months (95% CI 7.3-26.6 months). Radionecrosis was confirmed on pathology in 4/55 (7.2%) of lesions. The median follow-up from date of SRS2 to local failure was 14.1 months (95% CI 7.6-24.3 months). The 2-yr local control rate was 74.8% (95% CI 61.7-90.7%). We recommend cautious monitoring of possible progression after radiosurgery, with consideration of resection for continuous progression, as a significant proportion of radiographic progression are ultimately pure RN. Management determined by pathology (observation for RN; additional radiation for confirmed tumor) leads to excellent control.

Cystic Brain Metastasis Outcomes After Gamma Knife Radiation Therapy

The response of cystic brain metastases (BMets) to radiation therapy is poorly understood, with conflicting results regarding local control, overall survival, and treatment-related toxicity. This study aims to examine the role of Gamma Knife (GK) in managing cystic BMets. Volumetric analysis was conducted to measure tumor and edema volume at the time of GK and follow-up magnetic resonance imaging studies. Survival was described using the Kaplan-Meier method, and the cumulative incidence of progression was described using the Aalen-Johansen estimator. We evaluated the association of 4 variables with survival using Cox regression analysis. Between 2016 and 2021, 54 patients with 83 cystic BMets were treated with GK at our institution. Lung cancer was the most common pathology (51.9%), followed by breast cancer (13.0%). The mean target volume was 2.7 cm3 (range, 0.1-39.0 cm3), and the mean edema volume was 13.9 cm3 (range, 0-165.5 cm3). The median prescription dose of single-fraction and fractionated GK was 20 Gy (range, 14-27.5 Gy). With a median follow-up of 8.9 months, the median survival time (MST) was 11.1 months, and the 1-year local control rate was 75.9%. Gamma Knife was associated with decreased tumor and edema volumes over time, although 68.5% of patients required steroids after GK. Patients whose tumors grew beyond baseline after GK received significantly more whole-brain radiation therapy (WBRT) before GK than those whose tumors declined after GK. Higher age at diagnosis of BMets and pre-GK systemic therapy were associated with worse survival, with an MST of 7.8 months in patients who received it compared with 23.3 months in those who did not. Pre-GK WBRT may select for BMets with increased radioresistance. This study highlights the ability of GK to control cystic BMets with the cost of high posttreatment steroid use.

Outcome of brain metastases from adrenocortical carcinoma: a pooled analysis

PurposeBrain metastases rarely complicate the natural history of patients with adrenocortical carcinoma (ACC). No information is available regarding the life expectancy and efficacy of treatments in ACC patients with brain involvement.MethodsA pooled analysis was performed by searching on PubMed and using the keywords: “brain metastases in adrenocortical carcinoma”, and “leptomeningeal metastases in adrenocortical carcinoma”. Four patients diagnosed at Spedali Civili Hospital in Brescia were added to the analysis. Data concerning demographic, disease characteristics, adopted treatments and patient prognosis were collected.ResultsA total of 27 patients (18 adults and 9 children) were included in this study, 22 of them had an adequate follow-up. Brain metastases occurred late in the natural history of adult patients but not in that of children. Surgery plus/minus radiation therapy was the treatment of choice. Adult patients with brain metastases had a poor prognosis with a median progression-free survival (PFS) and overall survival (OS) of 2 and 7 months, respectively. Median PFS and OS were not attained in children.ConclusionBrain metastases in ACC patients are rare and are associated with poor prognosis, particularly in adults. Surgery plus/minus radiotherapy is the only therapeutic approach that can offer patients a chance to obtain durable local disease control.

EGFR-Driven Mutation in Non-Small-Cell Lung Cancer (NSCLC) Influences the Features and Outcome of Brain Metastases.

