Screening For Brain Metastases Research Articles

Survival Analysis, Clinical Characteristics, and Predictors of Cerebral Metastases in Patients with Colorectal Cancer.

Colorectal cancer (CRC) is the third most common cancer globally and a leading cause of cancer-related deaths. While liver metastasis is common, brain metastasis (BM) is rare, occurring in 0.1% to 14% of cases. Risk factors for BM include lung metastasis at diagnosis, rectal cancer, and mutations in RAS and KRAS genes. Due to its rarity, guidelines for BM screening and treatment are limited. The aim of this study is to identify the clinical characteristics and predictors of BM at the time of the initial diagnosis of CRC. We evaluated patients ≥18 years old with metastatic colorectal cancer and brain metastases at diagnosis from the SEER database (2010-2021). A retrospective cohort study was conducted to analyze overall survival and predictive factors for brain metastasis, utilizing multivariate logistic regression, Kaplan-Meier survival analysis, and the Cox proportional hazards models, with p-values < 0.05 considered significant. Out of 24,703 patients with metastatic colorectal cancer (mCRC), 228 (0.92%) had brain metastasis (BM) at diagnosis. BM was more prevalent in average-onset mCRC (≥50 years) compared to early-onset (<50 years) (1% vs. 0.55%, p = 0.004). Certain factors, such as older age and adenocarcinoma subtype, were associated with BM. Additionally, Asians/Pacific-Islanders (HR 1.83 CI: 1.01-3-33, p = 0.045) and American Indians/Alaska Natives (HR 4.79 CI 1.15-19.97, p = 0.032) had higher mortality rates, while surgical treatment and chemotherapy were linked to decreased mortality. Patients with BM had significantly worse overall survival (6 months vs. 21 months, p < 0.001). BM in mCRC is uncommon, but it is associated with significantly worse outcomes, including markedly reduced overall survival. Our study highlights several critical factors associated with the presence of BM, such as older age and specific racial/ethnic groups, which may inform risk stratification and early-detection strategies. Our findings emphasize the need for heightened awareness and screening for BM in high-risk mCRC patients, as well as the inclusion of these patients in clinical trials to explore tailored therapeutic approaches aimed at improving survival and quality of life.

Brain Metastases in Differentiated Thyroid Cancer: Clinical Presentation, Diagnosis, and Management.

Background: Brain metastases (BM) are the most common intracranial neoplasms in adults and are a significant cause of morbidity and mortality. The brain is an unusual site for distant metastases of thyroid cancer; indeed, the most common sites are lungs and bones. In this narrative review, we discuss about the clinical characteristics, diagnosis, and treatment options for patients with BM from differentiated thyroid cancer (DTC). Summary: BM can be discovered before initial therapy due to symptoms, but in most patients, BM is diagnosed during follow-up because of imaging performed before starting tyrosine kinase inhibitors (TKI) or due to the onset of neurological symptoms. Older male patients with follicular thyroid cancer (FTC), poorly differentiated thyroid cancer (PDTC), and distant metastases may have an increased risk of developing BM. The gold standard for detection of BM is magnetic resonance imaging with contrast agent administration, which is superior to contrast-enhanced computed tomography. The treatment strategies for patients with BM from DTC remain controversial. Patients with poor performance status are candidates for palliative and supportive care. Neurosurgery is usually reserved for cases where symptoms persist despite medical treatment, especially in patients with favorable prognostic factors and larger lesions. It should also be considered for patients with a single BM in a surgically accessible location, particularly if the primary disease is controlled without other systemic metastases. Additionally, stereotactic radiosurgery (SRS) may be the preferred option for treating small lesions, especially those in inaccessible areas of the brain or when surgery is not advisable. Whole brain radiotherapy is less frequently used in treating these patients due to its potential side effects and the debated effectiveness. Therefore, it is typically reserved for cases involving multiple BM that are too large for SRS. TKIs are effective in patients with progressive radioiodine-refractory thyroid cancer and multiple metastases. Conclusions: Although routine screening for BM is not recommended, older male patients with FTC or PDTC and distant metastases may be at higher risk and should be carefully evaluated for BM. According to current data, patients who are suitable for neurosurgery seem to have the highest survival benefit, while SRS may be appropriate for selected patient.

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.

