Efficacy Of TKI Combined With SBRT For The Pulmonary Lesion In Advanced NSCLC Patients With Sensitive EGFR-mutated

Objective To investigate whether tyrosine kinase inhibitors combined with SBRT for the pulmonary lesion in advanced NSCLC with sensitive EGFR mutations can improve patients' survival.Method The patients' clinical stage was redefined according to the AJCC version 8 at the time of initial diagnosis.Sensitive EGFR mutations were clearly identified by genetic testing.The treatment process included targeted therapy with first-generation EGFR tyrosine kinase inhibitors and SBRT for the pulmonary lesion(primary or metastatic).Kaplan-Meier method was used to calculate Progression-Free Survival(PFS)and Overall Survival(OS)in different treatment groups.Results The survival data of tyrosine kinase inhibitors combined with the Cyberknife performing radiotherapy to the pulmonary lesion in 51 patients with advanced NSCLC with sensitive EGFR mutations was analyzed retrospectively from December 21 st 2015 to May 17 th 2018.The median PFS was 16.1 ms(95% CI: 11.9 to 20.3),and the 1-year PFS rate was 65.8%.The mPFS of patients with first-line treatment combined with SBRT for the pulmonary lesion(FLPS group)was significantly longer than the patients with multi-line treatment combined with SBRT for the pulmonary lesion(MLPS group)(19.6ms,95% CI: 14.1~25.1 vs 10.7ms,95% CI: 5.3~16.1,P = 0.113),1-year PFS rate was 71.4% and 44.4% respectively.A subgroup analysis of 33 patients in the FLPS group showed a median time interval(MTI)of 6.4 ms from initiation of TKI to initiation of the pulmonary lesion with SBRT.The mPFS of patients with MTI ? 6.4ms was significantly longer than that of patients with MTI<6.4ms(24.3ms,95% CI:22.3~26.3 vs 14.7ms,95% CI: 9.7~19.7,P = 0.021),1-year PFS rate was 88.2% and 51.1% respectively.Seventeen(51.5%)patients were treated with TKI-targeted therapy with Pemetrexed/platinum-based chemotherapy or ENDOSTAR/Bevacizumab-based anti-angiogenic therapy(sequential or synchronized,TKI plus group),16 patients(48.5%)were only treated with TKI after diagnosis and were not combined with other systemic therapy(TKI alone group);The mPFS of the TKI plus group was improved significantly(23.1 ms,95% CI: 19.4-26.7 vs 14.8 ms,95% CI: 9.5~20.1,P = 0.366),the 1-year PFS rate was 81.3% and 60.9% separately.At the cutoff date of March 2nd 2019,only 8/51 patients died,and OS data is still immature.The incidence of radiation pneumonitis in CT image was 37.3% in the duration of 3 to 6 months after radiotherapy.There were no records of occurrence of radiation pneumonitis above grade 2.The incidence of radiation pneumonitis in the FLPS and MLPS groups was 36.4% and 38.9% respectively(P = 0.859).All patients did not have a record of hospitalization for radiation pneumonitis and there was no record of radiation esophagitis.Conclusion Tyrosine kinase inhibitors combined with SBRT for the pulmonary lesion in advanced NSCLC with sensitive EGFR mutations is doable and valid.The first-line treatment combined with SBRT for the pulmonary lesion before the disease progressing can prolong PFS significantly.And it's time to start SBRT for the pulmonary lesion when patients have been treated with TKI over 6 months without disease progression.First-line therapy combined with chemotherapy or anti-vascular therapy can also improve PFS significantly in patients with a better physical condition.