Real-World Data on Prognostic Factors for Overall Survival in EGFR-Mutant Non-Small-Cell Lung Cancer Patients with Brain Metastases

Abstract

Background : With the wide application of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), the survival of EGFR-mutant non-small-cell lung cancer (NSCLC) patients with brain metastasis (BM) has been significantly improved. However, prognosis analysis for patients with EGFR mutation and BM is still lacking, and the prognostic factors remain to be determined. Materials and methods : A total of 746 NSCLC patients with BM were identified between January 2013 and December 2016 at our institution. Overall, 261 patients harboring EGFR mutation and meeting the inclusion criteria for the study were enrolled. Exclusion criteria included KPS<50, diagnosed with BM during treatment with EGFR-TKIs, or insufficient follow-up. Overall survival (OS) was measured from the date of brain metastases. Independent prognostic factors were confirmed using a Cox regression model. Results : The median follow-up time for these patients was 32.7 months (95% CI, 23.5-41.9). The median OS after development of brain metastases was 23.0 months (95% CI, 20.01-25.99). By univariate analysis, significantly shorter OS was noted in patients older than 65 years (p=0.025), KPS <70 (p=0.003), presence of extracranial metastases (ECM) (p=0.00), without intracranial local treatment (p=0.000), and without chemotherapy (p=0.001). There was no difference in OS with respect to EGFR mutation type and number of BM (p=0.343, p=0.729, respectively). The Cox proportional hazards regression model revealed that performance status (KPS<70, p=0.010), ECM (p=0.001), receiving intracranial local treatment (p=0.005) and chemotherapy (p=0.005) were independent prognostic factors for OS, while age was not (p=0.087). Patients with higher diagnosis-specific graded prognostic assessment (DS-GPA) and Lung-molGPA scores corresponded to better prognosis (p=0.000). Conclusion : This retrospective analysis demonstrated that performance status (KPS≥70), absence of ECM metastases, administration of local treatment and chemotherapy were associated with superior OS in patients with EGFR-mutant NSCLC who developed BM. The DS-GPA and Lung-molGPA indexes still applied to NSCLC patients with mutant genotypes and BM.

Efficacy and Safety of Anlotinib in Patients with Advanced Non-Small Cell Lung Cancer: A Real-World Study

“… 18 Related studies have proved that the use of upfront radiotherapy can improve OS and intracranial PFS (iPFS) in EGFR positive patients with brain metastases. 19 Because of the side effects of whole brain radiotherapy on neurocognitive function, most patients with EGFR mutations in this study were treated with EGFR-TKIs previously. After first-line or second-line treatment, salvage craniocerebral radiotherapy is considered only when the intracranial lesions progressed or accompanied with severe brain metastases symptoms, which may lead to the shortening of OS in EGFR positive patients in this study.…”

Applicability of the adjusted graded prognostic assessment for lung cancer with brain metastases using molecular markers (Lung‐molGPA) in a Chinese cohort: A retrospective study of multiple institutions

“…As a valuable independent predictor for the prognosis of NSCLC with BM, driver gene alteration has been incorporated into the prognosis assessment models that are widely used. 8,[13][14][15][16]20 In the adjusted Lung-molGPA model for adenocarcinoma, patients with Lung-molGPA scores of 0-1.0, 1.5-2.0, 2.5-3.0, and 3.5-4.0 had median OS of 18.4, 23.9, 35.5, and 49.0 months, which were longer than those obtained in the studies by Li, 15 Sperduto, 13 and Nieder. 14 The adjusted Lung-molGPA model estimates of the prognosis of adenocarcinoma with BM, both via whole (p = 0.000, C-index = 0.615) and adjacent stratification analyses (p = 0.012 for 0-1.0 vs 1.5-2.0, p = 0.000 for 1.5-2.0 vs 2.5-3.0 and p = 0.007 for 2.5-3.0 vs 3.5-4.0) were statistical significance.…”

“…As a valuable independent predictor for the prognosis of NSCLC with BM, driver gene alteration has been incorporated into the prognosis assessment models that are widely used 8,13–16,20 . In the adjusted Lung‐molGPA model for adenocarcinoma, patients with Lung‐molGPA scores of 0‐1.0, 1.5‐2.0, 2.5‐3.0, and 3.5‐4.0 had median OS of 18.4, 23.9, 35.5, and 49.0 months, which were longer than those obtained in the studies by Li, 15 Sperduto, 13 and Nieder 14 .…”

The construction and validation of the model for predicting the incidence and prognosis of brain metastasis in lung cancer patients

“…Yet, the National Comprehensive Cancer Network (NCCN) suggests that brain MRI should only be recommended for patients diagnosed with stage II to IV and high-risk stage 1B nonsmall-cell lung cancer; no unanimous screening guidelines for identifying BM exists, until now (8,9). Previous studies found several risk and prognostic factors for BM, shedding light on methods to identify high-risk patients, predict survival, and conduct targeted therapy (10)(11)(12)(13). However, due to the relatively small sample size, the results were not consistent (7,14,15).…”