Predictors of time to brain metastasis and survival in patients diagnosed with breast cancer.

e13122 Background: Patients with breast cancer (BC) who develop brain metastases (BM) have poor survival outcomes. We aimed to identify significant predictors of time to develop BM and survival after diagnosis. Methods: Patient records were retrospectively reviewed from the Cleveland Clinic database between 2010-2020. Patients with a BC and a BM diagnosis were included for analysis. One way ANOVA was used to compare mean time to BM across subgroups (mean ± SE), and Kaplan-Meier method was used to compute median overall survival (mOS) after BM diagnosis (95% CI). Results: N=109 patients were included in the analysis with a mean age of 52 ± 13 years, mean time to developing BM of 42 ± 35 months, and mOS after BM of 12.00 months (8.99-15.01). The patients’ characteristics were as follows: female (98.2%), white (83.5%), married (56%), privately insured (43.1%), had a Karnofsky Performance Status (KPS) &gt;80 (61.7%), and 21% had stage IV at initial diagnosis. In terms of BC characteristics, 80.4% of cases were ductal, 63.7% were Grade III, 52.3% were HR+, and 31.5% were HER2+, and 32.4% were triple negative. Most patients had extracranial metastases (ECM) at the time of BM diagnosis (67.8%), had at least 2 sites of BM (71.6%), parenchymal only BM (75%), and 10-30 mm BM (44.2%). 15.8% of patients underwent craniotomy and 86.2% received at least one form of radiotherapy (RT) for BM. The HR+/HER2- group had the longest time to BM compared to the shortest in the triple negative group (61.29 ± 6.95 vs 28.59 months ± 4.80, p&lt;0.001). Patients receiving hormonal therapy had longer time to BM compared to those who didn’t (50.83 ± 5.04 vs 35.98 ± 4.67 months, p=0.034). Patients with Stage I disease had the longest time to develop BM (68.50 ± 13.66 months, p=0.009), while grade III status had the shortest time to BM (34.46 ± 3.46 months, p=0.002). Uninsured patients had the shortest time to BM (22.92 ± 4.09 months, p=0.003). After BM diagnosis, the HR+/HER2+ group achieved the best mOS at 35.00 months (14.20-55.80, p=0.040). Patients receiving Gamma Knife Radiosurgery (GKRS) achieved longer mOS than the other RT modalities at 30.00 months (11.46-48.51) vs 20.00 (1.26-38.74) in GKRS + Whole Brain RT (WBRT), 9.00 (3.43-14.57) in the WBRT, and 2.00 (1.12-2.88) in no RT group (p=0.022). Patients with a KPS of &lt;80 had a shorter mOS compared to those with a KPS of &gt;80 [5.00 (2.02-7.98) vs 17.00 (9.41-24.6), p=0.002]. Patients receiving hormonal therapy had longer mOS compared to those who did not [17.00 (6.58-27.43) vs 9.00 (3.72-14.28), p=0.016]. Patients with stage I disease had longer mOS compared to those with stage II-IV disease [41.00 (22.70-59.30) vs 10.00 (6.60-13.40), p=0.025]. Conclusions: This study identifies significant clinical predictors for BM development and survival in patients with BC including Hormone receptor status, treatment modalities, stage, and KPS. These findings emphasize the need for early BM screening in high-risk patients to improve survival.

Deep learning-based metastasis detection in patients with lung cancer to enhance reproducibility and reduce workload in brain metastasis screening with MRI: a multi-center study

ObjectivesTo assess whether a deep learning-based system (DLS) with black-blood imaging for brain metastasis (BM) improves the diagnostic workflow in a multi-center setting.Materials and methodsIn this retrospective study, a DLS was developed in 101 patients and validated on 264 consecutive patients (with lung cancer) having newly developed BM from two tertiary university hospitals, which performed black-blood imaging between January 2020 and April 2021. Four neuroradiologists independently evaluated BM either with segmented masks and BM counts provided (with DLS) or not provided (without DLS) on a clinical trial imaging management system (CTIMS). To assess reading reproducibility, BM count agreement between the readers and the reference standard were calculated using limits of agreement (LoA). Readers’ workload was assessed with reading time, which was automatically measured on CTIMS, and were compared between with and without DLS using linear mixed models considering the imaging center.ResultsIn the validation cohort, the detection sensitivity and positive predictive value of the DLS were 90.2% (95% confidence interval [CI]: 88.1–92.2) and 88.2% (95% CI: 85.7–90.4), respectively. The difference between the readers and the reference counts was larger without DLS (LoA: −0.281, 95% CI: −2.888, 2.325) than with DLS (LoA: −0.163, 95% CI: −2.692, 2.367). The reading time was reduced from mean 66.9 s (interquartile range: 43.2–90.6) to 57.3 s (interquartile range: 33.6–81.0) (P <.001) in the with DLS group, regardless of the imaging center.ConclusionDeep learning-based BM detection and counting with black-blood imaging improved reproducibility and reduced reading time, on multi-center validation.

