Single brain metastases - prognostic factors and impact of residual tumor burden on overall survival.

Background: Brain metastases (BM) are a common and challenging issue, with their incidence on the rise due to advancements in systemic therapies and increased patient survival. Most patients present with single BM, some of them without any further extracranial metastasis (i.e., solitary BM). The significance of postoperative intracranial tumor volume in the treatment of singular and solitary BM is still debated. Objective: This study aimed to determine the impact of resection and postoperative tumor burden on overall survival (OS) in patients with single BM. Methods: Patients with surgically treated single BM between 04/2007-01/2020 were retrospectively included. Residual tumor burden (RTB) was determined by manual segmentation of early postoperative brain MRI (72 h). Survival analyses were performed using Kaplan-Meier estimates for univariate analysis and Cox regression proportional hazards model for multivariate analysis, using preoperative Karnofsky performance status scale (KPSS), age, sex, RTB, incomplete resection and singular/solitary BM as covariates. Results: 340 patients were included, median age 64 years (54-71). 119 patients (35%) had solitary BM, 221 (65%) singular BM. Complete resection (RTB=0) was achieved in 73%, median preoperative tumor burden was 11.2 cm3 (5-25), and RTB 0 cm3 (0-0.2). Median OS of patients with singular BM was 13 months (4-33) vs 20 months (5-92) for solitary BM; p=0.062. Multivariate analysis revealed singular BM as independent risk factor for poorer OS: HR 1.840 (1.202-2.817), p=0.005. Complete vs. incomplete resection showed no significant OS difference (13 vs. 13 months, p=0.737). When focusing on solitary BM, complete resection led to a longer OS than incomplete resection (21 vs. 8 months), without statistical significance(p=0.250). Achieving RTB=0 resulted in higher OS for patients with solitary BM compared to singular BM (21 vs. 12 months, p=0.027). Patients who received postoperative radiotherapy (RT) had significantly longer OS compared to those without it (14 vs. 4 months, p<0.001), with favorable OS in those receiving stereotactic radiosurgery (SRS) (15 months (3-42), p<0.001) or hypofractionated stereotactic radiotherapy (HSRT). Conclusion: When complete intracranial tumor resection RTB=0 is achieved, patients with solitary BM have a favorable outcome compared to singular BM. Singular BM was confirmed as independent risk factor. There is a strong presumption that complete resection leads to an improved oncological prognosis. Patients with solitary BM tend to benefit with a favorable outcome following complete resection. Hence, surgical resection should be considered as a treatment option for patients presenting with either no or minimal extracranial disease. Furthermore, the highly favorable impact of postoperative RT on OS was demonstrated and confirmed, especially with SRS or HSRT.

Prostate cancer brain metastases: Monitoring response to treatment with PSMA PET/CT.

Prostate cancer brain metastases are rare but increasingly recognized with prostate-specific membrane antigen (PSMA) PET/CT. Distinguishing tumor response from postradiation changes are challenging on MRI. PSMA PET/CT may clarify equivocal brain lesions after radiotherapy. A 71-year-old man with metastatic prostate cancer developed 2 new brain lesions on PSMA PET/CT. Lesions were high PSMA-avid and MRI follow up showed enhancing masses with edema, consistent with metastases. He underwent whole-brain radiation. Follow-up PSMA PET/CT after radiotherapy demonstrated significantly decreased lesion size and activity, with activity lower than blood pool, indicating a treatment response. MRI also showed near-resolution of the lesions. This case highlights the potential utility of PSMA PET/CT for detecting prostate cancer brain metastases and monitoring treatment response. PSMA PET/CT provides valuable complementary information to MRI for managing irradiated prostate cancer brain metastases.

Classification of high-grade glioblastoma and single brain metastases using a new SCAT-inception model trained with MRI images.

