Frequency Of Brain Metastases Research Articles

Frequency of metastases within the hypothalamic–pituitary area and the associated high-risk factors in patients with brain metastases

ObjectiveBrain radiotherapy often results in impairment of hypothalamic–pituitary (HT-P) function, which in turn causes secretory dysfunction of related hormones. In this paper, the frequency of metastasis in the HT-P area and its high-risk factors in patients with brain metastasis were retrospectively analyzed, and thus provide experimental evidence for protecting HT-P area during whole brain radiotherapy (WBRT).MethodsA retrospective analysis was performed on the data of patients with brain metastasis diagnosed by cranial magnetic resonance imaging (MRI) at the First Hospital of Lanzhou University from 2017 to 2020. The anatomical positions of the hypothalamus and pituitary were delineated, followed by their expansion by 5 mm outwards, respectively, in the three-dimensional direction, and the hypothalamus +5 mm and pituitary +5 mm were obtained as the avoidance area, in which the frequency of brain metastasis was evaluated. Univariate and multivariate logistic regression models were used to analyze the high risk factors of brain metastasis in HT-P area.ResultsA total of 3,375 brain metastatic lesions from 411 patients were included in the analysis. The rates of brain metastasis in the hypothalamus +5 mm and pituitary +5 mm in the whole group of cases were 2.9% (12/411) and 1.5% (6/411) respectively; the frequency of lesions was 0.4% (13/3375) and 0.2% (6/3375) respectively. Univariate and multivariate analyses showed that the number of brain metastases (OR = 14.946; 95% CI = 4.071–54.880; p < 0.001), and the occurrence of brain metastasis in the pituitary (OR = 13.331; 95% CI = 1.511–117.620; p = 0.020) were related to brain metastasis in the hypothalamus, and that the only relevant factor for brain metastasis in the pituitary was the occurrence of that in the hypothalamus (OR = 0.069; 95% CI = 0.010–0.461; p = 0.006). There was no correlation between tumor pathological types, the maximum diameter, the total volume of brain metastatic lesions and the risk of brain metastasis in hypothalamus and pituitary.ConclusionThe frequency of brain metastasis in the HT-P area is extremely low. The risk of brain metastases in the hypothalamus is correlated with their number. The larger the number of metastatic lesions, the higher the frequency of brain metastasis. Protection of the HT-P area during WBRT may be unlikely to compromise the tumor recurrence rate for patients with a relatively small number of brain metastases.

Clinicogenomic factors and treatment patterns among patients with advanced non-small cell lung cancer with or without brain metastases in the United States.

This retrospective, real-world study evaluated the prevalence of brain metastases, clinicodemographic characteristics, systemic treatments, and factors associated with overall survival among patients with advanced non-small cell lung cancer (aNSCLC) in the US. We also described the genomic characterization of 180 brain metastatic specimens and frequency of clinically actionable genes. De-identified electronic health records-derived data of adult patients diagnosed with aNSCLC between 2011 and 2017 were analyzed from a US-nationwide clinicogenomic database. Of 3257 adult patients with aNSCLC included in the study, approximately 31% (n = 1018) had brain metastases. Of these 1018 patients, 71% (n = 726) were diagnosed with brain metastases at initial NSCLC diagnosis; 57% (n = 583) of patients with brain metastases received systemic treatment. Platinum-based chemotherapy combinations were the most common first-line therapy; single-agent chemotherapies, epidermal growth factor receptor tyrosine kinase inhibitors, and platinum-based chemotherapy combinations were used in second line. Patients with brain metastases had a 1.56 times greater risk of death versus those with no brain metastases. In the brain metastatic specimens (n = 180), a high frequency of genomic alterations in the p53, MAPK, PI3K, mTOR, and cell-cycle associated pathways was observed. The frequency of brain metastases at initial clinical presentation and associated poor prognosis for patients in this cohort underscores the importance of early screening for brain metastasis in NSCLC. Genomic alterations frequently identified in this study emphasize the continued need for genomic research and investigation of targeted therapies in patients with brain metastases.

