Screening For Brain Metastases Research Articles

Lifetime Occurrence of Brain Metastases Arising from Lung, Breast, and Skin Cancers in the Elderly: A SEER-Medicare Study.

The Surveillance, Epidemiology, and End Results (SEER) Program recently released data on brain metastases (BM) diagnosed during primary cancer staging workup ("synchronous" BM, or SBM); this study examines the incidence of SBM compared with that of lifetime BM (LBM) identified using Medicare claims for patients diagnosed with lung cancer, breast cancer, or melanoma. Incidence proportions (IP) and age-adjusted rates for each of SEER SBM and Medicare LBM are presented along with measures of concordance between the two sources of data, where Medicare LBM were defined by several combinations of diagnosis and putative diagnostic imaging procedure codes. The SBM IP in lung, breast, and melanoma cancers were 9.6%, 0.3%, and 1.1%, respectively; the corresponding LBM IP were 13.5%, 1.8%, and 3.6%. The greatest SBM IP among patients with lung cancer was 13.4% for non-small cell lung cancer, and among patients with breast cancer was 0.7% for triple-negative breast cancer. The greatest LBM IP among lung cancers was 23.1% in small-cell lung cancer, and among breast cancers was 4.2% for cases of the triple negative subtype. Using a large dataset that is representative of the elderly population in the United States, these analyses estimate synchronous and lifetime incidence of BM in lung cancers, breast cancers, and melanomas. These and other population-based estimates may be used to guide development of BM screening policy and evaluation of real-world data sources.

Brain metastases in patients with neuroendocrine neoplasms: risk factors and outcome

BackgroundBrain metastases (BM) are rarely reported in patients with neuroendocrine carcinoma (NEC) of non-lung origin and neuroendocrine tumors (NET) of the gastroenteropancreatic (GEP) or bronchopulmonary system. However, symptomatic brain metastases are associated with dismal prognosis, so early detection and treatment could be advisable.MethodsWe retrospectively analyzed 51 patients with GEP-NEN and bronchopulmonary NEN excluding small cell lung cancer. All patients were treated at the University Hospital Marburg and Halle (Saale) between 2000 and 2017. The median overall survival (mOS) and mOS after diagnosis of brain metastases (BM) were calculated using Kaplan-Meier analysis. Risk factors for poor prognosis were evaluated using univariate and multivariate Cox regression method.ResultsOverall, 51 patients with a median age of 58 years presented BM. Lung (n = 23, 45.1%) was the most frequent primary localization. Most patients had NEC (n = 31, 60.8%), including 26 carcinomas (51%) with Ki-67 indices > 55%. Singular BM were present in 16 patients (31.4%), but 21 patients (41.2%) had multiple lesions. Overall, the median period from first diagnosis of the tumor disease up to diagnosis of brain metastasis was 5.0 months. Palliative radiation was the most common therapy (n = 31, 60.8%). Median OS after initial diagnosis and diagnosis of BM was 23.0 and 11.0 months, respectively. Univariate and multivariate analysis for prognostic indicators depicted differentiation (NEC HR 4.2, 95% CI 1.1–16.1) and age (≥60 HR 3.0, 95% CI 1.2–7.5) as markers for poor outcome.ConclusionsOverall, the risk for symptomatic brain metastases is low in GEP-NEN and bronchopulmonary NEN patients. Age above 60 and poor tumor differentiation may deteriorate the overall survival. Therefore, screening for brain metastases could be advisable in NEC patients.

CT-Based Radiomics Model for Predicting Brain Metastasis in Category T1 Lung Adenocarcinoma.