Metastasis infiltrating tumor to meningioma: a case report

BackgroundThere have been many reports of tumor-to-tumor metastasis, in which cancer metastasizes directly into meningiomas. However, metastasis infiltrating tumors in which cancer metastasizes around meningiomas are rare. Therefore, we report a case of metastasis originating from lung cancer that infiltrated meningioma.Case presentationA 79-year-old Japanese woman underwent head magnetic resonance imaging for brain metastasis screening before lung cancer surgery. At that time, asymptomatic meningioma of the left frontal region was accidentally found. Magnetic resonance imaging 6 months later revealed a lesion suspected to be a metastatic brain tumor close to the meningioma. Brain tumor resection was performed, and histopathological diagnosis was meningioma and metastatic brain tumor. Metastatic cancer had invaded the meningioma at the boundary between the brain tumor and metastasis.ConclusionsA sudden change in imaging findings on routine examination of meningiomas in patients with lung carcinoma may indicate a metastatic brain tumor. The form of cancer metastasis to meningioma is not limited to tumor-to-tumor metastasis, but also includes metastasis infiltrating tumors near the meningioma.

An evaluation of radiographers’ extended practice in the detection of brain metastases on magnetic resonance images

IntroductionPatients who undergo magnetic resonance (MR) imaging to confirm or rule out metastatic brain disease are required to wait for image review by a radiologist before leaving the department at the institute where this study was carried out. The aim was to evaluate whether radiographers can review images and reduce waiting times in those patients without metastases. MethodsProspective observational study of MR radiographers (n = 11) was undertaken. Radiographers commented on images to confirm whether the images showed evidence of metastatic disease, pathology but no metastases, or no pathology. Responses were compared to the radiological report (reference standard). Online questionnaires determined the views and opinions of radiographers (n = 8) and consultant radiologists (n = 6) towards radiographers expanding their scope of practice to include the confirmation or exclusion of brain metastases. ResultsDespite a lack of formal training for image reviewing, overall level of agreement between the radiographer reviews and reference standard was 77.9 % (κ = 0.45). Pooled sensitivity and specificity were 88.6 % & 71.3 % respectively. Kendall's τ = −0.03 (bootstrap 95 % CI -0.73 to 0.61, p = 0.925). Positive predictive value (PPV) was 65.5 % (CI 59.2%–71.4 %) and negative predictive value (NPV) 91.1 % (CI 84.9%–94.9 %). Radiographers and radiologists surveyed demonstrated a willingness to engage with role expansion. ConclusionBased on our small study and interdisciplinary survey, local radiographers and radiologists agree, following a program of radiographer training, screening for brain metastases by radiographers could be implemented. Implications for practiceWith appropriate governance and training support, the introduction of formal radiographer screening for patients referred to exclude brain metastases could provide more efficient working practice.

Brain metastasis screening in the molecular age.

The incidence of brain metastases (BM) amongst cancer patients has been increasing due to improvements in therapeutic options and an increase in overall survival. Molecular characterization of tumors has provided insights into the biology and oncogenic drivers of BM and molecular subtype-based screening. Though there are currently some screening and surveillance guidelines for BM, they remain limited. In this comprehensive review, we review and present epidemiological data on BM, their molecular characterization, and current screening guidelines. The molecular subtypes with the highest BM incidence are epithelial growth factor receptor-mutated non-small cell lung cancer (NSCLC), BRCA1, triple-negative (TN), and HER2+ breast cancers, and BRAF-mutated melanoma. Furthermore, BMs are more likely to present asymptomatically at diagnosis in oncogene-addicted NSCLC and BRAF-mutated melanoma. European screening standards recommend more frequent screening for oncogene-addicted NSCLC patients, and clinical trials are investigating screening for BM in hormone receptor+, HER2+, and TN breast cancers. However, more work is needed to determine optimal screening guidelines for other primary cancer molecular subtypes. With the advent of personalized medicine, molecular characterization of tumors has revolutionized the landscape of cancer treatment and prognostication. Incorporating molecular characterization into BM screening guidelines may allow physicians to better identify patients at high risk for BM development and improve patient outcomes.

Therapeutic Options for Brain Metastases in Gynecologic Cancers.

