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

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. 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. 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. The SII and its dynamic change may have a prognostic value in patients with EGFR-mutant lung adenocarcinoma treated with BM radiotherapy.

Wang Q ，Tan X ，Deng G ，Fu S ，Li J ，Li Z ... -  《BMC Pulmonary Medicine》

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

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. 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. 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). 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.

Chen D ，Qin H ，Deng G ，Wang Q ，Wang H ，Liu X ... -  《-》

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

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. 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. 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. In patients with BM from EGFR-mutated NSCLC, cerebral radiotherapy with bevacizumab markedly improved OS. This improvement was more evident after cerebral radiotherapy.

Zhou Y ，Li J ，Li Y ，Deng G ，Wang Q ，Qin H ，Li J ，Li Z ... -  《-》

The Value of the Systemic Immune-Inflammation Index in Predicting Survival Outcomes in Patients with Brain Metastases of Non-Small-Cell Lung Cancer Treated with Stereotactic Radiotherapy.

As a parameter integrating platelet (P), neutrophil (N), and lymphocyte (L) levels, the systemic immune-inflammation index (SII) has been used as a prognostic marker for patient survival in various types of solid malignant tumors. However, there is no in-depth study in non-small-cell lung cancer (NSCLC) patients with brain metastases after stereotactic radiotherapy. Therefore, we performed a retrospective analysis to determine the clinical and prognostic value of the SII in NSCLC patients with brain metastases who underwent stereotactic radiotherapy. We enrolled 124 NSCLC patients with brain metastases treated with stereotactic radiotherapy in our hospital between May 2015 and June 2018. We obtained all baseline blood samples within one week prior to stereotactic radiotherapy. The SII was calculated by the following formula: neutrophil counts × platelet counts/lymphocyte counts. The optimal cutoff value of the SII for predicting prognosis was assessed by receiver operating characteristic (ROC) curves with the maximum log-rank values. The discriminative ability of predicting prognosis was calculated and compared using the Kaplan-Meier method and log-rank test. The hazard ratio (HR) and 95% confidence interval (CI) were combined to evaluate the prognostic impact of the blood index on overall survival (OS) and progression-free survival (PFS). Only those parameters that proved to be associated with statistically significant differences in clinical outcomes were compared in multivariate analysis using a multiple Cox proportional hazard regression model to identify independent prognostic factors. Of the total enrolled patients, 53.2% and 46.8% have high SII and low SII, respectively. In this study, Kaplan-Meier curve analysis revealed that the median PFS was 9 months (range: 2-22 months) and the median OS was 18 months (range: 4-37 months). Applying an optimal cutoff of 480 (SII), the median PFS was better in the low SII group patients (11.5 vs. 9 months), and the median OS was significantly longer in the low SII group patients (20 vs. 18 months). A SII > 480 was significantly associated with worse OS (HR: 2.196; 95% CI 1.259-3.832; P = 0.006) and PFS (HR: 2.471; 95% CI 1.488-4.104; P < 0.001) according to univariate analysis. In multivariate analysis, only age (HR: 2.159; 95% CI 1.205-3.869; P = 0.010), KPS (HR: 1.887; 95% CI 1.114-3.198; P = 0.018), and SII (HR: 1.938; 95% CI 1.046-3.589; P = 0.035) were independently correlated with OS, and SII (HR: 2.224; 95% CI 1.298-3.810; P = 0.004) was an independent prognostic predictor of PFS, whereas we found that other inflammation-based indices lost their independent value. The SII, which is an integrated blood parameter based on platelet, neutrophil, and lymphocyte counts, may be an independent prognostic indicator and may be useful for the identification of NSCLC patients with brain metastases after stereotactic radiotherapy at high risk for recurrence.

Zhang Y ，Chen Z ，Jin F ，Guo D ，Chen Q ，Liu Z ，Ji S ，Gao G ... -  《-》

Prognostic role of the systemic immune-inflammation index in brain metastases from lung adenocarcinoma with different EGFR mutations.

Li H ，Wang G ，Zhang H ，Song X ，Cao J ，Zhang X ，Xue R ，Wang W ，Jia S ，Li Z ... -  《-》