| Purpose: Accompanying dramatic improvements in imaging technology and systemic disease control rate,non-small cell lung cancer(NSCLC)patients have a particularly high propensity to develop brain metastases(about 40%).There is a great heterogeneity among patients with NSCLC brain metastases,and accurate prognostic evaluation is the basis of personalized medicine.This study sought to investigate prognostic values of clinical and hematological indicators for NSCLC patients with brain metastases treated with radiotherapy and establish a prognostic model,so as to separate the subgroups of patients and maximize clinical benefits.Materials and Methods: We retrospectively reviewed the clinical and hematological indicators of NSCLC patients with brain metastases treated with brain radiotherapy.Descriptive analysis was used to summarize the baseline information of clinical and hematological indicators.Receiver operating characteristic(ROC)curve was performed to evaluate the optimal cut-off points.Comparisons between groups were done utilising contingency tables with Pearson’s chi-squared test and two-sided Fisher’s exact tests or rank sum test for categorical parameters.Kaplan–Meier survival analysis and Cox regression analyses were used to evaluate survival.R software drawn a nomogram and verified it.Results: 214 patients were included and median overal survival time(m OS)was18months(range:1-143 months),and median intracranial progression-free survival was13months(range:1-138 months).The 1-year,2-year,3-year and 5-year survival rates were 68.2%,36.4%,18.8% and 8.3%,respectively.Radiotherapy modalities were associated with survival,and the m OS of whole-brain radiotherapy(WBRT)group,WBRT plus focal radiation boost(WBRT+local radiotherapy)group,local radiotherapy group and postoperative radiotherapy group were 14 months,21months,17 months and41months,respectively(P<0.001).WBRT+local radiotherapy group compared with postoperative radiotherapy group P=0.059,WBRT+local radiotherapy group compared with WBRT group P< 0.001,WBRT+local radiotherapy group compared with local radiotherapy group P=0.128.The addition of targeted therapy with tyrosine kinase inhibitors(TKIs)after brain metastasis has achieved prolonged survival,the m OS of non-targeted therapy group,brain metastasis occurred during targeted therapy and then terminated targeted therapy(targeted therapy before bra in metastasis group),targeted therapy started from the diagnosis of brain metastases(targeted therapy after brain metastasis group),brain metastasis occurred during targeted therapy and then replaced targeted drug or continued the original targeted drug until it progresses again and replaced the targeted drug(targeted therapy before and after brain metastasis group)were 16 months,9 months,25 months and 17 months,respectively(P=0.002).The m OS of patients in the targeted therapy after brain metastasis group was significantly longer than that of the non-targeted therapy group(m OS: 25 m vs.16m;P=0.006)and the targeted therapy before brain metastasis group(m OS: 25 m vs.9m;P<0.001);there was no significant difference in survival between the targeted therapy after brain metastasis group and the targeted therapy before and after brain metastasis group(m OS: 25 m vs.17m;P=0.300).In terms of hematological index ratio,patients with elevated prognostic nutritional index(PNI)had significantly better prognosis than patients with reduced PNI(m OS: 22 months vs.13 months,P<0.001).In addition,age at brain metastasis(P=0.017),smoking history(P=0.004),radical resection of the primary tumor(P=0.045),intracranial symptoms(P=0.017),and number of brain metastases(P=0.030)were independent prognostic factors for the risk of death in NSCLC patients with brain metastases.The m OS of patients in the long-term survival group(OS≥24 months)was36 months,and the long-term survival patients had the following characteristics: radical resection of the primary tumor(P<0.001),no smoking history(P=0.004),no intracranial symptoms(P=0.002),single brain metastasis(P=0.006),high advanced lung inflammation index(ALI)(P<0.001),high PNI(P=0.009),high lymphocyte-monocyte ratio(LMR)(P=0.010)and low systemic immune-inflammation index(SII)(P<0.001).This study further verified the prognostic evaluation of Radiation Therapy Oncology Group—recursive partitioning analysis(RTOG-RPA)and Graded Prognostic Assessment for Lung Cancer Using Molecular Markers(Lung-mol GPA)in NSCLC brain metastasis.The prognosis of patients with RTOG-RPA class I and Lung-mol GPA2.5-4.0 points were significantly better than that of patients with RTOG-RPA class IIIII(35m vs.16 m,P <0.001)and Lung-mol GPA 0-2.0 points(18m and 37 m vs.10 m and15m,P <0.001).In this study,six predictors of age,radical resection of the primary tumor,brain metastasis symptoms,smoking history,extracranial metastases,and absolute monocyte count(AMC)level were included to establish a prognostic model and draw a nomogram for NSCLC patients with brain metastases received brain radiotherapy.In the internal verification,the area under the curve(AUC)of the timedependent ROC curve was 0.789;in the external verification,the time-dependent ROC curve AUC was 0.730.According to the risk score of the nomogram,patients were divided into 4 prognostic groups.Survival analysis showed that the m OS of the low-risk group,low-intermediate risk,high-intermediate risk,and high-risk group was 27 months,22 months,13 months,and 10 months,respectively(P<0.001).Conclusions: WBRT+local radiotherapy may be the preferred radiotherapy modalities for patients with NSCLC brain metastases.If the patient has indications for surgery,surgery combined with postoperative radiotherapy is one of the preferred treatment modes for patients with NSCLC brain metastases.For patients with sensitive gene mutations,regardless of whether they have received TKIs targeted therapy before brain metastasis,radiotherapy combined with TKIs targeted therapy after brain metastasis can achieve survival benefits.PNI may provide valuable information for prognostic evaluation of patients with brain metastasis from NSCLC.Furthermore,nomogram prognostic model and Lung-mol GPA were reliable prognostic models for patients with NSCLC brain metastases. |
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