Background and objectives: Glioblastoma (GBM) and brain metastasis (MET) are the two most common intracranial tumors. However, the different pathogenesis of the two tumors leads to completely different treatment options. In terms of magnetic resonance imaging (MRI), GBM and MET are extremely similar, which makes differentiation by imaging extremely challenging. Therefore, this study explores an improved deep learning algorithm to assist in the differentiation of GBM and MET. Materials and methods: For this study, axial contrast-enhanced T1 weight (ceT1W) MRI images from 321 cases of high-grade gliomas and solitary brain metastasis were collected. Among these, 251 out of 270 cases were selected for the experimental dataset (127 glioblastomas and 124 metastases), 207 cases were chosen as the training dataset, and 44 cases as the testing dataset. We designed a new deep learning algorithm called SCAT-inception (Spatial Convolutional Attention inception) and used five-fold cross-validation to verify the results. Results: By employing the newly designed SCAT-inception model to predict glioblastomas and brain metastasis, the prediction accuracy reached 92.3%, and the sensitivity and specificity reached 93.5 and 91.1%, respectively. On the external testing dataset, our model achieved an accuracy of 91.5%, which surpasses other model performances such as VGG, UNet, and GoogLeNet. Conclusion: This study demonstrated that the SCAT-inception architecture could extract more subtle features from ceT1W images, provide state-of-the-art performance in the differentiation of GBM and MET, and surpass most existing approaches.

Machine learning-driven prediction of brain metastasis in lung adenocarcinoma using miRNA profile and target gene pathway analysis of an mRNA dataset.

BACKGROUND: Brain metastasis (BM) is common in lung adenocarcinoma (LUAD) and has a poor prognosis, necessitating predictive biomarkers. MicroRNAs (MiRNAs) promote cancer cell growth, infiltration, and metastasis. However, the relationship between the miRNA expression profiles and BM occurrence in patients with LUAD remains unclear. METHODS: We conducted an analysis to identify miRNAs in tissue samples that exhibited different expression levels between patients with and without BM. Using a machine learning approach, we confirmed whether the miRNA profile could be a predictive tool for BM. We performed pathway analysis of miRNA target genes using a matched mRNA dataset. RESULTS: We selected 25 miRNAs that consistently exhibited differential expression between the two groups of 32 samples. The 25-miRNA profile demonstrated a strong predictive potential for BM in both Group 1 and Group 2 and the entire dataset (area under the curve [AUC] = 0.918, accuracy = 0.875 in Group 1; AUC = 0.867, accuracy = 0.781 in Group 2; and AUC = 0.908, accuracy = 0.875 in the entire group). Patients predicted to have BM, based on the 25-miRNA profile, had lower survival rates. Target gene analysis of miRNAs suggested that BM could be induced through the ErbB signaling pathway, proteoglycans in cancer, and the focal adhesion pathway. Furthermore, patients predicted to have BM based on the 25-miRNA profile exhibited higher expression of the epithelial-mesenchymal transition signature, TWIST, and vimentin than those not predicted to have BM. Specifically, there was a correlation between EGFR mRNA levels and BM. CONCLUSIONS: This 25-miRNA profile may serve as a biomarker for predicting BM in patients with LUAD.

Identification of a gene expression signature associated with brain metastasis in colorectal cancer.

PURPOSE: Brain metastasis (BM) in colorectal cancer (CRC) is a rare event with poor prognosis. Apart from (K)RAS status and lung and bone metastasis no biomarkers exist to identify patients at risk. This study aimed to identify a gene expression signature associated with colorectal BM. METHODS: Three patient groups were formed: 1. CRC with brain metastasis (BRA), 2. exclusive liver metastasis (HEP) and, 3. non-metastatic disease (M0). RNA was extracted from primary tumors and mRNA expression was measured using a NanoString Panel (770 genes). Expression was confirmed by qPCR in a validation cohort. Statistical analyses including multivariate logistic regression followed by receiver operating characteristic (ROC) analysis were performed. RESULTS: EMILIN3, MTA1, SV2B, TMPRSS6, ACVR1C, NFAT5 and SMC3 were differentially expressed in BRA and HEP/M0 groups. In the validation cohort, differential NFAT5, ACVR1C and SMC3 expressions were confirmed. BRA patients showed highest NFAT5 levels compared to HEP/M0 groups (global p = 0.02). High ACVR1C expression was observed more frequently in the BRA group (42.9%) than in HEP (0%) and M0 (7.1%) groups (global p = 0.01). High SMC3 expressions were only detectable in the BRA group (global p = 0.003). Only patients with BM showed a combined high expression of NFAT5, ACVR1C or SMC3 as well as of all three genes. ROC analysis revealed a good prediction of brain metastasis by the three genes (area under the curve (AUC) = 0.78). CONCLUSIONS: The NFAT5, ACVR1C and SMC3 gene expression signature is associated with colorectal BM. Future studies should further investigate the importance of this biomarker signature.

Desmoplastic Small Round Cell Tumor Presenting as an Intra/Extracranial Mass.