OBJECTIVE. The purpose of this study is to develop and evaluate an unenhanced CT-based radiomics model to predict brain metastasis (BM) in patients with category T1 lung adenocarcinoma. MATERIALS AND METHODS. A total of 89 eligible patients with category T1 lung adenocarcinoma were enrolled and classified as patients with BM (n = 35) or patients without BM (n = 54). A total of 1160 quantitative radiomic features were extracted from unenhanced CT images of each patient. Three prediction models (the clinical model, the radiomics model, and a hybrid [clinical plus radiomics] model) were established. The ROC AUC value and 10-fold cross-validation were used to evaluate the prediction performance of the models. RESULTS. In terms of predictive performance, the mean AUC value was 0.759 (95% CI, 0.643-0.867; sensitivity, 82.9%; specificity, 57.4%) for the clinical model, 0.847 (95% CI, 0.739-0.915; sensitivity, 80.0%; specificity, 81.5%) for the radiomics model, and 0.871 (95% CI, 0.767-0.933; sensitivity = 82.9%, specificity = 83.3%) for the hybrid model. The hybrid and radiomics models (p = 0.0072 and 0.0492, respectively) performed significantly better than the clinical model. No significant difference was found between the radiomics model and the hybrid model (p = 0.1022). CONCLUSION. A CT-based radiomics model presented good predictive performance and great potential for predicting BM in patients with category T1 lung adenocarcinoma. As a promising adjuvant tool, it can be helpful for guiding BM screening and thus benefiting personalized surveillance for patients with lung cancer.

1365PD - Screening for brain metastases (BM) in patients (pts) with stage III non-small cell lung cancer (NSCLC), magnetic resonance imaging (MRI) or dedicated contrast-enhanced computed tomography (dCE-CT)? A prospective observational study

1365PD - Screening for brain metastases (BM) in patients (pts) with stage III non-small cell lung cancer (NSCLC), magnetic resonance imaging (MRI) or dedicated contrast-enhanced computed tomography (dCE-CT)? A prospective observational study

Non-small cell lung cancer brain metastasis screening in the era of positron emission tomography-CT staging: Current practice and outcomes.

Several clinical guidelines indicate that brain metastasis screening (BMS) should be guided by disease stage in non-small cell lung cancer (NSCLC). We estimate that screening is performed more broadly in practice, and patients undergo brain imaging at considerable cost with questionable benefit. Our aim was to quantify the use and detection rate of BMS in a contemporary cohort staged with 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT). We conducted a retrospective review of prospectively collected data from three major lung cancer referral centres in Brisbane between January 2011 and December 2015. Patients included had a new diagnosis of NSCLC and had undergone a PET-CT to stage extra-cranial disease. BMS was defined as dedicated brain imaging with contrast-enhanced computed tomography (CE-CT) or magnetic resonance (MR), in the absence of clinically apparent neurological deficits. A total of 1751 eligible cases were identified and of these 718 (41%) underwent BMS. The majority had CE-CT imaging (n=703). Asymptomatic brain metastases (BM) were detected in 18 patients (2.5%). Of these patients, 12 had concurrent non-brain metastases. Only six patients (0.8%) had BM alone. The rate of detection increased with N-stage (P=0.02) and overall stage (P<0.001). It was 0.5%, 1%, 1.6% and 7.3% for stage I, II, III and IV respectively. The overall screening rate increased with T-stage (P=0.001), N-Stage (P<0.001) and overall stage (P<0.001). Non-small cell lung cancer BMS practices remain at odds with published guidelines. The low number of occult BMs detected supports the existing international recommendations. Rationalising BMS would minimise the burden on patients and the health care system.

Abstract P1-07-11: Risk factors for the development of brain metastases (BM) in 506 patients with HER2-positive breast cancer (HER2+ BC): A single institutional retrospective analysis

