Diagnosed Brain Metastases Research Articles

Epidemiological Analysis of Cancer Patients Diagnosed With Cranial Metastasis at Initial Presentation

Introduction: Metastatic lesions are the most common brain tumors, comprising 52% of all cases. Early diagnosis is crucial to improve patient outcomes, but many cases remain undiagnosed until advanced stages. This study aimed to investigate the characteristics of patients diagnosed with brain metastasis concurrently with their primary malignancy, examine prognostic factors, and compare these findings with brain metastases of known primary origins. Method: A retrospective analysis was conducted on 184 patients between 18-80 years diagnosed with brain tumors between January 2018 and January 2019. Patient data were collected from clinical records, and statistical analyses were performed using SPSS 26.0. Results: Out of the total patients, 43% were diagnosed brain metastases. Among these, 33% had no known primary malignancy at diagnosis. In this group, 92.3% were over 50 years old, and 77% were male. The most frequent primary cancer was lung cancer (81%). Males had an average time to metastasis diagnosis approximately twice as long as females. A higher incidence of metastasis correlated with a lower Karnofsky Performance Score, indicating reduced operability and quality of life. Conclusion: Early diagnosis is critical to improving outcomes. Routine cranial imaging for patients over 50 may aid in early intervention.

Laser interstitial thermal therapy followed by consolidation stereotactic radiosurgery (LITT-cSRS) in patients with newly diagnosed brain metastasis.

The efficacy and safety of laser interstitial thermal therapy followed by consolidation radiosurgery (LITT-cSRS) was previously studied in brain metastasis that recurs locally after initial radiosurgery (BMRS). Here, we characterize the clinical outcome of LITT-cSRS in patients with newly diagnosed brain metastasis. Between 2017 and 2023, ten consecutive cancer patients with newly diagnosed brain mass of unclear etiology who underwent stereotactic needle biopsy (SNB) and LITT in the same setting followed by consolidation SRS (cSRS) with > 6 months follow-up were identified retrospectively. Clinical and imaging outcomes were collected. The histology of the BM were: breast cancer (n = 3), melanoma (n = 3), non-cell cell lung cancer (n = 3), colon (n = 1). There were no wound or procedural complications. All patients were discharged home, with a median one-day hospital stay (range: 1-2 days). All patients were off corticosteroid therapy by the one-month follow-up. cSRS were carried out 12-27 days (median of 19 days) after SNB + LITT. There were no subsequent emergency room presentation, 30-day or 90-day re-admission. The Karnofsky Performance Score (KPS) remains stable or improved at the 3 months-follow-up. With a median follow-up of 416 days (13.8 mo; range: 199-1,096 days), there was one local recurrence at 384 days (12.8 mo) post-LITT-cSRS. With exception of this patient with local recurrence, all patients showed decreased FLAIR volume surrounding the LITT-cSRS treated BMRS by the six-month follow-up. To our awareness, this case series represent the first to describe LITT-cSRS in the setting of newly diagnosed BM. The results presented here provide pilot data to support the safety and efficacy of LITT-cSRS and lay the foundation for future studies.

Role of Contrast-Enhanced MRI in Diagnosing Brain Metastases in Patients With Lung Cancer

Introduction: Lung cancer is one of the most common cancers in the world. Approximately 40% of all metastases make up brain metastases that occur in 3% of patients at early stages of lung cancer. Early diagnosis of brain metastases directly affects patients’ survival and quality of life.Objective: To study the role of contrast-­enhanced magnetic resonance imaging (MRI) in detecting brain metastases at the outpatient stage in patients with newly diagnosed and histologically confirmed lung cancer and to compare the findings to that of computed tomography (CT).Materials and methods: Our study was conducted at the premises of the Scientific Research Institute – Ochapovsky Regional Clinical Hospital No. 1 (Krasnodar, Russian Federation) between November 2022 and January 2023. Seventy­five patients with histologically confirmed lung cancer underwent brain MRI on a Philips Panorama 1.0T MRI scanner and intravenous administration of Clariscan to detect metastatic lesions. As a diagnostic method, we used a “short” scanning protocol in T1­-WI (TR: 450, TE: 15, slice thickness 5 mm), T2­-WI (TR: 4533, TE: 100, slice thickness 5 mm) and DWI (TR: 3712, TE: 97, slice thickness 5 mm) modes in the axial plane, then the Clariscan contrast agent was injected intravenously at the rate of 0.2 ml per 1 kg of the patient's weight, after which the scan was repeated using 3D T1 (TR: 450, TE: 15, slice thickness 1 mm).Results: The average age of the patients was 60 years. The majority of the participants were male. Of all the patients, the majority had central lung cancer (57.3%). During contrast-­enhanced brain MRI, brain metastases that accumulated a contrast agent in 100% of cases were detected in 30 patients (40%) of the total number of patients. In 7% of the patients, there were non-­metastatic findings undetected by prior contrast­-enhanced CT, such as pontine cavernoma and venous malformations. After MRI for brain metastases, management strategies changed in 30 (40%) patients.Discussion: Contrast-­enhanced MRI is one of the most effective methods for diagnosing metastatic lesions. It allows to localize brain metastases and helps the clinician choose the most effective management strategy. The introduction of contrast­-enhanced brain MRI into routine medical practice could improve the accuracy and quality of brain metastasis detection in patients with lung cancer.