Brain metastases (BM) are rare in gynecologic cancers. Overall BM confers a poor prognosis but other factors such as number of brain lesions, patient age, the presence of extracranial metastasis, the Karnofsky Performance Status (KPS) score, and the type of primary cancer also impact prognosis. Taking a patient's whole picture into perspective is crucial in deciding the appropriate management strategy. The management of BM requires an interdisciplinary approach that frequently includes oncology, neurosurgery, radiation oncology and palliative care. Treatment includes both direct targeted therapies to the lesion(s) as well as management of the neurologic side effects caused by mass effect. There is limited evidence of when screening for BM in the gynecology oncology patient is warranted but it is recommended that any cancer patient with new focal neurologic deficit or increasing headaches should be evaluated. The primary imaging modality for detection of BM is MRI, but other imaging modalities such as CT and PET scan can be used for certain scenarios. New advances in radiation techniques, improved imaging modalities, and systemic therapies are helping to discover BM earlier and provide treatments with less detrimental side effects.

Screening for Brain Metastases in Patients With NSCLC: A Qualitative Study on the Psychologic Impact of Being Diagnosed With Asymptomatic Brain Metastases

IntroductionThe brain is a frequent site of metastases in NSCLC, and screening for asymptomatic brain metastases (BM) is increasingly advised in NSCLC guidelines. An asymptomatic BM diagnosis may trigger anxiety for future neurologic problems and can negatively affect quality of life of patients and their relatives. Therefore, we performed this qualitative study. MethodsThree focus group discussions were organized with patients with NSCLC and asymptomatic BM (N = 3–4 per group) and separately with their relatives, to explore this psychosocial impact. Two researchers independently performed an inductive content analysis. ResultsA total of 10 patients and 10 relatives participated in six focus groups. A diagnosis of BM caused feelings of distress and anxiety in both patients and relatives. These feelings diminished over time in case of a tumor responding to systemic therapy. The diagnosis of BM was not perceived as more distressful than other metastases, and scan-related anxiety was not experienced. Although magnetic resonance imaging screening and follow-up were thought of as burdensome, follow-up was valued. The coping strategies of both groups seemed related to personality and to the efficacy of the given systemic therapy. Relatives appreciated peer support of other relatives during the focus groups, and they seemed open for future psychological support. ConclusionsAsymptomatic BM diagnosis can cause anxiety and distress, but this diminishes over time with effective systemic treatment. Although patients perceive magnetic resonance imaging as burdensome, they value follow-up screening and imaging. Relatives highly appreciated peer support, and psychological distress of relatives should not be overlooked.

Abstract OT1-07-01: MRI screening versus symptom-directed surveillance for brain metastases among patients with triple negative or HER2+ metastatic breast cancer: A pilot study (nct03881605)

Abstract Background: The incidence of brain metastases (BrM) has steadily increased over time as women with metastatic breast cancer (MBC) live longer and survive to experience spread of cancer to the central nervous system (CNS). Women with triple negative and HER2+ MBC, which represent 30-40% of the MBC population, are at particularly high risk of BrM. At present, MBC patients are not screened for BrM; rather, they undergo imaging of the brain only after symptoms suggestive of CNS involvement develop. Unfortunately, by the time that patients experience potentially debilitating symptoms of BrM, they often have a significant burden of disease with limited treatment options and a poor prognosis. We hypothesize that early detection of BrM via magnetic resonance imaging (MRI)-based screening may allow for early intervention and, ultimately, improved outcomes for MBC patients. Methods: A multi-centre, open-label prospective phase II study, randomizing 50 women with triple negative or HER2+ MBC to either MRI-based BrM screening or symptom-directed surveillance. Randomization is stratified for tumor subtype. Intervention arm: Contrast-enhanced MRI of the brain at baseline, 4-, 8- and 12-months with concurrent chemical exchange saturation transfer (CEST) imaging, a new metabolic MRI sequence that may detect BrM even earlier than standard MRI. Control arm: Symptom-directed surveillance (brain imaging only if patients develop symptoms suggestive of BrM). All participants complete questionnaires at baseline, 6- and 15-months to assess overall (EORTC QLQ BN20) and neurologic-specific (FACT-BR tools) quality of life (QoL) as well as cancer-related anxiety (NCI PRO-CTCAE). A blood sample is collected for ctDNA analysis at baseline in all patients at diagnosis of BrM, if applicable. Key inclusion criteria: 1) Age ≥18; 2) Triple negative MBC, with metastatic disease diagnosed ≤12 weeks prior to study entry OR HER2+ MBC with no restrictions regarding timeline of diagnosis; 3) No symptoms of BrM or known asymptomatic BrM at study entry. Key exclusion criteria: 1) ECOG&amp;gt;2; 2) Inability to complete an MRI (e.g., claustrophobia). Analyses: The primary goal of this study is to determine the feasibility of a randomized trial of BrM screening versus symptom-directed surveillance in the proposed patient population. The pilot study will be considered “not feasible” if &amp;lt;30% of eligible patients enroll, &amp;lt;50% complete the study protocol, and/or &amp;gt;50% of patients allocated to the control arm are screened for BrM with CT or MRI. Overall survival will be assessed as a secondary endpoint. We will also investigate how screening for BrM influences the detection rate of BrM and explore how subsequent intervention affects both overall and neurologic-specific QoL. Our data will enable a power calculation to determine a sample size for a future, larger trial. 28 of 50 planned patients have enrolled in the study to-date. Citation Format: Katarzyna J Jerzak, Arjun Sahgal, Gregory Pond, Priscilla K Brastianos, Orit Freedman, Gregory Stanisz, Ellen Warner. MRI screening versus symptom-directed surveillance for brain metastases among patients with triple negative or HER2+ metastatic breast cancer: A pilot study (nct03881605) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-07-01.