Abstract Introduction: BC is the most common malignancy in women. HER2+ BC is the 2nd leading cause of BM after lung cancer. The prognosis of BC patients with BM is poor. Determining risk factors for the development of BM is warranted in order to establish more accurate screening for patients at risk. Material and Methods: This is a retrospective analysis of patients with HER2+ BC treated at Institut Jules Bordet, Belgium, between 2000 and 2014. Patients' charts were reviewed for disease characteristics, treatment regimens for primary and metastatic disease as well as clinical outcomes. Statistical analyses were conducted with SAS 9.4 using Cox regression analyses, log-rank test and Kaplan-Meier method. Results: A total of 506 patients with HER2+ BC were included in the analysis. Median age was 52.7 years (range, 21.5-89.2 years). In total, 138 (27.3%) were diagnosed with metastatic BC and 74 (14.6%) had BM. Among the 138 metastatic patients, 12 (8.7%) had BM as a first site of metastatic disease and 3 (2.2%) developed BM as only site of distant relapse. Median overall survival (OS) for patients with BM was 1.74 years (range, one month-3.2 years). In multivariate analysis, risk factors for the development of BM at time-point of initial BC diagnosis were de-novo metastatic disease (hazard ratio [HR] 4.46; p&amp;lt;0.0001), postmenopausal status (HR 16.65; p&amp;lt;0.0001), and adjuvant breast radiotherapy (HR 1.79; p=0.0198). Identified risk-factors for BM at the time-point of metastatic disease were postmenopausal status (HR 1.90; p=0.0464), the presence of lung metastases (HR 2.61; p=0.0004), an interval of more than one year between initial BC diagnosis and development of metastatic disease (HR 1.91; p=0.0179) and age of &amp;lt;40 years (HR 1.78; p=0.0353). In this cohort, biological factors such as hormone receptor status, degree of HER2 amplification and tumor grade had no impact on the development of BM both in univariate and multivariate analysis. Furthermore, the type of systemic treatment in the adjuvant or metastatic setting (chemotherapy, anti-HER2 treatment) did not modulate the risk for BM. The combination of local treatment (surgery, stereotactic radiosurgery [SRS] or whole brain radiotherapy [WBRT]) and anti-HER2 directed therapy as first-line therapy for BM was associated with an improvement in overall survival (OS) that was more pronounced for tyrosine kinase inhibitors (HR 0.13; 95% confidence interval [CI] 0.05-0.33); p&amp;lt;0.0001) than for trastuzumab and/or pertuzumab (HR 0.53; 95% CI 0.24-1.15; p=0.1085). Conclusion: The development of BM is a common complication in patients experiencing metastatic HER2+ BC. Until now, no imaging screening for BM is recommended in this patient population. Compared to WBRT, surgery and SRS are associated with an improvement in OS and/or less cognitive impairment. However, these treatment approaches are limited to patients with less extensive BM disease. In this context, randomized trials examining the role of MRI screening for BM in metastatic HER2+ BC with high risk features are warranted. Citation Format: Maurer C, Tulpin L, Dumitrescu C, de Azambuja E, Moreau M, Paesmans M, Nogaret J-M, Piccart M, Awada A. Risk factors for the development of brain metastases (BM) in 506 patients with HER2-positive breast cancer (HER2+ BC): A single institutional retrospective analysis [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-11.

Breast cancer subtype and stage are prognostic of time from breast cancer diagnosis to brain metastasis development.

Breast cancer brain metastasis (BCBM) is associated with high morbidity and mortality. Patients with breast cancer risk factors associated with rapid development of BCBM could potentially benefit from early brain metastasis screening. We retrospectively reviewed all BCBM patients treated with brain radiotherapy at our institution from 1997 to 2015. Interval time to BCBM was defined as date of pathologic breast cancer diagnosis to date of radiographic evidence of brain metastasis. Patients were stratified by breast cancer molecular subtype and stage at diagnosis. Kaplan Meier analysis was conducted on time to development of BCBM. Breast cancer risk factors were correlated with time to BCBM on Cox proportion hazard analysis. The study cohort comprised 121 BCBM patients, with median interval time to BCBM of 46 months. Times to BCBM for Her2+/2HR+, Her2+, Her2-/HR+, and triple-negative (TNBC) subtypes were 70, 44, 42, and 28 months respectively (p = 0.002). Time to BCBM for stages I, II, III, and IV were 70, 54, 29, and 24 months, respectively (p = 0.000). BCBM patients were further stratified by both molecular subtype (TNBC vs. non-TNBC) and stage (I, II vs. III, IV). Median times to BCBM for non-TNBC/stage I-II, TNBC/stage I-II, non-TNBC stage III-IV, and TNBC/stage III-IV were 68, 47, 29, and 6 months respectively (p = 0.000). Subtype and stage were associated with shorter time to BCBM on multivariate analysis. Subtype and initial stage are independently correlated with decreased time to development of BCBM. Patients with advanced high stage and triple negative breast cancer develop brain metastases significantly earlier.

Brain metastasis in patients with metastatic breast cancer in the real world: a single-institution, retrospective review of 12-year follow-up.

