Diagnosis Of Brain Metastases Research Articles

Breast Cancer Patients with Brain Metastases: A Cross-Sectional Study

The prognosis of breast cancer patients with brain metastasis is poor. It was aimed to define the clinicopathological features of breast cancer patients with brain metastases and to determine the risk factors and survival outcomes associated with brain metastasis. This is a single-center, retrospective, cross-sectional study. A total number of 127 patients diagnosed with breast cancer and who developed brain metastasis between January 2011 and March 2021 were retrospectively analyzed. The survival and clinicopathological data of these patients according to 4 biological subtypes were evaluated (luminal A, luminal B, HER-2 overexpressing, and triple-negative). The median overall survival for all patients was 45.6 months. The median time from the diagnosis of breast cancer to the occurrence of brain metastasis was 29.7 months, and the median survival time after brain metastasis was 7.2 months. The time from the diagnosis of breast cancer to brain metastasis development was significantly shorter in HER-2 overexpressing and triple-negative subtypes than in luminal A and B subtypes. The median time from breast cancer diagnosis to brain metastasis was 33.5 months in luminal A, 40.6 months in luminal B, 16.8 months in HER-2 overexpressing, and 22.8 months in the triple-negative groups (p=0.003). We found the worst median survival after brain metastasis in the triple-negative group with 3.5 months. Early and close surveillance of high-risk patients may help early diagnosis of brain metastasis and may provide to perform effective treatments leading to longer overall survival times for this patient population.

Radiation therapy for melanoma brain metastases: a systematic review.

BackgroundRadiation therapy (RT) for melanoma brain metastases, delivered either as whole brain radiation therapy (WBRT) or as stereotactic radiosurgery (SRS), is an established component of treatment for this condition. However, evidence allowing comparison of the outcomes, advantages and disadvantages of the two RT modalities is scant, with very few randomised controlled trials having been conducted. This has led to considerable uncertainty and inconsistent guideline recommendations. The present systematic review identified 112 studies reporting outcomes for patients with melanoma brain metastases treated with RT. Three were randomised controlled trials but only one was of sufficient size to be considered informative. Most of the evidence was from non-randomised studies, either specific treatment series or disease cohorts. Criteria for determining treatment choice were reported in only 32 studies and the quality of these studies was variable. From the time of diagnosis of brain metastasis, the median survival after WBRT alone was 3.5 months (IQR 2.4–4.0 months) and for SRS alone it was 7.5 months (IQR 6.7–9.0 months). Overall patient survival increased over time (pre-1989 to 2015) but this was not apparent within specific treatment groups.ConclusionsThese survival estimates provide a baseline for determining the incremental benefits of recently introduced systemic treatments using targeted therapy or immunotherapy for melanoma brain metastases.

A PROSPECTIVE INTERVENTIONAL STUDY TO COMPARE THE TREATMENT OUTCOMES IN PATIENTS WITH TWO DIFFERENT FRACTIONATION SCHEDULE OF WHOLE BRAIN RADIOTHERAPY WITH MULTIPLE BRAIN METASTASES

Purpose of study : To compare the treatment outcomes in patients with brain metastasis treated with two different fractionation schedules of whole brain radiotherapy. A prospective randomised study was carried out on newly diagnosed cancer patients with MRIMaterials and methods: diagnosis of brain metastasis. Patients with multiple bm with Eastern Cooperative Oncology Group performance status 0-4 were included. In Arm A, patients received whole brain radiotherapy (WBRT) of total dose 30 GY , 3Gy/fraction/10# over 2 weeks ,whereas , in Arm-B patients received total dose of 20 GY in 4Gy/fraction/5# over 1 week. Assessment of improvement in clinical symptoms was done using BARTHEL'S ADJUSTED DAILY LIVE (ADL)14 Score before treatment, just after treatment and 6 week of treatment and improvement was analysed. At three months follow up , radiological response was carried out by MRI scan of brain. Acute toxicities were assessed during treatment and follow up ( up to 90 days post EBRT ) using clinical status, laboratory investigations and radiological test and graded according to RTOG/EORTC criteria. Results: Signicant improvement in terms of ADL score was observed in both arms , however when both arms were compared , no signicant difference was found out. There was no statistically signicant difference in response or morbidity between the two treatment arms. In theConclusions: palliative setting short duration of treatment with minimum discomfort to the patient is desirable. 20 Gy in 5 fractions is equally effective as 30 Gy in 10 fractions, with slight advantage in terms of toxicity. Thus 20 Gy in 5 fractions can be preferred in brain metastasis patients, especially those with poor performance status.