A pre-operative MRI-based brain metastasis risk-prediction model for triple-negative breast cancer.

Triple-negative breast cancer (TNBC) patients have a high 2-year post-operative incidence of brain metastasis (BM). Currently, there is no early prediction tool to predict the risk of BM in TNBC patients. Data of breast cancer patients, who had been scanned, resected, and pathologically diagnosed at a local hospital from May 2012 to June 2018 were collected. Primary and radiological secondary exclusion criteria were used to determine patients' eligibility for inclusion in the study. Data for the TNBC cohort included qualified 2-year post-operative follow-up information, BM status, and pre-operative MRI data. Age-based propensity score matching (PSM) was used to build a comparable study cohort. The tumor regions of interest were segmented and used for lattice radiomics feature extraction. The filtered and normalized lattice radiomics features were then trained with BM status using the random forest (RF), support vector machine (SVM), k-nearest neighbor, least absolute shrinkage and selection operator regression, naïve Bayesian, and neural network algorithms. The generated prediction models were evaluated using 10-fold cross verification, and the areas under the curve (AUCs), accuracy, sensitivity, and specificity were reported. Data from 643 breast cancer patients were collected. Among these, 84 TNBC cases (comprising 42 pairs) were included in this study after primary exclusion, radiological secondary exclusion, and PSM. We extracted 3,854 lattice radiomics features from the pre-operative MRI. Of these, 2,480 were used for model training after filtration. The 10-fold verification results showed that the BM risk-prediction model, which was based on the normalized and filtered lattice radiomics features of collected cases trained by naïve Bayesian algorithm, had a high AUC (0.878), accuracy (0.786), specificity (81.0%), and sensitivity (76.2%). The pre-operative MRI data of TNBC patients can be used to predict 2-year BM risk. This application could help to achieve better early stratification, BM screening, and the overall prognosis.

Brain Metastases in HER2-Positive Breast Cancer: Current and Novel Treatment Strategies.

Simple SummaryDevelopment of brain metastases is an important event for patients with breast cancer, and it affects both their survival and their quality of life. Patients with HER2-positive breast cancer are more commonly affected by brain metastases compared to patients with HER2-negative/hormone receptor-positive breast cancer. It is essential to find proper therapies that reduce the risk for metastasis in the brain, as well as agents that are active when metastatic lesions develop. Management of HER2-positive breast cancer has drastically improved in recent years due to the development of several drugs targeting the HER2 receptor. This review aims to provide insight into current and novel treatment strategies for patients with brain metastases from HER2-positive breast cancer.Development of brain metastases can occur in up to 30–50% of patients with breast cancer, representing a significant impact on an individual patient in terms of survival and quality of life. Patients with HER2-positive breast cancer have an increased risk of developing brain metastases; however, screening for brain metastases is not currently recommended due to the lack of robust evidence to support survival benefit. In recent years, several novel anti-HER2 agents have led to significant improvements in the outcomes of HER2-positive metastatic breast cancer. Despite these advances, brain and leptomeningeal metastases from HER2-positive breast cancer remain a significant cause of morbidity and mortality, and their optimal management remains an unmet need. This review presents an update on the current and novel treatment strategies for patients with brain metastases from HER2-positive breast cancer and discusses the open questions in the field.