The data of 589 metastatic breast cancer (MBC) patients in a single institution were reviewed to determine the outcomes of patients with brain metastasis (BM) and assess the efficacy of BM screening. The patients with BM among the 589 MBC patients who underwent treatment at Shizuoka Cancer Center (Shizuoka, Japan) from 09/2002 to 03/2014 were retrospectively analyzed. During the study period, BM developed in 187 (31.7%) patients. The tumor subtypes were as follows: luminal (hormone receptor [HR]+, HER2-), 44.9%; luminal-HER2 (HR+, HER2+), 14.9%; HER2 (HR-, HER2+), 21.3%; and triple-negative (TN), 16.0%. BM was detected in 48.6% of the patients by screening MRI. While 137 of 187 patients underwent local therapy, whole-brain irradiation was the most frequently applied therapy (63.5%). The median overall survival from the diagnosis of BM was as follows: luminal, 7.0months (M); luminal-HER2, 13.3M; HER2, 17.7M; TN, 4.2M. The HER2 status (hazard ratio [HR]: 0.58, 95% confidence interval [CI] 0.38-0.88) and nonprogressive extracranial lesion(s) (HR: 0.45, 95% CI 0.29-0.71) were identified as prognostic factors in a multivariate analysis. When limited to HER2-overexpressed MBC patients, the multivariate analysis revealed that non-progressive extracranial lesion(s) (HR: 0.20, 95% CI 0.088-0.47) and stereotactic irradiation (STI) as an initial treatment (HR: 0.18, 95% CI 0.061-0.56) were prognostic factors. Our retrospective review showed that early detection of BM by screening MRI, followed by STI, improved the prognosis of HER2-overexpressed MBC patients with BM. A further prospective randomized study is needed to confirm our findings.

MA06.05 Screening for Brain Metastases in Patients with Stage III NSCLC, MRI or CT? A Prospective Study

MA06.05 Screening for Brain Metastases in Patients with Stage III NSCLC, MRI or CT? A Prospective Study

32: Screening for brain metastases in non small cell lung cancer (NSCLC)

32: Screening for brain metastases in non small cell lung cancer (NSCLC)

587P - Clinical characteristics of colorectal cancer patients with brain metastases: An "Association des Gastro-Éntérologues Oncologues" (AGEO) multicenter study

Brain metastases (BM) from colorectal cancer (CRC) are rare (1-3%) but their incidence seems to be increasing due to improvement of CRC prognosis. The prognosis of patients with BM from CRC is poor. The objective of this study was to evaluate the clinico-biological criteria of CRC with BM. This multicenter retrospective study included all patients with BM from CRC between 1995 and 2015. Overall Survival was calculated using the Kaplan-Meier method. A total of 135 patients were included. Mean age at diagnosis of CRC was 63.5 years [range 34-87] and 57.8% were men. Primary tumors were located preferentially in the rectum (37.1%) or sigmoid (24.3%). The median interval from CRC diagnosis to BM diagnosis was 34.2 months [IC95%: 28.2-38.7] and the one from the diagnosis of CRC metastases to BM diagnosis 20.7 months [IC95%: 13.2-26.1]. BM were mostly revealed by neurological symptoms (93.3%), predominantly unifocal (50.4%) and supratentorial (74.1%). At BM diagnosis, 71.1% of patients had lung metastases, 48.9% liver metastases and 11.9% had no extra-cerebral metastasis. BM resection was performed in 37.1% of the cases and 76.3% of patients underwent a brain radiotherapy. The mean overall survival from the time of BM diagnosis was 8.7 months [IC95%: 6.7-10.7], respectively 14.8 months [IC95%: 10.8-18.7] in the group of patients who underwent surgical resection versus 4.9 months [IC95%: 3.0-6.8] for the others (p < 0.0001). Overall survival was 12.3 months [IC95%: 9.0-15.7] for patients with unifocal BM versus 4.9 months [IC95%: 3.2-6.6] for patients with multifocal BM (p < 0.0001). Molecular analyses (RAS and BRAF) are ongoing and will be presented at the congress. Among the 34 CRC with available KRAS status, KRAS mutation was observed in 58.8% of the cases. The prognosis of patients with BM from CRC remains poor. Patients with BM from CRC have frequently lung metastases. The time between diagnosis of CRC metastases and BM raises the question of BM screening at 1-2 years of metastatic disease. Early detection of BM from CRC can allow curative-intent aggressive treatment with an expected benefit on survival and quality of life.