Staged radiosurgery alone versus postoperative cavity radiosurgery for patients with midsize-to-large brain metastases: a propensity score matching analysis.

The authors investigated and compared the results of staged stereotactic radiosurgery (S-SRS) alone and those of postoperative cavity SRS (C-SRS) for patients with midsize-to-large brain metastases (BMs). Patients with BMs who had undergone S-SRS or C-SRS during the period from 2010 to 2020 were retrospectively identified from an institutional database. The two treatment groups were generated by propensity score matching (PSM; match ratio 2:1) based on 13 potential prognostic covariates: sex, age, Karnofsky Performance Status, type of primary cancer, timing of BM diagnosis, extracranial disease status, driver mutations, molecular target therapy, neurological symptoms, number of BMs, location of BMs treated with S-SRS or C-SRS, maximal tumor or cavity volume, and cumulative intracranial tumor volume. Patient survival and control of intracranial disease were compared between the S-SRS and C-SRS groups using time-dependent analyses taking into account competing events. In total, 110 patients in the S-SRS group and 62 in the C-SRS group were selected by PSM. In the S-SRS group, the median interval between the two radiosurgical sessions was 21 days, and the median total prescription dose was 28 Gy at 50%. In the C-SRS group, the median time from surgery to C-SRS was 16 days, and the median prescription dose delivered to the surgical cavity was 15 Gy at 55%. At the time point of data set fixation, 129 patients had died, 43 were alive, and none had been lost to follow-up. The 2-year survival rates for the S-SRS and C-SRS groups after the initial intervention were 33% and 37% and the median survival times were 14.8 and 17.5 months, respectively (p = 0.33). The 2-year cumulative neurological mortality rates were 11% and 9%, respectively (p = 0.65). The 2-year local failure rates were 32% and 12% (p = 0.036) and the 2-year distant recurrence rates were 55% and 58%, respectively (p = 0.53). The 2-year leptomeningeal disease development rates were 9% and 25%, respectively (p = 0.007). The present study revealed no significant difference in overall survival or cumulative neurological mortality between the S-SRS and C-SRS groups. The local control failure rate was significantly higher in the S-SRS group, whereas the incidence of leptomeningeal disease development was significantly higher in the C-SRS group.

Racial disparities in inpatient clinical presentation, treatment, and outcomes in brain metastasis.

Few studies have assessed the impact of race on short-term patient outcomes in the brain metastasis population. The goal of this study is to evaluate the association of race with inpatient clinical presentation, treatment, in-hospital complications, and in-hospital mortality rates for patients with brain metastases (BM). Using data collected from the National Inpatient Sample between 2004 and 2014, we retrospectively identified adult patients with a primary diagnosis of BM. Outcomes included nonroutine discharge, prolonged length of stay (pLOS), in-hospital complications, and mortality. Minority (Black, Hispanic/other) patients were less likely to receive surgical intervention compared to White patients (odds ratio [OR] 0.70; 95% confidence interval [CI] 0.66-0.74, p < 0.001; OR 0.88; 95% CI 0.84-0.93, p < 0.001). Black patients were more likely to develop an in-hospital complication than White patients (OR 1.35, 95% CI 1.28-1.41, p < 0.001). Additionally, minority patients were more likely to experience pLOS than White patients (OR 1.48; 95% CI 1.41-1.57, p < 0.001; OR 1.34; 95% CI 1.27-1.42, p < 0.001). Black patients were more likely to experience a nonroutine discharge (OR 1.25; 95% CI 1.19-1.31, p < 0.001) and higher in-hospital mortality than White (OR 1.13; 95% CI 1.03-1.23, p = 0.008). Our analysis demonstrated that race is associated with disparate short-term outcomes in patients with BM. More efforts are needed to address these disparities, provide equitable care, and allow for similar outcomes regardless of care.

The Management and Outcomes of Patients with Extra-Pulmonary Neuroendocrine Neoplasms and Brain Metastases.