Evaluation of Serum Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Screening and Monitoring Biomarkers for Brain Metastases.

Simple SummaryApproximately 20% of patients with cancer develop brain metastases (BM). Early BM diagnosis is critical to enable less invasive or toxic approaches. Sensitive and easy-to-use blood-based BM biomarkers may allow early diagnosis and appropriate timely treatment and may improve overall survival. This study aimed to evaluate the potential roles of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) for diagnosing and monitoring BM. We found significant differences in the sNfL and the sGFAP levels between patients with and without BMs. The optimal cutoff-levels of sNfL and sGFAP had sensitivities of 91% and 91%, respectively, and combining the two biomarkers (sNfL or sGFAP) improved the sensitivity to up to 98%, with an overall accuracy higher than 91%. Thus, sNfL and sGFAP may be used as biomarkers for BM screening in patients with cancer.We evaluated the potential serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) roles in diagnosing and monitoring brain metastases (BMs). We included 70 patients with newly diagnosed BMs, 71 age- and cancer type-matched patients without BMs, and 67 healthy controls (HCs). We compared sNfL and sGFAP levels among the groups using a single-molecule array immunoassay. We prospectively followed 26 patients with BMs every 2–3 months by measuring sNfL and sGFAP levels and performing magnetic resonance imaging (MRI) scans. The sNfL and the sGFAP levels were higher in patients with BMs (medians: sNfL, 63.7 µL; sGFAP, 819.5 pg/µL) than in those without BMs (sNfL, 13.3 µL; sGFAP, 154 pg/µL; p < 0.001) and HCs (sNfL, 12.5 µL; sGFAP, 135 pg/µL; p < 0.001). The sNfL and the sGFAP cutoff levels had a sensitivity and a specificity of 91%. The sGFAP cutoff level had a sensitivity of 91% and a specificity of 97%. The sNfL and the sGFAP levels were related to the BM size but not to the primary cancer type. After BM treatment, sNfL and sGFAP levels decreased with reduced BM lesions on MRI; however, they increased when BMs progressed. sNfL and sGFAP are potential biomarkers for BM screening in cancer patients.

Clinical utility of head computed tomography scan during systemic therapy for metastatic renal cell carcinoma

The utility of brain metastasis screening in asymptomatic metastatic renal cell carcinoma is controversial. Our study evaluated the utility of routine head computed tomography during systemic therapy. We retrospectively investigated 152 metastatic renal cell carcinoma patients who did not initially have brain metastasis at Yamagata University Hospital from January 2008 to July 2019. Patients who routinely received head computed tomography scan together with routine contrast-enhanced chest/abdominal/pelvic computed tomography scan every 2-4months during systemic therapy ("Routine head computed tomography" group, n=95) and patients without routine head computed tomography ("No routine head computed tomography" group, n=57) were compared. Brain metastasis occurred in 16 patients in the "Routine head computed tomography" group and six patients in the "No routine head computed tomography" group. There was no statistical difference in overall survival after metastatic renal cell carcinoma diagnosis between groups (53.4 vs 37.3months, respectively, P=0.357) and neurological symptom-free survival after metastatic renal cell carcinoma diagnosis (53.4 vs 36.6months, P=0.336). Although there was no statistical difference on incidence of unrecovered neurological symptom (25.0% vs 50.0%, P=0.334), fewer patients in the "Routine head computed tomography" group required craniotomy (0% vs 66.7%, P=0.002). In the "No routine head computed tomography" group, the neurological symptom resolved for all patients without craniotomy. Routine head computed tomography during systemic therapy for metastatic renal cell carcinoma is not significantly associated with improved brain metastasis prognosis. However, routine head computed tomography enables brain metastasis diagnosis in the asymptomatic phase, which can avoid craniotomy.

Development of CNS metastases in breast cancer patients treated with curative intent: a case-control study.

Background:The aim of this study was to identify risk factors that may predispose breast cancer patients to the development of CNS metastases.Materials & methods:We conducted a matched case–control study of breast cancer patients treated with surgery with curative intent. A total of 71 cases and 71 controls were analyzed, matched by year of surgery.Results:In our multivariable model, positive lymph node status (odds ratio [OR]: 5.08; CI: 2.04–12.65), the use of neoadjuvant chemotherapy (OR: 6.02; CI: 2.06–17.57) and triple-negative breast cancer (OR: 5.44; CI: 1.99–14.90) were statistically significant predictors of the development of CNS metastases.Conclusion:Women with certain risk factors have an increased odds of developing CNS metastases and evaluation of utility in brain metastases screening should be considered.