Desmoplastic small round cell tumors (DSRCTs) are highly malignant tumors, with distinct reciprocal chromosome translocation (11;22)(p13;q12). Intracranial metastasis is a very rare complication of this tumor, with only a few cases reported in the literature. To our knowledge, this is the only case presenting an extracranial extension of intracranial metastasis of DSRCT. A 33-year-old man was diagnosed with DSRCT in the pelvic cavity. He presented with a scalp lump and right-sided weakness. A biopsy showed metastasis from DSRCT. Metastatic DSRCT to the brain is extremely rare. Surgical resection followed by adjuvant treatment, including chemotherapy and radiation, is indicated as it has a poor prognosis. Moreover, aggressive treatment is warranted to prevent progression and relapse.

Habitat-Based Radiomics for Predicting EGFR Mutations in Exon 19 and 21 From Brain Metastasis.

RATIONALE AND OBJECTIVES: To explore and externally validate habitat-based radiomics for preoperative prediction of epidermal growth factor receptor (EGFR) mutations in exon 19 and 21 from MRI imaging of non-small cell lung cancer (NSCLC)-originated brain metastasis (BM). METHODS: A total of 170, 62 and 61 patients from center 1, center 2 and center 3, respectively were included. All patients underwent contrast-enhanced T1-weighted (T1CE) and T2-weighted (T2W) MRI scans. Radiomics features were extracted from the tumor active (TA) and peritumoral edema (PE) regions in each MRI slice. The most important features were selected by the least absolute shrinkage and selection operator regression to develop radiomics signatures based on TA (RS-TA), PE (RS-PE) and their combination (RS-Com). Receiver operating characteristic (ROC) curve analysis was performed to access performance of radiomics models for both internal and external validation cohorts. RESULTS: 10, four and six most predictive features were identified to be strongly associated with the EGFR mutation status, exon 19 and exon 21, respectively. The RSs derived from the PE region outperformed those from the TA region for predicting the EGFR mutation, exon 19 and exon 21. The RS-Coms generated the highest performance in the primary training (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.955 vs. 0.946 vs. 0.928), internal validation (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.879 vs. 0.819 vs. 0.882), external validation 1 (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.830 vs. 0.825 vs. 0.822), and external validation 2 (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.812 vs. 0.818 vs. 0.800) cohort. CONCLUSION: The developed habitat-based radiomics model can be used to accurately predict the EGFR mutation subtypes, which may potentially guide personalized treatments for NSCLC patients with BM.

High expression of SULF1 is associated with adverse prognosis in breast cancer brain metastasis.

BACKGROUND: Breast cancer is the most common cancer in women, and in advanced stages, it often metastasizes to the brain. However, research on the biological mechanisms of breast cancer brain metastasis and potential therapeutic targets are limited. METHODS: Differential gene expression analysis (DEGs) for the datasets GSE43837 and GSE125989 from the GEO database was performed using online analysis tools such as GEO2R and Sangerbox. Further investigation related to SULF1 was conducted using online databases such as Kaplan-Meier Plotter and cBioPortal. Thus, expression levels, variations, associations with HER2, biological processes, and pathways involving SULF1 could be analyzed using UALCAN, cBioPortal, GEPIA2, and LinkedOmics databases. Moreover, the sensitivity of SULF1 to existing drugs was explored using drug databases such as RNAactDrug and CADSP. RESULTS: High expression of SULF1 was associated with poor prognosis in advanced breast cancer brain metastasis and was positively correlated with the expression of HER2. In the metastatic breast cancer population, SULF1 ranked top among the 16 DEGs with the highest mutation rate, reaching 11%, primarily due to amplification. KEGG and GSEA analyses revealed that the genes co-expressed with SULF1 were positively enriched in the 'ECM-receptor interaction' gene set and negatively enriched in the 'Ribosome' gene set. Currently, docetaxel and vinorelbine can act as treatment options if the expression of SULF1 is high. CONCLUSIONS: This study, through bioinformatics analysis, unveiled SULF1 as a potential target for treating breast cancer brain metastasis (BM).

Anti-EGFR ScFv functionalized exosomes delivering LPCAT1 specific siRNAs for inhibition of lung cancer brain metastases.