Subcentimetric papillary thyroid carcinoma with extensive lymph node and brain metastasis: case report and review of literature.

We report a 61-year-old male patient without personal history of thyroid carcinoma or radiation exposure. In 2011, he presented with a cervical mass whose biopsy diagnosed a papillary thyroid carcinoma (PTC) in a lymph node metastasis (LNM). Total thyroidectomy with lymphadenectomy of central and ipsilateral compartment was performed. Histopathology identified a 2 mm follicular variant of PTC and LNM in 25/25 lymph nodes. The patient was treated with 150 mCi of radioactive iodine (RAI), followed by levothyroxine suppressive therapy. In 2016, a retrotracheal mass was diagnosed, suggesting local recurrence; patient was submitted to surgical excision and RAI therapy (120 mCi). Due to seizures, in 2019, a brain CT was performed that diagnosed brain metastases. The patient underwent debulking of the main lesion. Histopathology analysis confirmed a metastatic lesion with variated morphology: classical PTC and follicular pattern and hobnail and tall cell features. Molecular analysis revealed BRAFV600E in LNM at presentation and BRAFV600E and TERT promoter (TERTp) mutations in the recurrent LNM and brain metastasis. Based upon this experience we review the reported cases of subcentimetric PTC with brain metastases and discuss the molecular progression of the present case. Papillary microcarcinoma (PMCs) usually have very good prognosis with low impact on patient survival. PMCs presenting in elderly patients with LNM at diagnosis may carry a guarded outcome. Brain metastasis although rare indicate aggressive phenotypic features. Patient risk stratification of PMCs based on histopathological analysis and genetic testing may have a significant impact on prognosis providing therapeutic markers, that may predict disease progression and overall outcome.

External Validation of the Graded Prognostic Assessment for Patients with Non-Small Cell Lung Cancer and Brain Metastases Using Molecular Markers (Lung-molGPA)

Patients with non-small cell lung cancer (NSCLC) and brain metastases represent a markedly heterogeneous population. The original diagnosis-specific graded prognostic assessment is a prognostic index based on data from patients diagnosed between 1985 and 2005 and includes patients age, performance status, extracranial disease, and number of brain metastases. An updated prognostic index (Lung-molGPA) that incorporates molecular features (EGFR and ALK alterations) was created in 2016 based on the North American retrospective database analysis of 2186 patients with NSCLC and newly diagnosed brain metastases between 2006 and 2014. The aim of this study is to validate the Lung-molGPA model in an independent Asian patient population. Four hundred thirty-three patients (368 adenocarcinoma and 65 nonadenocarcinoma) with NSCLC with newly diagnosed brain metastasis between 2005 and 2017 were reviewed retrospectively and scored using the Lung-molGPA model. The overall median survival for the cohort in the present study was 14 months (16.5 months in the adenocarcinoma and 8.0 months in the nonadenocarcinoma, respectively; p = 0.003). For patients with adenocarcinoma, the median survival for patients with a Lung-molGPA score of 3.5 to 4.0 was 44.7 months, while the median survival was only 8.9 months in patients scoring 0-1.0, 17.0 months in patients scoring 1.5-2.0, and 30.2 months for scores of 2.5-3.0 (p <0.0001). For patients with nonadenocarcinoma, the median survival for scores 0-1.0, 1.5-2.0, and 2.5-3.0 were 6.7, 10.3, and 13.2 months, respectively (p = 0.038). Survival for patients with NSCLC and brain metastases varies widely. This study provides an independent validation of the 2016 Lung-molGPA in Asian patients.

Deep learning-based detection and quantification of brain metastases on black-blood imaging can provide treatment suggestions: a clinical cohort study