Background: Brain metastases (BMs) is one of the most frequent metastatic sites for non-small-cell lung cancer (NSCLC). It is a matter of debate whether EGFR mutation in the primary tumor may be a marker for the disease course, prognosis, and diagnostic imaging of BMs, comparable to that described for primary brain tumors, such as glioblastoma (GB). This issue was investigated in the present research manuscript. Methods: We performed a retrospective study to identify the relevance of EGFR mutations and prognostic factors for diagnostic imaging, survival, and disease course within a cohort of patients affected by NSCLC-BMs. Imaging was carried out using MRI at various time intervals. The disease course was assessed using a neurological exam carried out at three-month intervals. The survival was expressed from surgical intervention. Results: The patient cohort consisted of 81 patients. The overall survival of the cohort was 15 ± 1.7 months. EGFR mutation and ALK expression did not differ significantly for age, gender, and gross morphology of the BM. Contrariwise, the EGFR mutation was significantly associated with MRI concerning the occurrence of greater tumor (22.38 ± 21.35 cm3 versus 7.68 ± 6.44 cm3, p = 0.046) and edema volume (72.44 ± 60.71 cm3 versus 31.92 cm3, p = 0.028). In turn, the occurrence of MRI abnormalities was related to neurological symptoms assessed using the Karnofsky performance status and mostly depended on tumor-related edema (p = 0.048). However, the highest significant correlation was observed between EGFR mutation and the occurrence of seizures as the clinical onset of the neoplasm (p = 0.004). Conclusions: The presence of EGFR mutations significantly correlates with greater edema and mostly a higher seizure incidence of BMs from NSCLC. In contrast, EGFR mutations do not affect the patient's survival, the disease course, and focal neurological symptoms but seizures. This contrasts with the significance of EGFR in the course and prognosis of the primary tumor (NSCLC).

NIMG-09. BRAIN METASTASIS FROM PANCREATIC CANCER: OUR EXPERIENCE AND SYSTEMATIC REVIEW

Abstract BACKGROUND AND PURPOSE The goal of this study was to systematically review the existing literature on neurosurgical management and outcomes of brain metastasis from pancreatic cáncer in comparison to our institutional experience of this patient cohort. METHODS Following the PRISMA guidelines, a systematic literature review was performed using PubMed, Ovid Embase, Scopus, and Web of Science databases from date of database inception to January 2022. Studies were selected based on predetermined inclusion and exclusión criteria. Simulteanously, a retrospective analysis was conducted on patients who underwent neurosurgical evaluation and treatment for intracranial metastatic lesions from pancreatic origin at a single institution. RESULTS Of the total 292 articles in the original literature search, 17 studies were ultimately selected. A total of 23 patients with brain metastases of pancreatic origin were included. Median overall survival from original diagnosis of pancreatic cancer was 22 months (3-84). In our institution’s cohort, 4 patients were identified with a median overall survival of 30.5 months (2- 108). Our institutional cohort experienced a prolonged median overall survival (3 vs 30.5 months, p=0.03) in comparison to the literature. CONCLUSIONS Brain metastasis is a rare and fatal outcome of pancreatic cancer that carries a poor survival. However, based on the data presented in this review, there are patient-specific and treatment-related factors that could signal better prognosis. Further studies are needed to elucidate multimodal therapy and survival to suggest a more personalized decision-making process.

