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Objective: To assess the technical safety, complications, and efficacy of CT-guided interstitial 3D brachytherapy in patients with peripheral NSCLC.Methods: 21 patients (Ⅱb/Ⅲa/Ⅲb/Ⅳ:1/7/11/2)were registered in this prospective phase Ⅰ trial(Chinese Clinical Trials Register NO.:ChiCTR-ONC-12002715).The median age was 68years(45-81).Primary tumors were treated with 3D brachytherapy (microSelectron-HDR,Nucletron).Distribution of implantation steel needles based on tumors size.The TPS (Oncentra, Nucletron) was used preoperatively to reconstruct 3D images of the patient.The dose of 30 Gy was delivered to the 95% isodose line of the GTV as a single dose.IMRT was performed on the regional positive lymph node.The total dose at least was given 70Gy by 6-MV X-ray to the NGTV, which meet the V20 of lung is kept below 30%.The plan was delivered with a daily dose of 2.0 to 2.2 Gy/F.We calculate the dose of organs at risk(ORS) after superimposing the external irradiation and braehytherapy plan.All procedures were performed under local anesthesia.During CCRT, the combined chemotherapy regimen of VP was used in 14 patients every 4 weeks.A follow-up CT was performed 4 weeks later and every 3 months post implantation.Results: Follow-up period was 4-31 months(median,18 months).The median diameter of the 21 lung tumors was 4.5cm (range, 2.5-8.2 cm).The median V20 of lung by brachytherapy and IMRT in terms of EQD2 were 6.12%(4.06-10.98%) and 22.3%(18.2-25.1%).Grade 3 or 4 toxicities of leukopenia, anemia,and thrombocytopenia were observed in 9.5%, 4.8%, and 0%, respectively.We did not observe other adverse acute radiation toxicity.Except for 2 patients who revealed mild pneumothorax by CT scan, there was no hemothorax, dyspnea, or pyothorax after undergoing the procedure.During the follow-up,Grade 1 irradiation pneumonitis was observed by CT scan in 2 patients without any symptoms.Overall responding rate (CR + PR) to the primary mass and positive lymph nodes were 90.1% and 80.9%.At the time of analysis,3patients died as a result of primary tumor pro-gression;4patients died of multi-organ failure or other metastases.14patients survived to follow-up.The l-year and 2-year overall survival (OS) rate were 76.5% and 44.4%, respectively, with a median OS of 17 months.Local control(LC) rate of the primary sites at 1 and 2 years were 82.4% and 66.7%, respectively, with a median LC of 14 months.The 1-year and 2-year Local control(LC) rate of the regional positive lymph node were 72.2% and 55.6%,respectively, with a median time of 13 months.Conclusion: CT-guided 3D interstitial brachytherapy is safe, acceptable,less complicated and effective in patients with peripheral NSCLC.The current result is a preliminary clinical report.We will continue to conduct the phase Ⅱ clinical trial.A larger population of patients and a longer follow-up period are needed to evaluate efficacy and toxicity.