Diagnosis Of Brain Metastases Research Articles

DISP-04. SEX DIFFERENCES IN LUNG CANCER BRAIN METASTASES ADVERSE EVENTS

Abstract While sexual dimorphism is evident among adverse events (AEs) in response to treatments for many cancers, including brain tumors, little is known about sexual dimorphism among AE in brain metastases (BrM). As over 50% of BrM cases arise from lung cancer (LC), we examined sex differences in AEs associated with LC-BrM among individuals in the SEER-Medicare dataset aged ≥66 years at the time of LC diagnosis. Multivariable logistic regression models adjusted for demographic variables and Elixhauser comorbidity scores were used to analyze sex differences in AEs among individuals with BrM derived from primary LC. Analyses were stratified by the following histological subtypes: small-cell, adenocarcinoma, squamous cell carcinoma, or other non-small cell carcinomas. Additional variables analyzed included BrM treatment, age at BrM diagnosis, and year of diagnosis (at or before 2013/after 2013) to account for the introduction of targeted therapies. Differences in AE profiles, based by sex, in individuals diagnosed with LC-BrM were observed. Females diagnosed after 2013 with either small-cell, squamous cell, or other non-small cell carcinoma BrMs were more likely to experience headaches compared to males. Males diagnosed after 2013 with adenocarcinoma were more likely to experience brain herniation compared to females. Additionally, females aged 76 and older with small-cell BrM demonstrated an elevated risk of developing vision difficulties relative to males, whereas no significant sex difference observed in those under 76 years. Risk of most AEs decreased across all histological subtypes with receiving treatment after BrM diagnosis when compared to no treatment. This study underscores the existence of sex-specific differences in AEs among individuals aged 66 years and older diagnosed with LC-BrM. The AEs observed varied across histological subtypes, age cohorts, year of diagnosis, and treatment. Notably, receipt of treatment demonstrates consistent reduction in AE risk across all histological subgroups, underscoring the therapeutic benefit of treatment.

PATH-67. THE ROLE OF STATUS OF HER-2, ESTROGEN-RECEPTOR, BRCA 1, AND BRCA 2, IN THE INCIDENCE OF BRAIN METASTASIS IN BREAST CANCER

Abstract Breast cancer (BC) is the most diagnosed tumor in women and the second-leading cause of brain metastasis (BM), with a prevalence ranging from 10-36%. According to the Epidemiological Strategy and Medical Economics research program, advanced BC patients face an estimated 25% risk of developing BM within 2-3 years after the initial diagnosis. The frequency of BM is significantly increased by the primary tumor profile, including larger tumors, higher nuclear grade, HER-2 positivity, estrogen-receptor negativity, and triple-negative status. A gap remains in the classification of the BM site relative to primary tumor biomarkers, and the absence of multimodality treatment methodologies poses challenges to survival rates and quality of life in BC patients. This retrospective cross-sectional study at Aga Khan University Hospital identified 52 cases of brain metastasis secondary to breast cancer over a 10-year period. The median age of patients was 55 years, ranging from 32 to 78 years. Primary breast tumors were predominantly high-grade ductal carcinomas (65%), followed by lobular carcinomas (25%) and other rare histological types (10%). Secondary brain metastases were primarily located in the cerebrum (60%), cerebellum (25%), and brainstem (15%). Tumor profiles indicated a significant correlation between HER-2 positivity and the development of brain metastasis, with 70% of HER-2 positive patients presenting with extensive brain metastasis. Tumor progression varied, with a median time to brain metastasis of 2.5 years from the initial breast cancer diagnosis. Despite aggressive multimodality treatments, including surgery, radiation, and chemotherapy, the overall prognosis remained poor. The study found that early detection of HER-2 positive and triple-negative tumors could potentially delay the progression of brain metastasis through targeted therapies. Mortality rates in this cohort were high, with a median survival of 8 months following the diagnosis of brain metastasis. These findings underscore the need for improved diagnostic, preventive, and therapeutic strategies to manage brain metastasis in breast cancer patients.