Treatment, Management and Outcomes of Brain Metastasis in Adult Sarcoma

<h3>Purpose/Objective(s)</h3> Metastases from adult sarcomas often develop in the lungs, bone, and liver, yet brain metastases are less common. Few studies have discussed the incidence and prognosis of sarcoma brain metastases, and limited data exists regarding the differences in treatment patterns and outcomes by treatment modality. <h3>Materials/Methods</h3> We performed a retrospective analysis of sarcoma patients with a diagnosis of brain metastasis treated at our institution between 2009-2020. Baseline patient and tumor characteristics were analyzed. Patients were stratified based on treatment modality (surgery, radiosurgery, external beam radiotherapy (RT), and surgery plus RT). Outcome measures were rates of local failure (LF) and toxicities with different modalities. Univariate analysis was performed to study associations between clinical factors and our primary endpoints. <h3>Results</h3> A total of 22 patients with 103 brain metastases were included. Most common histologies were leiomyosarcoma (5 patients, 22%), pleomorphic sarcoma (4 patients, 18%), chondrosarcoma and round cell sarcoma (2 patients each, 9%). Of the 103 lesions included, 4 (18%) were solitary lesions with a median size of 1.7cc (range 0.3 – 12.0 cm). All patients received treatment, 4 underwent surgery alone (18%), 5 received RT alone, and 13 underwent surgery plus RT. Radiotherapy techniques included radiosurgery or external beam RT. 63 lesions (61%) were treated with stereotactic radiosurgery with a median dose of 24 Gy (range 15-60 Gy). The median OS was 62 months (95% CI 18-74). At 1 year, the cumulative incidence of local failure was 8.1% (95% CI 3.5% - 15.2%). Rates of LF differed by treatment modality – 5 failures occurred with surgery alone (20%), 2 with RT alone (3.4%), and 1 with surgery plus RT (1.1%). Grade I-IV toxicities were higher with surgery plus RT (n=13, 59%) compared to surgery (n=4, 18.1%) or RT alone (n=5, 18.1%). <h3>Conclusion</h3> Our study describes tumor presentation, management, and outcomes for metastatic intracranial sarcoma. We show that surgery and radiotherapy are effective modalities to utilize in management of these patients with low rates of local failure. Use of multimodal therapy (surgery plus RT) may further improve tumor control rates, though may be associated with higher rates of toxicities.

The Impact of Chemosensitivity on the Outcome of Brain Metastases in Small-Cell Lung Cancer: A Retrospective Analysis.

Purpose: The purpose of this study was to investigate the prognostic differences between patients with small-cell lung cancer (SCLC) with different chemosensitivity to first-line chemotherapy who developed brain metastasis (BM) as the first site of progression. Methods: Patients with a BM after first-line treatment in the Tianjin Cancer Hospital were retrospectively analyzed. According to the time-free interval (TFI) between the completion of first-line chemotherapy and the onset of the BM, the patients were divided into the chemo-sensitive group (TFI ≥ 90 days, n = 145) and the chemo-resistant group (TFI < 90 days, n = 97). The survival time, which was calculated from the diagnosis of the BM, was analyzed after the onset of brain metastasis (BM-OS). Survival curves were plotted using the Kaplan–Meier method, and differences between groups were compared using the log-rank test. Results: In total, the median BM-OS was 8.4 months. The median BM-OS in the chemo-sensitive group was 8.8 months, and it was 8.0 months in the chemo-resistant group (p = 0.538). In patients without extracranial progression (n = 193), the median BM-OSes in the chemo-sensitive and chemo-resistant groups were 9.4 months and 9.7 months, respectively (p = 0.947). In patients with extracranial progression (n = 49), the median BM-OSes in the chemo-sensitive and chemo-resistant groups were 5.4 months and 4.2 months, respectively (p = 0.161). Conclusions: After the development of a BM as the first site of progression following chemotherapy in patients with SCLC, the prognosis of chemo-sensitive patients was not necessarily superior to chemo-resistant patients, especially in patients without extracranial progression.

Brain Metastasis from Pancreatic Cancer: Our Experience and Systematic Review

To systematically review existing literature on the neurosurgical management and outcomes of brain metastasis from pancreatic cancer in comparison with our institutional experience of this patient cohort. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature review was performed using PubMed, Ovid Embase, Scopus, and Web of Science databases from date of database inception to March 2022. Studies were selected based on predetermined inclusion and exclusion criteria. Simultaneously, a retrospective analysis was conducted of patients who underwent neurosurgical evaluation and treatment for intracranial metastatic lesions from pancreatic origin at a single institution. The original literature search yielded 292 articles, of which 17 studies comprising 23 patients with brain metastases of pancreatic origin were ultimately selected. Median overall survival from primary diagnosis of pancreatic cancer was 22 months (interquartile range: 3-84) and 3 months (interquartile range: 1-36) after diagnosis of brain metastasis. In our institutional cohort, 4 patients were identified with a median overall survival of 30.5 months (interquartile range: 2-108). Our institutional cohort experienced a prolonged median overall survival (3 months vs. 30.5 months, P= 0.03) compared with the literature. Brain metastasis from pancreatic cancer is rare and associated with a fatal outcome. However, based on the data presented in this review, patient-specific and treatment-related factors could signal better prognosis. Further studies are needed to elucidate multimodal therapy and survival to suggest a more personalized decision-making process.

