High Risks For Brain Metastases After Prophylactic Cranial Irradiation In Small Cell Lung Cancer

Backgrounds Despite administration of prophylactic cranial irradiation(PCI),some small cell lung cancer(SCLC)patients still suffer from brain metastases(BM)with unknown risk factors.We conducted this study to identify high risks for BM after PCI.Patients and MethodsThe characteristics of all SCLC patients underwent PCI in our institute from July 2003 to June 2014 were analyzed.Kaplan-Meier method was applied to estimate brain metastases-free survival(BMFS),extracranial progression-free survival(ECPFS),progression-free survival(PFS)and overall survival(OS).Cox regression analyses were performed to explore risk factors for BM.ResultsA total of 175 patients with median age of 55 years(range,29-76)were eligible,among whom 36(20.6%)developed BM at the median follow-up period of 42.1 months.Univariate analyses showed TNM classification(p = 0.009,HR = 2.525,95%CI 1.259-5.064)and thoracic hyperfractionated accelerated radiotherapy(HART)(p = 0.023,HR = 2.171,95%CI 1.111-4.243)were associated with BM.In the multivariate hazard model including TNM classification,HART(p = 0.014,HR = 2.748,95%CI 1.227-6.157)was an independent high risk for BM;TNM classification(p = 0.073,HR = 2.119,95%CI 0.932-4.821)tended to be an independent risk factor for BM(Table 1).While in the multivariate hazard model including two-stage system,HART(p = 0.026,HR = 2.448,95%CI 1.116-5.372)was still an independent high risk for BM,but two-stage system(p = 0.280)was not.Two-stage system was not related with BMFS,ECPFS,PFS or OS(p > 0.05),while TNM classification was significantly associated with BMFS(p = 0.009,HR = 2.525,95% CI 1.259-5.064),ECPFS(p = 0.006,HR = 1.786,95% CI 1.177-2.712),PFS(p = 0.005,HR = 1.795,95% CI 1.193-2.702)or OS(p = 0.010,HR = 2.002,95% CI 1.180-3.395).Median OS in symptomatic BM group was shorter than asymptomatic one(28.2 months vs.36.3 months,p = 0.002).ConclusionsTNM classification and thoracic radiotherapy scheme were independent risks for BM after PCI in SCLC.Patients with stage IIIB-IV and HART were more likely to develop BM after PCI.Radiologic examinations of brain should be performed regularly after PCI to detect BM earlier and improve survival,especially for patients with highrisks.TNM classification was more valuable on prognosis than two-stage system.We suppose the current definition of two-stage system should be revised as IA-IIIA being classified into limited stage and IIIB-IV into extensive stage.Further studies are needed to confirm our findings.Backgrounds To compare the brain metastases(BM)rates after prophylactic cranial irradiation(PCI)with hyperfractionated accelerated radiotherapy(HART)and once-daily radiotherapy(QDRT)in small cell lung cancer(SCLC).MethodsThe patients with SCLC who had received HART or QDRT in addition to chemotherapy and PCI from two hospitals were reviewed.A propensity score matching approach was used to control confounding.The primary endpoint was BM rate.The secondary endpoints included local recurrence(LR)rate,were progression-free survival(PFS)and overall survival(OS).BM rate and LR rate were evaluated using Fine and Gray's method.OS and PFS were evaluated using Kaplan-Meier method and Cox regression.ResultsBetween 2003 and 2014,a total of 347 consecutive patients were screened and a subset of 303 with complete data were included for further analyses.After propensity score matching,272 patients were matched successfully.Baseline characteristics were balanced between groups before and after matching.At a median follow-up time of 28.8 months(range,3.9-104.9 months),166(61%)patients died,52(18.8%)experienced BM,158(58%)experienced extracranial failure,112(41.2%)experienced LR.The 3-year cumulative rate of BM was 13.0% in QDRT and 31.8% in HART(p = 0.003,HR = 2.280,95%CI 1.320-3.920).The 3-year cumulative LR rate was 36.9% in QDRT and 41.7% in HART(p = 0.790,HR = 1.060,95%CI 0.710-1.570).The 3-year rate of OS and PFS was 52.8% vs.49.1%(p = 0.502,HR = 1.120,95% CI 0.804-1.561)and 33.2% vs.24.8%(p = 0.202,HR = 1.211,95% CI 0.903-1.626)for QDRT vs.HART.Adverse events were not significantly different between these two groups.ConclusionIn SCLC patients who had received PCI,thoracic HART appeared to have a higher BM rate than QDRT,though there was no significant differences in OS and PFS.Further investigations are needed to confirm our findings.