ObjectivesWe aimed to evaluate whether deep learning–based detection and quantification of brain metastasis (BM) may suggest treatment options for patients with BMs.MethodsThe deep learning system (DLS) for detection and quantification of BM was developed in 193 patients and applied to 112 patients that were newly detected on black-blood contrast-enhanced T1-weighted imaging. Patients were assigned to one of 3 treatment suggestion groups according to the European Association of Neuro-Oncology (EANO)-European Society for Medical Oncology (ESMO) recommendations using number and volume of the BMs detected by the DLS: short-term imaging follow-up without treatment (group A), surgery or stereotactic radiosurgery (limited BM, group B), or whole-brain radiotherapy or systemic chemotherapy (extensive BM, group C). The concordance between the DLS-based groups and clinical decisions was analyzed with or without consideration of targeted agents. The performance of distinguishing high-risk (B + C) was calculated.ResultsAmong 112 patients (mean age 64.3 years, 63 men), group C had the largest number and volume of BM, followed by group B (4.4 and 851.6 mm3) and A (1.5 and 15.5 mm3). The DLS-based groups were concordant with the actual clinical decisions, with an accuracy of 76.8% (86 of 112). Modified accuracy considering targeted agents was 81.3% (91 of 112). The DLS showed 95% (82/86) sensitivity and 81% (21/26) specificity for distinguishing the high risk.ConclusionDLS-based detection and quantification of BM have the potential to be helpful in the determination of treatment options for both low- and high-risk groups of limited and extensive BMs.Clinical relevance statementFor patients with newly diagnosed brain metastasis, deep learning–based detection and quantification may be used in clinical settings where prompt and accurate treatment decisions are required, which can lead to better patient outcomes.Key Points• Deep learning–based brain metastasis detection and quantification showed excellent agreement with ground-truth classifications.• By setting an algorithm to suggest treatment based on the number and volume of brain metastases detected by the deep learning system, the concordance was 81.3%.• When dividing patients into low- and high-risk groups, the sensitivity for detecting the latter was 95%.

LMAP-15 INTRACRANIAL RADIOTHERAPY WITH TUCATINIB FOR BRAIN METASTASIS FROM HER2-POSITIVE BREAST CANCER: A SINGLE-INSTITUTION SERIES

Abstract BACKGROUND Tucatinib, a HER-2 TKI, has demonstrated intracranial efficacy in the HER2CLIMB study. Treatment of brain metastases frequently includes stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT); however, HER2CLIMB did not detail outcomes with RT. METHODS Patients who received tucatinib at our institution from 2020-2022 were identified. Patients who had brain metastases and received intracranial RT within 6 months of receiving tucatinib were included. Patients with history of prior leptomeningeal disease (LMD) were excluded. The Kaplan-Meier (KM) method was used to estimate intracranial failure (ICF), overall survival (OS), and local control (LC). Adverse events and details regarding symptomatic radionecrosis were collected. RESULTS Between 2020 and 2022, 50 patients were treated with tucatinib. Forty patients had diagnosed brain metastasis and received intracranial RT. Median age at tucatinib start was 51 years (range: 33-83). All patients were HER-2+, 47.5% were HR+. Fifty-four separate RT courses were delivered within 6 months of tucatinib, including 45 courses of stereotactic RT (83%) and 9 (17%) WBRT. Twenty-three patients (57.5%) underwent concurrent tucatinib and intracranial RT, defined as RT within 2 months of tucatinib initiation. Median follow up for surviving patients was 18.9 months. Fifteen patients (37%) died at the time of analysis. Median OS was 25.1 months with 24-month KM OS of 52%. Median time to ICF was 12.5 months with 24-month KM ICF of 48%. At the time of ICF, 7 patients (17.5%) developed LMD. In total, 132 discrete lesions were treated with SRS. Ten lesions (7.5%) underwent local failure, with 24-month KM LC of 82%. Three patients (9.1%) undergoing SRS developed symptomatic radionecrosis; all completely resolved with dexamethasone. DISCUSSION In this first series reporting outcomes with RT and tucatinib, no evidence of excess toxicity was noted. Intracranial control appears favorable compared to previous reports. Concurrent RT with tucatinib should be assessed prospectively.

Risk of seizures in a population of women with BRCA-positive metastatic breast cancer from an electronic health record database in the United States

BackgroundIncidence and risk factors for seizures among women with advanced breast cancer (BC) and brain metastases are not well characterized across treatment-related or clinical subtypes. This study leveraged a large real-world dataset to describe incidence and risk factors for seizures in BRCA-associated metastatic breast cancer.MethodsThe Optum® de-identified electronic health records database was used. Females with a BC diagnoses between 2008 and 2018, with clinic visits 12 months before BC index date, evidence of BRCA mutation (BRCA+), evidence of metastasis, and no previous cancers were included. Analyses were stratified by the overall BRCA+ cohort and 4 molecular phenotypes: HER2+/HR- (human epidermal growth factor 2/hormone receptor), HER2−/HR+, HER2+/HR+, and triple negative BC (TNBC; HER2−/HR-). Seizures were identified using diagnosis codes and natural language processing. Incidence, occurrence rates, and cumulative incidence of seizures from the diagnosis of metastasis to the end of follow up were calculated. Comparisons were made between phenotypes and stratified on PARP inhibitor use, diagnosed brain metastases, history of seizures, and anticonvulsants use before BC. All comparisons included age at metastasis, number of prior lines of treatment, and metastasis location as covariates.Results27.8% of 7941 BRCA+ patients had ≥1 seizure over a mean follow-up time of 2.35 years. Incidence and occurrence rates were 11.83 (95% CI: 11.35–12.33) and 201.3 (95% CI: 198.05–204.50), respectively, per 100 person-years. HER2−/HR+ and TNBC patients had the lowest and highest seizure incidence rates, respectively (10.94 [95% CI: 10.23–11.71] and 16.83 [95% CI: 15.34–18.46]). With HER2−/HR+ as the reference group in a competing risk analysis, TNBC (hazard ratio, HR = 1.35; 95%CI: 1.21, 1.52; p < 0.001) and HER2+/HR- (HR = 1.29; 95%CI: 1.07, 1.56; p < 0.01) patients had a greater risk of seizures. Patients with diagnosed brain metastases or a history of seizures had higher seizure rates. Incidence trended higher with PARP inhibitor use, but patient numbers were low.ConclusionsThis study provides novel real-world evidence on seizure incidence rates in BRCA+ BC patients, even those without diagnosed brain metastases, and underscores the need to understand patients’ tumor phenotypes when assessing seizure risk. These findings may have implications for clinical practice and assessment of benefit-risk ratios of new therapeutic agents.