Background: Brain metastases (BMs) in patients with extra-pulmonary neuroendocrine neoplasms (EP–NENs) are rare, and limited clinical information is available. The aim of this study was to detail the clinicopathological features, management and outcomes in patients with EP–NENs who developed BMs. Methods: A retrospective single-centre analysis of consecutive patients with EP–NENs (August 2004–February 2020) was conducted. Median overall survival (OS)/survival from BMs diagnosis was estimated (Kaplan–Meier). Results: Of 730 patients, 17 (1.9%) had BMs, median age 61 years (range 15–77); 8 (53%) male, unknown primary NEN site: 40%. Patients with BMs had grade 3 (G3) EP–NENs 11 (73%), G2: 3 (20%), G1: 1 (7%). Eight (53%) had poorly differentiated NENs, 6 were well-differentiated and 1 was not recorded. Additionally, 2 (13%) patients had synchronous BMs at diagnosis, whilst 13 (87%) developed BMs metachronously. The relative risk of developing BMs was 7.48 in patients with G3 disease vs. G1 + G2 disease (p = 0.0001). Median time to the development of BMs after NEN diagnosis: 15.9 months (range 2.5–139.5). Five patients had a solitary BM, 12 had multiple BMs. Treatment of BMs were surgery (n = 3); radiotherapy (n = 5); 4: whole brain radiotherapy, 1: conformal radiotherapy (orbit). Nine (53%) had best supportive care. Median OS from NEN diagnosis was 23.6 months [95% CI 15.2–31.3]; median time to death from BMs diagnosis was 3.0 months [95% CI 0.0–8.3]. Conclusion: BMs in patients with EP–NENs are rare and of increased risk in G3 vs. G1 + G2 EP–NENs. Survival outcomes are poor, and a greater understanding is needed to improve therapeutic outcomes.

Brain Metastasis from Pancreatic Cancer: Our Experience and Systematic Review

To systematically review existing literature on the neurosurgical management and outcomes of brain metastasis from pancreatic cancer in comparison with our institutional experience of this patient cohort. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature review was performed using PubMed, Ovid Embase, Scopus, and Web of Science databases from date of database inception to March 2022. Studies were selected based on predetermined inclusion and exclusion criteria. Simultaneously, a retrospective analysis was conducted of patients who underwent neurosurgical evaluation and treatment for intracranial metastatic lesions from pancreatic origin at a single institution. The original literature search yielded 292 articles, of which 17 studies comprising 23 patients with brain metastases of pancreatic origin were ultimately selected. Median overall survival from primary diagnosis of pancreatic cancer was 22 months (interquartile range: 3-84) and 3 months (interquartile range: 1-36) after diagnosis of brain metastasis. In our institutional cohort, 4 patients were identified with a median overall survival of 30.5 months (interquartile range: 2-108). Our institutional cohort experienced a prolonged median overall survival (3 months vs. 30.5 months, P= 0.03) compared with the literature. Brain metastasis from pancreatic cancer is rare and associated with a fatal outcome. However, based on the data presented in this review, patient-specific and treatment-related factors could signal better prognosis. Further studies are needed to elucidate multimodal therapy and survival to suggest a more personalized decision-making process.

Prostate Cancer Brain Metastasis: Review of a Rare Complication with Limited Treatment Options and Poor Prognosis.

Brain metastases (BM) are perceived as a rare complication of prostate cancer associated with poor outcome. Due to limited published data, we conducted a literature review regarding incidence, clinical characteristics, treatment options, and outcomes of patients with prostate cancer BM. A literature analysis of the PubMed, MEDLINE, and EMBASE databases was performed for full-text published articles on patients diagnosed with BM from prostate cancer. Eligible studies included four or more patients. Twenty-seven publications were selected and analyzed. The sources of published patient cohorts were retrospective chart reviews, administrative healthcare databases, autopsy records, and case series. BM are rare, with an incidence of 1.14% across publications that mainly focus on intraparenchymal metastases. Synchronous visceral metastasis and rare histological prostate cancer subtypes are associated with an increased rate of BM. Many patients do not receive brain metastasis-directed local therapy and the median survival after BM diagnosis is poor, notably in patients with multiple BM, dural-based metastases, or leptomeningeal dissemination. Overall, prostate cancer BM are rare and associated with poor prognosis. Future research is needed to study the impact of novel prostate cancer therapeutics on BM incidence, to identify patients at risk of BM, and to characterize molecular treatment targets.

MiRNAs in Serum Exosomes for Differential Diagnosis of Brain Metastases.