Brain metastasis (BM) is one of the leading causes of cancer-related deaths in patients with advanced non-small cell lung cancer (NSCLC). However, limited treatments are available due to the presence of the blood-brain barrier (BBB). Upregulation of lysophosphatidylcholine acyltransferase 1 (LPCAT1) in NSCLC has been found to promote BM. Conversely, downregulating LPCAT1 significantly suppresses the proliferation and metastasis of lung cancer cells. In this study, we firstly confirmed significant upregulation of LPCAT1 in BM sites compared to primary lung cancer by analyzing scRNA dataset. We then designed a delivery system based on a single-chain variable fragment (scFv) targeting the epidermal growth factor receptor (EGFR) and exosomes derived from HEK293T cells to enhance cell-targeting capabilities and increase permeability. Next, we loaded LPCAT1 siRNA (siLPCAT1) into these engineered exosomes (exoscFv). This novel scFv-mounted exosome successfully crossed the BBB in an animal model and delivered siLPCAT1 to the BM site. Silencing LPCAT1 efficiently arrested tumor growth and inhibited malignant progression of BM in vivo without detectable toxicity. Overall, we provided a potential platform based on exosomes for RNA interference (RNAi) therapy in lung cancer BM.

Brain metastasis of non-small cell lung cancer after disease-free survival of 5 years: case series and comprehensive literature review.

BACKGROUND: In the treatment of non-small cell lung cancer (NSCLC), a disease-free survival (DFS) of 5 years is a criterion for cure. This study aimed to evaluate the characteristics and outcomes of patients with brain metastases of NSCLC after a DFS of 5 years (late recurrent brain metastasis, LRBM). METHODS: We reviewed 1,281 consecutive patients with brain metastasis of lung cancer at a single institute between November 2014 and December 2022. Relevant articles were retrieved from PubMed. Only peer-reviewed journals published in English were included. RESULTS: Six patients (0.47%) showed LRBM. Three were male. The median age at lung cancer diagnosis was 45 years. The histological diagnosis of all patients was adenocarcinoma. Driver gene mutations were observed in five patients. The median latency period from lung cancer treatment to the development of brain metastasis was 13 years. All patients had no metastasis to any other organs and underwent craniotomies. The median follow-up duration after craniotomy was 3.5 years. No local intracranial recurrences were observed. Three patients had distant intracranial recurrences at 7, 2, and 0.6 years after craniotomy. Five patients survived for 8, 4, 3, 2, and 0.3 years after craniotomy. One patient experienced re-recurrence in the lung 4 years after craniotomy and died 3.7 years later. In our systematic review, only six studies described LRBM of NSCLC. CONCLUSIONS: LRBM is rare in patients with NSCLC. In our institution, many of these patients harbored driver gene mutations, and achieved long-term survival with aggressive local therapy. Multicenter analysis is mandatory.

Mesothelin promotes brain metastasis of non-small cell lung cancer by activating MET.

BACKGROUND: Brain metastasis (BM) is common among cases of advanced non-small cell lung cancer (NSCLC) and is the leading cause of death for these patients. Mesothelin (MSLN), a tumor-associated antigen expressed in many solid tumors, has been reported to be involved in the progression of multiple tumors. However, its potential involvement in BM of NSCLC and the underlying mechanism remain unknown. METHODS: The expression of MSLN was validated in clinical tissue and serum samples using immunohistochemistry and enzyme-linked immunosorbent assay. The ability of NSCLC cells to penetrate the blood-brain barrier (BBB) was examined using an in vitro Transwell model and an ex vivo multi-organ microfluidic bionic chip. Immunofluorescence staining and western blotting were used to detect the disruption of tight junctions. In vivo BBB leakiness assay was performed to assess the barrier integrity. MET expression and activation was detected by western blotting. The therapeutic efficacy of drugs targeting MSLN (anetumab) and MET (crizotinib/capmatinib) on BM was evaluated in animal studies. RESULTS: MSLN expression was significantly elevated in both serum and tumor tissue samples from NSCLC patients with BM and correlated with a poor clinical prognosis. MSLN significantly enhanced the brain metastatic abilities of NSCLC cells, especially BBB extravasation. Mechanistically, MSLN facilitated the expression and activation of MET through the c-Jun N-terminal kinase (JNK) signaling pathway, which allowed tumor cells to disrupt tight junctions and the integrity of the BBB and thereby penetrate the barrier. Drugs targeting MSLN (anetumab) and MET (crizotinib/capmatinib) effectively blocked the development of BM and prolonged the survival of mice. CONCLUSIONS: Our results demonstrate that MSLN plays a critical role in BM of NSCLC by modulating the JNK/MET signaling network and thus, provides a potential novel therapeutic target for preventing BM in NSCLC patients.