402PD - Impact of neurological symptom burden on the survival prognosis in a real-life cohort of patients with non-small cell lung cancer brain metastases

BackgroundThe high efficacy of targeted treatments in a- to oligosymptomatic non-small cell lung cancer (NSCLC) brain metastases (BM) revived the long discussion on BM screening. Therefore, we aimed to investigate the prognostic impact of symptomatic burden in patients with newly NSCLC BM in a large real-life cohort. MethodsPatients with newly diagnosed NSCLC BM were identified from the Vienna Brain Metastasis Registry. Results1531 patients (male 57.4%, female 42.3%; median age 62 years) were available for further analysis. Neurological symptoms including neurological deficits (952/153; 62.2%), symptoms of increased intracranial pressure (456/153; 29.8%) and epileptic seizures (199/1531; 13.0%) were evident in 1125/1531 (73.5%) patients. Oligo-to asymptomatic BM were significantly more frequently observed in patients with synchronous diagnosis of BM and NSCLC (p<0.001). Patients with oligo- to asymptomatic BM presented with a longer median overall survival after diagnosis of BM compared to patients with symptomatic BM (11 vs. 7 months; p<0.001). In detail, presence of increased intracranial pressure and seizures showed no impact on survival prognosis (p>0.05), while the median overall survival was significantly longer in patients without neurological deficits (11 vs. 7 months; p<0.001): memory disorders (6 vs. 8 months; p>0.05), ataxia (7 vs. 8; p=0.041) and vertigo (6 vs. 9; p=0.007). In multivariate analysis with DS-GPA (HR 1.41; 95% CI 1.33-1.50; p<0.001), the presence of neurological symptoms was independently associated with survival prognosis from diagnosis of BM (HR 1.19; 95% CI 1.05-1.36; p=0.007). Interestingly, the prognostic impact of neurological symptoms was more pronounced in patients with lower DS-GPA class II-IV (class II: 15 vs. 11; p=0.002, class III: 10 vs. 6; p<0.001, class IV: 6 vs. 3; p=0.018) compared to patients with DS-GPA class I (19 vs. 14; p=0.230). ConclusionsPresence of neurological symptoms presented with a strong and independent association with survival prognosis from diagnosis of BM especially in patients with lower DS-GPA and should be further evaluated for inclusion in the prognostic assessment of patients with newly diagnosed NSCLC BM. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureM. Preusser: Research grant / Funding (self): Böhringer-Ingelheim; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (self): GlaxoSmithKline; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Merck Sharp & Dome; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Gerson Lehrman Group; Honoraria (self), Advisory / Consultancy: CMC Contrast; Honoraria (self), Advisory / Consultancy: Mundipharma; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Medahead; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo. A.S. Berghoff: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Daiichi Sankyo; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Bristol-Meyers Squibb; Honoraria (self), Advisory / Consultancy: Merck; Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: AbbVie. All other authors have declared no conflicts of interest.

THER-07. DEVELOPMENT OF A NEW MOLECULAR PREDICTOR FOR RISK OF BRAIN METASTASES AND EFFICACY OF TARGETED THERAPY IN MELANOMA

Despite therapeutic advances in the treatment of melanoma, development of brain metastases (BM) continues to be a major manifestation of treatment failure. The ability to identify those patients who are at highest risk of developing brain metastases is limited with current methods. Development of sensitive and specific biomarkers to predict which stage II-III melanoma patients are at highest risk of BM would enable initiation of prospective clinical trials focused on both intensive surveillance and therapeutic prevention. To accomplish this goal, we embarked on an effort to optimize a combined molecular/clinical/pathologic predictor of BM risk. We firstanalyzed multiple gene expression datasets including TCGA (n = 437) and an independent series from Australia (n = 183) and identified a list of 60 consensus genes that is robustly predictive of development of melanoma BM (p < 0.05; FDR 5%). Next, we performed a similar analysis of association of miRNAs and melanoma BM risk which identified a set of miRNAs with significant predictive power. An optimized combined set of mRNA and miRNA markers was a better predictor of BM risk than either mRNA or miRNA list alone when applied to the TCGA data set. The combined predictor was most sensitive in separating patients with no metastases from those with either BM or systemic metastases. Current efforts are focused on optimizing miRNA and mRNA separation of patients specifically with BM from those with other mets, and with integrating the expression classifier with other clinical and pathologic predictive factors including: age, stage, thickness, location, histology, ulceration, gender. The sensitivity and specificity of the resulting clinical/molecular predictor will be validated in an independent retrospective cohort, and subsequently implemented in a prospective BM screening trial to determine real-world utility of this approach in preparation for prospective BM adjuvant/chemoprevention trials utilizing both immunotherapy and targeted therapy approaches.