Comparative Analysis of Gender-Based Differences in NSCLC between Europe and Asia

Background: The demographic makeup of lung cancer has shifted over the last decades. Females are more likely to be non-smokers, diagnosed at a younger age, earlier stage, have adenocarcinoma and a family history of cancer. Objectives: the primary objective is to analyze the gender-based differences with regards to clinicopathologic features in Europe and Asia. Methods: This study was based on Oncology Dynamics, using a physician questionnaire. In Q1 2022, IQVIA engaged 1,181 physicians from Europe and 1,402 from Asia. The following items were analyzed: gender, age, smoking status, clinical stage, oncogenic driver status, location of metastases, ECOG, and comorbidities. Results: A total of 18217 cases were analyzed; 7006 (38.5%) were females (F) and 11211 (61.5%) males (M). The percentage of Asian female non-smokers was substantially higher compared to males and European population. Females had more adenocarcinoma and less squamous cell carcinoma cases on both continents. Most patients had metastatic disease at diagnosis. However, in Asia there was a higher proportion of localized disease compared to Europe regardless of sex. The frequency of brain metastases in Asian females was significantly higher (20%) than in Asian males (14%) or the European population (F: 16%, M: 10%). EGFR mutation was the most common oncogenic driver in both genders, but its prevalence was higher in Asian females. Conclusion: This research highlights the differences in cancer staging between Asian and European patients and the importance of gender-based differences suggesting that lung cancer may be increasingly considered a distinct disease in females.

Breast Cancer Subtypes and Incidence of Brain Metastases in the SEER Database

<h3>Purpose/Objective(s)</h3> Despite the recognition that women with triple-negative (TNBC) and HER2+ breast cancer have a higher risk of developing brain metastases than other subtypes of breast cancer, the recently updated NCCN guidelines for breast cancer do not recommend MR imaging of the brain in women with either primary or metastatic breast cancer (of any type) unless there are neurologic signs/symptoms suspicious for brain metastases. We investigated the relative distribution of synchronous and metachronous brain metastases over the past decade. <h3>Materials/Methods</h3> We evaluated the Surveillance, Epidemiology, and End Results (SEER) SEER-18 database for breast cancer patients diagnosed from 2010-2017. Female patients with complete data regarding presence of brain metastases, stage, breast cancer subtype, and survival were selected. Relative frequencies of subtypes at diagnosis for all patients (localized and metastatic), synchronous brain metastases, and metachronous brain metastases were calculated. Metachronous brain metastases were defined as patients who had both a primary and localized breast cancer diagnosis and subsequent brain metastases diagnosis both recorded in SEER as separate entries from different years with the same patient identifying number. <h3>Results</h3> We found 394,153 patients who fit criteria. The percent incidence of brain metastases at diagnosis did not change significantly over the years examined (range 0.33-0.39%, chi-squared p=0.59) Overall frequency of brain metastases was 0.67%, 0.22%, 1.17%, and 0.71% for luminal B, luminal A, HER2+, TNBC, respectively (chi-squared p<0.001). Relative frequency of breast cancer subtypes among all cases, synchronous brain metastases, and metachronous brain metastases showed increasing proportion of patients with TNBC. Only 26 patients were found that had metachronous brain metastases in the database. Of those patients, 38.5% had TNBC. <h3>Conclusion</h3> This SEER-based analysis shows that although presentation with synchronous brain metastases is relatively balanced across all molecular subtypes, metachronous brain metastases are most commonly seen in TNBC patients, perhaps indicative of the prevalence of occult brain metastases at presentation in patients with TNBC. Unfortunately, metachronous brain metastases are not robustly recorded in SEER. Better data is needed on the prevalence of brain metastases at the time of initial diagnosis and when systemic progression occurs in TNBC patients.

EP08.02-166 Brain Metastases in Patients with ALKrearranged or ROS1-fusion Non-small-Cell Lung Cancers in China

Brain metastases (BM) are common in ALK rearranged or ROS1-fusion non-small-cell lung cancer (NSCLC) and are usually associated with a poor outcome, but the baseline incidence and evolution of BM over time in those NSCLCs are seldom reported. In this study, we evaluated the frequency of BM in patients with anaplastic lymphoma kinase (ALK)-rearranged or c-ros oncogene 1(ROS1)-fusion NSCLC.

