Prevalence Of Brain Metastases Research Articles

Clinical and molecular features and survival in thyroid cancer with brain metastases.

2023 Background: Brain metastases (BM) in advanced thyroid cancer are rare; however, they may be underreported as staging brain imaging is not routine. Prognostic features and molecular alterations for this group are poorly described. We characterized the clinical and molecular features of thyroid cancer with BM and evaluated differences in survival. Methods: In this single-center retrospective analysis, patients with metastatic radioactive iodine refractory well-differentiated, poorly-differentiated, or medullary thyroid carcinoma seen at the Princess Margaret Cancer Center from 2007-2022 were included. Electronic medical records were reviewed to collect clinicopathologic and treatment data. All patients had tumor next-generation sequencing (NGS) by a targeted gene panel. Overall survival (OS) from initial medical oncology consultation was analyzed using the Kaplan-Meier method and univariate and multivariate Cox proportional hazards models. Results: Of 248 patients with advanced thyroid cancer, 41(17%) were diagnosed with BM. The median interval from thyroid cancer diagnosis to BM development was 6.49 years (y) (IQR 3.51- 14.35 y). The median age at the time of BM diagnosis was 63.6 y and 23 (56%) were male. Most (76%) were asymptomatic at the diagnosis of BM and 80% had an ECOG of 0-1. Among patients with well-differentiated histology, 27 (18%) developed BM, while 7 (12%) with poorly-differentiated and 7 (19%) with medullary thyroid cancer developed BM. The most common molecular alterations included BRAFV600E (n=19), TERT (n=11), RAS (n=9), RET (n=8), and FANCA (n=3). Patients were treated with surgery (n=5), stereotactic radiation (n=21), whole brain radiation therapy (n=12), or a combination of both (n=2). OS was similar in patients with BM compared to those without (6.05 vs 6.45 y). There were no differences in histology or molecular alterations between patients that developed BM compared to those who did not. The median survival from the time of BM was 3.23 y. Patients with BM with ≥4 lesions had worse survival (0.52 vs 5.09 y, p=0.01). There were no differences in survival based on histology, symptoms, treatment or molecular alterations among those with BM. Conclusions: This is one of the largest reported thyroid BM cohorts and the first with complete NGS. The prevalence of BM in our cohort was higher than previously described, often diagnosed incidentally. Screening for BM in advanced thyroid cancer may detect higher rates, offering prognostic insights. While the number of BM was predictive of survival, molecular alterations did not predict BM development or survival and larger studies are needed.

Abstract PO2-05-05: ELECTRA: An open-label, multicenter, phase 1b/2 study of elacestrant in combination with abemaciclib in patients with brain metastasis (mets) from estrogen receptor-positive (ER+), HER2-negative (HER2-) breast cancer (BC)

Abstract Background: Currently, there are no approved systemic treatment options specifically for patients with ER+/HER2- BC who have brain metastasis. The prevalence of brain metastases from ER+/HER2- BC is approximately 14% of women (Aversa, 2014). Elacestrant is a next-generation oral SERD that was evaluated in a pivotal phase 3 trial, EMERALD, as monotherapy vs. standard of care (SOC) endocrine therapy. The EMERALD trial reported significantly prolonged progression-free survival (PFS) with elacestrant vs SOC endocrine therapy in patients with ER+/HER2− ESR1 mutated (ESR1-mut) mBC following progression on prior endocrine therapy (Bidard, 2022). Elacestrant was well tolerated with a manageable safety profile. Most adverse events, including nausea, were low-grade and consistent with other endocrine therapies. A clinical study in healthy postmenopausal women demonstrated the ability of elacestrant to cross the blood-brain barrier (Conlan, 2020). Abemaciclib, a CDK4/6i, has been shown to achieve therapeutic concentrations in brain metastases tissue (Tolaney, 2020). Given the lack of current systemic treatments, elacestrant is now being evaluated with abemaciclib in patients with ER+/HER2- BC and brain metastasis (NCT05386108). Methods: ELECTRA (NCT05386108) is an open-label phase 1b/2, multicenter study evaluating elacestrant in combination with abemaciclib in patients with brain metastasis from ER+, HER2- BC. Eligibility are patients with ER+/HER2− locally advanced or mBC and measurable brain metastasis. For phase 1b, the presence of brain metastases is allowed but not required for eligibility. For phase 2, patients must have ≥ 1 active and measurable brain metastasis per RECIST v1.1. Patients must have received prior therapy in the metastatic setting, including ≥ 1 ET, ≤2 chemotherapy regimens, and 0-2 prior CDK4/6i (excluding abemaciclib). The primary objectives of Phase 1b are to determine the recommended Phase 2 dose (RP2D). Phase 1b secondary objectives include safety, PK, objective response rate (ORR), duration of response (DoR), clinical benefit rate (CBR), PFS, and overall survival (OS). Phase 2 primary objective is ORR per RECIST version 1.1. Phase 2 secondary objectives include intracranial response rate (RR), DoR, CBR, PFS, OS, PK, and quality of life (QoL). The phase 1b portion evaluated dose-limiting toxicities (DLTs) of the combination during the first cycle (28 days) of treatment in up to three 6-patient cohorts, starting at elacestrant 300 mg daily plus abemaciclib 100 mg twice daily. Here we report initial safety results from the phase 1b portion. Results: As of June 2023, 15 patients have been enrolled in the phase 1b portion of the trial. At dose level 1, elacestrant 300 mg QD + abemaciclib 100 mg BID, no patient experienced DLTs, and the combination was feasible. Dose level 2, elacestrant 400 mg QD + abemaciclib 100 mg BID has been completed, and no patients experienced DLTs. In dose level 1, 4/7 patients remain on treatment at cycle 5. Additional safety and PK data for the cohorts will be provided. Conclusion: In the phase 1b portion of ELECTRA, dose level 1 and dose level 2 have been completed. No patients experienced DLTs in either dose level 1 or dose level 2, and the combination was considered feasible in the respective dose levels. Dose level 3 (elacestrant 400 mg QD + abemaciclib 150 mg BID) is proceeding. Recruitment is actively ongoing, enabling oral-oral combinations to determine a RP2D. Citation Format: Nuhad Ibrahim, Sung-Bae Kim, Nancy Lin, Ahmad Awada, Eva Ciruelos Gil, Giulia Tonini, Bartomeu Piza Vallespir, Kathy Puvana Theall, Erika Hamilton. ELECTRA: An open-label, multicenter, phase 1b/2 study of elacestrant in combination with abemaciclib in patients with brain metastasis (mets) from estrogen receptor-positive (ER+), HER2-negative (HER2-) breast cancer (BC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-05-05.