Iodine-125 brachytherapy treatment for newly diagnosed brain metastasis in non-small cell lung cancer: A biocentric analysis.

The aim of the present study is to evaluate the safety and efficacy of iodine-125 brachytherapy for newly diagnosed brain metastasis in patients with non-small cell lung cancer (NSCLC). The study included 158 NSCLC patients diagnosed with brain metastasis from December 2003 to August 2017. Ninety-nine patients underwent external beam radiotherapy (EBRT group), and 59 patients received iodine-125 brachytherapy (125I group). In addition, the 6- and 12-month progression-free survival (PFS) rates and the 12- and 24-month overall survival (OS) rates were compared between the EBRT group and the 125I group. Median OS and PFS were analyzed using the Kaplan-Meier method with a log-rank test. The 6-month PFS rate was significantly higher in the 125I group (p = 0.002) than in the EBRT group, while no differences were found in the 12-month PFS rate (p = 0.184). Additionally, the 12- (p = 0.839) and 24-month (p = 0.284) OS rates were not significantly different between the two groups. No significant differences in median OS (p = 0.525) or PFS (p = 0.425) were found between the two groups. Iodine-125 brachytherapy is an alternative therapy for patients unable to undergo surgical resection.

Risk of seizures in a population of women with BRCA-positive metastatic breast cancer in the United States.

e13056 Background: Real-world evidence on the risk of seizures in subgroups of women with advanced breast cancer (BC) across treatment-related or clinical subtypes is limited. A large electronic health record (EHR) dataset was used in this study to measure incidence and risk factors for seizures among women diagnosed with BRCA-associated metastatic BC (mBC). Methods: We used the Optum EHR database, which includes natural language processing (NLP) abstracted details from physicians’ notes, to identify a cohort of females with mBC (based on secondary malignancy ICD-9/-10 codes or NLP) diagnosed between 2008-2018 with 12 months of pre-index history, evidence of BRCA mutation positive (BRCA+) status, and no history of prior cancers. Analyses were stratified by the overall BRCA+ cohort and 4 molecular phenotypes: HER2+/HR-, HER2-/HR+, HER2+/HR+, and triple negative BC (TNBC). Incidence of seizures was measured using diagnosis codes and NLP, and incidence rates were calculated as the number of women with a seizure over the period from metastasis to first seizure or the end of follow up. Incidence rates were also measured across the following risk factors: PARP inhibitor use, diagnosed brain metastases, history of seizures, and anticonvulsant use before BC diagnosis, while controlling for age at metastasis, number of prior lines, and metastasis location. Results: Of the 7,941 BRCA+ patients identified, 27.8% had ≥1 seizure during mean follow-up of 2.35 years, with an incidence rate of 11.83 (95% CI: 11.35-12.33) per 100 person-years. The HER2-/HR+ and TNBC subgroups had the lowest and highest seizure incidence rates, respectively (10.94 [95% CI: 10.23-11.71] and 16.83 [95% CI: 15.34-18.46]). Kaplan-Meier analysis of time to seizure showed that HR- phenotype was associated with a longer time to first seizure. Patients with diagnosed brain metastases or a history of seizures had higher seizure incidence rates compared to patients without the respective risk factors (42.55 [95% CI: 28.59-63.30] vs 5.26 [4.20-6.59] and 34.76 [23.24-52.01] vs 6.35 [5.11-7.88]). Incidence trended higher with PARP inhibitor use, but patient numbers were low. Conclusions: Using both diagnosis codes and NLP, this study shows that seizures occur frequently in women with BRCA+ mBC, even those without diagnosed brain metastases. The seizure incidence rates by phenotype underscore their relevance when assessing seizure risk. These findings may have implications for clinical practice and for assessing benefit-risk ratios of novel agents.[Table: see text]

PO-1157 Comprehensive comparison of prognostic scores for patients with newly diagnosed brain metastases