Brain metastases in malignant pleural mesothelioma.

The brain is a rare site of metastasis in malignant pleural mesothelioma (MPM), and its clinical features and prognosis remain unclear. The aim of this study was to investigate the incidence, prognosis, and risk factors for brain metastases (BM) in MPM patients. Between July 1993 and October 2014, 150 patients with histologically proven MPM were included in this retrospective study. The cumulative incidence of BM was estimated with the Kaplan-Meier method, and differences between groups were analyzed by the log-rank test. Multivariate logistic regression analysis was applied to assess risk factors for BM. The median follow-up time was 11 months (range 0-154.0 months). A total of eight patients (5.3 %) developed BM during the course of their illness. Multivariate analysis identified age <65 years (odds ratio [OR] = 5.83, p = 0.038) and International Mesothelioma Interest Group stage IV (OR = 1.69, p = 0.040) as independent factors related to increased risk of developing BM. The 1-and 2-year cumulative rates of BM were 4.0 % (95 % confidence intervals [CI] 1.4-8.5 %) and 5.3 % (95 % CI 2.3-10.2 %), respectively. Our study showed that the overall survival (OS) of patients with BM was worse than that of patients without BM (median OS 6.5 vs. 11.0 months, p = 0.037). The prognosis for BM in MPM patients is poor. Clinicians should perform careful screening for BM, especially in patients with risk factors.

Current Perspectives in the Management of Brain Metastases.

Brain metastases (BMs) are diagnosed in 10%-40% of all patients with cancer, and the incidence continues to increase along with the number of long-term survivors. When BMs occur, they are often associated with a myriad of symptoms, including neurologic dysfunction and functional decline; both are difficult to manage and can be distressing for patients and their caregivers. Although clinically significant findings have not kept up with the rapid pace of scientific breakthroughs in understanding the mechanisms of BMs, novel approaches that affect the prognosis of patients with BMs have been introduced in clinical practice. At a Glance • Screening for brain metastases (BMs) is not routinely performed in patients with no neurologic symptoms. However, screening is indicated in lung cancer and possibly in the context of high-risk cancers. • Individual differences in patients warrant a personalized approach in the management of BMs. • Whole brain radiation therapy and steroids are considered to be the cornerstones of treatment for BMs.

Abstract P6-16-06: Impact of early detection of brain metastasis in metastatic breast cancer patients: A single institutional experience