BIOM-34. INTRACRANIAL MANAGEMENT OF HER-2 OVEREXPRESSION BREAST CANCER WITH EXTENSIVE VOLUME OR SYMPTOMATIC BRAIN METASTASES

Abstract BACKGROUND HER-2 overexpression in breast cancer often leads to brain metastases, necessitating effective intracranial control strategies. This study aimed to evaluate the correlation between intracranial disease volume, symptomatic presentation, and treatment outcomes in HER-2 overexpressing breast cancer patients with brain metastases. METHODS A retrospective analysis was conducted on cases of HER-2 overexpressing breast cancer patients with brain metastases. Clinical records were reviewed to extract patient demographics, treatment modalities, and intracranial disease characteristics. Intracranial tumor burden was quantified at diagnosis and post-initial treatment. High intracranial tumor burden was defined as either total metastatic volume >15 cc, or the largest lesion >3 cm. Responses were assessed using established criteria. The correlation between intracranial disease parameters and intracranial progression-free survival (PFS) and overall survival (OS) was determined. RESULTS The study comprised 65 patients with HER-2 overexpression breast cancer and brain metastases. Symptomatic presentation was observed in 69.2% of patients at the diagnosis of brain metastases. Treatment with HER-2 target therapy alone or in combination with other modalities resulted in substantial intracranial responses, with 81.5% achieving at least a partial response at 3 months from therapy initiation. Median intracranial PFS and OS for patients with high intracranial burden were 9 and 22 months, respectively. Patients with high intracranial burden and symptomatic presentation at diagnosis demonstrated worse PFS and OS to those with lower burden and absence of symptoms (p < 0.05 for each). CONCLUSION Intracranial control in HER-2 overexpressing breast cancer patients with large volume or symptomatic brain metastases appears promising with combination with HER-2 targeted therapy and radiotherapy. Despite the varying intracranial disease burdens and symptomatic presentations, the use of HER-2 targeted therapy combined with radiotherapy demonstrates favorable intracranial responses, highlighting their potential in managing such cases.

NIMG-20. DWIBS FOR PRIMARY CANCER DETECTION IN INTRACRANIAL METASTASIS: TWO CASE REPORTS

Abstract INTRODUCTION Diffusion Weighted Whole Body Imaging with background body signal Suppression (DWIBS) is an imaging technique that encompasses comprehensive imaging of the entire body through diffusion-weighted imaging (DWI). In recent years, it has been increasingly utilized for investigating the etiology of fever or primary cancer. Here we present two cases of DWIBS for searching for primary cancer in patient with intracranial metastasis. CASE PRESENTATION Case1: A 60-year-old man presented with headache and diplopia and was admitted to our hospital. MRI revealed a tumor in the clivus exhibiting contrast enhancement. Endoscopic transsphenoidal surgery confirmed the diagnosis of squamous cell carcinoma. DWIBS demonstrated high intensity in a region similar to the esophagus seen on contrast-enhanced CT, leading to the diagnosis of brain metastasis from esophageal cancer. Case 2: A 50-year-old man presented with left facial paralysis and left hemiplegia and was admitted to our hospital. MRI revealed a tumor in the right middle frontal gyrus. Craniotomy confirmed the diagnosis of adenocarcinoma. Although the primary cancer remained unidentified upon initial examination, subsequent investigations revealed it originated from the lung. DWIBS showed high intensity in a region similar to the lung. DISCUSSION While FDG-PET is commonly utilized for cancer detection, its invasiveness and limitations prompt consideration of alternative modalities such as DWIBS. Recently there are some studies that have shown DWIBS to be superior to FDG PET in detecting esophageal and lung cancers. Thus, DWIBS may serve as a viable option for primary cancer screening in hospitals or communities where access to FDG PET is limited. CONCLUSION Its non-invasive nature makes DWIBS an appealing option for primary cancer detection, and further advancements are anticipated.

Tumor-Infiltrating B Cells and Tissue-Resident Memory T Cells as Prognostic Indicators in Brain Metastases Derived from Gastrointestinal Cancers