PO-1157 Comprehensive comparison of prognostic scores for patients with newly diagnosed brain metastases

Characterization of plasma circulating small extracellular vesicles in patients with metastatic solid tumors and newly diagnosed brain metastasis

ABSTRACT Nearly 40% of the advanced cancer patients will present brain metastases during the course of their disease, with a 2-year life expectancy of less than 10%. Immune system impairment, including the modulation of both STAT3 and PD-L1, is one of the hallmarks of brain metastases. Liquid biopsy could offer several advantages in brain metastases management, such as the possibility of noninvasive dynamic monitoring. Extracellular vesicles (EVs) have been recently proposed as novel biomarkers especially useful in liquid biopsy due to their secretion in biofluids and their role in cell communication during tumor progression. The main aim of this work was to characterize the size and protein cargo of plasma circulating EVs in patients with solid tumors and their correlation with newly diagnosed brain metastases, in addition to their association with other relevant clinical variables. We analyzed circulating EVs in the plasma of 123 patients: 42 patients with brain metastases, 50 without brain metastases and 31 healthy controls. Patients with newly diagnosed brain metastases had a lower number of circulating EVs in the plasma and a higher protein concentration in small EVs (sEVs) compared to patients without brain metastases and healthy controls. Interestingly, melanoma patients with brain metastases presented decreased STAT3 activation and increased PD-L1 levels in circulating sEVs compared to patients without central nervous system metastases. Decreased STAT3 activation and increased PD-L1 in plasma circulating sEVs identify melanoma patients with brain metastasis.

Salvage Surgical Resection after Linac-Based Stereotactic Radiosurgery for Newly Diagnosed Brain Metastasis.

Background: This study aimed to assess the clinical outcomes of salvage surgical resection (SSR) after stereotactic radiosurgery and fractionated stereotactic radiotherapy (SRS/fSRT) for newly diagnosed brain metastasis. Methods: Between November 2009 and May 2020, 318 consecutive patients with 1114 brain metastases were treated with SRS/fSRT for newly diagnosed brain metastasis at our hospital. During this study period, 21 of 318 patients (6.6%) and 21 of 1114 brain metastases (1.9%) went on to receive SSR after SRS/fSRT. Three patients underwent multiple surgical resections. Twenty-one consecutive patients underwent twenty-four SSRs. Results: The median time from initial SRS/fSRT to SSR was 14 months (range: 2–96 months). The median follow-up after SSR was 17 months (range: 2–78 months). The range of tumor volume at initial SRS/fSRT was 0.12–21.46 cm3 (median: 1.02 cm3). Histopathological diagnosis after SSR was recurrence in 15 cases, and radiation necrosis (RN) or cyst formation in 6 cases. The time from SRS/fSRT to SSR was shorter in the recurrence than in the RNs and cyst formation, but these differences did not reach statistical significance (p = 0.067). The median survival time from SSR and from initial SRS/fSRT was 17 and 74 months, respectively. The cases with recurrence had a shorter survival time from initial SRS/fSRT than those without recurrence (p = 0.061). Conclusions: The patients treated with SRS/fSRT for brain metastasis need long-term follow-up. SSR is a safe and effective treatment for the recurrence, RN, and cyst formation after SRS/fSRT for brain metastasis.

MET-5 Salvage surgical resection after linac-based stereotactic radiosurgery and radiotherapy for brain metastasis

Methods: Between November 2009 and December 2018, 335 consecutive patients with 1085 brain metastases were treated with SRS/fSRT for newly diagnosed brain metastasis at our hospital. Nineteen of 335 patients (5.6%) and 19 of 1044 brain metastases (1.8%) went on to receive SSR after SRS/fSRT during this study period. Two patients underwent multiple surgical resections. Nineteen consecutive patients underwent 21 SSRs. Results: The median time from initial SRS/fSRT to SSR was 14 months (range: 2–96 months). The median follow-up after SSR was 15 months (range: 2–76 months). The range of tumor volume at initial SRS/fSRT was 0.12–21.46 cm3 (median: 2.19 cm3). Histopathological diagnosis after SSR was recurrence, radiation necrosis (RN) and cyst formation in 13 and 6 cases, respectively. The time from SRS/fSRT to SSR were shorter in the recurrence than in the RNs and cyst formation, but these differences did not reach statistical significance (p = 0.07). The median survival time from SSR and from initial SRS/fSRT was 17 months and 74 months, respectively. The cases with recurrence had a significantly shorter survival time from initial SRS/fSRT than those without recurrence (p=0.045).Conclusion: The patients treated with SRS/fSRT for brain metastasis need long-term follow-up. SSR is a safe and effective treatment for the recurrence, RN, and cyst formation after SRS/fSRT for brain metastasis.

