Management Of Medically Inoperable And Tyrosine Kinase Inhibitor-na(?)ve Stage Ⅰ-Ⅲ Lung Adenocarcinoma With Epidermal Growth Factor Receptor Mutations

Objective:Stereotactic radiotherapy(SBRT),external beam radiation(EBRT),epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs)are treatment options for medical unresectable stage I-III patients with EGFR mutant lung adenocarcinoma.The clinical value of combined local radiation and EGFR-TKIs for medically inoperable and TKI-na(?)ve early-stage lung adenocarcinoma patients with EGFR mutations has not yet been determined.In previous retrospective studies,radiotherapy combined with TKI was mostly concentrated in patients with advanced lung cancer.With the application of SBRT,more patients in early stage can safely receive this effective and non-invasive local treatment.In this study,we aimed to pool multi-institutional data to compare the therapeutic effect of EGFR-TKI treatment alone and combined radiation and TKI treatment on the survival outcomes in this patient subgroup.Methods:A total of 132 cases of medically inoperable stage I to III EGFR mutant lung adenocarcinoma were retrospectively reviewed based on data from 5 centers on January 1,2010 and December 31,2011.Among these patients,65 received combined radiation and EGFR-TKI therapy(R+TKI)(49.2%),while 67 received EGFR-TKI(50.8%)treatment alone.All enrolled patients were followed up from the end of the initial treatment,and all patients were followed until death.Univariate and multivariate prognostic analyses were performed for the patients in this group.The primary outcome measure was progression-free survival and secondary outcome measure was overall survival.Results:A total of 132 patients were collected.For the R+TKI group,the median overall survival(OS)after primary therapy was 42.6 months,while that of the TKI alone group was 29.4 months(log-rank P<0.001).In terms of progression-free survival(PFS),the median PFS in these two treatment groups was 24 months and 14.7 months respectively(log-rank P<0.001).Multivariate analysis showed that R+TKI was independently associated with improved OS(adjusted HR 0.420;95%CI 0.287 to 0.614;P<0.001)and PFS(adjusted HR 0.420;95%CI 0.291 to 0.605;P<0.001)compared to TKI alone.Further subgroup analysis revealed that overall survival of the R+TKI group was better than that of the TKI group(P<0.001)for stage Ⅲ lung adenocarcinoma.For stage Ⅱ lung adenocarcinoma,progression free survival was better in the R+TKI group than in the TKI group(P=0.022).Conclusion:Upfront radiation to primary sites with subsequent TKI treatment is a feasible option for patients with medically inoperable EGFR-mutant lung adenocarcinoma during first-line EGFR-TKI treatment,with significantly improved PFS and OS compared with those yielded by TKI treatment alone,especially in patients with stage Ⅲ lung adenocarcinoma.