| PART 1:A nomogram for predicting brain metastasis inⅢA-N2 non-small cell lung cancer after complete resection:A Competing Risk AnalysisBackground:Brain metastasis is one of the most common failure patterns of pⅢA-N2 non-small cell lung cancer after complete resection.Prophylactic Cranial Irradiation(PCI)can improve intracranial control but not overall survival.Thus,it is particularly important to identify risk factors that are associated with brain metastasis and subsequently provide instructions for selecting patients who will optimally benefit from PCI.Methods and materials:Between January 1,2011 and December 31,2014,patients with p Ⅲ A-N2 non-small cell lung cancer who underwent complete resection in our institution were reviewed and enrolled in the study.Clinical characteristics,pathological parameters,treatment mode,Brain metastasis time and overall survival(OS)were analyzed.A nomogram was built based on the corresponding parameters by Fine and Gray’s competing risks analysis to predict the 1-year,3-year,and 5-year probabilities of brain metastasis ROC curves and calibration curves were chosen for validation.Statistically significant difference was set as P<0.05.Results:A total of 517 patients were enrolled in our retrospective study.The median follow-up time for surviving patients was 53.2 mo(range,5.2-123.2 mo).The median age was 57(range,25-80)years.Of the 517 patients,122(23.6%)had squamous cell carcinoma,391(75.6%)received adjuvant chemotherapy and 144(27.3%)received post-operative radiotherapy.The 1-,3-and 5-year survival rates were 94.0%,72.9%and 66.0%respectively.The 1-,3-and 5-year brain metastasis rates were 5.4%,15.7%and 22.2%,respectively.According to the univariate analysis,female,non-smokers,patients with non-squamous cell carcinoma,bronchial invasion,perineural invasion,and patients who received adjuvant chemotherapy were more likely to develop brain metastasis.In multivariate analysis,non-squamous cell carcinoma(subdistribution hazard ratios[SHR]:3.97,95%confidence interval[CI]:1.74-9.04;P=0.001),bronchial invasion(SHR:2.04,95%CI:1.33-3.14;P=0.001),perineural invasion(SHR:2.51,95%CI:1.068-5.98;P=0.037),and adjuvant chemotherapy(SHR:2.82,95%CI:1.42-5.59;P=0.003)were independent risk factors for brain metastasis.A nomogram model was established based on the final multivariable analysis result.The AUC was 0.77(95%CI:0.76-0.78).Conclusions:For patients with pⅢA-N2 non-small cell lung cancer after complete resection,a nomogram was established based on clinicopathological factors and treatment patterns for predicting the brain metastasis.Based on this nomogram,patients with a high risk of brain metastasis who may benefit from PCI can be screened.PART 2:Efficacy analysis of radiotherapy and crizotinib for patients with brain metastasis from ALK-rearranged non-small-cell lung cancerBackground:Radiotherapy and anaplastic lymphoma kinase(ALK)inhibitors are treatment options for brain metastasis(BM)in patients with ALK-rearranged non-small cell lung cancer(NSCLC).This study aimed to find the optimal treatment strategy for patients with BM from ALK-rearranged NSCLC.Methods:Between January 1,2012 and December 31,2017,consecutive patients with BM from ALK-rearranged NSCLC treated with crizotinib and radiotherapy in our institution were reviewed and enrolled into the study.Patients were treated with sequential radiotherapy and crizotinib(upfront radiotherapy or crizotinib followed by the other at intracranial progression),or concurrent radiotherapy and crizotinib.The cumulative incidence of intracranial progression free survival(iPFS)and overall survival(OS)were estimated by the Kaplan-Meier method,the log-rank test was used to analyze differences between the groups,HR was estimated by Cox proportional risk model,and Cox regression model was used for multivariate analysis.A two-sided p value<0.05 were considered statistically significant.Results:Totally 41 patients were enrolled,including 24(58.5%)with sequential treatment and 17(41.5%)with concurrent treatment.The diagnosis-specific graded prognostic assessment(DS-GPA)score was 0-2 in 25(61.0%)patients and>2 in 16(39.0%)patients,respectively.There were 18(43.9%),13(31.7%),and 10(24.4%)patients treated with stereotactic radiosurgery(SRS)/stereotatic radiotherapy,(SRT),whole brain radiotherapy(WBRT),and WBRT with simultaneous in-field boost(SIB),respectively.The median iPFS and OS in all patients were 33.5(95%CI 30.8-36.2)months and 63.9(95%CI 46.0-81.9)months,respectively.Multivariate analysis showed that age(P=0.006),KPS score(P=0.026)and radiotherapy pattern(P<0.001)were the independent influencing factors of patients with brain metastasis from ALK-rearranged non-small-cell lung cancer.There was no significant difference of iPFS or OS between the sequential treatment group and the concurrent treatment group.However,in DSGPA scores of 0-2,the iPFS was longer in the sequential treatment group than concurrent treatment group(67.9 months vs.32.6 months,P=0.045),but the difference of OS was not significant between the two groups(38.9 months vs.32.6 months,P=0.829).Moreover,the median iPFS of patients receiving SRS,WBRT alone,and WBRT with SIB was 33.5 months,43.6 months,and 63.9 months(P=0.047).The corresponding median OS was not reached,26.0 months,and 67.9 months,respectively(P<0.001).Conclusions:For patients with BM from ALK-rearraged NSCLC in our study,sequential crizotinib and brain radiotherapy for patients with DS-GPA score of 0-2 achieve better iPFS.In addition,WBRT with SRS/SRT achieves the best iPFS. |
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