Estimating population-based incidence of brain metastases – a comprehensive incident cohort study

Abstract Aims Brain metastases are the most common intracranial tumour and affect approximately 20% of adult cancer patients, most commonly from lung, breast, melanoma, and kidney cancer. However, the true incidence of brain metastasis is unknown. England’s cancer registration system only reliably captures brain metastases present at diagnosis (rather than those that develop later), and the same is true for US-based data. Although it is relatively easy to identify patients receiving some treatments for brain metastases (surgery, stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT)), identifying those receiving chemotherapy or no treatment is much harder. As a result, the existing literature is heavily biased towards reporting treated populations. This study attempts to find an unbiased estimate of the true number of patients developing brain metastases, based on data from a single centre. Method Cases of brain metastasis were retrospectively identified from the radiology information system database (SolitonTM). We performed a Boolean search for specific keywords in the radiology reports of all CT and MRI head scans performed at the trust between 1st January 2018 and 31st December 2019. The following keywords were searched for “metastases”, “metastatic“, “metastasis”, “mets”, “deposit”, “deposits”, “secondaries”, “secondary” and “disseminated”. Duplicate cases were then removed and the subsequent list was manually reviewed We identified all patients who received any treatment for brain metastases who were diagnosed at our centre. We only included patients with newly diagnosed brain metastases (included: leptomeningeal; excluded: skull-based metastases). We excluded patients who were diagnosed in other centres and treated here or diagnosed outside the study period. We then extracted data on primary diagnosis, admissions, and survival. Results 1192 patients had a CT or MRI of the head with a mention of “brain metastases” in the report; of these 305 were newly diagnosed with brain metastases during the study period (432 had metastases; 127 diagnosed earlier). Of these 305 patients, 217 (71.1%) were treated locally (SRS = 88; WBRT = 74; surgery = 88; systemic therapy = 16; multiple treatments = 45) and 10 (3.3%) were referred elsewhere. 78 (25.6%) patients received no treatment. Of the 217 treated patients, 124 were female, and the median age was 61. Of the 78 untreated patients, 38 were females, and the median age was 70 years old. The commonest primary diagnoses in both groups were lung (39%) and breast (21%) cancer. 16 (21%) of the untreated patients had an unbiopsied primary tumour. Median survival for patients having (any) treatment was 52 weeks compared to 5 weeks for those not having treatment. Conclusion We have presented an unbiased single-centre estimate of brain metastases occurrence. Unlike previous work, we manually reviewed all imaging reports that suggested metastasis, and included all patients diagnosed with brain metastases at any timepoint. We reduced the bias associated with being a tertiary centre by only including patients who were diagnosed here, rather than referred from other centres. 25% of our cohort received no treatment, and survival in this group is poor. This is broadly in line with the only other study on this topic (Bentley, 2019) that reported a large minority (39%) of untreated patients. Our key conclusions are: When assessing the incidence of brain metastases, studies that do not account for untreated patients are likely to significantly underestimate incidence, and over-estimate survival. Improving outcomes in patients with brain metastases might be best achieved by addressing earlier identification and intervention in those who currently receive no treatment

Resection and Surgically Targeted Radiation Therapy for the Treatment of Larger Recurrent or Newly Diagnosed Brain Metastasis: Results From a Prospective Trial.

IntroductionAchieving durable local control (LC) for larger (e.g., >2-3 cm) brain metastasis whether newly diagnosed or recurrent remains problematic. Resection (R) alone is typically insufficient and adding radiation therapy (RT) still results in a 12-month recurrence rate of 20% or more in many series. Hypothesizing that R plus immediate radiation utilizing brachytherapy may improve outcomes for this cohort of patients, we designed and prospectively evaluated a permanently implanted surgically targeted radiation therapy (STaRT) device consisting of cesium-131 (Cs-131) seeds positioned within a collagen carrier (GammaTile, GT Medical Technologies, Tempe, AZ). The device was designed to prevent direct source-to-brain contact and maintain inter-source spacing after closure.MethodsThis was a subgroup analysis of a cohort of patients with either recurrent or previously untreated brain metastases enrolled in a prospective, multi-histology single-arm trial (ClinicalTrials.gov, NCT#03088579), conducted between February 2013 and February 2018, of resection and tumor bed brachytherapy with Cs-131 containing permanently implanted collagen tiles to deliver 60 Gray (Gy) at .5 cm depth. No additional local therapy was given without progression.ResultsA total of 16 metastases in 11 patients were treated; 12 tumors were recurrent and four were previously untreated. The median preoperative maximum diameter was 3.2 cm (range: 1.9-5.1 cm). Histology was seven breasts, six lungs, and three sarcomas. The median age was 60 years (range: 41-80 years); the Karnofsky Performance Status (KPS) was 70 (range: 70-90). The cohort consisted of seven females and four males. The mean time for implantation completion was five minutes. The median overall survival (OS) was 9.3 months. At a median radiographic follow-up of 9.5 months' treatment, site progression was found in 1/16 (6%) at 10.9 months, and the median treatment site time-to-progression (TTP) has not been reached [95% confidence interval (CI): >10.9 months]. At 12 months, the Kaplan-Meier (K-M) estimates for LC after R+STaRT for all tumors was 83%; for previously untreated tumors, LC at 12 months was 100% and for recurrent tumors, it was 80%. Two tumor beds (12.5%) experienced radiation brain changes: one had grade two and the other grade three. No surgical adverse events occurred.ConclusionIn this single-arm precommercial study, R+STaRT demonstrated excellent safety and LC in this cohort. The device has recently received FDA clearance for use in newly diagnosed and recurrent brain metastasis, and randomized clinical trials vs. standard of care treatments in both settings are scheduled to open in 2020.