Abstract Background/Introduction Since brain metastasis (BM) is commonly seen in metastatic breast cancer (MBC) patients (pts), it may be an important prognostic factor. It has been believed that screening MRI would not improve a pt’s outcome, however, an appropriate diagnosis and early initiation of therapy, especially screening MRI followed by stereotactic irradiation (STI), might contribute to a pt’s survival. Patients and methods We reviewed our medical records for 589 MBC pts who were treated between September 2002 and March 2014. COX regression analyses were applied to identify the survival risk factors, and the Kaplan-Meier method with a log-rank test was utilized to evaluate the survival rates. Results Upon checking our medical records, 187 pts, or 37.1% of MBC pts, developed BM with the median time to BM of 585.0 days (95% confidence interval [CI] 501.0-647.0). The tumor subtypes of primary lesion were luminal, 44.9%; luminal-HER2, 14.9%; HER2+, 21.3%; triple-negative (TN), 16.0% and unavailable, 2.6%. The median overall survival (OS) from the diagnosis of BM was as follws: all pts, 292.0 days (95%CI 220.0-345.0); luminal, 212.0 days (150.0-293.0); luminal-HER2, 400.0 days (258.0-613.0); HER2+, 531.0 days (423.0-670.0) and TN, 127.0 days (43.0-185.0). Accompanying visceral and/or bone lesion(s) at the diagnosis of BM were as follows: lung, 49.7%; liver, 45.9% and bone, 64.7%. The development of BM in the HER2+ pt was significantly less frequently associated with progression of known visceral/bone lesions than other subtypes (HER2+ 41.0% versus luminal 64.2% or TN 70.0%; P&amp;lt;0.01, Chi-square test), and the pts who developed BM without progression of other lesion(s) showed a significantly superior OS (hazard ratio [HR] 0.48, 95%CI 0.32-0.70, P&amp;lt;0.001) regardless of the subtype. The 91 pts with BM (48.6%) whose lesions were detected by screening MRI showed a significantly superior OS from BM than did the pts with BM with any symptoms (median 359.0 days, 95%CI 249.0-439.0 versus 222.0 days, 95%CI 159.0-292.0; P&amp;lt;0.05). STI was performed as initial therapy in 20.3% of pts, and improved their OS from BM in all subtypes (median 439.0 days with STI, 293.0 days without STI; P&amp;lt;0.05), STI or the use of a tyrosine kinase inhibitor (TKI) significantly improved the OS from BM in HER2+ pts (median 661.0 days with STI versus 423.0 days without STI; P&amp;lt;0.05, median 622.0 days with TKI versus 287.0 days without TKI; P&amp;lt;0.01) The univariate COX analysis indicated that HER2+, 2&amp;gt;ECOG performance status at the diagnosis of BM, no other progressive lesions at the diagnosis of BM, &amp;lt;5 brain lesions and STI were favorable factors for the OS. When limited to HER2+ pts, the multivariate COX analysis showed that the lack of other progressive lesions at the diagnosis of BM (HR 0.20, 95%CI 0.09-0.47, P&amp;lt;0.001) and STI (HR 0.18, 95%CI 0.06-0.56, P&amp;lt;0.01) markedly decreased the risk of death for HER2+ pts. Conclusions From our institutional review, there seemed to be no special strategy for improving the OS of luminal or TN pts, however, HER2+ pts showed an improved OS after BM following the early detection and appropriate therapies for the BM. We conclude that HER2+MBC pts are good candidates for a BM screening program. Citation Format: Satomi Matsuo, Junichiro Watanabe, Koichi Mitsuya, Yoko Nakasu. Impact of early detection of brain metastasis in metastatic breast cancer patients: A single institutional experience [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-16-06.

CNS metastases in breast cancer patients: prognostic implications of tumor subtype.

Development of brain metastases (BM) in breast cancer leads to limited survival. The therapeutical options are limited. There are less data about the risk factors and prognostic importance in BM. Objective is to investigate predictors of central nervous system metastases and outcome after diagnosis of BM according to tumor subtype. Based on medical records, 80 consecutive patients with primary non-metastatic operable breast cancer, treated at Department of Gynecology, University of Tübingen, and who developed BM during follow-up, were retrospectively analyzed. Clinicopathological parameters and their prognostic impact were evaluated. A node involvement (40%), ER/PR negative (53.75 vs. 61.25%), triple negative (28.75%) and HER2+ status (40%) were associated with BM. BM in breast cancer patients lead to a shortened survival. In cerebral metastatic breast cancer patients with HER2-negative and triple-negative, patients had significant shorter survival after detection of BM compared with HER2-positive and non-triple-negative patients (p=0.001; p=0.03). Risk of BM varies significantly by subtype. Understanding the biology of metastases can help categorize patients into prognostically useful categories and tailor treatment regimens for individual patients. Prospective clinical trials would be required for evaluating the potential role of screening for asymptomatic BM and of treatment of triple-negative patients.

Whole-brain black-blood imaging with magnetization-transfer prepared spin echo-like contrast: a novel sequence for contrast-enhanced brain metastasis screening at 3T

In contrast-enhanced (CE) brain metastasis screening, coexistence of enhanced blood vessel suppression and higher tumor-to-parenchyma contrast may improve radiologists' performances in detecting brain metastases compared with conventional sequences. In this study, we propose a new scheme, allowing both suppression of blood signals and improvement of tumor-to-parenchyma contrast, using motion-sensitized driven equilibrium prepared 3D low-refocusing flip-angle turbo spin echo (TSE) ("magnetization transfer prepared spin echo"-like contrast volume examination: MATLVE) for brain metastasis screening at 3.0 T, and we compare MATLVE to conventional three-dimensional (3D)-gradient recalled echo (GRE) and 3D-TSE sequences. With the use of MATLVE, the signal intensity of CE blood decreased substantially. Furthermore, the contrast ratio of tumor-to-white matter was significantly higher than in either conventional 3D-GRE or 3D-TSE. MATLVE can be used for 3D volumetric post-CE black-blood imaging, and it may be effective in detecting small brain metastases by selectively enhancing tumor signals while suppressing blood signals.