Abstract A081: Real-world treatment patterns and clinical outcomes in patients with HER2+ metastatic breast cancer receiving systemic therapy in Ontario, Canada

Abstract Background: Real-world data on treatment patterns and prevalence of brain metastases in patients with HER2+ metastatic breast cancer (mBC) are limited. This study described treatment patterns and clinical outcomes among patients with HER2+ mBC in Canada. Methods: This was a retrospective chart review of adult patients diagnosed with de-novo or recurrent HER2+ mBC between Jan 1, 2014 and Mar 1, 2021 (prior to wide availability of new treatments) at Sunnybrook Research Institute and Sinai Health, two large BC treatment centres in Canada. Data on patient characteristics and treatment regimens were extracted. Treatment patterns, time to next treatment (TTNT; as a proxy for progression-free survival), and presence of brain metastases were assessed in the first-line (1L), second-line (2L), and third-line (3L) settings. TTNT analyses used Kaplan-Meier methodology to account for censoring. Results: Of 121 patients with HER2+ mBC, the median (IQR) age was 54.0 (17.0) years. 38.0% of patients had de-novo disease and 62.0% had recurrent mBC; 12 (9.9%) had brain metastases at the time of mBC diagnosis. Systemic therapies generally aligned with Canadian funded regimens for 1L (101 of 121 patients [83.5%] received trastuzumab + pertuzumab ± chemotherapy ± subsequent endocrine therapy; 8/121 [6.6%] received endocrine therapy only) and 2L (50/68 [73.5%] received T-DM1 ± endocrine therapy; 9/68 [13.2%] received endocrine therapy only). However, treatment patterns were heterogeneous in the 3L setting (14/46 [30.4%] received anti-HER2 TKI + chemotherapy ± trastuzumab; 10/46 [21.7%] received endocrine therapy only; 10/46 [21.7%] received chemotherapy). Median (95% CI) TTNT in months was 21.4 (16.1, 27.2) in 1L, 11.0 (8.5, 16.5) in 2L, and 8.7 (5.4, 15.6) in 3L. Median (IQR) follow-up was 29.9 (25.2) months. In total, 57 patients (47.1%) were diagnosed with brain metastases during the study period (17 pre-1L, 24 post-1L/pre-2L, 6 post-2L/pre-3L) and of these, 73.7% received radiation therapy. Conclusions: In patients with HER2+ mBC in Canada, 3L treatment patterns are heterogeneous, median TTNT is <1 year, and almost half develop brain metastases. These data from two large treating centres in Ontario suggest a high unmet need for more effective treatment regimens in later lines of therapy, particularly 3L, for patients with HER2+ mBC. Citation Format: Katarzyna J Jerzak, Ruth Moulson, Ling-I Hsu, Chris Lenhu, Dhivo Krishnathasan, Jessica Weiss, Christine Brezden-Masley. Real-world treatment patterns and clinical outcomes in patients with HER2+ metastatic breast cancer receiving systemic therapy in Ontario, Canada [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A081.