Background/Objectives: Tumor-infiltrating B cells (TIBs) and tissue-resident memory T cells (TRMs) play significant roles in antitumor immunity. However, their prognostic relevance in brain metastases (BMs) derived from gastrointestinal (GI) cancers remains unclear. This study aimed to investigate the prognostic significance of TIBs and TRMs in GI cancer-derived BMs (GIBMs). Methods: Retrospective histopathological analyses were performed on surgically resected GIBM tissues from 13 patients. The densities of tumor-infiltrating lymphocytes (TIL) subsets (TIBs, CD4+ T cells, CD8+CD103+ TRMs, and CD8+CD103- non-TRMs) were quantified and correlated with clinical parameters and overall survival (OS) including the Graded Prognostic Assessment (GPA). Results: TIBs and CD4+ T cells were predominantly accumulated in the tumor stroma, particularly around blood vessels, where they formed lymphocyte clusters without characteristics of tertiary lymphoid structures (TLSs). In contrast, TRMs more deeply infiltrated into the tumor epithelium than their counterpart non-TRMs. Positive correlations were found between TIB density and both the prognostic prediction of GPA and overall survival (OS) after BM diagnosis or surgery. Furthermore, increased densities of TIBs and TRMs were associated with enhanced survival after BM diagnosis. Conclusions: TIB and TRM densities in BM tissues could serve as reliable prognostic indicators for survival in patients with GIBMs. This study provides crucial insights for the development of novel immunotherapeutic strategies against this lethal disease.

Multidisciplinary management strategies for recurrent brain metastasis after prior radiotherapy: An overview.

As cancer patients with intracranial metastatic disease experience increasingly prolonged survival, the diagnosis and management of recurrent brain metastasis pose significant challenges in clinical practice. Prior to deciding upon a management strategy, it is necessary to ascertain whether patients have recurrent/progressive disease vs adverse radiation effect, classify the recurrence as local or distant in the brain, evaluate the extent of intracranial disease (size, number and location of lesions, and brain metastasis velocity), the status of extracranial disease, and enumerate the interval from the last intracranially directed intervention to disease recurrence. A spectrum of salvage local treatment options includes surgery (resection and laser interstitial thermal therapy [LITT]) with or without adjuvant radiotherapy in the forms of external beam radiotherapy, intraoperative radiotherapy, or brachytherapy. Nonoperative salvage local treatments also range from single fraction and fractionated stereotactic radiosurgery (SRS/FSRS) to whole brain radiation therapy (WBRT). Optimal integration of systemic therapies, preferably with central nervous system (CNS) activity, may also require reinterrogation of brain metastasis tissue to identify actionable molecular alterations specific to intracranial progressive disease. Ultimately, the selection of the appropriate management approach necessitates a sophisticated understanding of patient, tumor, and prior treatment-related factors and is often multimodal; hence, interdisciplinary evaluation for such patients is indispensable.

Brain metastasis burden and management in patients with small cell lung cancer in Canada: a retrospective, population-based cohort study

Patients with small cell lung cancer (SCLC) have historically been characterised by poor overall survival (OS) and high risk for brain metastasis (BM), but large-scale real-world evidence on clinical presentation and treatment in this population is lacking. Our aim was to describe the clinical characteristics and outcomes of patients with SCLC and BM in Ontario, Canada. This population-based, retrospective cohort study included all patients in Ontario, Canada, who were diagnosed with SCLC between April 1, 2010, and March 31, 2018. Data were analysed between June 2, 2022, and December 20, 2023. Patients with second cancer diagnosis were excluded. Patients were identified and data retrieved from the Institute for Clinical Evaluative Sciences (ICES) databases. Kaplan-Meier and multivariable Cox regression analyses were performed to compare OS between patient cohorts stratified by disease stage, BM diagnosis, and intracranial treatment modality. Propensity score-matching based on age, disease stage, time to BM, and receipt of chemotherapy was performed to compare OS between intracranial treatment modalities. 8705 patients were included (male: 4433, female: 4272). Median age at diagnosis was 68 years (interquartile range, IQR, 61-75). Median OS of all patients was 7.46 months (95% confidence interval, CI, 7.23-7.69). 32% (n=2686) of patients developed BM (synchronous, 43.7%; asynchronous, 56.3%) with median OS of 9.76 months (95% CI, 9.36-10.22). 102 (4%), 1654 (62%), and 930 (35%) patients received stereotactic radiosurgery (SRS), whole brain radiation therapy (WBRT), or no treatment, respectively, for their BM in the first-line setting or after prophylactic cranial irradiation (PCI). In propensity score-matched analyses, OS from time of BM diagnosis was non-inferior between SRS- and WBRT-treated cohorts among patients who did not receive PCI (hazard ratio, HR, 0.68, 95% CI, 0.44-1.06, p=0.091, n=86) and in favour of SRS for those who received PCI prior to BM development (HR, 0.47, 95% CI, 0.31-0.72, p=0.0042, n=112). OS for patients with SCLC remains poor, and many patients present with BM. With careful selection, patients with SCLC and BM may benefit from SRS treatment. Future research should incorporate information on burden of intracranial disease and novel immunotherapies. None.