Screening for brain metastases in patients with stage III non-small cell lung cancer: Is there additive value of magnetic resonance imaging above a contrast-enhanced computed tomography of the brain?

IntroductionStage III NSCLC patients are candidates for treatment with curative intent. Current guidelines advise post contrast magnetic resonance imaging (MRI) or contrast enhanced computed tomography (CE-CT) of the brain in these patients to exclude brain metastases (BM). In previous small studies MRI was reported to be superior to CE-CT. However, CT and MR technology have evolved and 18F-deoxyglucose-positron-emission-tomography (18FDG-PET) has been implemented in staging of NSCLC. If CE-CT, performed together with 18FDG-PET-CT shows the same yield of BM detection as an additionally performed MRI, substantial gain in time and resources is expected. MethodsAll NSCLC patients who underwent a staging 18FDG-PET-CT between January 2008 and September 2011 were reviewed. Neurological asymptomatic patients with stage III NSCLC who were eligible for treatment with curative intent were selected, without taking into account the results of brain MRI. CT was compared to MRI to investigate whether additional BM were detected on MRI. Development of BM within a year after negative MRI was recorded. Results97/429 NSCLC patients who underwent a PET-CT had stage III disease. Three otherwise stage III patients already had occult BM on CE-CT. 77/97 (79%) patients underwent MRI, 45/77 (58%) CE-CT and 32/77 (42%) LD-CT. In none of the CE-CT, but in 5/32 (16%) LD-CT patients BM were detected on MRI. 9/72 patients (13%) without BM on MRI at diagnosis developed BM within a year. ConclusionsThis retrospective study suggests that there is no additive value of MRI to 18FDG-PET-CT with CE-CT in screening for BM in neurological asymptomatic patients with stage III NSCLC.

Brain Metastases as First Metastatic Site in HER2 Positive Breast Cancer – Evaluation from Single Institution Prospective Breast Cancer Brain Metastases Data Base

Breast cancer (BC) brain metastases (BM) are the most disturbing metastatic event, causing specific morbidity with various mental, cognitive and neurological disfunction, and despite treatment, limmited survival to few minths In metastatic BC, symptomatic BM are reported in 15-16% patients, but autopsy studies reported indcidence as high as 30%. Although BM can not be predicted, some predisposing factors, has been sugested, such as younger age, lungs metastases, estrogen receptor negativity, and most importantly, HER2 overexpression It seems that patients with metastatic HER2 3+BC, has the highest risk for BM, but seemingly, more often if treated with trastuzumab, either in metastatic or adjuvant setting. However, there are no recommendations for routine brain screening in asymptomatic patients, regardless of any clinical and pathological parameters, or BC stage. The aim of this paper is to evaluate the incidence of BM as a first metastatic site in patients with HER2 3+ BC. Better characterization of this patient`s subgroup, might define candidates for whom BM screening can be a reasonable option.

P4-17-03: Incidence Rate of Asymptomatic Brain Metastases in Patients with HER2+ Metastatic Breast Cancer Screened for EGF111438/CEREBEL Study.

