Dataset Information

Associated Factors of Spontaneous Hemorrhage in Brain Metastases in Patients with Lung Adenocarcinoma.

ABSTRACT:

Background

Hemorrhage in brain metastases (BMs) from lung cancer is common and associated with a poor prognosis. Research on associated factors of spontaneous hemorrhage in patients with BMs is limited. This study aimed to investigate the predictive risk factors for BM hemorrhage and assess whether hemorrhage affects patient survival.

Methods

We retrospectively evaluated 159 BMs from 80 patients with lung adenocarcinoma from January 2017 to May 2022. Patients were classified into hemorrhagic and non-hemorrhagic groups. Patient demographics, lung cancer molecular subtype, treatment type, and tumor-node-metastasis stage were compared between the groups. Multivariate generalized estimating equation (GEE) analysis and gradient boosting were performed. To determine whether BM hemorrhage can stratify overall survival after BM (OSBM), univariate survival analysis was performed.

Results

In the univariate analysis, hemorrhagic BMs were significantly larger and had a history of receiving combination therapy with tyrosine kinase inhibitor (TKI) and intracranial radiation (p < 0.05). Multivariate GEE showed that tumor size and combination therapy were independent risk factors for BM hemorrhage (p < 0.05). Gradient boosting demonstrated that the strongest predictor of BM hemorrhage was tumor size (variable importance: 49.83), followed by age (16.65) and TKI combined with intracranial radiation (13.81). There was no significant difference in OSBM between the two groups (p = 0.33).

Conclusions

Hemorrhage in BMs from lung adenocarcinomas may be associated with BM tumor size and a combination of TKI and intracranial radiotherapy. BM hemorrhage did not affect OSBM.

SUBMITTER: Kim SS

PROVIDER: S-EPMC9913139 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

Associated Factors of Spontaneous Hemorrhage in Brain Metastases in Patients with Lung Adenocarcinoma.

Kim Song Soo SS Lee Seoyoung S Park Mina M Joo Bio B Suh Sang Hyun SH Ahn Sung Jun SJ

Cancers 20230119 3

<h4>Background</h4>Hemorrhage in brain metastases (BMs) from lung cancer is common and associated with a poor prognosis. Research on associated factors of spontaneous hemorrhage in patients with BMs is limited. This study aimed to investigate the predictive risk factors for BM hemorrhage and assess whether hemorrhage affects patient survival.<h4>Methods</h4>We retrospectively evaluated 159 BMs from 80 patients with lung adenocarcinoma from January 2017 to May 2022. Patients were classified into ...[more]

PMID: 36765577

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Project description:BackgroundThe data about efficacy of immunotherapy for non-small cell lung cancer with brain metastases (BMs) from real-word settings are controversial. This real-word study is aimed to evaluate the clinical outcome of immune checkpoint inhibitor (ICI)-based treatment in lung adenocarcinoma patients with brain metastases (BMs) and explore potential risk factors, with a focus on the spatial distribution of BMs as previous studies suggested spatial heterogeneity on the brain immune microenvironment.MethodsAdvanced lung adenocarcinoma patients with non-oncogene-addicted, who received ICI monotherapy or plus chemotherapy, were enrolled. Efficacy was assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Intergroup comparisons were performed using Pearson's χ2 or Fisher's exact tests for categorical variables. The progression-free survival (PFS) was estimated using Kaplan-Meier method and compared using log-rank test. Cox proportional hazards model was used for multivariate analyses. Peripheral blood was collected from 15 patients with BMs. Tumor-derived exosomes in plasma were isolated by size exclusion chromatography and the cDNA library preparations for miRNA were sequenced on an Illumina Hiseq platform. Differentially expressed genes in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed.ResultsA total of 198 patients were enrolled and brain metastasis occurred in 20.7% patients (N=41). Compared with patients without BMs, those with BMs had a comparable objective response rate (ORR; 29.3% vs. 43.9%; P=0.089), a lower disease control rate (DCR; 58.5% vs. 78.3%; P=0.01), and a shorter PFS (3.6 vs. 8.6 months; P=0.069). For patients with BMs, factors, including the presence of neurological symptoms, the treatment of intracranial radiotherapy, and the combination of ICI with chemotherapy, had no impact on PFS, whereas cerebellum metastasis was significantly associated with shorter PFS (2.8 vs. 13.8 months, P=0.007). Six upregulated miRNAs were identified in patients with cerebellum metastases (N=8) compared with those without (N=7). The enrichment of differentially expression genes in the KEGG pathways indicated upregulated sulfur metabolism pathway in patients with cerebellum metastases.ConclusionsFor lung adenocarcinoma patients, those with BMs have inferior response to ICI-based treatment, but not significantly, and cerebellum metastasis is an independent risk factor with poor outcome for such patients, might attributing to the upregulated sulfur metabolism.

Project description:BackgroundBrain metastases are associated with considerable negative effects on patients' outcome in lung adenocarcinoma (LADC). Here, we investigated the proteomic landscape of primary LADCs and their corresponding brain metastases.Materials and methodsProteomic profiling was conducted on 20 surgically resected primary and brain metastatic LADC samples via label-free shotgun proteomics. After sample processing, peptides were analyzed using an Ultimate 3000 pump coupled to a QExactive HF-X mass spectrometer. Raw data were searched using PD 2.4. Further data analyses were carried out using Perseus, RStudio and GraphPad Prism. Proteomic data were correlated with clinical and histopathological parameters and the timing of brain metastases. Mass spectrometry-based proteomic data are available via ProteomeXchange with identifier PXD027259.ResultsOut of the 6821 proteins identified and quantified, 1496 proteins were differentially expressed between primary LADCs and corresponding brain metastases. Pathways associated with the immune system, cell-cell/matrix interactions and migration were predominantly activated in the primary tumors, whereas pathways related to metabolism, translation or vesicle formation were overrepresented in the metastatic tumors. When comparing fast- versus slow-progressing patients, we found 454 and 298 differentially expressed proteins in the primary tumors and brain metastases, respectively. Metabolic reprogramming and ribosomal activity were prominently up-regulated in the fast-progressing patients (versus slow-progressing individuals), whereas expression of cell-cell interaction- and immune system-related pathways was reduced in these patients and in those with multiple brain metastases.ConclusionsThis is the first comprehensive proteomic analysis of paired primary tumors and brain metastases of LADC patients. Our data suggest a malfunction of cellular attachment and an increase in ribosomal activity in LADC tissue, promoting brain metastasis. The current study provides insights into the biology of LADC brain metastases and, moreover, might contribute to the development of personalized follow-up strategies in LADC.

Dataset Information

Associated Factors of Spontaneous Hemorrhage in Brain Metastases in Patients with Lung Adenocarcinoma.

Background

Methods

Results

Conclusions

Publications

Associated Factors of Spontaneous Hemorrhage in Brain Metastases in Patients with Lung Adenocarcinoma.

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