Simple SummaryCurrent methods for the detection of brain malignancies often display low sensitivity and specificity. Noninvasive biomarkers can complement imaging techniques to improve the diagnosis of these tumors. The aim of this study was to identify circulating miRNAs in serum exosomes useful in all phases of the diagnostic and therapeutic path of patients with malignant brain lesions. Our data show a signature of exosomal miRNAs useful for the differential diagnosis of brain metastases and for monitoring tumor evolution over time.Circulating miRNAs are increasingly studied and proposed as tumor markers with the aim of investigating their role in monitoring the response to therapy as well as the natural evolution of primary or secondary brain tumors. This study aimed to evaluate the modulation of the expression of three miRNAs, miR-21, miR-222 and miR-124-3p, in the serum exosomes of patients with high-grade gliomas (HGGs) and brain metastases (BMs) to verify their usefulness in the differential diagnosis of brain masses; then, it focused on their variations following the surgical and/or radiosurgical treatment of the BMs. A total of 105 patients with BMs from primary lung or breast cancer, or melanoma underwent neurosurgery or radiosurgery treatment, and 91 patients with HGGs were enrolled, along with 30 healthy controls. A significant increase in miR-21 expression in serum exosomes was observed in both HGGs and BMs compared with healthy controls; on the other hand, miR-124-3p was significantly decreased in BMs, and it was increased in HGGs. After the surgical or radiosurgical treatment of patients with BMs, a significant reduction in miR-21 was noted with both types of treatments. This study identified a signature of exosomal miRNAs that could be useful as a noninvasive complementary analysis both in the differential diagnosis of BMs from glial tumors and in providing information on tumor evolution over time.

Prognostic factors for brain metastasis in women presenting cervical cancer.

Although rare, brain metastases (BM) from cervical cancer (CC) are highly lethal. Adequate patient selection for specific treatments can improve survival rates in patients afflicted by this condition. This study aimed to describe the characteristics of CC patients who developed BM and overall survival-associated factors. Brain metastasis impact on the overall survival was assessed as a secondary objective. This assessment comprises a retrospective cohort study on 3394 women presenting CC diagnosed between January 2010 and December 2017 at a single referral center. Incident BM cases were included. Descriptive statistics were calculated. Kaplan-Meier curves were used for the survival analysis and a Cox proportional hazards regression model was applied to explore the risk of death according to the analyzed independent variables. A total of 48 incident BM cases were identified. The median time between CC diagnosis and BM development was 1.5years. Headaches (29.2%), dizziness/altered balance (29.2%), vertigo (29.2%) and motor disturbances (25.0%) were the most common signs and symptoms at presentation. Median overall survival after BM diagnosis was of 1.6months (95% CI 0.9-2.3) while in the group of women without BM it was 5.5years (95% CI 4.9-6.1). Concerning the Cox multivariate analysis, presenting one extracerebral metastases site (HR 2.8; 95% CI 1.3-6.2; p = 0.009) and receiving supportive treatment (HR 13.7; 95% CI 3.1-60.5; p 0.001) were independently associated with the risk of death. The median survival of women with BM following CC was poor. Women without extracerebral metastases and undergoing multimodal treatment displayed better overall survival rates.

Emerging Systemic Treatment Perspectives on Brain Metastases: Moving Toward a Better Outlook for Patients.

The diagnosis of brain metastases has historically been a dreaded, end-stage complication of systemic disease. Additionally, with the increasing effectiveness of systemic therapies that prolong life expectancy and improved imaging tools, the incidence of intracranial progression is becoming more common. Within this context, there has been increasing attention directed at understanding the molecular underpinnings of intracranial progression. Exploring the unique features of brain metastases compared with their extracranial counterparts to identify aberrant signaling pathways, which can be targeted pharmacologically, may help lead to new treatments for this patient population. Additionally, critical discoveries outside the sphere of the central nervous system are increasingly being applied to brain metastases with the emergence of immune checkpoint inhibition, becoming a prevalent treatment option for patients with brain metastases across multiple histologies. As novel treatment strategies are considered, they require thoughtful incorporation of agents that can cross the blood-brain barrier and can synergize with pre-existing agents through rational combinations. Lastly, as clinicians and scientists continue to understand key molecular features of these tumors, they will continue to influence the treatment algorithms that are developing for the management of these patients. Due to the complexity of treatment decisions for patients with brain metastases, an emerging tool is the utilization of multidisciplinary brain metastasis tumor boards to ensure optimal treatment decisions are made and that patients are provided access to applicable clinical trials. Looking to the future, the collective effort to understand the various tumor-intrinsic and tumor-extrinsic factors that promote central nervous system seeding and propagation will have the potential to change the clinical trajectory for these patients.

CSCO expert consensus on the diagnosis and treatment of breast cancer brain metastasis.

