The Radiation Biology And Clinical Research Of Lung Cancer Treated By CyberKnife Radiotherapy

Objective:To observe the effects of high dose radiation at different intervals in human lung adenocarcinoma xenografts and detect the cell cycle distribution and the rates of hypoxia inducible factor at different intervals after high-dose radiation. Guiding the radiotherapy for early stage lung cancer in clinical treatment;To evaluate the toxicity and efficacy in a population of patients with early stage lung cancer treated by CyberKnife stereotactic radiotherapy.Methods:(1) Using of the lung adenocarcinoma xenografts in nude mice model, measuring changes of xenografts size. Experiment was divided into two parts when average diameter of tumor achieved about 8mm.Group one:Total radiation dose of 16Gyx2F, irradiated at different time intervals(one day to six day). Group two:After single radiation 16Gy,five mice were killed at one to six day,Tumor tissues were obtained and used for immunohistochemical staining for HIF and cell cycle detected by flow cytometry.(2) We retrospectively reviewed 30 inoperable patients with early stage lung cancer(18 with T1 tumors and 12 with T2 tumors) from November 2006 to July 2009.17 patients were treated with the Synchrony Respiratory Tracking System needing one-to-two fiducial markers implantation.13 patients were treated with the X-sight technology.A total dose of 45-60Gy(median,54Gy)was delivered to the PTV in three to six equal fractions in one week or less than 2 weeks.Results:(1) 16Gyx2 fractiongs irradiated lung adenocarcinoma xenografts in nude mice at different intervals(one to six days), the tumors were significantly inhibited,especially two days intervals.Two-month observation after irradiation,the volume of tumors were significantly reduced in the 1 day,2 days interval group,while the volume of the tumors increased comparing with the volume before irradiation in the 5 days,6 days interval group. (2)After 16Gy radiation dose at different intervals the immunohistochemical expression of HIF-la was no significant difference(P<0.05).(3)16Gy radiation dose after 1 day,2 days on the cell cycle is mainly caused significant G2/M phase arrest.G1 cell cycle phase fraction was higher than G2/M phase in the day 3,4,5,6 after radiotherapy.(4) All the tumors responded to treatment in 2-12 months.22(73.3%) patients achieved complete response(CR),and 8(26.7%) achieved partial response(PR).With a median follow-up of 36 months,the primary tumor control rate was 96.7%.The rates for disease-free survival and overall survival at 3-year were 54.8% and 75.4%,respectively.All patients completed treatment without noteworthy side effects.Mild fatigue was reported in 21(70%) patients.Acute grade III radiation pneumonitis was observed in 2 (6.7%) patients.Pneumothorax requiring tube thoracostomy occurred in one patient(5.9%) following CT-guided fiducial placement.Conclusion:The lung adenocarcinoma xenografts are significantly inhibited by high-dose irradiation,and fractionated irradiation interval is one of the factors influencing efficacy. Cyberknife stereotactic radiotherapy is a reasonable therapeutic modality in early stage lung cancer with high primary tumor local control rate and minimal toxicity.More optimal fractionation model requires further study and exploration.