Bevacizumab improved prognosis for advanced EGFR-mutant lung adenocarcinoma with brain metastasis receiving cerebral radiotherapy.

OBJECTIVE: This study aimed to determine whether the combined use of bevacizumab could improve overall survival (OS) in patients with brain metastasis (BM), epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) undergoing cerebral radiotherapy. MATERIALS AND METHODS: A total of 237 patients with EGFR-mutant lung adenocarcinoma and BM met the inclusion criteria for this retrospective study, including 102 patients in the bevacizumab treatment group and 135 in the non-bevacizumab group. The Kaplan-Meier method was used for survival analysis. Univariate and multivariate analyses were performed to identify EGFR-mutated BM prognostic factors for these patients. RESULTS: At the end of the last follow-up period, 176 patients (74.3%) had died, and the median overall survival (OS) was 34.2 months. We observed a significant difference in the median OS between the bevacizumab and non-bevacizumab groups (45.8 months vs 30.0 months, P < 0.0001). Among the 178 (75.1%) patients who received cerebral radiotherapy, the median OS of patients in the bevacizumab + cerebral radiotherapy group was 45.8 months versus 32.0 months in the non-bevacizumab + cerebral radiotherapy group, respectively (P = 0.0007). Patients treated with bevacizumab after cerebral radiotherapy had a longer median OS than patients treated with bevacizumab before cerebral radiotherapy (59.4 months vs 33.7 months, P = 0.0198). In the univariate analysis, smoking status, Lung-molGPA scores, and bevacizumab therapy showed correlations (HR = 1.450, P = 0.045; HR = 0.700, P = 0.023; HR = 0.499, P < 0.001). Multivariate analysis showed that bevacizumab therapy alone (hazard ratio [HR] = 0.514; P < 0.001) was independently associated with improved OS. CONCLUSION: In patients with BM from EGFR-mutated NSCLC, cerebral radiotherapy with bevacizumab markedly improved OS. This improvement was more evident after cerebral radiotherapy.

Effect of EGFR-TKIs combined with craniocerebral radiotherapy on the prognosis of EGFR-mutant lung adenocarcinoma patients with brain metastasis: A propensity-score matched analysis.

Background and Purpose: Epidermal growth factor receptor (EGFR)-mutant lung cancers are associated with a high risk of developing brain metastases (BM). Craniocerebral radiotherapy is a cornerstone for the treatment of BM, and EGFR-TKIs act on craniocerebral metastases". However, whether EGFR-TKIs combined with craniocerebral radiotherapy can further increase the efficacy and improve the prognosis of patients is unclear. This study aimed to evaluate the difference in efficacy between targeted-therapy alone and targeted-therapy combined with radiotherapy in EGFR-mutant lung adenocarcinoma patients with BM. Materials and Methods: A total of 291 patients with advanced non-small cell lung cancer (NSCLC) and EGFR mutations were enrolled in this retrospective cohort study. Propensity score matching (PSM) was conducted using a nearest-neighbor algorithm (1:1) to adjust for demographic and clinical covariates. Patients were divided into two groups: EGFR-TKIs alone and EGFR-TKIs combined with craniocerebral radiotherapy. Intracranial progression-free survival (iPFS) and overall survival (OS) were calculated. Kaplan-Meier analysis was used to compare iPFS and OS between the two groups. Brain radiotherapy included WBRT, local radiotherapy, and WBRT+Boost. Results: The median age at diagnosis was 54 years (range: 28-81 years). Most patients were female (55.9%) and non-smokers (75.5%). Fifty-one pairs of patients were matched using PSM. The median iPFS for EGFR-TKIs alone (n=37) and EGFR-TKIs+craniocerebral radiotherapy (n=24) was 8.9 and 14.7 months, respectively. The median OS for EGFR-TKIs alone (n=52) and EGFR-TKIs+craniocerebral radiotherapy (n=52) was 32.1 and 45.3 months, respectively. Conclusion: In EGFR-mutant lung adenocarcinoma patients with BM, targeted therapy combined with craniocerebral radiotherapy is an optimal treatment.