ACSS2 regulates ferroptosis in an E2F1-dependent manner in breast cancer brain metastatic cells.

Brain metastasis diagnosis in breast cancer patients is considered an end-stage event. The median survival after diagnosis is measured in months, thus there is an urgent need to develop novel treatment strategies. Breast cancers that metastasize to the brain must adapt to the unique brain environment and are highly dependent on acetate metabolism for growth and survival. However, the signaling pathways that regulate survival in breast cancer brain metastatic (BCBM) tumors are not known. Primary brain tumor cells can convert acetate to acetyl-CoA via phosphorylation of acetyl-CoA synthetase 2 (ACSS2) by the cyclin-dependent kinase-5 (CDK5) regulated by the nutrient sensor O-GlcNAc transferase (OGT). Here, we show that breast cancer cells selected to metastasize to the brain contain increased levels of O-GlcNAc, OGT and ACSS2-Ser267 phosphorylation compared to parental breast cancer cells. Moreover, OGT and CDK5 are required for breast cancer cell growth in the brain parenchyma in vivo. Importantly, ACSS2 and ACSS2-S267D phospho-mimetic mutant are critical for in vivo breast cancer growth in the brain but not in the mammary fat pad. Mechanistically, we show that ACSS2 regulates BCBM cell survival by suppressing ferroptosis via regulation of E2F1-mediated expression of anti-ferroptotic proteins SLC7A11 and GPX4. Lastly, we show treatment with a novel brain-permeable small molecule ACSS2 inhibitor induced ferroptosis and reduced BCBM growth ex vivo and in vivo . These results suggest a crucial role for ACSS2 in protecting from ferroptosis in breast cancer brain metastatic cells and suggests that breast cancer brain metastatic cells may be susceptible to ferroptotic inducers.

Real-world outcomes in patients with brain metastases secondary to HR+/HER2- MBC treated with abemaciclib and local intracranial therapy.

Real-world data are limited for patients with brain metastases secondary to metastatic breast cancer (MBC) and treated with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). This study describes real-world outcomes in patients with hormone receptor-positive, human epidermal growth factor 2-negative (HR+/HER2-) MBC with brain metastases diagnosis before abemaciclib initiation. A nationwide electronic health record-derived de-identified MBC database (January 2011-December 2021) was assessed retrospectively. Patients with HR+/HER2- MBC who were treated with abemaciclib (monotherapy or in combination) following diagnosis of brain metastases were included. Real-world best response reflected clinician-documented response assessment of the brain imaging (intracranial) and change in disease burden following radiographic imaging (extracranial); these were reported descriptively. Time to treatment discontinuation (TTD), real-world progression-free survival (rwPFS), and overall survival (rwOS) were assessed using Kaplan-Meier methods from abemaciclib initiation (index date). Among 82 included patients (mean age 57.0 years; 98.8% female), 22.0% and 19.5% received CDK4/6i and chemotherapy before abemaciclib initiation, respectively, and the majority (80.5%) received radiation/local surgery to the brain before abemaciclib initiation. Patients mostly received abemaciclib as monotherapy (n = 6) or in combination with endocrine therapy (n = 68). Median TTD was 7.1 (95% CI 4.6-11.3) months, rwPFS was 9.2 (95% CI 6.0-11.6) months, and rwOS was 20.8 (95% CI 13.9-26.0) months. Intracranial and extracranial objective response rates, as determined by treating physicians, were 45.1% (n = 23/51) and 56.7% (n = 34/60), respectively. Intracranial and extracranial clinical benefit rates were 62.7% (n = 32/51) and 70.0% (n = 42/60), respectively. In this real-world study of patients diagnosed with brain metastases and initiating abemaciclib, most patients received radiation/local surgery to the brain before abemaciclib initiation. Although the outcomes in this real-world study are encouraging, it is unclear if the benefit was due to local therapy, abemaciclib, or the combination, and causality cannot be inferred. Further prospective clinical studies are needed to confirm the clinical benefit of this approach.

Brain Metastases from Genito-Urinary Cancers in the Canton of Geneva (Switzerland): Study of Incidence, Management and Outcomes.