Multi-cancer brain metastasis risk score development and validation using 220,246 whole transcriptomes and machine learning.

2039 Background: Brain metastases occur in multiple cancer types with higher prevalence in lung, breast, melanoma, and GI cancers. The prognoses of patients who develop brain metastases are very poor and identification of brain metastasis risk could be useful for prognostication, monitoring, and therapy selection. Methods: Data from the whole transcriptome of 220,246 tumor profiles were analyzed and multiple machine learning models were trained on various molecular subtypes. The dataset was split 50% for training and the other 50% for testing, UMAP was employed for dimensionality reduction and the patterns learned across the entirety of the training dataset irrespective of brain metastasis were leveraged on the testing data set. Patients with brain metastasis were identified using the presence of ICD-10 code C79.31 (Secondary malignant neoplasm of the brain). As the absence of C79.31 could be due to the event not happening yet, patients without brain metastasis were stratified into groups based on 3, 4 or greater than 5 years without a C79.31 ICD-10 code. The brain metastasis risk score was defined by empirical evaluation of the positive predictive value in 7 groups of risk probabilities. The validation set contained 1,217 patients with brain metastasis and 4,631 without an observed brain metastasis within 3 years. Results: In the validation set, the prevalence of brain metastases within the risk scores across all cancer types ranged from 4% with the lowest risk score to 94% in the highest with 71% of cases receiving the lowest 2 risk scores, 15% the 2 intermediate risk scores, and 14% the 3 highest risk scores. For breast, lung and colon cancers, the prevalence of brain metastasis ranged from 4-10% in patients with the lowest risk scores to 92-100% in patients with the highest however the distribution of cases with each risk score was markedly different across cancer type. Breast cancer had 62% of cases receiving the lowest 2 risk scores versus 27% in lung, and 92% in colon. Breast cancer had 18% of cases receiving the 3 highest risk scores while lung had 42% and colon only 2% of cases with those 3 highest scores. Conclusions: Whole transcriptome data can be leveraged by a machine learning platform that employs dimensionality reduction techniques along with transfer learning to predict the risk of brain metastasis. This tool can be used to augment the clinical picture of cancer patients an unmet clinical opportunity to inform prognosis, monitoring, and therapeutic selection.

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.

Incidence and clinical profile of brain metastasis treated with whole brain radiotherapy in a tertiary hospital in eastern India: A retrospective audit.

Management of brain metastases (BM) is witnessing marked advancement worldwide and modern technologies with better outcomes are gradually being adopted in developing countries. However, data regarding current practice in this field is lacking from the Indian subcontinent prompting us to plan the current study. A retrospective, single institutional audit was performed on 112 patients with solid tumors metastasizing to the brain treated over the last 4 years at a tertiary care center in eastern India, of which 79 were ultimately evaluable. Demography, patterns of incidence, and overall survival (OS) were determined. The prevalence of BM was 5.65% among all patients with solid tumors. The median age was 55 years with a slight male preponderance. Lung followed by breast were the most common primary subsites. Multiple BM (54%), left-sided (61%), and frontal lobe lesions (54%) were the more common. Metachronous BM was found in 76% of patients. All patients received whole brain radiation therapy (WBRT). The median OS for the entire cohort was 7 months (95% confidence interval [CI]: 4 - 19 months). The median OS for lung and breast primaries were 6.5 and 8 months and for recursive partitioning analysis (RPA) classes I, II, and III the OS were 11.5, 7, and 3 months, respectively. Median OS did not differ by number of or other sites of metastases. The outcomes from our series about BM from solid tumors in patients from eastern Indian are in congruence to those available in the literature. Patients with BM are still largely treated with WBRT in resource-limited settings.

Pattern of failure in inoperable stage III non-small cell lung cancer patients treated with chemoradiotherapy with/without immune checkpoint inhibition.