МЕТАСТАТИЧЕСКОЕ ПОРАЖЕНИЕ ГОЛОВНОГО МОЗГА. ДИАГНОСТИКА И ЛЕЧЕНИЕ

The article provides an overview of the current literature on the diagnosis and treatment of second-ary (metastatic) damage to the brain substance.&#x0D; Over the past years, Russia has seen a high incidence of malignant neoplasms, with a clearly observed upward trend. In 2019, this figure was 376.3 per 100,000 population compared to 369.6 per 100,000 population in 2018 and 293.7 per 100,000 population in 2000. However, thanks to modern methods of diagnosis and treatment, the life span of patients suffering from malignant neo-plasms is significantly increased, and, as a result, the chance of “surviving” before the onset of a metastatic lesion of the brain substance increases. Today, this formidable complication of the tumor process occurs in approximately 8-10% of cancer patients, while in most of them they are symptomatic. In some nosological forms of malig-nant neoplasms (small cell lung cancer, melanoma), the frequency of brain metastasis can reach 80% or more.

Factors Affecting the Risk of Brain Metastasis in Limited-Stage Small Cell Lung Cancer After Prophylactic Cranial Irradiation.

BackgroundProphylactic cranial irradiation (PCI) can reduce the risk of brain metastases (BM) and improve overall survival (OS) in patients with limited-stage small cell lung cancer (LS-SCLC) after partial or complete response to primary therapy. However, some SCLC patients still develop BM after PCI. This study aimed to evaluate the risk factors of BM in patients with LS-SCLC after PCI and identify characteristics of patients who may not benefit from PCI.Methods and MaterialsWe identified 550 patients with LS-SCLC who received chemoradiotherapy at Zhejiang Cancer Hospital between 2002 and 2017. All patients received PCI. Kaplan–Meier analyses and Cox regression analyses were used to identify factors affecting OS and brain metastasis-free survival (BMFS).ResultsFor this patient population, the median survival time was 27.9 months, and the 5-year OS rate was 31%. The median survival time was 24.9 months (95% CI: 22.6–27.2 months), and 30.2 months (95% CI: 24.2–36.3 months) in patients with or without BM (P = 0.000). The overall BM rate was 15.6% (86/550). The frequency of BM in patients with pathologic stages I, II, and III were 9.3% (4/43), 13.4% (7/52), and 16.5% (75/455). The patients with tumors ≥5 cm had an increased risk of BM (HR: 1.781, 95% CI: 1.044–3.039, P = 0.034) but not death (HR: 1.126, 95% CI: 0.925–1.663, P = 0.182). The median survival time among patients <60 years was significantly longer than patients ≥60 years (34.9 months vs 24.6 months, P = 0.001); however, the difference in the BM risk between the two groups was not statistically significant.ConclusionPCI remains the standard of care for LS-SCLC patients who achieve complete or partial response after completion of chemoradiotherapy. However, patients with tumors ≥5 cm may have a higher risk of developing BM after PCI.

Brain metastasis: Recent treatment modalities and future-perspectives.

With the advent of novel systemic therapies, such as molecular targeted therapy and immune checkpoint inhibitors, the treatment of advanced-stage cancer is markedly transitioning. The treatment for brain metastasis is influenced by these new therapies. Moreover, the frequency of brain metastasis is associated with cancer genetics. Since conventional cytotoxic chemotherapeutic drugs cannot easily cross the brain-blood barrier, radiotherapy plays a major role in the management of brain metastasis. Whole-brain radiotherapy (WBRT) has been frequently used, especially for multiple metastatic brain tumors; however, late adverse effects on cognitive function are a significant clinical problem of WBRT in patients with an otherwise good prognosis and overall survival rate. Some novel systemic agents are effective against brain metastasis. Moreover, advances in radiotherapy technology have made it possible to deliver optimal radiation doses to patients with brain metastasis, with fewer adverse events. Brain metastasis has a significant impact on the quality of life of patients with advanced-stage cancer; therefore, its appropriate management is an important factor in the comprehensive treatment of cancer.

Identification of a high-risk group for brain metastases in non-small cell lung cancer patients.