Incidence of brain metastases is precisely unknown and there is no clear consensus on their management. We aimed to determine the incidence of brain metastases among patients with genito-urinary primaries, present patients' characteristics and identify prognostic factors. We identified 51 patients treated in Geneva University Hospitals between January 1992 and December 2019. We retrospectively correlated their overall survival with 23 variables. We repeated a multivariate analysis with significant variables. Overall incidence of Brain Metastases (BMs) among Genito-Urinary (GU) patients is estimated to be 1.76% (range per primary GU tumour type: 0.00-6.65%). BMs originate from germ cell tumours in two cases (3.92%), from urothelial cell carcinoma in 15 cases (29.41%), from prostate cancer in 13 cases (25.49%), and from renal cell carcinoma in 21 cases (41.18%); there are no BMs from penile cancer in our cohort. The median age at BM diagnosis is 67 years old (range: 25-92). Most patients (54%) have a stage IV disease at initial diagnosis and 11 patients (22%) have BM at initial diagnosis. Only six patients (12%) are asymptomatic at BM diagnosis. The median Overall Survival (OS) from BM diagnosis is 3 months (range: 0-127). Five patients (10%) are long survivors (OS > 24 months). OS is significantly influenced by patient performance status and administration of systemic treatment. In the absence of meningeal carcinomatosis, OS is influenced by systemic treatment and stereotactic radiosurgery. We also apply the Graded Prognostic Assessment (GPA) score to our cohort and note significant differences between groups. Brain metastases from solid tumours is not a uniform disease, with a prognosis varying a lot among patients. The optimal management for patients with genito-urinary malignancies with brain metastases remain unclear and further research is needed.

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.

Metastatic prostate adenocarcinoma to the brain – a clinicopathologic analysis of 21 cases

BackgroundBrain metastasis from prostate adenocarcinoma (PCa) is rare, often leading to death within a year. Its infrequent occurrence and atypical histopathologic features contribute to lower consideration in the differential diagnosis of tumor brain metastasis. This study aims to assess the clinical characteristics and distinctive histopathologic features of metastatic PCa in the brain for timely and enhanced diagnostic accuracy.DesignA retrospective search spanning 20 years (2003–2022) was conducted on our archives and identified 21 cases diagnosed as “metastatic prostate adenocarcinoma (mPCa)” in brain biopsies and resections. All existing slides were thoroughly reviewed to evaluate the histopathology of the mPCa.ResultThe mean age at presentation for brain metastasis was 70 years. Of 21 cases, 5 were dural-based lesions, 16 were true intraparenchymal metastases, including 2 sellar/suprasellar masses, 3 frontal, 3 temporal, 3 occipital, 1 cerebellum, and 4 involving multiple brain lobes. The average interval between initial diagnosis and brain metastasis was 90.75 months. Notably, brain metastasis was the initial presentation for one patient, while another patient, initially diagnosed with prognostic grade group (GG) 2 PCa in 1/12 cores, presented with isolated brain metastasis two years later. Architecturally, tumor cells were arranged in sheets or nests in most cases; however, four cases showed histologic cribriform patterns, and five displayed papillary architecture. Cytohistology varied from uniform monomorphic to highly pleomorphic cells with prominent nucleoli (8/19) and high mitotic activity. Interestingly, 1 case showed small round blue cell morphology, another had focal areas of rhabdoid and spindle cell differentiation, and 6 had cytoplasmic clearing. Almost half of the cases (47%) showed necrosis.ConclusionmPCa to the brain can present with variable histomorphology. Therefore, consideration of mPCa in the differential diagnosis of metastatic brain lesions, even with non-suggestive imaging, is imperative in male patients with or without a history of primary disease. Accurate and prompt diagnosis is crucial, given the recent advancements in treatment that have improved survival rates.

Stereotactic radiosurgery practice patterns for treatment of brain metastases: A large national cancer database study.