Breast cancer is one of the most common malignancies among women worldwide. According to the International Agency for Research on Cancer, breast cancer affected more Chinese women than any other cancer in 2020. The brain is an increasingly common metastatic sites of breast cancer. Although the risk of developing brain metastases (BMs) is lower in breast cancer than in lung cancer and melanoma, due to its high prevalence, it is the second most common cause of BM among solid tumors, being second only to lung cancer. The incidence of breast cancer brain metastasis (BCBM) differs by molecular subtype. Half of patients with advanced human epidermal growth factor receptor-2 (HER2)-positive and one-third of patients with triple-negative breast cancer (TNBC) develop BM. The clinical manifestations of leptomeningeal metastasis (LM) are often non-specific and may manifest as a variety of signs and symptoms, mainly including brain parenchyma involvement and meningeal irritation syndromes cranial nerve involvement, increased intracranial pressure, and progressive brain dysfunction. Therefore, the Chinese Society of Clinical Oncology (CSCO) Breast Cancer Committee has developed this expert consensus on BM, in an effort to improve the overall prognosis of BCBM and promote the standardized diagnosis and treatment of this disease. During the development of this expert consensus, we carried out a comprehensive literature review and referred to some of the most authoritative guidelines in China and abroad. In this consensus, we will discuss clinical manifestations, imaging examinations, pathological diagnosis, treatments, prognosis, follow-up and monitoring. We hope this consensus will be of help to all the clinicians majored in breast cancer and other similar professions.

Re-irradiation in patients with progressive or recurrent brain metastases from extracranial solid tumors: A novel prognostic index.

Most studies evaluating factors associated with the survival of patients with brain metastases (BM) have focused on patients with newly diagnosed BM. This study aimed to identify prognostic factors associated with survival after brain re-irradiation in order to develop a new prognostic index. This 5-year retrospective study included patients treated with repeat-radiotherapy for recurrent BM at the "Instituto Nacional de Cancerología" of Mexico between 2015 and 2019. Significant variables in the multivariate Cox regression analysis were used to create the brain re-irradiation index (BRI). Survival and group comparisons were performed using the Kaplan-Meier method and the log-rank test. Fifty-seven patients receiving brain re-irradiation were identified. Most patients were women (75.4%) with a mean age at BM diagnosis of 51.4 years. Lung and breast cancer were the most prevalent neoplasms (43.9% each). Independent prognostic factors for shorter survival after re-irradiation were: Age >50 years (hazard ratio [HR]:2.5 [95% confidence interval [CI], 1.1-5.8]; p=0.026), uncontrolled primary tumor (HR:5.5 [95% CI, 2.2-13.5]; p < 0.001), lesion size >20 mm (4.6 [95% CI, 1.7-12.2]; p=0.002), and an interval <12 months between radiation treatments (HR:4.3 [95% CI, 1.7-10.6]; p=0.001). Median survival (MS) after re-irradiation was 14.6months (95% CI, 8.2-20.9).MS of patients stratified according to the BRI score was 17.38, 10.34, and 2.82 months, with significant differences between all groups. The new BRI can be easily implemented for the prognostic classification of cancer patients with progressive or recurrent BM from extracranial solid tumors.

Brain Metastasis of Papillary Ovarian Adenocarcinoma

Brain metastasis from epithelial ovarian cancer is a rare diagnostic entity with a reported incidence of 1- 2%. Serous epithelial ovarian cancer is usually associated with a poor prognosis and is the most common malignancy metastasizing to the brain. The median time from primary diagnosis to development of cerebral lesions is directly correlated with the initial tumour grade and stage.&nbsp; The median survival after diagnosis of brain metastases is 6 months. It is suggested that brain imaging studies should be included in the follow up of patients after treatment for ovarian carcinoma. We report a case of brain metastasis of ovarian adenocarcinoma 2 years post-surgery and six cycles of chemotherapy.

Brain metastases in ovarian cancer: Association of outcomes with timing of diagnosis.