Abstract BACKGROUND Brain metastases constitute a major clinical concern occurring in 28–43% of women treated for HER2+ metastatic breast cancer (MBC). The initial diagnosis of Central Nervous System (CNS) lesion is commonly based upon development of neurological symptoms. Data to address incidence of CNS lesions in asymptomatic patients are rare and not generally reported. EGF111438/CEREBEL study requires systematic screening for brain metastases by brain MRI and the ineligible patients due to detection of asymptomatic brain metastases are reported here. METHODS The patients screened for CEREBEL have consented to a multi-centre, open-label Phase III study in subjects with HER2+ metastatic breast cancer who received prior treatment with anthracyclines or taxanes and trastuzumab in the adjuvant or metastatic setting. Eligible subjects must not have any history of CNS metastases (including leptomeningeal involvement) or have evidence of benign or malignant brain tumours and/or clinical evidence of spinal cord metastases at baseline. In order to confirm this, subjects must have negative brain MRI at baseline as confirmed by independent review (IR). All MRI scans of the brain had to be acquired with gadolinium contrast agent (T1 only) and 3mm slice thickness without gaps. The primary endpoint of CEREBEL is the incidence of CNS lesions as first site of relapse. A total of 650 subjects (325 per group) are expected to be randomized between capecitabine + trastuzumab versus capecitabine + lapatinib. RESULTS The study is currently recruiting with 322 patients enrolled as of 15.06.2011. At this date, the total number of patients screened were 492 and 170 of these patients were screen failures. There are 15 patients in screening. The percentage of screen failures due to asymptomatic brain metastases assessed by investigators was 13.5% (23/170). The overall incidence of clinically asymptomatic brain metastases assessed by investigators for this study is 4.7% (23/492). CONCLUSIONS Around 5% of all screened patients (14% of screen failures) in this study who were clinically thought to be free of brain lesions actually had brain metastases verified by brain MRI. We therefore conclude that screening for occult brain metastases by MRI is important for trials with defined CNS endpoints. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-17-03.

P4-17-05: Brain Metastasis Free Survival (BMFS) Differs between Breast Cancer Subtypes.

Abstract BACKGROUND Brain metastases (BM) are frequently diagnosed in patients (pts) with Her2-positive metastatic breast cancer (BC); a rising incidence was also reported in triple-negative disease. We hypothesized that pts with triple-negative or Her2-positive tumours had shorter BMFS as compared to other BC subtypes. Therefore, we aimed to compare BMFS in pts with Her2-positive, estrogen receptor (ER) positive and triple-negative BC treated at the Medical University of Vienna from 1999–2009. In Her2-positive tumours, we further investigated the influence of ER co-expression on BMFS, as Her2-positive / ER-positive tumours were reported to express less aggressive biological properties. METHODS BMFS was defined as primary study endpoint and measured as the interval from diagnosis of metastatic BC until diagnosis of BM. A total of 168 pts were identified from a breast cancer database. 34 pts were excluded from this analysis as brain was the first site of disease progression; hence complete datasets from 134 pts were available (69 Her2-positive; 33 triple-negative; 32 ER-positive). Her2 status was analyzed by immunohistochemistry (IHC) and reanalyzed by FISH if a score of 2+ was gained. ER was analyzed by IHC; ER negative tumours were defined by a cut-off value of &amp;lt;10% positively stained tumour cells. BMFS was estimated with the Kaplan-Meier product limit method and compared with the log-rank test; factors significantly associated with BMFS in the univariate analysis were included into a Cox proportional hazard model. RESULTS Median BMFS in triple-negative pts was 14 months (m) (95% CI 12.17−15.83), as compared to 25 m (95% CI 13.37−36.62) in Her2-positive (p=0.001) and 35 m (95% CI 19.79−50.22) in ER-positive pts (p&amp;lt;0.001), respectively. In Her2-positive pts, prior trastuzumab treatment for metastatic disease prolonged median BMFS (29 vs. 11 m; p&amp;lt;0.001); BMFS was further improved by trastuzumab in multiple lines (p=0.045) and co-positivity for ER and Her2 (30 vs. 15 m; p&amp;lt;0.001). ER-expression (HR 2.03; 95%CI 1.22−3.36; p&amp;lt;0.05) and prior trastuzumab (HR 2.72; 95%CI 1.20−6.17; p=0.017) remained independent predictors of longer BMFS in the Cox regression model. In ER-positive, triple-negative as well as Her2-positive pts, no correlation was found between BMFS and factors such as grading, histological subtype, stage IV disease at primary diagnosis, disease-free interval &amp;lt;24 months from primary treatment to diagnosis of metastatic disease, presence of visceral metastases, presence of lung metastases, and prior capecitabine exposure. CONCLUSIONS BMFS in triple-negative disease is significantly shorter as compared to Her2-positive or ER-positive tumours, mirroring the aggressiveness of this breast cancer subtype. Probably due to improved systemic disease control, trastuzumab significantly prolonged BMFS in Her2-positive pts. Longer BMFS in ER/Her2 co-positive disease reflects a less aggressive subtype of Her2-positive breast cancer which is less likely to benefit from strategies of BM screening or prevention. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-17-05.