123 Background: Brain metastases (BM) portend high mortality rates. While whole brain radiation therapy (WBRT) is a commonly used treatment strategy for BM, stereotactic radiosurgery (SRS) has less neurocognitive toxicity with comparable survival. The objective of this study was to compare treatment practice patterns for SRS vs WBRT using a large national hospital database. Methods: The National Cancer Database (NCDB) was queried for patients ≥18 years treated with radiotherapy (RT) for a BM diagnosis between 2004-2020 and with known follow-up. Twelve cancers were included based on highest prevalence: breast, colorectal, kidney/bladder, liver, lung, lymphoma, melanoma, oral cavity, pancreas, prostate, and thyroid. Patients were grouped by first course RT modality (SRS vs WBRT) confirmed by fraction number (SRS: 1-5; WBRT: 5-15). Multivariable logistic regression assessed predictors of SRS as adjusted odds ratios (aOR) with 95% confidence intervals (95%CI). Analyses were adjusted for patient and cancer characteristics. Results: Of 112,232 patients with BM, 30,805 (27%) received SRS. Median age was 64 years. Most patients were White (84%), diagnosed in 2012-2020 (64%), with a higher income (56%), more education (55%), and Medicare/Medicaid (60%). The most common cancer treated with RT for BM was lung (85%). Patients were less likely to be treated with SRS if they were Korean (aOR=0.68; 95%CI=0.47-0.95), lower income (aOR=0.88; 95%CI=0.84-0.91), lower education (aOR=0.88; 95%CI=0.85-0.91), with Medicare/Medicaid (aOR=0.86; 95%CI=0.83-0.89) or no insurance (aOR=0.48; 95%CI=0.44-0.53), at a Midwest hospital (aOR=0.79; 95%CI=0.76-0.83; vs Northeast), and at a community (aOR=0.31; 95%CI=0.28-0.33; vs academic) or comprehensive community cancer program (aOR=0.56; 95%CI=0.54-0.58). Patients were more likely to be treated with SRS if they were Asian Indian or Pakistani (aOR=1.41; 95%CI =1.08-1.85), older (aOR=1.01; 95%CI=1.01-1.01), diagnosed in 2012-2020 (aOR=3.92; 95%CI=3.78-4.07; vs 2004-2011), lived farther from the hospital (aOR=1.00; 95%CI=1.00-1.00), and received chemotherapy (aOR=1.17; 95%CI=1.13-1.21). Conclusions: In one of the largest BM studies with over 110,000 US patients, disparities in SRS treatment patterns were identified. On adjusted analysis, SRS was less likely to be used for patients who were lower income, lower educational attainment, without private insurance, and treated at community centers. The data highlight populations with cancer and BM who may benefit from increased access to SRS.

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.

Brain Metastases from Ovarian Cancer: A Comprehensive Review

Ovarian Cancer Ovarian cancer (OC) is the current leading cause of gynecological cancer deaths. Despite its fatal outcome, only 20% of ovarian cancers are detected in the early stage. The reason involves a combination of factors — there is no reliable screening for ovarian cancer, and any symptoms of ovarian cancer tend to be vague and easily ignored. Consequently, OC is given the advantage of metastasizing due to ignorance. However, recently, overall survival from ovarian carcinoma has been reported to increase after improvements in treatment (Siegel et al., 2020). Brain Metastases from OC Central nervous system (CNS) metastasis from epithelial ovarian carcinoma (EOC) is uncommon, with an incidence of brain metastases ranging from 1–3% (Zumrut et al., 2020). Moreover, the treatment of brain metastases from ovarian carcinoma is currently ill-defined because of its rarity and the small affected population. The median survival after diagnosis of brain metastases was six months, meaning BMs mainly occurred while the patient was in stages III or VI of OC. Nevertheless, the median interval between diagnosis of ovarian carcinoma and consequent brain metastases is also quite long, approximately 2 years (Piura et al., 2011). However, neuro-cognition and quality of life across therapies are increasingly recognized as essential endpoints for patients as survival continues to increase. This paper is a comprehensive review of brain metastases from ovarian cancer, investigating tumour proliferation, metastatic mechanisms, the role of BRCA 1/2, and several therapy options, such as PARP inhibitors.

Neurološki simptom kao prvi znak kolorektalnog karcinoma

Aim: To present a rare case of a patient with an isolated brain metastasis from colorectal carcinoma in whom an extensive diagnostic workup failed to identify the primary tumour. Case report: A 73-year-old female patient was admitted to the Neurology Department due to weakness in the right side of her body. Imaging with multislice computed tomography (MSCT) and brain magnetic resonance (MR) confirmed an expansive lesion in the left frontal region with surrounding oedema. Radiological findings suggested either a metastasis or a high-grade primary glioma. As the diagnostic workup did not reveal the primary tumour, the patient was transferred to Clinical Hospital Dubrava for surgical treatment. An intracranial tumour resection was performed with a histopathological confirmation of colon carcinoma metastasis. Postoperative brain irradiation was administered. A positron emission tomography scan (PET) showed focal accumulation of radioisotopes without clear pathological substrate in the appendix and cecoascedent junction area. Repeated colonoscopy did not find any pathological mucosal changes. The patient declined systemic treatment. Overall survival was 11 months, in line with literature data. Conclusion: The diagnosis of brain metastases from colorectal carcinoma is very rare, and even rarer is the diagnosis of isolated brain metastases without extracranial progression, counting for <0.5%. Therapeutic options for brain metastases from colorectal carcinoma include surgery, radio-neurosurgery, stereotactic radiotherapy, and brain irradiation. In our opinion, diagnostic evaluation of the central nervous system in patients with colorectal carcinoma should be considered if the patient has neurological symptoms or if there is an increase in carcinoembryonic antigen (CEA) levels without signs of extracranial disease progression.