Identification of a high-risk group of brain metastases (BM) in patients with non-small cell lung cancer (NSCLC) could lead to early interventions and probably better prognosis. The objective of the study was to identify this group by generating a multivariable model with recognized and accessible risk factors. A retrospective cohort from patients seen at a single center during 2010-2020, was divided into a training (TD) and validation (VD) datasets, associations with BM were measured in the TD with logit, variables significantly associated were used to generate a multivariate model. Model´s performance was measured with the AUC/C-statistic, Akaike information criterion, and Brier score. From 570 patients with NSCLC who met the strict eligibility criteria a TD and VD were randomly assembled, no significant differences were found amid both datasets. Variables associated with BM in the multivariate logit analyses were age [P 0.001, OR 0.96 (95% CI 0.93-0.98)]; mutational status positive [P 0.027, OR 1.96 (95% CI 1.07-3.56); and carcinoembryonic antigen levels [P 0.016, OR 1.001 (95% CI 1.000-1.003). BM were diagnosed in 24% of the whole cohort. Stratification into a high-risk group after simplification of the model, displayed a frequency of BM of 63% (P < 0.001). A multivariate model comprising age, carcinoembryonic antigen levels, and mutation status allowed the identification of a truly high-risk group of BM in NSCLC patients.

Exploration of spatial distribution of brain metastasis from small cell lung cancer and identification of metastatic risk level of brain regions: a multicenter, retrospective study

ObjectivesThis study aimed to explore the spatial distribution of brain metastases (BMs) from small cell lung cancer (SCLC) a homogenous sample, and to identify the metastatic risk levels in brain regions.MethodsT1-enhanced magnetic resonance imaging (MRI) from SCLC patients were retrospectively reviewed from three medical institutions in China. All images were registered to the standard brain template provided by the Montreal Neurological Institute (MNI) 152 database, followed by transformation of the location of all BMs to the space of standard brain. The MNI structural atlas and Anatomical Automatic Labeling (AAL) atlas were then used to identify the anatomical brain regions, and the observed and expected rates of BMs were compared using 2-tailed proportional hypothesis testing. The locations and sizes of brain lesions were analyzed after image standardization.ResultsA total of 215 eligible patients with 1033 lesions were screened by MRI, including 157 (73%) males and 58 (27%) females. The incidence of crucial structures were as follows: hippocampus 0.68%, parahippocampal 0.97%, brainstem 2.05%, cauate 0.68%, putamen 0.68%, pallidum 0.2%, thalamus 1.36%. No BMs were found in the amygdala, pituitary gland, or pineal gland. The cumulative frequency of the important structures was 6.62%. Based on the results of MNI structural atlas, the cerebellum, deep white matter and brainstem was identified as a higher risk region than expected for BMs (P = 9.80 ×10−15, 9.04 ×10−6), whereas temporal lobe were low-risk regions (P = 1.65 ×10−4). More detailed AAL atlas revealed that the low-risk regions for BMs was inferior frontal gyrus (P = 6.971 ×10−4), while the high-risk regions for BMs was cerebellar hemispheres (P = 1.177 ×10−9).ConclusionMany crucial structures including the hippocampus, parahippocampus, pituitary gland and thalamus etc. have low frequency of brain metastases in a population of SCLC patients. This study provides the help to investigate the clinical feasibility of HA-WBRT and non-uniform dose of PCI in a population of SCLC patients.

P52.12 Incidence of Brain Metastasis in Advanced Non-Small Cell Lung Cancer at Presentation-An Experience From Tertiary Care Centre in South India

