Risk factors for brain metastases in patients with non-small-cell lung cancer.
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ABSTRACT:
SUBMITTER: An N
PROVIDER: S-EPMC6308070 | biostudies-literature | 2018 Dec
REPOSITORIES: biostudies-literature
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Risk factors for brain metastases in patients with non-small-cell lung cancer.
An Ning N Jing Wang W Wang Haoyi H Li Ji J Liu Yang Y Yu Jinming J Zhu Hui H
Cancer medicine 20181108 12
Brain metastases (BM) are severe incidents in patients with non-small-cell lung cancer (NSCLC). The controversial value of prophylactic cranial irradiation (PCI) in NSCLC in terms of survival benefit prompted us to explore the possible risk factors for BM in NSCLC and identify the potential population most likely to benefit from PCI. Risk factors for brain metastases in NSCLC are reviewed in this article. Identifying patients with a higher risk of BM could possibly increase the benefit of PCI wh ...[more]
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Project description:BackgroundBrain metastases (BM) happen frequently in lung cancer patients and lead to a poor prognosis as well as a lower quality of life. The aim of this study was to identify risk factors for BM in locally advanced non-small cell lung cancer (LA-NSCLC) patients receiving radical radiotherapy, which will be useful for selecting appropriate patient population for further intervention and future trial design.MethodsThis was a retrospective cohort study. Patients with inoperable stage IIB-IIIC NSCLC were treated consecutively with definitive thoracic radiotherapy from January 2018 to December 2021, and were retrospectively reviewed and enrolled. Patients with various clinical variables were analyzed to clarify their impact on BM with competing risk models by Fine and Gray.ResultsA total of 134 patients were enrolled in this study. The median follow-up for all patients was 37 months [95% confidence interval (CI): 30.5-43.5 months]. BM occurred in 25 patients at the time of analysis. The 1-year and 3-year cumulative BM incidence were 10.5% and 19.9%, respectively. Patients with BM had worse overall survival than those without BM [stratified hazard ratio (HR) for death: 2.83; 95% CI:1.31-6.11; P<0.001]. Based on univariate analyses, non-squamous cell carcinoma (non-SCC), biological effective dose (BED) and planning target volume (PTV) were used as input variables in multivariable analysis (P<0.01). According to multivariate analysis, non-SCC (P<0.001; HR: 6.08; 95% CI: 2.26-16.37), BED <72 Gy (P=0.017; HR: 2.81; 95% CI: 1.20-6.57), and PTV >157.73 cm3 (P=0.043; HR: 2.56; 95% CI: 1.03-6.35) were independent risk factors for BM. In subgroup analysis of adenocarcinoma with known epidermal growth factor receptor (EGFR) mutation status, PTV >157.73 cm3 and positive EGFR mutation were independent predictors for BM.ConclusionsIn this retrospective study, we found that BED <72 Gy and PTV >157.73 cm3 were significantly associated with BM development and we validated that non-SCC and positive EGFR mutation were risk factors for BM. More research is required to screen the high-risk patient population.
| S-EPMC10894422 | biostudies-literature
Project description:Despite administration of prophylactic cranial irradiation (PCI), some small cell lung cancer (SCLC) patients still suffer from brain metastases (BM) with unknown risk factors. We conducted this study to identify patients with higher BM risk after PCI and improve their outcome. The characteristics and survival of all the SCLC patients underwent PCI in our institute from 2003 to 2014 were analyzed. Kaplan-Meier method was applied to estimate BM free survival (BMFS) and overall survival (OS). Cox regression analyses were performed to explore risk factors for BM. A total of 175 patients with the median age of 55 years (range, 29-76) were eligible, among whom 36 (20.6%) developed BM with median follow-up of 42 months. Both univariate and multivariate analyses showed HART and TNM classification (p?<?0.05) were associated with BM. Two-stage system was not related with BMFS or OS (p?>?0.05). Stage IIIB-IV and HART were independent risk factors for BM after PCI in SCLC. TNM classification was more valuable on prognosis than two-stage system. Further large-scale studies are needed to confirm our findings.