402. BRAIN METASTASES FROM ESOPHAGEAL CANCER AFTER MULTIMODAL TREATMENT: EARLY DETECTION AND AGGRESSIVE LOCAL TREATMENT CAN LEAD TO BETTER OUTCOMES

Abstract Background International guidelines do not recommend imaging investigations to rule out the presence of BM (brain metastases) during clinical staging or follow-up in patients with oesophageal cancer. Patients with single or up to three BM can be considered oligometastatic: in our study we analysed patients with BM focusing on the management and outcomes of BM. Methods We retrospectively identified patients who underwent surgical resection for oesophageal adenocarcinoma or squamous cell carcinoma from 2006 to 2022 in our Upper GI division and subsequently developed brain metastasis (BM). Starting from January 2018, a brain CT scan was added to the routine follow-up procedures in our centre. We divided patients in two groups based on the treatment received for BM: local therapy group treated with surgery and/or stereotactic body radiation therapy/stereotactic radiosurgery (SBRT/SRS) versus no local therapy group treated with chemotherapy or whole brain radiotherapy (WBRT). Results 34 patients developed BM (three didn’t receive treatment); 23 patients in local therapy versus 8 in no local therapy group. Median overall survival (OS, from BM diagnosis to patient’s death or last follow-up) in local therapy group was 14.52 months whereas in no-local therapy 3.41 months, p<0.001. At univariable analysis predictors of OS were pathological stage, pathological response, GI-GPA score, number of metastases, treatment. In multivariable analysis, only pathological stage was statistically significative. We diagnosed 17 BM recurrence before 2018 (17 patients of 355, 4,7%) and 17 after 2018 with introduction of routine brain CT (17 of 217, 7.8%). Conclusion BM from oesophageal cancer benefit from local aggressive treatment in terms of overall survival and to apply a local treatment is necessary that BM are diagnosed early. The introduction of brain CT scan during follow up may have improved the detection rate of BM and therefore in our opinion routine brain CT scan could be necessary.

Outcomes of EGFR, ALK, ROS1, BRAF, MET, and RET mutated non-small cell lung cancer with brain metastases (NSCLC BM).

201 Background: Non-small cell lung cancer (NSCLC) is a leading cause of brain metastases. Advances in gene-directed therapies have shifted the focus away from traditional platinum-based chemotherapies. Key targeted mutations in NSCLC include EGFR, ALK, BRAF, MET exon skipping, RET fusions, and ROS1 rearrangements. This retrospective study aims to explore overall survival (OS) and progression-free survival (PFS) in NSCLC BM patients with these gene mutations. Methods: In this retrospective study, conducted by the Department of Medical Oncology at Beijing Tiantan Hospital and the First Medical Center, PLA General Hospital, we reviewed 1526 patients with NSCLC brain metastasis from 2010 to 2022. Data collected included molecular marker status, systemic therapies, and dates of progression. The analysis focused on determining OS and PFS from the time of brain metastasis diagnosis to the last follow-up or death. Statistical analysis used the Cox proportional hazards model. Results: The study reviewed 1526 patients, identifying the following mutation distribution: EGFR mutations in 628 patients, ALK rearrangements in 207 patients, ROS1 rearrangements in 64 patients, BRAF mutations in 31 patients, MET exon skipping in 55 patients, and RET fusions in 42 patients. Significant variations in median OS (mOS) and median PFS (mPFS) were observed across these mutation groups. Patients with EGFR and ALK mutations demonstrated longer mOS and mPFS. Patients with RET and ROS1 mutations also showed better outcomes compared to those with BRAF and MET mutations. Conclusions: This study highlights the importance of molecular mutations in NSCLC BM as prognostic indicators and therapeutic targets. EGFR and ALK mutations were associated with more favorable outcomes, emphasizing the need for personalized medicine in managing NSCLC BM. The study suggests further research focused on specific mutation types is crucial to refine treatment strategies and improve patient care.