Screening for brain metastases in patients with stage III non–small-cell lung cancer, magnetic resonance imaging or computed tomography? A prospective study

IntroductionNon–small-cell lung cancer (NSCLC) guidelines advise to screen stage III NSCLC patients for brain metastases (BMs), preferably by magnetic resonance imaging (MRI) or when contraindicated or not accessible a dedicated contrast enhanced–computed tomography (dCE-CT), which can be incorporated in the staging 18Fluodeoxoglucose–positron emission tomography (18FDG-PET-CE-CT). In daily practice, often a dCE-CT is performed instead of a MRI. The aim of the current study is to evaluate the additive value of MRI after dCE-CT, incorporated in the 18FDG-PET-CE-CT. Patients and methodsIt is an observational prospective multicentre study (NTR3628). Inclusion criteria included stage III NSCLC patients with a dCE-CT of the brain incorporated in the 18FDG-PET and an additional MRI of the brain. Primary end-point is percentage of patients with BM on MRI without suspect lesions on dCE-CT. Secondary end-points are percentage of patients with BM on dCE-CT and percentage of patients with BM ≤ 1 year of a negative staging MRI. ResultsSixteen (7%) patients with extracranial stage III had BM on dCE-CT and were excluded. One hundred forty-nine patients were enrolled. 7/149 (4.7%) had BM on MRI without suspect lesions on dCE-CT. One hundred eighteen patients had a follow-up of at least 1 year (four with BM on baseline MRI); eight of the remaining 114 (7%) patients developed BM ≤ 1 year after a negative staging brain MRI. ConclusionAlthough in 7% of otherwise stage III NSCLC patients, BMs were detected on staging dCE-CT, MRI brain detected BMs in an additional 4.7%, which we consider clinically relevant. Within 1 year after a negative staging MRI, 7% developed BM.

Clinical characteristics, treatment (Tx) patterns, and overall survival (OS) in advanced (Adv) NSCLC patients (Pts) with and without brain metastases (BM).

2035 Background: BM in NSCLC pts are associated with significant morbidity and mortality. This analysis describes the frequency and timing of BM development, pt characteristics, systemic txs, and OS in NSCLC pts with and without BM. Methods: This retrospective observational study identified pts from the Flatiron-Foundation Medicine NSCLC Clinico-Genomic Database diagnosed from 1 Jan 2011 to 31 Oct 2017 with adv NSCLC and a tumor sample analyzed via FoundationOne. Tx pattern data were summarized by period (1 Jan 2011-1 Mar 2015; 2 Mar 2015-31 Dec 2017), therapy class (eg, anti-VEGF and EGFR, platinum-based), and BM occurrence. Descriptive statistics were used to summarize data; Chi-square and t-tests assessed statistically significant differences. OS was measured by site of met (BM only vs no-BM only vs BM and no-BM) via K-M methods from adv diagnosis until death or last activity date (censored). Results: Of 3257 pts, 1018/3257 (31.3%) had BM during follow-up; 726/1018 (71.3%) presented with BM within 30 days of adv diagnosis. The median age at adv diagnosis was 66.2 yrs. Relative to pts without BM, BM pts were younger, more likely to be female, of Asian descent, have stage IV disease, ≥2 met sites (including BM) at initial presentation, ≥3 met sites (including BM) during follow-up, and non-squamous histology (all p &lt; 0.01). Approximately 78% (n = 2534) were treated with ≥1 systemic tx; platinum-based chemo-combinations were the most common 1st line tx, regardless of BM status. Increased use of PD-1/L1 tx was seen in 1st, 2nd, and 3rdline during the latter vs earlier period. No statistically significant difference in OS was observed in pts with BM only (17.1 mos; 95% CI 12.5-29.9), no-BM only (21 mos; 95% CI 19.4-22.8), or BM and no-BM (20.4 mos; 95% CI 18.9-23.3) (log rank p = 0.3027). Conclusions: In met NSCLC pts with a tumor sample that was molecularly profiled, OS was comparable, regardless of site(s) of disease; additional multivariate analyses including molecular profiles are needed. BM screening at initial diagnosis is important given the frequency in NSCLC. Future studies should assess whether the shift in systemic tx patterns impact the development and clinical outcomes.