Pre-radiotherapy systemic immune inflammation index associated with overall survival in patients with advanced EGFR mutant non-small cell lung cancer receiving thoracic radiotherapy

Purpose This study aimed to investigate the prognostic potential of the pre-radiotherapy systemic immune-inflammation index (SII) for the survival of advanced lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutations, which might provide a basis for optimizing the comprehensive treatment scheme. Methods A total of 111 lung adenocarcinoma patients with EGFR mutations, who received thoracic radiotherapy, were included in this retrospective study. The primary endpoint of the study was based on the overall survival (OS) of patients. The receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off value of each immune inflammation index. Kaplan–Meier analysis was performed for the comparison of OS. The Cox proportional-hazard model was used for the multivariate and univariate regression analyses to determine the correlations of prognostic factors with the disease. Results SII was divided into the high SII group (≥ 620.2; 45.95%) and the low SII group (SII < 620.2; 54.05%) based on the optimal cutoff values. The median OS rates were 53.3 and 33.3 months in the low and high SII groups, respectively, showing statistically significant differences ( hazard ratio (HR) = 0.459; 95% CI 0.286–0.736; P < 0.001). The multivariate analysis showed that, after adjusting for the significant covariates, the SII values were independently associated with the improved OS of the patients (adjusted HR = 0.444; 95% CI 0.279–0.709; P = 0.001). The low NLR values were associated with the better OS of patients (HR = 0.509; 95% CI 0.326–0.792; P = 0.005) and vice versa (HR = 0.422; 95% CI 0.213–0.836; P < 0.001). The patients in the low LMR group before radiotherapy exhibited longer OS as compared to those in the high LMR group (HR = 0.497; 95% CI 0.308–0.802; P = 0.001) (AU)

Pre-radiotherapy systemic immune inflammation index associated with overall survival in patients with advanced EGFR mutant non-small cell lung cancer receiving thoracic radiotherapy.

PURPOSE: This study aimed to investigate the prognostic potential of the pre-radiotherapy systemic immune-inflammation index (SII) for the survival of advanced lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutations, which might provide a basis for optimizing the comprehensive treatment scheme. METHODS: A total of 111 lung adenocarcinoma patients with EGFR mutations, who received thoracic radiotherapy, were included in this retrospective study. The primary endpoint of the study was based on the overall survival (OS) of patients. The receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off value of each immune inflammation index. Kaplan-Meier analysis was performed for the comparison of OS. The Cox proportional-hazard model was used for the multivariate and univariate regression analyses to determine the correlations of prognostic factors with the disease. RESULTS: SII was divided into the high SII group (≥ 620.2; 45.95%) and the low SII group (SII < 620.2; 54.05%) based on the optimal cutoff values. The median OS rates were 53.3 and 33.3 months in the low and high SII groups, respectively, showing statistically significant differences ( hazard ratio (HR) = 0.459; 95% CI 0.286-0.736; P < 0.001). The multivariate analysis showed that, after adjusting for the significant covariates, the SII values were independently associated with the improved OS of the patients (adjusted HR = 0.444; 95% CI 0.279-0.709; P = 0.001). The low NLR values were associated with the better OS of patients (HR = 0.509; 95% CI 0.326-0.792; P = 0.005) and vice versa (HR = 0.422; 95% CI 0.213-0.836; P < 0.001). The patients in the low LMR group before radiotherapy exhibited longer OS as compared to those in the high LMR group (HR = 0.497; 95% CI 0.308-0.802; P = 0.001). CONCLUSIONS: This study showed that these inflammatory indices might have an important prognostic potential for advanced lung adenocarcinoma patients with EGFR mutations, receiving thoracic radiotherapy and might provide a basis for the individualized treatment of these patients.

Dynamic changes in the systemic immune-inflammation index predict the prognosis of EGFR-mutant lung adenocarcinoma patients receiving brain metastasis radiotherapy.