e17565 Background: Brain metastases (BM) in ovarian cancer (OC) are rare and late events during the disease course. We report our data on patients with OC who developed BM and compared the outcomes with subjects with evidence of BM at the time of diagnosis from the Surveillance, Epidemiologic, and End Results (SEER) national database. Methods: Retrospective chart review of all patients with brain metastasis in the setting of previously diagnosed ovarian cancer was performed in single NCI designated comprehensive cancer institute. Inclusion criteria were: primary cancer documented as ovarian or tubal, evidence of BM, treatment and follow up information. For comparison and due to rare nature of ovarian cancer cases with BM we utilized the SEER database. SEER data base reports only on patients with OC who had BM at the time of diagnosis. Study groups were: 1- BM at diagnosis 2- BM during disease course. Primary outcomes were overall death, and overall survival (OS) months. Secondary outcome was survival months after diagnosis of BM. Variables are reported as median and interquartile range (IQR) or number (%). Mean survival was calculated using Kaplan Meier analysis and Mantel-Cox rank test. Cox regression analysis was performed to calculate adjusted hazard ratios (HR). Results: 106 and 24 subjects were included with evidence of BM at diagnosis (Group 1, 2010-2016, SEER database) and during the disease (Group2, 1992-2017, institutional data), respectively. Age at diagnosis of OC was significantly higher in group 1 (64 year vs. 55 year, p = 0.002). In group 2, BM were diagnosed at median interval of 33.5 months. The median OS month was 3 [1, 10] months and 58 [21, 122] in group 1 and 2, respectively (p &lt; 0.001). Although overall mortality rate was not statistically significantly different between the study groups, survival months after diagnosis of BM in group 2 was significantly higher than group 1 (14 months [4, 32] versus 3 months [1, 10], p = 0.002). Cox-regression analysis revealed 58% decrease in the hazard of overall death when the BM is diagnosed during the disease course. (Adjusted HR = 0.42, 95% CI: 0.19-0.91, p = 0.03). Conclusions: Outcomes of OC with BM is poor with high mortality rate regardless of timing of diagnosis of BM. Our study revealed that patients with diagnosis of BM during the disease course have statistically significantly longer survival after diagnosis of BM compared to those with BM at the time of diagnosis. In order to understand the occurrence of BM in OC and these differences, it is necessary to gain knowledge in the genetic and immune mechanisms that drive and allow the development of BM in ovarian cancer. This will allow for development of effective therapeutic strategies to treat BM, which is of critical importance now as we are gaining better control of peripheral disease in women with ovarian cancer.

Real-world assessment of clinical outcomes in NSCLC patients with MET exon 14 skipping mutation and brain metastases (BM) treated with capmatinib.

e21171 Background: Capmatinib, a highly selective and potent MET inhibitor, was approved for patients (pts) with advanced MET exon 14 NSCLC in the US in 2020 based on the GEOMETRY mono-1 trial data. Subgroup analyses from that study showed intracranial (IC) efficacy in pts with BM. However, there were no data on the effectiveness of capmatinib in pts with BM in the real-world setting; IC effectiveness is particularly challenging to study as many pts are also treated with radiation therapy (RT) to the brain. The current study examined real-world clinical outcomes of pts with NSCLC with MET exon 14 skipping mutation and BM who were treated with capmatinib, including those who were RT-naïve. Methods: A retrospective medical record review was performed by panel-based oncologists recruited nationwide in the US. Eligible pts were aged ≥ 18 years, had confirmed BM diagnosis and MET exon 14 skipping mutated NSCLC, started capmatinib therapy in any line following BM diagnosis (with ≥ 1 IC lesion ≥ 10 mm), and had a follow up of ≥ 6 months after starting capmatinib (except death). Modified (pseudo) RECIST and RANO-BM criteria were used for response assessments. Key outcomes were IC and systemic real-world best overall response rate (rwORR), disease control rate (rwDCR), progression-free survival (rwPFS), and time-to-treatment discontinuation (TTD) assessed separately for first-line (1L) capmatinib and immunotherapy (IO)-containing regimens alone or in combination with chemotherapy (CT). The analyses are descriptive in nature. Outcomes were also analyzed in RT-naïve pts (no prior/concurrent BM RT). Results: A total of 68 eligible pt charts were abstracted (median age at BM diagnosis, 64.3 years; 60.3% male; 72.1% treated in academic setting; 83.8% de novo metastatic). For the 1L therapy after BM diagnosis, 80.9% (n = 55) received capmatinib, 16.2% (n = 11) received IO-containing regimens, and 2.9% received CT alone; 29 pts were RT-naive. The IC rwORR in RT-naïve pts was 85.0% for capmatinib 1L and 11.1% for IO 1L (Table). In the overall cohort, the IC rwORR was 87.3% (rwDCR 96.4%) for capmatinib 1L and 27.3% (rwDCR 45.5%) for IO 1L. Median systemic rwPFS was 14.1 months for capmatinib 1L and 5.1 months for IO 1L. The 1-year systemic rwPFS rate was 70.8% for capmatinib 1L and 18.2% for IO 1L. TTD was 13.2 months for capmatinib 1L and 5.1 months IO 1L. Conclusions: This study shows a substantial systemic and IC effectiveness associated with capmatinib 1L use in pts with NSCLC with MET exon 14 and BM in the real-world setting. These findings remain true in RT-naïve pts.[Table: see text]

Selecting optimal timing of cranial radiotherapy-based on the graded prognostic assessment for lung cancer using molecular markers (Lung-molGPA) in patients with non-small cell lung cancer and brain metastases.