Multi-Omics Analysis of Brain Metastasis Outcomes Following Craniotomy.

BackgroundThe incidence of brain metastasis continues to increase as therapeutic strategies have improved for a number of solid tumors. The presence of brain metastasis is associated with worse prognosis but it is unclear if distinctive biomarkers can separate patients at risk for CNS related death.MethodsWe executed a single institution retrospective collection of brain metastasis from patients who were diagnosed with lung, breast, and other primary tumors. The brain metastatic samples were sent for RNA sequencing, proteomic and metabolomic analysis of brain metastasis. The primary outcome was distant brain failure after definitive therapies that included craniotomy resection and radiation to surgical bed. Novel prognostic subtypes were discovered using transcriptomic data and sparse non-negative matrix factorization.ResultsWe discovered two molecular subtypes showing statistically significant differential prognosis irrespective of tumor subtype. The median survival time of the good and the poor prognostic subtypes were 7.89 and 42.27 months, respectively. Further integrated characterization and analysis of these two distinctive prognostic subtypes using transcriptomic, proteomic, and metabolomic molecular profiles of patients identified key pathways and metabolites. The analysis suggested that immune microenvironment landscape as well as proliferation and migration signaling pathways may be responsible to the observed survival difference.ConclusionA multi-omics approach to characterization of brain metastasis provides an opportunity to identify clinically impactful biomarkers and associated prognostic subtypes and generate provocative integrative understanding of disease.

175P Incidence and treatment outcomes of brain metastasis in advanced non-small cell lung cancer at presentation: An experience from south India

Background: Brain metastasis is one of the significant problems in patients with lung cancer. Most of the patients are asymptomatic at presentation. Prognosis and survival in these patients are lacking. Many studies that looked upon the incidence of brain metastasis at the presentation of NSCLC are retrospective. In India, brain metastasis frequency in patients with NSCLC at the presentation has not been well studied. This study has been planned to evaluate the incidence of brain metastasis in NSCLC patients treated in our center. Methods: It is a prospective observational study conducted in medical oncology at our tertiary care center from Sep 2019- Sep 2020. A total of 150 patients with lung cancer were registered in the department. Among them, 112 patients had advanced non-small cell carcinoma of the lung (NSCLC), and they were enrolled in the study. MRI brain was taken at the time of diagnosis. Results: The mean age at presentation was 60 years. The Median follow-up was 15 months. Median overall survival in the study was 11 months. Patients with brain metastasis had a median survival of 7 months, whereas patients without brain metastasis had 13 months. Clinical profile, performance status, demographic characteristics, and imaging findings were noted at the presentation time and the results were analyzed as follows. Table 175PBaseline characteristicsNo of Patients (%)Mean age60 years<6044 (39%)>6068 (61%)SexMale69 (62%)Female43 (38%)Adenocarcinoma86 (77%)Squamous cell carcinoma26 (23%)Brain metastasis39 (35%)Male19 (49%)Female20 (51%)Adenocarcinoma32 (82%)Squamous cell carcinoma7 (18%)Asymptomatic12 (30%)Symptomatic27 (70%)Synchronous metastasis21 (19%)Contralateral lung metastasis12 (57%)Bone metastasis5 (23%) Open table in a new tab Conclusions: The study period is short, so that data on molecular abnormalities in patients with brain metastasis was not included in the data. Our study found that female patients were at higher risk for brain metastasis. Other risk factors were adenocarcinoma histology and age less than 60 years. There are no biomarkers to predict brain metastasis in NSCLC due to its molecular heterogeneity. The study will serve as a baseline platform of clinical predictors of brain metastasis in NSCLC. Our future direction and research will be clinical predictors along with molecular driver mutations in NSCLC in detecting brain metastasis. Legal entity responsible for the study: Rajiv Gandhi Government General Hospital, Madras Medical College. Funding: Has not received any funding. Disclosure: The author has declared no conflicts of interest.