e20570 Background: We compared pattern of failure in patients treated with chemoradiotherapy (CRT) with concurrent and/or sequential Programmed Cell Death 1 (PD-1) or Ligand 1 (PD-L1) immune checkpoint inhibition (IO, immuno-oncology therapy) and CRT alone for inoperable stage III NSCLC. Methods: Prospective data of thirty nine consecutive patients who completed CRT-IO with sequential durvalumab (72%, 28 patients) or concurrent and sequential nivolumab (28%, 11 patients) and a sensitive propensity score matched (PSM adjusted for patients age, gender, T- and N-status, PTV, histology) cohort of 39 patients treated with CRT alone were analyzed. First site of failure was compared between the CRT-IO and the CRT alone subgroup. Results: All patients were treated with conventionally fractionated thoracic irradiation to a total dose of at least 60Gy (range: 60-66Gy), all patients received either sequential or simultaneous chemotherapy while 95% (74 patients; CRT-IO: 38/39; CRT alone: 36/39) received two cycles of concurrent platinum-based chemotherapy. Median follow-up for the entire cohort was 33.3 (range: 1.5-102.9) months; median overall survival (OS) was 34.9 (95%CI: 10.7-59.1) months (CRT-IO: not reached; CRT alone: 24.4, p = 0.003); median progression-free survival (PFS) was 13.6 (95% CI: 10.5-6.7) months (CRT-IO: 26.3; CRT alone: 8.3; p &lt; 0.001). At the time of evaluation 21 (53.8%) vs. 7 (17.9%) patients of the CRT-IO vs. CRT alone subgroup were progression free and alive (p = 0.003); 4 (10.3%) vs. 3 (7.7%) had brain metastases as first site of failure; 7 (17.9%) vs. 6 (15.4%) had ≤ 3 extracranial metastasis and 3 (7.7%) vs. 4 (10.3%) had multi-organ progression. Local-regional recurrence (LRR) as first site of failure was significantly less frequent in patients treated with CRT-IO vs. CRT alone, namely 3 (7.7%) vs. 12 (30.8%) patients (p = 0.001); median time to LRR was not reached vs. 15.0 (95%CI: 0.9-33.7) months. Conclusions: Pattern of failure differ significantly in patients treated with CRT-IO vs. CRT alone; CRT-IO patients are significantly less likely to develop a LRR. No differences in the prevalence of brain metastases as first site of failure could be detected.

Cardiac Angiosarcomas: Risk of Brain Metastasis and Hemorrhage Warrants Frequent Surveillance Imaging and Early Intervention.

We evaluated a cohort of patients with cardiac angiosarcomas (CA) who developed brain metastases (BM) to define outcomes and intracranial hemorrhage (IH) risk. We reviewed 26 consecutive patients with BM treated between 1988 and 2020 identified from a departmental CA (n=103) database. Causes of death were recorded, and a terminal hemorrhage (TH) was defined as an IH that caused death or prompted a transfer to hospice. The prevalence of BM was 25% (n=26/103). A total of 23 patients (88%) had IH, including 21 (81%) at initial BM diagnosis, of which 18 (86%) required hospitalization. The median platelet count at the time of IH was 235k (interquartile range, 108 to 338k).Nearly all patients died of disease (n=23, 88%) and most patients died from TH (n=13, 57%). TH occurred at BM presentation in 6 (46%) patients, whereas 3 (23%) had TH from known but untreated lesions, 2 (15%) had continued uncontrolled IH during radiation therapy, and 2 (15%) from new BM. Platelet count <50k was not associated with TH (P=0.25).Subsequent IH occurred in 9 patients (35%), and importantly, no patients who completed radiation therapy (n=10) for BM died from TH. Patients with CA frequently develop BM, and the risk of IH is high, resulting in an alarming rate of TH despite normal platelet counts. Therefore, early diagnosis and intervention are warranted. We recommend surveillance brain imaging, and importantly, once BM is detected, prompt local therapy is warranted to try and mitigate the risk of TH.

Advanced Non-Small-Cell Lung Cancer (NSCLC) Patients Treated at Phramongkutklao Hospital between 2011 and 2018: Comparison between Those With and Without Brain Metastases

Background: Brain metastases (BM) remain a significant problem in NSCLC patients. The reports of factors associated with BM are varied in previous studies including age, histology subtypes, and oncogenic driver alterations. Objective: To determine the prevalence and factors associated with BM in advanced NSCLC patients and to analyze the median overall survival (OS) of the patients that had BM at the time of diagnosis of NSCLC and during the course of the disease. Materials and Methods: The medical records of 552 advanced NSCLC patients between 2011 and 2018 were reviewed. The prevalence of BM was calculated by descriptive statistics. Factors associated with BM were analyzed by using univariate and multivariate analyses. Kaplan-Meier methods were used to analyze the median OS of NSCLC patients with BM. Results: Between January 2011 and December 2018, of the 552 patients newly diagnosed with advanced NSCLC, there were 164 patients who had BM. The prevalence of BM was 29.7%. In multivariate analysis, younger age (adjusted odd ratio [OR] 1.547, 95% confidence interval [CI] 1.049 to 2.280), and adenocarcinoma subtype (adjusted OR 2.529, 95% CI 1.262 to 5.067) were significantly associated with BM. The median OS of patients who had BM at time of advanced NSCLC diagnosis was 7.5 months (95% CI 6.4 to 8.5) and the median OS of patients who had BM during the course of disease was 14.4 months (95% CI 12.2 to 16.5). Conclusion: One-third of the advanced NSCLC patients developed BM. Younger age and adenocarcinoma subtype were associated with BM. Patients who had BM during the course of diseases had better survival outcomes compared to those who had BM at the time of advanced NSCLC diagnosis. Keywords: Advanced NSCLC; Brain metastases