Brain metastasis is one of the most significant problems in patients with lung cancer. Many patients with brain metastasis are asymptomatic at presentation.Due to its prognostic significance and bad survival, many studies looked upon the incidence of brain metastasis at the presentation of NSCLC. Most of them are retrospective studies conductedin different parts of the world. To the best of our knowledge, the frequency of brain metastasis in patients with NSCLC at initial presentation in India has not been studied.So we planned a study to evaluate the incidence of brain metastasis in NSCLC patients treated in our center. It is a prospective observational study conducted in the department of medical oncology at our tertiary care center from Sep 2019- March 2020. A total of 80 patients with lung cancer were registered in the department. Among them,66 patients had advanced non- small cell carcinoma of the lung (NSCLC),and they were enrolled in the study.Clinical profile,performance status, demographic characteristics, smoking history, and imaging findings were noted at the time of presentation. MRI brain was taken for all advanced NSCLC patients,and the results were analyzed. . Mean age at presentation was 60 years. 20(30%) patients were smokers and 46(70%) were non-smokersAmong 66 patients, 33% had brain metastasis. 15 (63%) patients were adenocarcinoma, whereas 9 (27%) patients had squamous cell carcinoma. 42% had asymptomatic brain metastasis at presentation. All patients with brain metastasis received radiotherapy. Other parameters are tabulated as follows.Tabled 1Baseline CharacteristicsParametersNo of Patients (%)Mean Age60 yearsMale36 (54%)Female30 (46%)ECOG0-256 (85%)310 (15%)Brain Metastasis24 (33%)Male10 (42%)Female14 (58%)Adenocarcinoma15 (63%)Squamous Cell Carcinoma9 (37%)Asymptomatic14 (58%)Symptomatic10 (42%)Hemorrhagic5 (21%)Non-hemorrhagic19 (79%)Synchronous metastasis12 (18%)Contralateral Lung Metastasis6 (9%)Liver4 (6%)Bone2 (3%) Open table in a new tab Our study has found that incidence of brain metastasis is higher in South India when compared to western data. The other findings include female patients had slightly higher predilection for brain metastasis. Adenocarcinoma histology and synchronous contralateral lung metastasis are common in patients with brain metastasis. There are no validated biomarkers to predict brain metastasis in NSCLC due to its molecular heterogeneity. As the study was conducted in resources limited setting molecular correlation in patients with brain metastasis was not done. 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

Incidence and Prognosis of Brain Metastases in Head and Neck Cancer Patients at Diagnosis.

Limited data is available on head and neck cancer (HNC) patients presenting with brain metastases (BM) at initial diagnosis. We sought to evaluate the incidence, management, and treatment outcomes of these patients using the National Cancer Database (NCDB). We identified 465,925 patients diagnosed with HNC between 2010 and 2015 in the NCDB. 14,583 of these patients presented with metastatic disease to any site. 440 of these patients had BM at the time of initial diagnosis. Overall survival was compared using the Kaplan-Meier method. Cox proportional hazard modeling, propensity score matching, and subgroup analyses were performed. The median age overall was 62.0 years. Nasopharynx NOS (13.2%) and Parotid Gland (10.9%) were the most common anatomical sites with the highest frequency of BM. The overall median survival time was 7.1 months. Predictors for the presence of BM included distant metastasis to the bone, liver, or lung on univariate analysis, and bone or lung on multivariate analysis. High-risk Human Papilloma Virus status was associated with a lower chance of BM. No pattern was determined when comparing lymph node level involvement and BM. The median survival for patients receiving radiation therapy and multi-agent chemotherapy was 8.4 and 11.7 months, respectively. Immunotherapy administered as first course therapy did not influence median survival. Most patients received radiation (62.7%) therapy and chemotherapy (50.2%). The data extracted and analyzed from the NCDB should work to aid in the surveillance and management of BM in patients with HNC. 4 Laryngoscope, 131:E2543-E2552, 2021.

Association of the neutrophil-to-lymphocyte ratio with brain metastases in Hispanic breast cancer patients.

BackgroundBreast cancer (BC) is one of the most common cancers and leading cause of cancer-related deaths in women. Metastatic disease, particularly brain metastases (BM), is associated with death in BC patients. The neutrophil-to-lymphocyte ratio (NLR) has been associated with BC prognosis, but it is not usually used in clinical practice and has not been associated with BM. We aimed to determine if there is an association between NLR and BM and if NLR is associated with survival in a Hispanic population. MethodsA retrospective cohort with a total of 2,104 patients with a confirmed diagnosis of BC at a single referral center were randomly divided into training and validation datasets. Univariable and multivariable analyses were performed to study the association of NLR with BM and/or survival. ResultsNo significant differences between datasets were identified. A high NLR (> 2.2) was associated with a higher frequency of BM after multivariable adjustment in both datasets. Overall survival was shorter in patients with a high NLR; however, the most important factor associated with outcome was the presence of BM. The interaction NLR/BM was not statistically significant. ConclusionA high NLR at BC diagnosis was associated with a higher frequency of BM, and the presence of BM was associated with worse overall survival in Hispanic BC patients.