| S-EPMC5311871 | biostudies-other
Project description:Brain metastases (BM) have been closely associated with increased morbidity and poor survival outcomes in patients with non‑small cell lung cancer (NSCLC). Excluding risk factors in histological subtypes, genomic alterations, including epidermal growth factor receptor mutations and anaplastic lymphoma kinase (ALK) rearrangements have been also regarded as greater risk factors for BM in the aspect of molecular subtypes. In the present study, 69 tumor tissues and 51 peripheral blood samples from patients with NSCLC were analyzed using a hybridization capture‑based next‑generation sequencing (NGS) panel, including 95 known cancer genes. Among the 90 patients with stage IV NSCLC, 26 cases suffered from BM and 64 cases did not. In total, 174 somatic mutations in 35 mutated genes were identified, and 12 of these genes were concurrently present in the BM group and the non‑BM group. Importantly, five mutated genes including ALK, cytidine deaminase (CDA), SMAD family member 4 (SMAD4), superoxide dismutase 2 (SOD2) and Von Hippel‑Lindau tumor suppressor (VHL) genes were uniquely detected in the BM group, and they were enriched in the Hippo signaling pathway, pyrimidine metabolism and pantothenate and co‑enzyme A (CoA) biosynthesis, as demonstrated using Kyoto Encyclopedia of Genes and Genomes enrichment analysis. RNA polymerase II transcription regulator complex and promyelocytic leukemia nuclear body were the top functional categories according to the Gene Ontology enrichment analysis in the BM group and non‑BM group, respectively. Furthermore, 43.33% (13/30) of mutated genes were detected by both tumor tissue deoxyribonucleic acid (DNA) and plasma‑derived circulating tumor DNA (ctDNA) in the non‑BM group, while this percentage was only limited to 29.41% (5/17) in the BM group. To summarize, significant differences in somatic mutations, somatic interactions, key signaling pathways, functional biological information, and clinical actionability for the therapy of targeted agents were founded between the BM group and the non‑BM group, and ctDNA analysis may by applied as a more credible alternative for genomic profiling in patients with advanced NSCLC without BM, due to its higher consistency for genomic profiling between ctDNA analysis and tissue DNA analysis.
| S-EPMC9291252 | biostudies-literature
Project description:Lung cancer is the leading cause of cancer-related death in the United States. Approximately 20% of these patients present with brain metastases (BMs). Surgical resection, stereotactic radiosurgery, and whole-brain radiation therapy have historically been the primary treatment modalities for patients with non-small-cell lung cancer (NSCLC) and BMs. The treatments for BMs have become complex with the discovery of targetable molecular drivers and the development of an astonishing number of tyrosine kinase inhibitors. Many of these tyrosine kinase inhibitors have robust and durable efficacy against CNS metastases. In many circumstances, these drugs can defer local therapy and even reduce the risk of CNS progression. More recently, immune checkpoint inhibitors have changed the treatment landscape for many patients with NSCLC; however, the role of immunotherapy in patients with BMs is the subject of ongoing investigations. This article will review the current data and our approach to patients with NSCLC and BMs.