High Terminal Hemorrhage Risk From Cardiac Angiosarcoma Brain Metastases Warrants Frequent Brain Imaging and Early Intervention

<h3>Purpose/Objective(s)</h3> Cardiac angiosarcomas (CA) often develop early distant disease with risk of brain metastases (BM) and have recognized hemorrhagic risk. However, limited data exists characterizing this presentation. Therefore, we evaluated a cohort of patients with CA who developed BM to better define outcomes and intracranial hemorrhage (IH) risk. <h3>Materials/Methods</h3> We reviewed 26 consecutive patients with BM treated between 1988 and 2020 identified from a departmental CA (n = 103) database. Institutional practice has shifted over the decades to include a CT head at diagnosis but with infrequent serial imaging. Causes of death were recorded, and a terminal hemorrhage (TH) was defined as an IH that caused death during hospitalization or prompted transfer to hospice. <h3>Results</h3> The prevalence of BM was 25% (n = 26/103) among patients with CA at a median age of 37 years (IQR 26-50). All primary tumors involved the right heart (atrium: n = 20, 77%), and 20 patients (77%) presented with metastases at initial diagnosis, of which only 4 had BM. The median time between initial CA diagnosis to BM was 11 m (IQR 3-18) resulting in a 6-m BM free survival of 65%. There was a median of 3 lesions (IQR 1-7), and a majority had 1-4 (n = 15, 58%). The median follow-up from the time of BM was short at 2 m (IQR 1-6.5) due to a high rate of TH. Nearly all patients died of disease (n = 23, 88%). The 6-m OS from the time of BM was 21%, and most patients died from TH (n = 13, 57%). TH occurred at BM presentation in 6 (46%) patients, whereas 3 (23%) had TH from known and untreated lesions, 2 (15%) had continued uncontrolled IH during RT, and 2 (15%) from new BM. The only factor associated with TH as the cause of death was platelet count as a continuous variable (median 162 vs 360k, <i>P</i> = 0.02; platelet count < 50 vs. ≥50, <i>P</i> = 0.25). Only 18 patients (69%) received treatment for BM due to a high rate of TH at presentation: RT alone in 10 (55%; WBRT n = 6; SRS n = 4), surgery for 4 (22%), surgery + RT for 2 (11%), and chemotherapy for 2 (11%). One patient (6%) developed local failure following surgery alone and 5 (28%) developed distant brain failure. A total of 23 patients (88%) had IH, including 21 (81%) at initial BM diagnosis, of which 18 (86%) required hospitalization. The median platelet count at the time of IH was 235k (IQR, 108-338k). Only 4 patients (17%) had a platelet count < 50k at the time of IH, whereas the majority were above 200k (n = 12, 71%). Subsequent IH occurred in 9 patients (35%), but in only 1 that completed RT, which was minor. No patients who completed RT for BM died from TH. <h3>Conclusion</h3> Patients with CA frequently develop BM, and the risk of IH is high resulting in an alarming rate of TH despite normal platelet counts. Therefore, early diagnosis and intervention is warranted. We recommend incorporating MRI brain imaging into the standard q2-3 month staging evaluation. And importantly, once BM are detected, prompt local therapy is recommended to try and mitigate the risk of TH.

Presentation and management of patients with brain metastases of primary melanoma, non-small cell lung cancer, and breast cancer origin.

2033 Background: As systemic therapy improves; the prevalence of brain metastases is increasing. Screening brain MRIs are currently recommended for all stage ≥ II non-small cell lung cancer (NSCLC) and stage IIIB–IV melanoma patients, but only when neurologic symptoms arise in stage IV or recurrent breast cancer (BC) patients. This study assessed the presentation and institutional outcomes treating brain metastases (BM) of BC, NSCLC, and melanoma origin. Methods: Patients with BM treated between 2014 and 2019 with primary melanoma, NSCLC, and BC were identified. Characteristics of initial BM diagnoses were retrieved from clinical chart review. Kruskal-Wallis and Pearson’s chi-square tests were used to test differences between groups. Overall survival (OS) was calculated from dates of initial BM diagnosis using the Kaplan–Meier method. Results: A total of 959 patients were identified (BC 18%, NSCLC 51%, melanoma 31%). BC patients were younger at initial presentation (BC median age: 57, NSCLC 65, melanoma 62, p&lt; 0.0001). At BM diagnosis, BC patients were more likely to have concurrent systemic metastasis (BC 77%, NSCLC 42%, melanoma 69%, p&lt; 0.0001), at least 5 BM (BC 27%, NSCLC 14%, melanoma 13%, p= 0.0004), and leptomeningeal disease (BC 23%, NSCLC 6%, melanoma 6%, p&lt; 0.0001). Patients with BC were significantly more likely to receive whole brain radiation therapy (WBRT) (BC 58%, NSCLC 37%, melanoma 22%, p&lt; 0.0001) and less likely to receive stereotactic radiation (BC 26%, NSCLC 48%, melanoma 58%, p&lt; 0.0001) following initial BM diagnosis. There were no significant differences in surgical resection between cancer types (BC 24%, NSCLC 24%, melanoma 29%, p =0.166). Median OS was shorter for BC (BC 9.9 months, NSCLC 10.3 months, melanoma 13.7 months, p= 0.0006) following BM diagnosis. Conclusions: Our institutional analysis found BC patients were more likely to be younger, present with more advanced brain disease, require WBRT, and have poorer OS than NSCLC and melanoma patients following initial brain metastasis diagnosis. This may be due in part to a lack of brain MRI screening recommendations in BC. Further investigation is needed to determine which BC patients are at sufficient risk to warrant brain MRI screening.