Retrospective analysis of salvage surgery for local progression of brain metastasis previously treated with stereotactic irradiation: diagnostic contribution, functional outcome, and prognostic factors

BackgroundStereotactic irradiation (STI) is a primary treatment for patients with newly diagnosed brain metastases. Some of these patients experience local progression, which is difficult to differentiate from radiation necrosis, and difficult to treat. So far, just a few studies have clarified the prognosis and effectiveness of salvage surgery after STI. We evaluated the diagnostic value and improvement of functional outcomes after salvage surgery. Based on these results, we reconsidered surgical indication for patients with local progression after STI.MethodsWe evaluated patients with brain metastases treated with salvage surgery for local progression from October 2002 to July 2019. These patients had undergone salvage surgery based on magnetic resonance imaging findings and/or clinical evidence of post-STI local progression and stable systemic disease. We employed two prospective strategies according to the eloquency of the lesions. Lesions in non-eloquent areas had been resected completely with a safety margin, utilizing a fence-post method; while lesions in eloquent areas had been treated with minimal resection and postoperative STI. Kaplan-Meier curves were used for the assessment of overall survival. Prognostic factors for survival were analyzed.ResultsFifty-four salvage surgeries had been performed on 48 patients. The median age of patients was 63.5 years (range 36–79). The median interval from STI to surgery was 12 months. The median overall survival was 20.2 months from salvage surgery and 37.5 months from initial STI. Primary cancers were lung 31, breast 9, and others 8. Local recurrence developed in 13 of 54 lesions (24%). Leptomeningeal dissemination occurred after surgery in 3 patients (5.6%). Primary breast cancer (breast vs. lung: HR: 0.17), (breast vs. others: HR: 0.08) and RPA class 1–2 (RPA 1 vs. 3, HR:0.13), (RPA 2 vs 3, HR:0.4) were identified as good prognostic factors for overall survival (OS) in multivariate analyses. The peripheral neutrophil-to-lymphocyte ratio (NLR) of ≤3.65 predicted significantly longer OS (median 25.5 months) than an NLR > 3.65 (median 8 months).ConclusionWe insist that salvage surgery leads to rapid improvement of neurological function and clarity of histological diagnosis. Salvage surgery is recommended for large lesions especially with surrounding edema either in eloquent or non-eloquent areas.

CMET-06. AN ANALYSIS OF RESPONSE ENDPOINTS FOR BRAIN METASTASIS PATIENTS TREATED WITH STEREOTACTIC RADIOSURGERY AND PD(L)-1 INHIBITORS

Abstract PURPOSE Recent trials have evaluated the role of anti-PD(L)-1 inhibitors alone in patients with newly diagnosed brain metastasis, resulting in a suggested paradigm shift. In the absence of randomized comparisons, an evaluation of outcomes for similar patients treated with radiotherapy are needed to provide baseline comparative data. METHODS This retrospective cohort study included patients diagnosed with brain metastasis from 2010–2017 at a single tertiary care institution who received SRS and at least one anti-PD(L)-1 inhibitor. Primary endpoints included the rate of best intracranial response (either a complete [CR] or partial response [PR]), rate of intracranial benefit (percentage of patients with stable disease [SD] for at least 6 months), and overall objective response rates. RESULTS 150 patients met the eligibility criteria for this study and the median follow-up time was 10 months (Range: 1–130 months). Only a minority of patients from this cohort would have been eligible for comparative systemic therapy alone trials: 8 (CheckMate 204, CM), 8 (ABC), and 50 patients (Yale Institutional trial, YI). Best intracranial objective response rates for these trial eligible patients were 64% (CM), 64% (ABC), and 72% (YI), respectively. The 6-month rates of intracranial benefit across patients were 75% (CM), 75% (ABC), and 93% (YI), respectively. The rates of either a CR, PR, or SD across trial eligible patients were 100% (CM), 100% (ABC), and 94% (YI), respectively. More than 50% of patients experienced out-of-field progression in each of the patient subgroups. CONCLUSIONS Over a seven year period, very few patients treated with SRS and anti-PD(L)-1 inhibitor therapy in a busy academic practice would have been eligible for systemic therapy alone per trial eligibility criteria. In these highly favorable subgroups, patients experience high rates of objective response, best intracranial response, and intracranial benefit after SRS and anti-PD(L)-1 therapy, representing optimal brain metastasis management.