| S-EPMC7098835 | biostudies-literature
Project description:The use of prophylactic cranial irradiation (PCI) for small cell lung cancer (SCLC) patients is controversial. Risk factors for brain metastasis (BM) development are largely lacking, hampering personalized treatment strategies. This study aimed to identify the possible risk factors for BM in SCLC.We systematically searched the Pubmed database (1 January 1995 to 18 January 2021) according to the PRISMA guidelines. Eligibility criteria: studies reporting detailed BM data with an adequate sample size (randomized clinical trials [RCTs]: N ≥50; non-RCTs: N ≥100) in patients with SCLC. We summarized the reported risk factors and performed meta-analysis to estimate the pooled hazard ratios (HR) if enough qualified data (i.e., two or more studies; the same study type; the same analysis method; and HRs retrievable) were available. In total, 61/536 records were eligible (18 RCTs and 39 non-RCTs comprising 13,188 patients), in which 57 factors were reported. Ten factors qualified BM data for meta-analysis: Limited stage disease (LD) (HR = 0.34, 95% CI: 0.17-0.67; P = 0.002) and older age (≥65) (HR = 0.70, 95% CI: 0.54-0.92; P = 0.01) were associated with less BM; A higher T stage (≥T3) (HR = 1.72, 95% CI: 1.16-2.56; P = 0.007) was a significant risk factor for BM. Male sex (HR = 1.24, 95% CI: 0.99-1.54; P = 0.06) tended to be a risk factor, and better PS (0-1) (HR = 0.66, 95% CI: 0.42-1.02; P = 0.06) tended to have less BM. Smoking, thoracic radiotherapy dose were not significant (P >0.05). PCI significantly decreased BM (P <0.001), but did not improve OS in ED-SCLC (P = 0.81). A higher PCI dose did not improve OS (P = 0.11). The impact on BM was conflicting between Cox regression data (HR = 0.59, 95% CI: 0.26-1.31; P = 0.20) and competing risk regression data (HR = 0.74, 95% CI: 0.55-0.99; P = 0.04). Compared to M0-M1a, M1b was a risk factor for OS (P = 0.01) in ED-SCLC, but not for BM (P = 0.19). As regular brain imaging is rarely performed, high-quality data is lacking. Other factors such as N-stage and blood biomarkers had no qualified data to perform meta-analysis. In conclusion, younger age, higher T stage, and ED are risk factors for BM, suggesting that PCI should be especially discussed in such cases. Individual patient data (IPD) meta-analysis and well-designed RCTs are needed to better identify more risk factors and further confirm our findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021228391, identifier CRD42021228391.
| S-EPMC9226404 | biostudies-literature
Project description:Brain metastases (BM) are common in non-small cell lung cancer patients including in molecularly selected populations, such as EGFR-mutant and ALK-rearranged tumors. They are associated with a reduced quality of life, and are commonly the first site of progression for patients receiving tyrosine kinase inhibitors (TKIs). In this review, we summarize incidence of BM and intracranial efficacy with TKI agents according to oncogene driver mutations, focusing on important clinical issues, notably optimal first-line treatment in oncogene-addicted lung tumors with upfront BM (local therapies followed by TKI vs. TKI monotherapy). We also discuss the potential role of newly emerging late-generation TKIs as new standard treatment in oncogene-addicted lung cancer tumors compared with sequential strategies.
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Project description:The most effective treatment approach for brain metastases in patients with non-small cell lung cancer (NSCLC) and activating epidermal growth factor receptor (EGFR) mutations is a current subject of investigation. Cranial irradiation is the standard treatment for brain metastases, but tyrosine kinase inhibitors (TKIs) such as erlotinib have also activity against brain metastases in this subset of patients. The combination of TKI and radiotherapy is a promising one, but data is lacking to indicate whether this is superior to erlotinib or whole brain radiation therapy (WBRT) alone. Retrospective data suggest that WBRT achieves more durable intracranial control compared to erlotinib alone. Randomized, prospective studies will be necessary to determine whether TKI, cranial irradiation, or both is the optimal initial treatment for brain metastases in EGFR-mutant NSCLC.