Assessment of Brain Metastasis at Diagnosis in Non-Small-Cell Lung Cancer: A Prospective Observational Study From North India.

PURPOSEThe incidence of symptomatic brain metastasis at diagnosis in non–small-cell lung cancer (NSCLC) is 5%-10%, and up to 40% develop during the disease course. There is a paucity of data supporting the role of brain imaging at diagnosis in asymptomatic cases particularly from resource-constraint settings. Here, we present our experience of mandatory baseline brain imaging with contrast-enhanced computed tomography (CECT) scans of all patients with NSCLC.MATERIALS AND METHODSThis was a prospective observation study of patients with NSCLC with mandatory baseline brain CECT and a CNS examination. All histology proven patients with NSCLC diagnosed between January 2018 and October 2019 were included irrespective of stage.RESULTSA total of 496 patients were enrolled. The median age was 57 years (range, 23-84) with majority being males (75%) and smokers (66%). The prevalence of epidermal growth factor receptor mutations and anaplastic lymphoma kinase fusions was 33.4% and 12%, respectively. Brain imaging leads to upstaging in 7% cases. The prevalence of brain metastases was 21% (n = 104), with half being asymptomatic (51%). Factors associated with higher proportion of brain metastasis were young age (≤ 40 years), adenocarcinoma histology, poor Eastern Cooperative Oncology Group performance status (3 and 4), and high neutrophil-lymphocyte ratio (NLR) (> 2.5). After a median follow-up of 10.8 months (95% CI, 7.33 to 12.73), the median overall survival was 7.46 versus 12.76 months (hazard ratio 0.67; 95% CI, 0.46 to 0.96; P = .03) in patients with and without brain metastases, respectively. On multivariate analyses, high NLR and molecular graded prognostic assessment affected the overall survival significantly.CONCLUSIONIn our study, 21% of patients had brain metastasis at diagnosis detected with a mandatory baseline brain imaging with CECT. NLR and molecular graded prognostic assessment are significant predictors of survival in patients with brain metastasis.

Real world outcomes in KRAS G12C mutation positive non-small cell lung cancer

BackgroundKRAS mutations are found in 20–30 % of non-small cell lung cancers (NSCLC) and were traditionally considered undruggable. KRASG12C mutation confers sensitivity to KRASG12C covalent inhibitors, however its prognostic impact remains unclear. This study assesses the frequency, clinical features, prevalence of brain metastases and outcomes in KRASG12C NSCLC in a real-world setting. MethodsPatients enrolled in the prospective Thoracic Malignancies Cohort (TMC) between July 2012 to October 2019 with recurrent/metastatic non-squamous NSCLC, available KRAS results, and without EGFR/ALK/ROS1 gene aberrations, were selected. Data was extracted from TMC and patient records. Clinicopathologic features, treatment and overall survival (OS) was compared for KRAS wildtype (KRASWT) and KRAS mutated (KRASmut); and KRASG12C and other (KRASother) mutations. ResultsOf 1386 NSCLC patients, 1040 were excluded: non-metastatic/recurrent (526); unknown KRAS status (356); ALK/EGFR/ROS1 positive (154); duplicate (4). Of 346 patients analysed, 144 (42 %) were KRASmut, of whom 65 (45 %) were KRASG12C. All patients with KRASG12C were active or ex-smokers, compared to 92 % of KRASother and 83 % of KRASWT. The prevalence of brain metastases during follow-up was similar between KRASmut and KRASWT (33 % vs 40 %, p = 0.17), and KRASG12C and KRASother (40 % vs 41 %, p = 0.74). The proportion of patients receiving one or multiple lines of systemic therapy was comparable. OS was similar between KRASmut and KRASWT (p = 0.54), and KRASG12C and KRASother (p = 0.39). ConclusionPatients with KRASmut and KRASWT, and KRASG12C and KRASother NSCLC have comparable clinical features, treatment and survival. While not prognostic, KRASG12C may be an important predictive biomarker as promising KRASG12C covalent inhibitors continue to be developed.