Correlation of Magnetic Resonance Spectroscopy Changes in Hippocampal and Perihippocampal Regions and Neuro-Psychologic Evaluation with Various Clinical Factors Following Whole Brain Radiotherapy in Brain Metastasis

Objectives: To study the correlation of magnetic resonance spectroscopy (MRS) changes in hippocampal and perihippocampal regions and neuro-psychologic evaluation with various clinical factors following whole brain radiotherapy in brain metastasis. Methods: A total of 33 patients with newly diagnosed brain metastasis, referred to our Department of Radiation Oncology were recruited after a prior informed written consent. All patients underwent baseline clinical/neurological evaluation, detailed MMSE examination, gadolinium enhanced MRI along with MRS (for ratio of Choline: NAA = CNI) from the bilateral hippocampal and perihippocampal areas. All patients then underwent WBRT by two opposing lateral portals on a linear accelerator to a dose of 30 gray in 10 fractions delivered over 2 weeks. Serial evaluations along with MRS and MMSE score were done at 1st, 3rd and 6 months after WBRT. The trends of CNI and MMSE scores at last follow-up were correlated with various clinical factors. Results: Our cohort had 33 patients, predominantly women (M:F, 12:21) with a median age of 47 years, median KPS (Karnofsky performance status) of 80, mean RPA (recursive partitioning analysis) class 2, primary histology (lung, breast, GI, Gy, GU, MUO (metastasis of unknown origin): 10, 11, 2, 4, 4, 2). Median survival of the cohort was 4 months. At the end of 14 months of follow-up 30% of the patients were alive with a mean KPS of 70. Trend in the CNI values with time showed that, KPS (P = 0.079), RPA class (P = 0.079), primary diagnosis site (P = 0.049), number of brain metastasis (P = 0.045) showed statistical significance in terms of change in mean value of CNI value at last follow-up. Site of primary (lung/breast vs. others, P = 0.02) and number of metastasis (solitary/oligo vs. multiple, P = 0.02) showed significant correlation with decline in CNI. The KPS at presentation (< 70 or > 70, P = 0.04); RPA class (class II or higher, P = 0.04); Site of primary (lung/breast vs. others, P = 0.01), presence of extracranial disease (yes or no, P = 0.045), number of metastasis (solitary/oligo vs. multiple, P = 0.06), Size of the largest metastatic lesion (< or > 4 cm, P = 0.02) showed significant correlation with decline in MMSE at last follow-up. Conclusions: Cognitive functioning after WBRT is influenced by a number of factors; patient related, systemic disease burden and local tumor load. Local disease control has significant impact on preservation of neurocognition. The trend in the CNI index and MMSE scores at last follow-up correlated with various factors and can be used as a guide to aid in patient selection for hippocampus- avoidance WBRT.

RADI-35. AN ANALYSIS OF RESPONSE ENDPOINTS FOR BRAIN METASTASIS PATIENTS TREATED WITH STEREOTACTIC RADIOSURGERY AND PD(L)-1 INHIBITORS

PURPOSE: Recent trials have evaluated the role of anti-PD(L)-1 inhibitors alone in patients with newly diagnosed brain metastasis, resulting in a suggested paradigm shift. In the absence of randomized comparisons, an evaluation of outcomes for similar patients treated with radiotherapy are needed to provide baseline comparative data. METHODS: This retrospective cohort study included patients diagnosed with brain metastasis from 2010–2017 at a single tertiary care institution who received SRS and at least one anti-PD(L)-1 inhibitor. Primary endpoints included the rate of best intracranial response (either a complete [CR] or partial response [PR]), rate of intracranial benefit (percentage of patients with stable disease [SD] for at least 6 months), and overall objective response rates. RESULTS: 150 patients met the eligibility criteria for this study and the median follow-up time was 10 months (Range: 1–130 months). Only a minority of patients from this cohort would have been eligible for comparative systemic therapy alone trials: 8 (CheckMate 204, CM), 8 (ABC), and 50 patients (Yale Institutional trial, YI). Best intracranial objective response rates for these trial eligible patients were 64% (CM), 64% (ABC), and 72% (YI), respectively. The 6-month rates of intracranial benefit across patients were 75% (CM), 75% (ABC), and 93% (YI), respectively. The rates of either a CR, PR, or SD across trial eligible patients were 100% (CM), 100% (ABC), and 94% (YI), respectively. More than 50% of patients experienced out-of-field progression in each of the patient subgroups. CONCLUSIONS: Over a seven year period, very few patients treated with SRS and anti-PD(L)-1 inhibitor therapy in a busy academic practice would have been eligible for systemic therapy alone per trial eligibility criteria. In these highly favorable subgroups, patients experience high rates of objective response, best intracranial response, and intracranial benefit after SRS and anti-PD(L)-1 therapy, representing optimal brain metastasis management.