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Project description:Bevacizumab is FDA-approved in the treatment of primary brain tumors, but its efficacy in patients with brain metastases could be better-studied. This study examines a population of non-small cell lung cancer (NSCLC) patients with synchronous brain metastases to identify predictors of the decision to use bevacizumab and survival following bevacizumab treatment. Primary cancer registry data were used to determine which NSCLC patients diagnosed in the years 2010 through 2012 had synchronous brain metastases at the time of diagnosis, and Medicare claims used to identify a population of patients treated with bevacizumab. Record of bevacizumab treatment was found for 81 and 666 patients with and without brain metastases, respectively. After adjusting for clinical and demographic characteristics, bevacizumab was associated with 0.88 times the hazard of mortality in the elderly NSCLC population (95% CI: 0.81-0.96, p: 0.003) and a corresponding hazard ratio of 0.75 in the population of elderly NSCLC patients with synchronous brain metastases (95% CI: 0.59-0.96, p: 0.020). Bevacizumab may benefit NSCLC patients with synchronous brain metastases more than it does patients without intracranial disease, possibly as a result of its multiple potential mechanisms of action simultaneously inhibiting angiogenesis and minimizing vasogenic edema.
| S-EPMC6882803 | biostudies-literature
Project description:Brain metastases are frequent in patients with lung cancer and a major cause of morbidity and mortality. Finding a biomarker predicting brain metastases could facilitate early start of treatment and thereby reduce morbidity and possibly improve overall survival. Previous studies suggest S100B as a possible biomarker for this purpose. This prospective study enrolled 185 patients with newly diagnosed stage IV non-small cell lung cancer (NSCLC). A total of 22 patients had brain metastases verified by magnetic resonance imaging or computed tomography at the time of enrollment. Serum S100B levels were measured in blood samples collected prior to any treatment from 22 patients who had brain metastases at enrollment and from 50 patients randomly selected from the remaining 163 patients without brain metastases at enrollment. No statistically significant difference was found in the levels of serum S100B between patients with and without brain metastases [range 0.018-0.209 µg/l, mean 0.049 µg/l, 95% confidence interval (CI), 0.032-0.061 µg/l] and (range 0.016-0.130 µg/i, mean 0.044 µg/l, 95% CI, 0.037-0.051 µg/l), respectively, (P=0.852). Univariate analysis of prognostic factors for S100B indicated a correlation (P<0.2) with sex (P=0.088) and histology (adenocarcinoma vs. squamous cell carcinoma/others) (P=0.028). In the multivariate analysis only histology (P=0.029) remained statistically significant. Conclusion: The present study found no significant correlation between the level of serum S100B and the presence of brain metastases in patients with advanced NSCLC. The clear cut-off of S100B in patients with and without brain metastases reported in other studies could not be verified in this study. Further studies investigating the role of S100B as a biomarker for brain metastases in non-small cell lung cancer are warranted.
| S-EPMC7054701 | biostudies-literature
Project description:Epidermal growth factor receptor (EGFR) mutations are present in 20-40% of non-small cell lung cancers (NSCLCs). Brain metastasis (BM) is more common in EGFR-mutated NSCLC (25-45%) compared to EGFR wild-type (15-30%). First and second-generation tyrosine kinase inhibitors (TKIs), such as erlotinib and afatinib have proven to be superior to chemotherapy in the front-line treatment of EGFR-mutated NSCLC. Osimertinib, a third-generation EGFR TKI, has demonstrated better blood brain barrier (BBB) penetration, higher rate of intracranial response (66% vs. 43%) and a lower rate of CNS progression when compared to first generation EGFR TKI. Evidence on upfront radiation vs. upfront osimertinib is limited, but rapidly evolving and being tested in ongoing comparative trials. Stereotactic radiation (SRS) is very effective in the control of BMs and has been increasingly used and consequently replacing resection of BMs. SRS also has been increasingly used in the treatment of multiple BMs. Considering the effectiveness of targeted agents such as third generation EGFR inhibitors clinicians now are more frequently faced with the decision, if systemic therapy is safe and effective enough to withhold SRS. Third generation EGFR inhibitors also have fewer adverse events as previous generations. This review discusses the current literature available for management of BM in EGFR-mutated NSCLC.
| S-EPMC8182502 | biostudies-literature