Risk factors for brain metastases in patients with non-small cell lung cancer: a meta-analysis of 43 studies

Chen, Shanshan; Hua, Xin; Jia, Jinfang; Wu, Ying; Wei, Shuzhen; Xu, Lu; Han, Shuhua; Zhang, Hongming; Zhu, Xiaoyun

doi:10.21037/apm-20-1722

Cited by 12 publications

(8 citation statements)

References 19 publications

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“…Lo et al also found that the assessment between reviewers and authors of the studies was very different (95). Interestingly, many studies that used the NOS cited this critical discussion instead of the original web-based link (96)(97)(98)(99), suggesting that researchers were using the problematic tool even though they were aware of the limitations.…”

Section: Discussionmentioning

confidence: 99%

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Risk Factors for Brain Metastases in Patients With Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

et al. 2022

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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.

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Section: Discussionmentioning

confidence: 99%

“…Most current meta-analyses focused on one aspect, such as PCI or not in SCLC (101), ED-SCLC (82,90), and resected SCLC (102). Chen et al conducted a meta-analysis to identify risk factors for BM in NSCLC (97). Unfortunately, they only searched for observational studies instead of RCTs.…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Brain Metastases in Patients With Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

et al. 2022

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“…The majority of these factors align with the risk factors for brain metastases in NSCLC identified in prior research. 25 - 27 Nevertheless, prior studies have not established numerous predictive factors for NSCLC individuals with radiotherapy and inoperable brain metastases.…”

Section: Discussionmentioning

confidence: 99%

Survival Predictive Nomograms for Non-Surgical Brain Metastases Patients From Non-Small Cell Lung Cancer Receiving Radiotherapy: A Population-Based Study

Li,

Luo,

Zheng

et al. 2024

Cancer Control

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Objective A high number of Non-Small Cell Lung Cancer (NSCLC) patients with brain metastasis who have not had surgery often have a negative outlook. Radiotherapy remains a most common and effective method. Nomograms were developed to forecast the cancer-specific survival (CSS) and overall survival (OS) in NSCLC individuals with nonoperative brain metastases who underwent radiotherapy. Methods Information was gathered from the Surveillance, Epidemiology, and End Results (SEER) database about patients diagnosed with NSCLC who had brain metastases not suitable for surgery. Nomograms were created and tested using multivariate Cox regression models to forecast CSS and OS at intervals of 1, 2, and 3 years. Results The research involved 3413 individuals diagnosed with NSCLC brain metastases who had undergone radiotherapy but had not experienced surgery. These participants were randomly divided into two categories. The analysis revealed that gender, age, ethnicity, marital status, tumor location, tumor laterality, tumor grade, histology, T stage, N stage, chemotherapy, tumor size, lung metastasis, bone metastasis, and liver metastasis were significant independent predictors for OS and CSS. The C-index for the training set for predicting OS was .709 (95% CI, .697-.721), and for the validation set, it was .705 (95% CI, .686-.723), respectively. The C-index for predicting CSS was .710 (95% CI, .697-.722) in the training set and .703 (95% CI, .684-.722) in the validation set, respectively. The nomograms model, as suggested by the impressive C-index, exhibits outstanding differentiation ability. Moreover, the ROC and calibration curves reveal its commendable precision and distinguishing potential. Conclusions For the first time, highly accurate and reliable nomograms were developed to predict OS and CSS in NSCLC patients with non-surgical brain metastases, who have undergone radiotherapy treatment. The nomograms may assist in tailoring counseling strategies and choosing the most effective treatment method.

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“… 7 In addition, advances in treatments are leading to improved survival, thereby increasing the risk of relapse and/or metastasis to the brain. 8 Although recent clinical guidelines have recommended screening for brain metastases for stage II NSCLC and above, most brain metastases are detected after symptoms develop. 9 , 10 Surgical resection, stereotactic radiosurgery, and whole-brain radiation therapy are the primary treatment modalities.…”

Section: Introductionmentioning

confidence: 99%

Clinicogenomic factors and treatment patterns among patients with advanced non–small cell lung cancer with or without brain metastases in the United States

et al. 2023

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Background This retrospective, real-world study evaluated the prevalence of brain metastases, clinicodemographic characteristics, systemic treatments, and factors associated with overall survival among patients with advanced non–small cell lung cancer (aNSCLC) in the US. We also described the genomic characterization of 180 brain metastatic specimens and frequency of clinically actionable genes. Materials and Methods De-identified electronic health records-derived data of adult patients diagnosed with aNSCLC between 2011 and 2017 were analyzed from a US-nationwide clinicogenomic database. Results Of 3257 adult patients with aNSCLC included in the study, approximately 31% (n = 1018) had brain metastases. Of these 1018 patients, 71% (n = 726) were diagnosed with brain metastases at initial NSCLC diagnosis; 57% (n = 583) of patients with brain metastases received systemic treatment. Platinum-based chemotherapy combinations were the most common first-line therapy; single-agent chemotherapies, epidermal growth factor receptor tyrosine kinase inhibitors, and platinum-based chemotherapy combinations were used in second line. Patients with brain metastases had a 1.56 times greater risk of death versus those with no brain metastases. In the brain metastatic specimens (n = 180), a high frequency of genomic alterations in the p53, MAPK, PI3K, mTOR, and cell-cycle associated pathways was observed. Conclusion The frequency of brain metastases at initial clinical presentation and associated poor prognosis for patients in this cohort underscores the importance of early screening for brain metastasis in NSCLC. Genomic alterations frequently identified in this study emphasize the continued need for genomic research and investigation of targeted therapies in patients with brain metastases.

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Risk factors for brain metastases in patients with non-small cell lung cancer: a meta-analysis of 43 studies

Cited by 12 publications

References 19 publications

Risk Factors for Brain Metastases in Patients With Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

Risk Factors for Brain Metastases in Patients With Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

Survival Predictive Nomograms for Non-Surgical Brain Metastases Patients From Non-Small Cell Lung Cancer Receiving Radiotherapy: A Population-Based Study

Clinicogenomic factors and treatment patterns among patients with advanced non–small cell lung cancer with or without brain metastases in the United States

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