Clinicogenomic predictors of survival and intracranial progression after stereotactic radiosurgery for colorectal cancer brain metastases.

Brain metastases (BM) from colorectal cancer (CRC) are associated with dismal prognosis. When BM-directed therapy is considered, better methods are needed to identify patients at risk of poor oncological outcomes in order to optimize patient selection for closer surveillance or escalated therapy. The authors sought to identify clinicogenomic predictors of survival and intracranial disease progression after CRC BM have been treated with stereotactic radiosurgery (SRS). Patients with newly diagnosed CRC BM treated with SRS between 2009 and 2022 who had next-generation genomic sequencing data available were included. Frameless SRS was delivered in 1-5 fractions, alone or after neurosurgical resection. Outcomes included overall survival (OS) and intracranial progression (IP), evaluated per patient treated with SRS, and local progression (LP), evaluated per BM. Associations between baseline clinicogenomic features and outcomes were evaluated with Cox regression and competing risk regression, with death as a competing risk. This analysis included 123 patients with 299 BM. At BM diagnosis, 111 patients (90%) had progressive extracranial disease, and 79 patients (64%) had ≥ 3 sites of extracranial metastasis. The median (IQR) number of BM was 2 (1-3) per patient. The median (IQR) biologically effective dose (BED) was 51.3 (51.3-65.1) Gy, corresponding to a prescription of 27 Gy in 3 fractions. OS, IP, and LP estimates at 1 year after SRS were 36%, 55%, and 12%, respectively. OS was independently associated with progressive extracranial disease (HR 4.26, 95% CI 1.63-11.2, p = 0.003) and ≥ 3 extracranial metastatic sites (HR 1.84, 95% CI 1.12-3.01, p = 0.02). LP was less likely when BM received BED ≥ 51.3 Gy (HR 0.24, 95% CI 0.07-0.78, p = 0.02), independent of BM diameter (HR 1.21/cm, 95% CI 0.8-1.84, p = 0.4). IP was independently associated with genomic alterations; TP53 driver alterations were associated with higher risk of IP (HR 2.71, 95% CI 1.26-5.79, p = 0.01), whereas MYC pathway alterations were associated with lower risk (HR 0.15, 95% CI 0.03-0.68, p = 0.01). The authors identified clinicogenomic features associated with adverse outcomes after SRS for CRC BM. Progressive and extensive extracranial metastases predicted worse OS. Insufficient SRS doses predicted greater risk of LP. Wild-type TP53 and alterations in the MYC pathway were independently associated with lower risk of IP. Patients at high risk of IP may be considered for closer surveillance or escalated therapy.

AB070. Roles of neutrophil to lymphocyte ratio in differentiating glioblastoma from brain metastasis.

Glioblastoma and brain metastasis are two types of brain tumors that have a significant impact on the global healthcare system, with high rates of morbidity and mortality. These tumors can be challenging to differentiate from each other, as they often present with similar symptoms and features on medical imaging. The purpose of this study was to investigate whether the neutrophil-to-lymphocyte ratio (NLR) could help distinguish between glioblastoma and brain metastasis. This is a retrospective cross-sectional analysis that utilized medical records from six hospitals located in Yogyakarta, Indonesia from the period of 2016 to 2021. The study included patients who were diagnosed with glioblastoma and brain metastasis. Laboratory data was collected upon initial admission, and the diagnosis of glioblastoma and brain metastasis was based on a histopathological examination. This study included a total of 393 subjects, with the glioblastoma group comprising 121 subjects and the brain metastasis group comprising 272 subjects. The group with glioblastoma had a higher NLR (11.12±11.56 vs. 8.75±9.18, P=0.006) than the brain metastasis group. The area under the curve from the receiver operating characteristic analysis was 0.587 (95% confidence Interval: 0.528-0.647, P=0.006). An NLR value greater than 7.14 was found to have 55.4% sensitivity and 62.5% specificity in predicting glioblastoma. According to this study, the NLR value of patients suffering from glioblastoma was significantly higher when compared to those with brain metastasis. This indicates that there is a higher degree of systemic inflammation in glioblastoma as compared to brain metastasis. Therefore, the NLR value can be a useful diagnostic tool to distinguish between glioblastoma and brain metastasis.