Gastric cancer with brain metastasis: from molecular characteristics and treatment.

Gastric cancer is one of the cancers with increasing incidence and ranks fourth globally among the most frequent causes of cancer-related mortality. Early gastric cancer is often asymptomatic or presents with atypical symptoms, and the majority of patients present with advanced disease upon diagnosis. Brain metastases are present in approximately 1% of gastric cancer patients at the time of diagnosis, which significantly contributed to the overall mortality of the disease worldwide. Conventional therapies for patients with brain metastases remain limited and the median overall survival of patients is only 8 months in advanced cases. Recent studies have improved our understanding of the molecular mechanisms underlying gastric cancer brain metastases, and immunotherapy has become an important treatment option in combination with radiotherapy, chemotherapy, targeted therapy and surgery. This review aims to provide insight into the cellular processes involved in gastric cancer brain metastases, discuss diagnostic approaches, evaluate the integration of immune checkpoint inhibitors into treatment and prognosis, and explore the predictive value of biomarkers in immunotherapy.

Comprehensive Analysis of Lung Adenocarcinoma and Brain Metastasis through Integrated Single-Cell Transcriptomics.

Lung adenocarcinoma (LUAD) is a highly prevalent and lethal form of lung cancer, comprising approximately half of all cases. It is often diagnosed at advanced stages with brain metastasis (BM), resulting in high mortality rates. Current BM management involves complex interventions and conventional therapies that offer limited survival benefits with neurotoxic side effects. The tumor microenvironment (TME) is a complex system where cancer cells interact with various elements, significantly influencing tumor behavior. Immunotherapies, particularly immune checkpoint inhibitors, target the TME for cancer treatment. Despite their effectiveness, it is crucial to understand metastatic lung cancer and the specific characteristics of the TME, including cell-cell communication mechanisms, to refine treatments. Herein, we investigated the tumor microenvironment of brain metastasis from lung adenocarcinoma (LUAD-BM) and primary tumors across various stages (I, II, III, and IV) using single-cell RNA sequencing (scRNA-seq) from publicly available datasets. Our analysis included exploring the immune and non-immune cell composition and the expression profiles and functions of cell type-specific genes, and investigating the interactions between different cells within the TME. Our results showed that T cells constitute the majority of immune cells present in primary tumors, whereas microglia represent the most dominant immune cell type in BM. Interestingly, microglia exhibit a significant increase in the COX pathway. Moreover, we have shown that microglia primarily interact with oligodendrocytes and endothelial cells. One significant interaction was identified between DLL4 and NOTCH4, which demonstrated a relevant association between endothelial cells and microglia and between microglia and oligodendrocytes. Finally, we observed that several genes within the HLA complex are suppressed in BM tissue. Our study reveals the complex molecular and cellular dynamics of BM-LUAD, providing a path for improved patient outcomes with personalized treatments and immunotherapies.

A rare presentation of primary cardiac myxofibrosarcoma: Case report and literature review.

BACKGROUND: Primary cardiac myxofibrosarcoma is a rare and aggressive malignancy, with the majority of approaching strategies relying on case reports. This article provides insights into its diagnosis and treatment. CASE PRESENTATION: This paper presents the case of a 40-year-old man with sudden onset hemoptysis, leading to the diagnosis of primary cardiac myxofibrosarcoma. Treatment involved open-heart surgery to excise the left atrium tumor, followed by 6 cycles of adjuvant chemotherapy. Unfortunately, brain metastasis developed, leading to the patient's death 1 year after initial diagnosis. CONCLUSION: Primary cardiac myxofibrosarcoma remains a clinical challenge with an unfavorable prognosis. Early diagnosis through advanced imaging is crucial, and research is needed to explore innovative treatments. This case underscores the complexities of managing this rare cardiac malignancy and highlights the necessity for ongoing investigations to enhance patient outcomes.

Self-Shielding Gyroscopic Radiosurgery: A Prospective Experience and Analysis of the First 100 Patients.