BACKGROUND: The systemic immune-inflammation index (SII) has recently emerged as a predictor of survival in non-small cell lung cancer patients. There is also tight correlation between radiotherapy and immune status, and brain metastases (BM) radiotherapy is an important treatment in patients with BM from lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations. Hence, this study aimed to present the prognostic value of SII and its dynamic changes during BM radiotherapy in EGFR-mutant lung adenocarcinoma patients with BM. METHODS: Patients with EGFR-mutant lung adenocarcinoma who received BM radiotherapy between November 2011 and April 2021 were included in this retrospective study. The SII was calculated using data acquired within 1 week before the start of radiation treatment and 1 week before its completion. According to the cutoff value of SII before radiation treatment determined using receiver operating characteristic curve analyses, we divided the patients into a high group and a low group. Patients were further classified into high-high, high-low, low-low, and low-high groups based on dynamic changes in SII. Prognostic values of the SII and other factors were determined using the Kaplan-Meier method, as well as univariate and multivariate Cox analysis. RESULTS: A total of 202 patients met the inclusion criteria, and the median overall survival (OS) of the entire cohort was 36 months. According to the SII cutoff of 859.79, an SII value below this cutoff was associated with longer OS (hazard ratio 0.6653, 95% confidence interval 0.4708-0.9402, P < 0.05). The patients in the low-low group, whose SII within 1 week before the start and end of BM radiotherapy were below the cutoff, had a median OS of 55.2 months, which was significantly longer than the OS in all other groups (P < 0.05). Univariate and multivariate analyses confirmed that dynamic SII change (P = 0.032), Lung-molGPA (P < 0.001), and thoracic radiation (P = 0.048) were independently correlated with OS. CONCLUSIONS: The SII and its dynamic change may have a prognostic value in patients with EGFR-mutant lung adenocarcinoma treated with BM radiotherapy.

Effect of brain radiotherapy strategies on prognosis of patients with EGFR-mutant lung adenocarcinoma with brain metastasis.

PURPOSE: Epidermal growth factor receptor (EGFR)-mutant lung cancers have a high risk of developing brain metastases (BM). Whole brain radiotherapy (WBRT), local radiotherapy, and WBRT + Boost are frequently used for treatment of BM. This retrospective study aimed to evaluate the difference in efficacy of these radiotherapy modes in patients with EGFR-mutant lung adenocarcinoma with BMs. Further, we determined the optimal radiotherapy regimen for patients based on Lung-molGPA. METHODS AND MATERIALS: We retrospectively enrolled 232 patients with EGFR-mutant lung adenocarcinoma with BMs. Patients were divided into three groups based on the different modes of brain radiotherapy: WBRT group, local radiotherapy group, and WBRT + Boost group. Graded prognostic assessment for lung cancer using molecular markers (Lung molGPA), overall survival (OS), and intracranial progression-free survival (iPFS) were calculated. Kaplan-Meier was used to compare iPFS and OS in different groups. RESULTS: The median OS for the WBRT (n = 84), local radiotherapy (n = 65), and WBRT + Boost (n = 83) cohorts was 32.8, 59.1, and 41.7 months, respectively (P = 0.0002). After stratification according to the Lung-molGPA score, the median OS for the WBRT (n = 56), local radiotherapy (n = 19), and WBRT + Boost (n = 28) cohorts was 32.5, 30.9, and 30.8 months, respectively, in subgroup with score 1-2 (P = 0.5097). In subgroup with score 2.5-4, the median OS for the WBRT (n = 26), local radiotherapy (n = 45), and WBRT + Boost (n = 54) cohorts was 32, 68.4, and 51 months, respectively (P = 0.0041). CONCLUSION: The present study showed that in patients with EGFR-mutant lung adenocarcinoma with BM, local radiotherapy and WBRT + Boost perform similarly well both in the subgroups with low and high scores of Lung-molGPA. Considering the side effect caused by whole brain radiotherapy, we recommended local radiotherapy as optimal brain radiation mode for those subtype lung cancer patients.