e21105 Background: The updated Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (Lung-molGPA) index will provide more accurate prediction of expected survival for patients with advanced non-small cell lung cancer (NSCLC) with brain metastases (BM). This retrospective study aims to evaluate optimal timing of cranial radiotherapy (RT) in NSCLC patients with BM stratified by Lung-molGPA index. Methods: This study retrospectively screened patients with NSCLC and initially diagnosed BM in our cancer center between February 2012 and July 2018. These enrolled patients were scored and stratified based on lung-molGPA index. The primary endpoint was overall survival time (OS), defined as the interval from the initiation of BM diagnosis to death caused by any reason or the last follow-up. And the secondary endpoint was progression free survival (PFS), referred to the interval from the initiation of BM diagnosis to disease progression or death caused by any reason. The effect of radiotherapy timing on survival time in groups stratified by lung-molGPA index was evaluated. The early RT was defined as receiving RT within three months after initial diagnosis of BM with no progression of BM prior to RT. And the delayed RT was defined as receiving RT after progression of BM or initial diagnosis of BM three months later. Results: Overall, 471 patients were enrolled in our study, including 260 patients receiving RT. The median follow-up time was 48 months. In entire cohort, median OS time and PFS were 15.0 and 9.0 months, respectively. In lung-molGPA0-2 group, OS of patients with or without RT was no statistical difference (HR, 0.78, 95%CI, 0.59-1.04, P= .071). While in lung-molGPA2.5-4 group, the addition of RT could prolong OS and PFS of patients (OS: HR, 0.51, 95%CI, 0.39-0.67, P&lt; .001; and PFS: HR, 0.66, 95%CI, 0.51-0.85, P&lt; .001). Moreover, in patients scored as 2.5-4.0, the median OS of early RT and delayed RT was 24.0 months and 15.0 months, respectively, and OS of patients receiving early RT was significantly superior to patients receiving delayed RT (HR, 0.50, 95%CI, 0.31-0.79, P&lt; .001). While for patients scored as 0-2, no statistical difference was between OS of patients receiving early RT and delayed RT (HR, 0.75, 95%CI, 0.51-1.10, P= .115). Conclusions: With regards as patients scored 2.5-4.0 based on lung-molGPA index, early addition of cranial radiotherapy could benefit patients’ survival. While for patients scored 0-2, the survival benefit from cranial radiotherapy was limited.

Genomic analysis and clinical correlations of non-small cell lung cancer (NSCLC) brain metastasis (BM).

2008 Background: Approximately 30% of patients with NSCLC present with BM, and up to 50% of patients ultimately develop BM. While modern NSCLC-directed agents yield excellent systemic response, most patients require focal treatment. Prior reports of BM genomics have been limited by low numbers, missing clinical data, and lack of matched specimens. Here, we report the largest cohort to date of molecularly profiled NSCLC BM samples with clinical correlates. Methods: Clinical data and outcomes for 244 patients with NSCLC and resected BM were identified, and BM samples were assessed with one of four versions (341, 410, 468, 505) of MSK-IMPACT, a custom FDA-approved next generation sequencing-based tumor sequencing assay. 51 (20.9%) patients had matched primary site tissue, and 44 (18%) patients had matched tissue from another metastatic site or CSF. Genomic alterations were filtered for driver variants using OncoKB. Results: Median age was 66 years (range 31-91), and median follow-up was 2.3 years (IQR 1.3-4.3). Adenocarcinoma was the most common histology (183, 78%). Half presented with a single BM, and 121 (51%) patients were treatment naive. Most (197, 83%) received adjuvant stereotactic radiosurgery (SRS) to the resection site and 28% received SRS to additional BM. After resection, 130 (55.1%) had CNS progression, often regional (54, 42%). SRS to new BMs (32%) was the most common salvage treatment. Median overall survival from BM diagnosis was 2.5 years (95%CI 2.1-3.2). Median CNS-progression-free survival was 1.2 years (95%CI 0.9-1.4). The most frequently altered genes in BM samples were TP53 (72%), CDKN2A (34%), KRAS (31%), KEAP1 (26%), and EGFR (21%). CDKN2A was more frequently altered in BM samples when compared to NSCLC primary samples (34% vs 14%, p = 0.003, q = 0.034). With regard to overrepresented gene sets, cell cycle pathway alterations were enriched in BM (56% vs 31%, p = 0.002, q = 0.022). BM samples had a significantly higher fraction of genome altered relative to the primary samples (p &lt; 0.0001, q &lt; 0.0001). After grouping patients based on type of CNS progression, we found that EGFR alterations were enriched in patients with leptomeningeal failures when compared to both patients without progression (42% vs 18%, p = 0.03, q = 0.93) and to patients with either local or regional progression (42% vs 19%, p = 0.03, q = 0.9). Conclusions: In the largest-ever assembled cohort of genomically-profiled NSCLC BM, we found significant enrichment for CDKN2A and cell cycle pathway alterations in BM compared to extracranial disease, as well as a higher fraction of genome altered, in BMs compared to matched primary tumor controls. We also observed EGFR alteration enrichment in patients who develop LMD, suggesting specific biologic underpinnings driving patterns of CNS failure. Further investigation into the role of systemic therapy and time course will elucidate potential mechanisms for CNS failure in patients with NSCLC.