Assessing the significance of KRAS G12C mutation: Clinicopathologic features, treatments, and survival outcomes in a real-world KRAS mutant non-small cell lung cancer cohort.

e19324 Background: KRASG12C mutations are present in 15% of non-small cell lung cancer (NSCLC) and have recently been shown to confer sensitivity to KRAS(G12C) inhibitors. This study aims to assess the clinical features and outcomes with KRASG12C mutant NSCLC in a real-world setting. Methods: Patients enrolled in an Australian prospective cohort study, Thoracic Malignancies Cohort (TMC), between July 2012 to October 2019 with metastatic or recurrent non-squamous NSCLC, with available KRAS test results, and without EGFR, ALK, or ROS1 gene aberrations, were selected. Data was extracted from TMC and patient records. Clinicopathologic features, treatment and overall survival was compared for KRAS wildtype ( KRASWT) and KRAS mutated ( KRASmut) patients, and between KRAS G12C ( KRASG12C) and other ( KRASother) mutations. Results: Of 1386 patients with non squamous NSCLC, 1040 were excluded for: non metastatic or recurrent (526); KRAS not tested (356); ALK, EGFR or ROS1 positive (154); duplicate (4). Of 346 patients analysed, 202 (58%) were KRASWT and 144 (42%) were KRASmut, of whom 65 (45%) were KRASG12C. 100% of pts with KRASG12C were smokers, compared to 92% of KRASother and 83% of KRASWT. The prevalence of brain metastases over entire follow-up period was similar between KRASmut and KRASWT (33% vs 40%, p = 0.17), and KRASG12C and KRASother (40% vs 41%, p = 0.74). Likewise, there was no difference in the proportion of patients receiving one or multiple lines of systemic therapy. Overall survival (OS) was also similar between KRASmut and KRASWT (p = 0.54), and KRASG12C and KRASother (p = 0.39). Conclusions: In this real-world prospective cohort, patients had comparable clinical features regardless of having a KRASmut, KRASG12C or KRASother mutation, or being KRASWT . Treatment and survival were also similar between groups. While not prognostic, KRASG12C may be an important predictive biomarker as promising KRAS G12C covalent inhibitors continue to be developed.

114 - Real-world data on management of brain metastases in non-small cell lung cancer, Queen Elizabeth Hospital, Birmingham: a retrospective study on progression free survival, overall survival of different treatment modalities for brain metastases and prevalence of brain metastases in NSCLC receiving immunotherapy

114 - Real-world data on management of brain metastases in non-small cell lung cancer, Queen Elizabeth Hospital, Birmingham: a retrospective study on progression free survival, overall survival of different treatment modalities for brain metastases and prevalence of brain metastases in NSCLC receiving immunotherapy

Prevalence of metastases within the hypothalamic-pituitary area in patients with brain metastases

AimTo quantify the prevalence of brain metastases involving the hypothalamic-pituitary (HT-P) area.IntroductionCognitive impairment and fatigue are common side effects of whole brain irradiation (WBI) comprising the quality of life (QoL) for survivors. While the former is related to radiation-induced hippocampal injury, the latter could be secondary to hormonal disbalance as a consequence of radiation of the HT-P area. Thus, sparing both regions from higher irradiation doses could reduce these sequelae.MethodsT1 contrast medium enhanced magnetic resonance imaging (MRI) scans of 865 patients with brain metastases (4,280 metastases) were reviewed. HT-P area was individually contoured with a margin of 5 mm in order to evaluate the prevalence of brain metastases in this region.ResultsInvolvement of the hypothalamic region was found in 26 patients (involvement rate of 3% for patients and 1% for metastases), involvement of the pituitary gland in 9 patients (1% for patients and < 1% for metastases). Binary logistical regression analysis revealed the presence of > 10 brain metastases as the only factor associated with hypothalamic involvement while no distinct factor was associated with an involvement of the pituitary gland.ConclusionThe low prevalence of metastases within the HT-P area in patients with brain metastases calls for further studies examining whether sparing of this region might improve patients QoL.

Lymph Node Size Predicts for Asymptomatic Brain Metastases in Patients With Non–small-cell Lung Cancer at Diagnosis