CTIM-02. TWO OUNCES OF PREVENTION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF VEGF AND IMMUNE CHECK POINT INHIBITION FOR PRIMARY AND SECONDARY PREVENTION OF BRAIN METASTASES

Abstract INTRODUCTION As treatments for cancer outside of the central nervous system improve, brain metastases (BMs) are becoming increasingly frequent. Despite novel treatment options, BMs remain a frequent cause of death for many advanced malignancies, and both the metastases and their treatments are associated with profound cognitive, quality of life, and economic costs. METHODS We conducted exhaustive, PRISMA-compliant systematic reviews of the literature from January 2000 to June 2020 for studies comparing the frequency of new BM in patients treated with chemotherapy regimens including and not including bevacizumab (“primary prevention”), and for studies comparing the frequency of new outside-of-treatment-field metastases in patients treated with stereotactic radiosurgery (SRS) with or without immune checkpoint inhibitors (“secondary prevention”). Pre-specified data was extracted and summary statistics were calculated using the inverse variance method and random effects model. RESULTS Seven studies (n=6,212) reported on BMs in breast, lung, and colon cancer patients treated with chemotherapy with or without bevacizumab. The relative risk (RR) and 95% confidence intervals [95% CI] for the development of new brain metastases was 0.71 [0.55–0.91, p=0.001]. A sensitivity analysis performed on the 3 breast cancer trials (n=2,350) showed a RR of 0.57 [0.34–0.94, p=0.027]. Seven studies (n=609) reported on patients with melanoma BM receiving SRS without or without an ICI. The RR for the development of new out-of-treatment field brain metastases was 0.70 [0.51–0.94, p=0.017]. Results were similar in sensitivity analyses examining only class I and class II trials. CONCLUSION This analysis suggests that the addition of bevacizumab to chemotherapy or ICI SRS+/- chemotherapy can reduce the development of first-ever or new BM by 30% in patients with advanced stage breast, lung, or colon cancer. Prospective trials of primary and secondary prevention in patient groups at high risk of developing BMs, and examining additional predictors of response, are currently underway.

Frequent brain metastases during treatment with BRAF/MEK inhibitors: A retrospective single institutional study.

Recent clinical trials revealed that both immune checkpoint inhibitors (ICI) and BRAF/MEK inhibitors significantly prolonged survival in melanoma patients when used for both advanced stage disease and postoperative adjuvant therapy. Although BRAF/MEK inhibitors are associated with a higher objective response rate than ICI, most patients relapse during treatment. However, progression patterns during treatment with BRAF/MEK inhibitors have not been extensively investigated. Here, we retrospectively collected the data of melanoma patients initially treated with BRAF/MEK inhibitors or anti-programmed death 1 (PD-1) antibody monotherapy at the University of Tsukuba Hospital and compared their results. The χ2 -test revealed that frequency of brain metastasis (BM) development was significantly higher in cases treated with BRAF/MEK inhibitors compared with those with anti-PD-1 antibody monotherapy. In addition, BM-free survival in cases treated with BRAF/MEK inhibitors was significantly shorter than those treated with anti-PD-1 antibody monotherapy. Our results indicate that BM development during treatment with BRAF/MEK inhibitors may be more frequent than anti-PD-1 antibody monotherapy, even though the extracranial metastases are well controlled. Therefore, we recommend frequent brain examinations during treatment with BRAF/MEK inhibitors to detect BM at an early stage and to promptly administrate ICI with local radiation therapy.

Frequency of brain metastases in patients with locally advanced triple negative breast cancer after neoadjuvant platinum-based chemotherapy: Impact of BRCA1/2 mutations.

