Evidence Based Medicine And Basic Research On The Optimal BED And Segmented Dose Of SBRT For Early NSCLC

Objective: Through meta-analysis of clinical studies of stereotactic body radiotherapy in the treatment of early stage non-small cell lung cancer,and the study of radiobiological changes in human lung cancer H460 cells irradiated with different doses of X-rays,to investigate the optimal biological effective dose and segmented dose of SBRT in the treatment of early stage NSCLC.Methods: PubMed,The Cochrane Library,EMBASE,Chinese Journal Full-text Database,Chinese Biomedical Literature Database and Wanfang Database were searched by computer and the references of included studies were traced to collect the relevant clinical studies/trials of SBRT for early stage non-small cell lung cancer.The literatures were screened and the data were extracted.STATA12.0 were used for meta-analysis.In vitro studies,H460 cells were irradiated with 0,2,4,6,8,10,15,and 20 Gy of X-rays.At 24 h,48 h and 72 h after irradiation,the cell proliferation was detected by CCK-8 assay,cell cycle distribution and apoptosis ratio were analyzed by flow cytometry.The expression of ?-H2 AX,Bax,Bcl-2 and Caspase-9 were detected by Western blotting.Results: A total of 108 studies were included for meta-analysis.The combined results of SBRT for early NSCLC showed that the 1-,2-,3-,and 5-year overall survival rates were 86.2%,71.6%,62.7%,and 44.9%,respectively.The 1-,2-,3-,and 5-year local control rates were 94.3%,90.5%,87.6%,and 88.5%,respectively.The 1-,2-,3-,and5-year cancer-specific survival rates were 96.0%,87.7%,80.9%,and 76.7%,respectively,and the 1-,2-,3-,and 5-year progression-free survival rates were 79.8%,67.7%,53.5%,and 46.3%,respectively.The results of subgroup analysis showed that tumor size(T1 vs T2),radiation dose,pathological type,and tolerance to surgical treatment have an impact on the survival rate and local control rate of SBRT for NSCLC.The results of cell experiments showed that the inhibition of cellproliferation,G2/M cell arrest and apoptosis of H460 cells after different doses of X-ray irradiation were dose-dependent.Compared with the control group,?-H2 AX protein levels were up-regulated in the 2-10 Gy groups and down-regulated in the 15 and 20Gy groups.The expression levels of pro-apoptosis-related proteins were higher in the 8,10,15,and 20 Gy groups than other irradiation groups.Conclusion: SBRT is a safe and effective method for the treatment of early stage NSCLC,which can obtain a good long-term local control rate and a very low incidence of serious adverse reactions.BED in the range of 105-112.5Gy seems to be sufficient for T1 NSCLC,which can obtain similar or better therapeutic efficacy compared with higher dose irradiation therapy,while for T2 NSCLC,the local control rate and survival rate are low when BED<132Gy,so higher doses are needed to improve the therapeutic effect.The changes in H460 cells at the cellular and molecular levels after different doses of X-ray irradiation showed that 8,10,15,and 20 Gy irradiation had a significant biological response and may be the optimal segmented dose,but in the related clinical trials,patients with central NSCLC tumors showed a high incidence of severe toxicity when irradiated with 20 Gy per fraction,so it needs to be further studied in combination with clinical factors in clinical application.