Background Stereotactic radiosurgery is a well-established treatment option for the management of various benign and malignant brain tumors. It can be delivered with several treatment platforms, usually requiring shielded radiation vaults to meet regulatory safety requirements. Recent technical advances have led to the first self-shielding platform enabling the delivery of gyroscopic radiosurgery (GRS). Given the limited number of GRS treatment platforms, the novelty of its characteristics, and the lack of available data, we report our prospective experience with the first 100 patients treated with GRS. Materials and methods Patients undergoing GRS for the treatment of intracranial tumors were enrolled in this prospective study. Patient and treatment characteristics, including patient satisfaction, were collected and analyzed. Results A total of 100 patients with 155 tumors were treated. The most commonly treated tumors comprised brain metastases (BM) (49%), vestibular schwannomas (31%), and meningiomas (14%). The median prescription dose for malignant and benign tumors was 20 and 13 Gy, respectively. The median prescription isodose line was 56%. Gross tumor volumes were small, with a median of 0.37 cc for BM and 0.92 cc for the other entities. The median total treatment time was 40 minutes. Dosimetric performance indices showed median values of 1.20 (conformity index), 1.24 (new conformity index), 1.74 (homogeneity index), and 3.13 (gradient index). Volumetric assessment of the treated tumors showed an overall decrease in size at the first available follow-up. Most patients were satisfied with the treatment experience. Conclusion Our first prospective experience of the use of GRS is favorable. Analyses of the dosimetric performance, treatment times, volumetric assessment, and patient satisfaction demonstrate its suitability for stereotactic treatments of intracranial tumors. Further prospective clinical and dosimetric analyses for GRS are pending.

Association Between 18F-FDG PET Activity and HER2 Status in Breast Cancer Brain Metastases.

Purpose: The objective of this study was to evaluate whether uptake on 18F-fluorodeoxyglucose (18F-FDG) PET could help differentiate HER2-positive from HER2-negative breast cancer brain metastases. Methods: In this retrospective, cross-sectional study of a cohort of 14 histologically proven breast cancer brain metastases, we analyzed both preoperative 18F-FDG PET/CT and HER2 status of the resected/biopsied brain specimens. The maximum standardized uptake values (SUVmax) of the lesions were normalized to contralateral normal white matter and compared using Mann-Whitney U tests. Results: The study cohort was comprised of 12 women with breast cancer with a mean age of 59 years (range: 43-76 years) with a total of 14 distinct brain metastatic lesions. The SUVmax ratio of HER2-positive breast cancer brain metastases was significantly greater than that of HER2-negative lesions (3.98 vs 1.79, U = 38.00, p = 0.008). Conclusion: The SUVmax ratio may help to identify the HER2 status of breast cancer brain metastases, if validated prospectively.

The efficacy of sacituzumab govitecan and trastuzumab deruxtecan on stable and active brain metastases in metastatic breast cancer patients-a multicenter real-world analysis.

BACKGROUND: Fifteen to thirty percent of all patients with metastatic breast cancer (MBC) develop brain metastases (BCBMs). Recently, the antibody-drug conjugates (ADCs) sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) have shown to be highly effective in the treatment of MBC. However, there are only limited data whether these macromolecules are also effective in patients with BCBMs. We therefore aimed to examine the efficacy of SG and T-DXd in patients with stable and active BCBMs in a multicenter real-world analysis. PATIENTS AND METHODS: Female patients with stable or active BCBMs who were treated with either SG or T-DXd at three breast centers in Germany before 30 June 2023 were included. As per local clinical praxis, chemotherapy efficacy was evaluated by whole-body computed tomography and cranial magnetic resonance imaging at baseline and at least every 3 months according to local standards. Growth dynamics of BCBMs were assessed by board-certified neuroradiologists. RESULTS: Of 26 patients, with a median of 2.5 prior therapy lines in the metastatic setting (range 2-15), 12 (43%) and 16 (57%) patients received SG and T-DXd, respectively. Out of the 12 patients who received SG, 2 (17%) were subsequently treated with T-DXd. Five out of 12 (42%) and 5 out of 16 (31%) patients treated with SG and T-DXd, respectively, had active BCBMs at treatment initiation. The intracranial disease control rate was 42% [95% confidence interval (CI) 13% to 71%] for patients treated with SG and 88% (95% CI 72% to 100%) for patients treated with T-DXd. After a median follow-up of 12.7 months, median intracranial progression-free survival was 2.7 months (95% CI 1.6-10.5 months) for SG and 11.2 months (95% CI 7.5-23.7 months) for T-DXd. CONCLUSIONS: SG and T-DXd showed promising clinical activity in both stable and active BCBMs. Further prospective clinical studies designed to investigate the efficacy of modern ADCs on active and stable BCBMs are urgently needed.