Characteristics of patients with brain metastases from human epidermal growth factor receptor 2-positive breast cancer: subanalysis of Brain Metastases in Breast Cancer Registry

BackgroundUp to 40% of patients with metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer develop brain metastases (BMs). Understanding of clinical features of these patients with HER2-positive breast cancer and BMs is vital.Patients and methodsA total of 2948 patients from the Brain Metastases in Breast Cancer registry were available for this analysis, of whom 1311 had primary tumors with the HER2-positive subtype.ResultsPatients with HER2-positive breast cancer and BMs were—when compared with HER2-negative patients—slightly younger at the time of breast cancer and BM diagnosis, had a higher pathologic complete response rate after neoadjuvant chemotherapy and a higher tumor grade. Furthermore, extracranial metastases at the time of BM diagnosis were less common in HER2-positive patients, when compared with HER2-negative patients. HER2-positive patients had more often BMs in the posterior fossa, but less commonly leptomeningeal metastases. The median overall survival (OS) in all HER2-positive patients was 13.2 months (95% confidence interval 11.4-14.4). The following factors were associated with shorter OS (multivariate analysis): older age at BM diagnosis [≥60 versus <60 years: hazard ratio (HR) 1.63, P < 0.001], lower Eastern Cooperative Oncology Group status (2-4 versus 0-1: HR 1.59, P < 0.001), higher number of BMs (2-3 versus 1: HR 1.30, P = 0.082; ≥4 versus 1: HR 1.51, P = 0.004; global P = 0.015), BMs in the fossa anterior (HR 1.71, P < 0.001), leptomeningeal metastases (HR 1.63, P = 0.012), symptomatic BMs at diagnosis (HR 1.35, P = 0.033) and extracranial metastases at diagnosis of BMs (HR 1.43, P = 0.020). The application of targeted therapy after the BM diagnosis (HR 0.62, P < 0.001) was associated with longer OS. HER2-positive/hormone receptor-positive patients showed longer OS than HER2-positive/hormone receptor-negative patients (median 14.3 versus 10.9 months; HR 0.86, P = 0.03), but no differences in progression-free survival were seen between both groups.ConclusionsWe identified factors associated with the prognosis of HER2-positive patients with BMs. Further research is needed to understand the factors determining the longer survival of HER2-positive/hormone receptor-positive patients.

Effect of Whole-body [18F]Fluoro-2-deoxy-2-d-glucose Positron Emission Tomography in Patients with Suspected Brain Metastasis

Abstract Background and Purpose [18F]Fluoro-2-deoxy-2-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) has a promising role in the workup and management of carcinoma of unknown primary (CUP). We have evaluated the effect of whole-body FDG PET/CT in assessing the patients presented with suspected brain metastasis (CUP-BM) on brain magnetic resonance imaging (MRI) or computed tomography (CT). Materials and Methods This retrospective study included FDG PET/CT of 50 patients (24 males, mean: 58 ± 12.2 years old) with a CUP-BM diagnosis based on MRI and CT imaging. The final diagnosis of primary brain neoplasm (BP) or brain metastases (BM) was based on FDG PET/CT findings and/or histopathology (HPE). Results On FDG PET/CT, 52% (26/50) of patients did not have any systemic lesion apart from a brain lesion. Out of these, 50% (13/26) had HPE confirmation of primary brain neoplasm (BP). FDG PET/CT identified multiple systemic lesions apart from brain lesions in the remaining 48% (24/50) of patients. They were categorized as the brain metastases (BM) group. The primary lesions were located in the lungs (n = 20), kidneys (n = 1), prostate (n = 1), esophagus (n = 1), and tongue (n = 1). Conclusion FDG PET/CT could suggest a diagnosis of BM based on the presence of systemic lesions. It also provides an easily accessible peripheral site for biopsy and systemic disease burden in a single scan. FDG PET/CT's up-front use in suspected CUP-BM on CT and/or MRI could differentiate the BM from BP in most cases and avoid brain biopsy in the BM group.