CT in the Differentiation of Gliomas from Brain Metastases: The Radiomics Analysis of the Peritumoral Zone

Due to their similar imaging features, high-grade gliomas (HGGs) and solitary brain metastases (BMs) can be easily misclassified. The peritumoral zone (PZ) of HGGs develops neoplastic cell infiltration, while in BMs the PZ contains pure vasogenic edema. As the two PZs cannot be differentiated macroscopically, this study investigated whether computed tomography (CT)-based texture analysis (TA) of the PZ can reflect the histological difference between the two entities. Thirty-six patients with solitary brain tumors (HGGs, n = 17; BMs, n = 19) that underwent CT examinations were retrospectively included in this pilot study. TA of the PZ was analyzed using dedicated software (MaZda version 5). Univariate, multivariate, and receiver operating characteristics analyses were used to identify the best-suited parameters for distinguishing between the two groups. Seven texture parameters were able to differentiate between HGGs and BMs with variable sensitivity (56.67–96.67%) and specificity (69.23–100%) rates. Their combined ability successfully identified HGGs with 77.9–99.2% sensitivity and 75.3–100% specificity. In conclusion, the CT-based TA can be a useful tool for differentiating between primary and secondary malignancies. The TA features indicate a more heterogenous content of the HGGs’ PZ, possibly due to the local infiltration of neoplastic cells.

Tucatinib (Tukysa)

CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec. This review assesses tucatinib (Tukysa), 50 mg and 150 mg tablets, orally. Tucatinib in combination with trastuzumab and capecitabine for the treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received prior treatment with trastuzumab, pertuzumab, and T-DM1 separately or in combination.

Screening and Identification of Novel Potential Biomarkers for Breast Cancer Brain Metastases

Brain metastases represent a major cause of mortality among patients with breast cancer, and few effective targeted treatment options are currently available. Development of new biomarkers and therapeutic targets for breast cancer brain metastases (BCBM) is therefore urgently needed. In this study, we compared the gene expression profiles of the brain metastatic cell line MDA-MB-231-BR (231-BR) and its parental MDA-MB-231, and identified a total of 84 genes in the primary screening through a series of bioinformatic analyses, including construction of protein-protein interaction (PPI) networks by STRING database, identification of hub genes by applying of MCODE and Cytohubba algorithms, identification of leading-edge subsets of Gene Set Enrichment Analysis (GSEA), and identification of most up-regulated genes. Eight genes were identified as candidate genes due to their elevated expression in brain metastatic 231-BR cells and prognostic values in patients with BCBM. Then we knocked down the eight individual candidate genes in 231-BR cells and evaluated their impact on cell migration through a wound-healing assay, and four of them (KRT19, FKBP10, GSK3B and SPANXB1) were finally identified as key genes. Furthermore, the expression of individual key genes showed a correlation with the infiltration of major immune cells in the brain tumor microenvironment (TME) as analyzed by Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA), suggesting possible roles of them in regulation of the tumor immune response in TME. Therefore, the present work may provide new potential biomarkers for BCBM. Additionally, using GSEA, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Enrichment Analysis, we determined the top enriched cellular functions or pathways in 231-BR cells, which may help better understand the biology governing the development and progression of BCBM.

Hemorrhagic Brain Metastases: A Diagnostic Dilemma and Diagnosis of Exclusion

Pleomorphic carcinoma is a malignant and aggressive primary lung carcinoma that occurs at a rate of approximately 0.3%. This rarely encountered tumor may present a diagnostic challenge to neuroradiologists and pathologists, as it has propensity to present as hemorrhagic brain metastasis with unknown primary and result in delay in diagnosis that could impact clinical outcome. Herein, we report a unique case in its presentation in a 56-year-old female, having symptomatic brain metastasis prior to the discovery of the pulmonary lesion.

Volume of Disease as a Predictor for Clinical Outcomes in Patients With Melanoma Brain Metastases Treated With Stereotactic Radiosurgery and Immune Checkpoint Therapy

Purpose/ObjectivesClinical trials of anti-Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein (CTLA-4) therapies have demonstrated a clinical benefit with low rates of neurologic adverse events in patients with melanoma brain metastases (MBMs). While the combined effect of these immunotherapies (ITs) and stereotactic radiosurgery (SRS) has yielded impressive results with regard to local control (LC) and overall survival (OS), it has also been associated with increased rates of radiation necrosis (RN) compared to historical series of SRS alone. We retrospectively reviewed patients treated with IT in combination with SRS to report on predictors of clinical outcomes.Materials and MethodsPatients were included if they had MBMs treated with SRS within 1 year of receiving anti-PD-1 and/or CTLA-4 therapy. Clinical outcomes including OS, LC, intracranial death (ID), and RN were correlated with type and timing of IT with SRS, radiation dose, total volume, and size and number of lesions treated.ResultsTwenty-nine patients with 171 MBMs were treated between May 2012 and May 2018. Patients had a median of 5 lesions treated (median volume of 6.5 cm3) over a median of 2 courses of SRS. The median dose was 21 Gy. Most patients were treated with ipilimumab (n = 13) or nivolumab-ipilimumab (n = 10). Most patients underwent SRS concurrently or within 3 months of receiving immunotherapy (n = 21). Two-year OS and LC were 54.4% and 85.5%, respectively. In addition, 14% of patients developed RN; however, only 4.7% of the total treated lesions developed RN. The median time to development of RN was 9.5 months. Patients with an aggregate tumor volume >6.5 cm3 were found to be at increased risk of ID (p = 0.05) and RN (p = 0.03). There was no difference in OS, ID, or RN with regard to type of IT, timing of SRS and IT, number of SRS courses, SRS dose, or number of cumulative lesions treated.ConclusionsIn our series, patients treated with SRS and IT for MBMs had excellent rates of OS and LC; however, patients with an aggregate tumor volume >6.5 cm3 were found to be at increased risk of ID and RN. Given the efficacy of combined anti-PD-1/CTLA-4 therapy for MBM management, further study of optimal selection criteria for the addition of SRS is warranted.

Primary systemic therapy for patients with brain metastases from lung cancer ineligible for targeted agents

Purpose The purpose of this study was to evaluate overall survival after systemic therapy, largely chemotherapy, in patients with small cell or non-small cell lung cancer and brain metastases. After completion of systemic therapy, some patients received planned brain irradiation, while others were followed. Methods Retrospective cohort study. Results Thirty-eight patients were included (28 small cell, 20 followed with imaging). Six of these 20 patients (30%) received delayed radiotherapy during follow-up. Planned radiotherapy (n = 18, intention-to-treat) was associated with longer survival from diagnosis of brain metastases, median 10.8 versus 6.1 months, p = 0.025. Delayed radiotherapy still resulted in numerically better survival than no radiotherapy at all (median 8.8 versus 5.3 months, not significant). If calculated from the start of delayed radiotherapy, median survival was only 2.7 months. In a multivariable analysis, both Karnofsky performance status ≥ 70 (p = 0.03) and planned radiotherapy (p = 0.05) were associated with better survival. Conclusion In patients ineligible for targeted agents, planned radiotherapy in a modern treatment setting was associated with longer survival compared to no radiotherapy. Timing and type of radiotherapy in such patients should be evaluated in prospective trials to identify patients who might not need planned radiotherapy.