Preoperative blood counts predict overall survival in patients undergoing surgical removal of brain metastasis.

OBJECTIVE: The prognosis for patients with cancer with brain metastasis (BM) requiring surgical removal is quite limited. Preoperative prognostic factors can provide meaningful information to surgeons, oncologists, and patients. This study evaluated the preoperative blood counts in patients with BM who were treated with surgical removal. METHODS: Between January 2011 and November 2021, 221 consecutive surgeries were conducted on 198 patients with BM. Among the 198 patients, 188 patients with sufficient blood test data and follow-up were analyzed in this study. The tumors originated from the lungs (n = 102, 54.3%), colon (n = 26, 13.3%), breast (n = 13, 6.9%), kidney (n = 8, 4.3%), stomach (n = 6, 3.2%), and others (n = 33, 17.6%). The blood test data included neutrophils, lymphocytes, monocytes, eosinophils, basophils, red blood cell count, hemoglobin, and albumin. RESULTS: The median follow-up and median survival times were both 11 months (range: 0-139 months). Higher neutrophil-lymphocyte ratio (NLR) ≥ 3.17, platelet-lymphocyte ratio (PLR) ≥112.7, systemic immune-inflammation index (SII) ≥594.4, systemic inflammation response index (SIRI) ≥1.25 were unfavorable predictors of prognosis for the patients treated with surgical removal for BM (p < 0.001). Furthermore, lower lymphocyte-monocyte ratio (LMR) <2.33 and prognostic nutritional index (PNI) <48.5 were unfavorable predictors. CONCLUSION: Simple, less expensive, routinely ordered preoperative blood count assessments, such as the NLR, PLR, LMR, SII, SIRI, and PNI, can predict the overall survival of patients treated with surgical removal for BM.

Galectin-3 depletion tames pro-tumoural microglia and restrains cancer cells growth.

Galectin-3 (Gal-3) is a multifunctional protein that plays a pivotal role in the initiation and progression of various central nervous system diseases, including cancer. Although the involvement of Gal-3 in tumour progression, resistance to treatment and immunosuppression has long been studied in different cancer types, mainly outside the central nervous system, its elevated expression in myeloid and glial cells underscores its profound impact on the brain's immune response. In this context, microglia and infiltrating macrophages, the predominant non-cancerous cells within the tumour microenvironment, play critical roles in establishing an immunosuppressive milieu in diverse brain tumours. Through the utilisation of primary cell cultures and immortalised microglial cell lines, we have elucidated the central role of Gal-3 in promoting cancer cell migration, invasion, and an immunosuppressive microglial phenotypic activation. Furthermore, employing two distinct in vivo models encompassing primary (glioblastoma) and secondary brain tumours (breast cancer brain metastasis), our histological and transcriptomic analysis show that Gal-3 depletion triggers a robust pro-inflammatory response within the tumour microenvironment, notably based on interferon-related pathways. Interestingly, this response is prominently observed in tumour-associated microglia and macrophages (TAMs), resulting in the suppression of cancer cells growth.

Transcriptome-Based Treatment for Melanoma With Brain Metastasis: A Case Report.

Malignant melanoma with brain metastasis has a high mortality rate. New approaches for diagnosis and treatment are urgently required to improve prognosis. Here we present a 60-year-old male with metastatic melanoma to the brain. Using a transcriptomics pipeline, we analyzed whole blood and resected tumor tissue, identifying enriched gene expression biomarkers and pathways - including seven upregulated ( BRAF, CDK4, EIF1AX, IK, NRAS, PIK3R2, and TP53) and 11 downregulated (CASP8, CDK10, CDKN2A, CTLA4, GNA11, HERC2, IRF4, MC1R, PLA2G6, RREB1, and TPCN2) genes in the blood (across 15 pathways), showing 14% enrichment, and 16 upregulated (CCND1, CDK4, CTLA4, EIF1AX, IK, IRF4, MITF, NRAS, PIK3CB, PIK3R2, PMEL, RREB1, SLC45A2, SOX10, TYR, and TYRP1) and three downregulated ( GNA11, KITLG, and PLA2G6) genes in tissue (across 17 pathways), showing 33% enrichment, with five shared markers and 12 shared pathways. The model connected CDK4 pathway overactivity observed in both samples to inhibitors like ribociclib, abemaciclib, and palbociclib as putative treatments. By enabling objective personalized therapy selection, this approach shows great promise for advancing patient outcomes.