BackgroundWe questioned whether the National Comprehensive Cancer Network recommendations for brain magnetic resonance imaging (MRI) for patients with stage ≥ IB non–small-cell lung cancer (NSCLC) was high-yield compared with American College of Clinical Pharmacy and National Institute for Health and Care Excellence guidelines recommending stage III and above NSCLC. We present the prevalence and factors predictive of asymptomatic brain metastases at diagnosis in patients with NSCLC without extracranial metastases. Materials and MethodsA retrospective analysis of 193 consecutive, treatment-naïve patients with NSCLC diagnosed between January 2010 and August 2015 was performed. Exclusion criteria included no brain MRI staging, symptomatic brain metastases, or stage IV based on extracranial disease. Univariate and multivariate logistic regression was performed. ResultsThe patient characteristics include median age of 65 years (range, 36-90 years), 51% adenocarcinoma/36% squamous carcinoma, and pre-MRI stage grouping of 31% I, 22% II, 34% IIIA, and 13% IIIB. The overall prevalence of brain metastases was 5.7% (n = 11). One (2.4%) stage IA and 1 (5.6%) stage IB patient had asymptomatic brain metastases at diagnosis, both were adenocarcinomas. On univariate analysis, increasing lymph nodal stage (P = .02), lymph nodal size > 2 cm (P = .009), multi-lymph nodal N1/N2 station involvement (P = .027), and overall stage (P = .005) were associated with asymptomatic brain metastases. On multivariate analysis, increasing lymph nodal size remained significant (odds ratio, 1.545; P = .009). ConclusionOur series shows a 5.7% rate of asymptomatic brain metastasis for patients with stage I to III NSCLC. Increasing lymph nodal size was the only predictor of asymptomatic brain metastases, suggesting over-utilization of MRI in early-stage disease, especially in lymph node-negative patients with NSCLC. Future efforts will explore the utility of baseline MRI in lymph node-positive stage II and all stage IIIA patients.

Non–small-cell Lung Cancer With Brain Metastasis at Presentation

BackgroundData on the prevalence of brain metastases at presentation in patients with non–small-cell lung cancer (NSCLC) are limited. We queried the National Cancer Data Base to determine prevalence, clinical risk factors, and outcomes of patients with NSCLC presenting with brain metastases. Patients and MethodsPatients with NSCLC diagnosed between 2010 and 2012 were identified using the National Cancer Data Base. The risk of brain metastases for individual variables was summarized by odds ratios and calculated using logistic regression analysis. The Kaplan-Meier product limit method was used to calculate the median and 1-, 2-, and 3-year overall survival (OS). ResultsBrain metastases were observed in 47,546 (10.4%) of the 457,481 patients with NSCLC overall. The prevalence of brain metastases was much higher (26%) in patients with stage IV disease at presentation. On multivariate analysis, younger age, adenocarcinoma or large cell histology, tumor size > 3 cm, tumor grade ≥ II, and node-positive disease were associated with brain metastases. The prevalence of brain metastases ranged from as low as 0.57% in patients with only 1 risk factor to as high as 22% in patients with all 5 risk factors. The median and 1-, 2-, and 3-year OS for patients with brain metastases were 6 months and 29.9%, 14.3%, and 8.4%, respectively, with the 3-year OS increasing to 36.2% in those with T1/2 and N0/1 undergoing surgery for the primary site. ConclusionsIn patients with NSCLC, the risk of brain metastases at presentation may be calculated based on 5 clinical variables. Selected patients with brain metastases at presentation may achieve prolonged benefit.

PC 02.03 PCI---YES

Radiation therapy (RT) has an important role in both limited stage and extensive stage (M1) small cell lung cancer (SCLC), although more recent randomized trial results have led to increasing discussion and opposing views regarding the indications and type and degree of benefit conferred. This is one such debate, in which I am arguing in favor of recommending Prophylactic Cranial Irradiation (PCI) in extensive stage (ES) SCLC. There is no disagreement about the prevalence of brain metastases (BM) in SCLC.

A nationwide multi-institutional retrospective study to identify prognostic factors and develop a graded prognostic assessment system for patients with brain metastases from uterine corpus and cervical cancer

BackgroundThe prevalence of brain metastases (BM) from uterine cancer has recently increased because of the improvement of overall survival (OS) of patients with uterine cancer due to its early detection and improved local control as a result of new effective treatments. However, little information is available regarding their clinical characteristics and prognosis, because oncologists have encountered BM from uterine cancer on rare occasions.MethodsRecords from 81 patients with uterine BM were collected from 10 institutes in Japan. These were used in a multi-institutional study to identify prognostic factors and develop a graded prognostic assessment (GPA) for patients with BM from uterine cancer.ResultsMedian OS after the development of BM was 7 months (95% confidence interval, 4 to 10 months). Multivariate analysis revealed that there were survival differences according to the existence of extracranial metastases and number of BM. In the present uterine-GPA, a score of 0 was assigned to those patients with ≥5 BM and extracranial metastasis, a score of 2 was assigned to those patients with one to four BM or without extracranial metastasis, and a score of 4 was assigned to those patients with one to four BM and without extracranial metastasis. The median OS for patients with a uterine-GPA scores of 0, 2, and 4 was 3, 7, and 22 months, respectively. A survival analysis confirmed the presence of statistically significant differences between these groups (p < 0.05). The results were validated by data obtained from the National Report of Brain Tumor Registry of Japan.ConclusionUterine GPA incorporates two simple clinical parameters of high prognostic significance and can be used to predict the expected survival times in patients with BM from uterine cancer. Its use may help in determining an appropriate treatment for individual patients with BM.