1079 Background: patients with triple negative breast cancer has poor survival outcomes. Achievement of pathological complete response (pCR) after neoadjuvant chemotherapy can significantly improve survival of these patients, however some patients will relapse even after pCR. Methods: we reviewed prospectively-maintained outcomes database of N.N. Blokhin NMRCO. We extracted information about patients with locally advanced non-metastatic (stage IIIA-IIIC) triple negative breast cancer who were treated with neoadjuvant platinum based chemotherapy in 2014-2018 years. All included patients were tested for the presence of BRCA1/2 mutation with whole-exome next-generation sequencing or for “founder” hot-spot mutations. Results: we identified 80 patients who received neoadjuvant treatment with various platinum-based regimens. Pathological complete response rate was 62.5%. BRCA-mutations was found at 22 (27.5%) patients. Median follow-up time was 35.6 months (17.0 – 61.3). 2-year DFS was 77.3%, and 3-year DFS was 70.0%, there was significant differences in DFS in patients, who achieved and patients with residual tumor – 85,2% vs 64,3% (p=0,028). 2-year OS was 91%, 3-year OS was 78,5%. 18 patient had disease progression, the most common sites of disease progression were brain (9 [50.0%]), lungs (5 [27.8%]), 3 (16.7%) patients had locoregional relapses and 1 (5,6%) liver metastases. We separately analysed characteristics of patients with brain metastases (table). There were no significant differences in tumour pathologic response and patient age. All patients, who relapced after pCR, had brain metastases. We also found, that 7 of 9 patients with brain metastases had different BRCA mutations. Brain metastases developed in 40,9% (9/22) of patients with BRCA1 mutations and 3,4% (2/58) of patients with wild type BRCA1 (p&lt;0,00001). Conclusions: BRCA1 mutation is significant prognostic factor for brain metastases development in locally advanced triple negative breast cancer. [Table: see text]

Defining the role of microglia in breast‐to‐brain metastasis

A diagnosis of brain metastasis is devastating to cancer patients, with survival measured in only months. Due to prolonged life expectancy of cancer patients, the frequency of brain metastasis is increasing, with the highest incidences occurring when the primary site is the lung, breast, and melanoma. Treatment of brain metastatic lesions is challenging; differences in the brain microenvironment and the encompassing blood‐brain barrier are two major obstacles to successful systemic therapy. A unique player in the brain tumor microenvironment (TME) are microglia, the resident innate immune cells of the central nervous system. How microglia influence metastatic tumor progression in the brain, and their therapeutic potential in this setting remain to be elucidated. To first characterize the role of microglia in a model of breast‐to‐brain metastasis, we deplete them using the orally available colony stimulating factor 1 receptor (CSF1R) inhibitor, PLX5622, which readily crosses the blood‐brain barrier. Brain metastatic development of a C57BL/6 syngeneic breast cancer line is monitored, and the resulting TME characterized histologically. Further, we utilize in vitro assays to investigate direct communication between microglia and neoplastic cells, measuring tumor cell migration and invasion, and microglial polarization. We also employ PLX5622 therapeutically, after the development of brain metastasis to understand whether dynamic elimination of microglia may be a viable therapy. Understanding microglia’s role in the development of metastatic disease and how these cells may be targeted therapeutically is critical to improving the treatment of brain metastasis.Support or Funding InformationThis work is supported by NIH IRACDA K12GM102779.

The impact of EGFR mutation status and single brain metastasis on the survival of non-small-cell lung cancer patients with brain metastases.

BackgroundMolecular and genetic alterations of non-small-cell lung cancer (NSCLC) now play a vital role in patient care of this neoplasm. The authors focused on the impact of epidermal growth factor receptor mutation (EGFR-mt) status on the survival of patients after brain metastases (BMs) from NSCLC. The purpose of the study was to understand the most desirable management of BMs from NSCLC.MethodsThis was a retrospective observational study analyzing 647 patients with NSCLC, including 266 patients with BMs, diagnosed at our institute between January 2008 and December 2015. EGFR mutation status, overall survival (OS) following diagnosis, OS following BMs, duration from diagnosis to BMs, and other factors related to OS and survival after BMs were measured.ResultsAmong 647 patients, 252 (38.8%) had EGFR mutations. The rate and frequency of developing BMs were higher in EGFR-mt patients compared with EGFR wildtype (EGFR-wt) patients. EGFR-mt patients showed longer median OS (22 vs 11 months, P < .001) and a higher frequency of BMs. Univariate and multivariate analyses revealed that good performance status, presence of EGFR-mt, single BM, and receiving local therapies were significantly associated with favorable prognosis following BM diagnosis. Single metastasis, compared with multiple metastases, exhibited a positive impact on patient survival after BMs in EGFR-mt patients, but not in EGFR-wt NSCLC patients.ConclusionsSingle BM with EGFR-mt performed better than other groups. Furthermore, effective local therapies were recommended to achieve better outcomes.

P1.12-12 Factors Affecting the Risk of Brain Metastasis in Limited-Stage Small Cell Lung Cancer After Prophylactic Cranial Irradiation

Prophylactic cranial irradiation (PCI) can reduce brain metastases (BM) and improve overall survival (OS) in patients with limited-stage small cell lung cancer (LS-SCLC) after complete response to primary therapy. However, some SCLC patients still suffer from BM after PCI with unknown risk factors.This study conducted to assess the factors affecting the risk of BM in patients with LS-SCLC after PCI and identify characteristics of patients who may not benefit from PCI. We identified 550 patients who received chemoradiotherapy at Zhejiang Cancer Hospital in 2002–2017. All patients received PCI. Kaplan–Meier analyses and Cox regression analyses were used to identify factors influencing OS and BM. The median survival time for this patient population was 27.9 months, and the 5-year overall survival rate was 31%. Pathologic stage not only correlated with overall survival but also significantly affected the risk of BM. For the whole group, 15.6% (86/550) of the patients had evidence of metastases to brain. The frequency of BM in patients with pathologic stages I, II, and III were 9.3% (4/43), 13.4% (7/52), and 16.5% (75/455), (P=0.026), Having tumors ≥5 cm increased the risk of BM (HR: 1.781 95%CI：1.044-3.039, P=0.034) but not death (HR:1.126 95%CI：0.925-1.663, P=0.182). The median survival time among patients <60 years were significantly higher than patients ≥60 years (34.9 months VS. 24.6 months, P=0.001), however, the difference of the BM risk in two group was not statistically significant. PCI remains standard therapy after complete response to chemoradiotherapy for LS-SCLC. However, patients with tumors ≥5 cm may have a higher risk of developing brain metastases after PCI. Further work is warranted to identify patients who may not benefit from PCI.

Frequency of Brain Metastasis in Breast Cancer Patients and Factors Leading to it

Objective: Breast cancer is the second commonest cause of brain metastasis after lung cancer.10-16% of patients diagnosed with breast cancer ultimately develop brain metastasis. As most of chemotherapeutic drugs do not cross blood brain barrier despite adequate management of breast cancer risk of CNS relapse persist. Prognosis for breast cancer patients after developing brain metastases is poor. Therefore, we sought to determine the frequency of brain metastasis in Pakistani breast cancer survivors, how often brain metastasis is the first site of recurrence and what are the risk factors that indicate greater likelihood of this event occurrence so that more accurate screening for patients at risk can be established. Methods: We retrospectively reviewed medical record of 507 patients with invasive breast cancer of all stages who received treatment in Liaquat National Hospital from January 2010 to December 2015. Patients who developed brain metastasis were identified and stratified according to risk factors. Result: Out of 507 patients 51(10%) developed brain metastasis. 14 patients had brain metastasis as first site of recurrence. On univariate analysis negative hormone receptor status, triple negative and her2 enriched subtype, higher tumor size, lymph node positivity, stages 3 and 4, lymphovascular and peri nodal extension, shorter diseasefree survival and recurrence with visceral metastasis had a statistically highly significant impact on brain metastasis occurrence, while young age at diagnosis (≤35 years), menopausal status, BMI and tumor histology showed no statistically significant impact. Conclusion: Brain metastases are more frequent in triple negative, Her2Neu positive and Estrogen and Progesterone receptor negative patients. Other factors associated with higher risk of brain metastases in breast cancer patients include larger tumor size, positive axillary lymph nodes, higher stage and lymphovascular and periodontal invasion. Frequency of brain metastasis in breast cancer patients and factors leading to it.