High-Dose Conventional Fractionation In 3DCRT For Non-Small-Cell Lung Cancer

Background:Non-small cell lung cancer(non-small cell lung cancer,NSCLC) as one of the most common tumors worldwide,features high incidence and high mortality.In China,incidence of NSCLC is high,because of such factors as environmental pollution,which is the threat to global health security.The standardized treatment for Early Stage NSCLC is surgery.However,some patients refuse surgery,and some with cardiopulmonary disease or others can not tolerate surgery,radiation therapy is the important local treatment.Due to low radiosensitivity in NSCLC,but also radiation injury of lung,esophagus and heart and other vital organs,conventional radiotherapy presents poor efficacy. Conformal radiation therapy(CRT) technology such as three-dimensional conformal radiotherapy(3DCRT) and intensity modulated radiation therapy (IMRT),has improved conformality index(CI) and selectivity index(SI) for target, and reduced the dose and volume of involved normal tissues.And it is technically feasible to increase fraction dose and total dose.Domestic and foreign experts are actively probing into application of CRT for NSCLC,and have discovered significant advantage of High-dose Fractionation in 3DCRT over Conventional Fractionation in short-term efficacy and long-term survival rate.Even under 3DCRT technologies,radiation complications of normal tissue still should not be ignored.According to radiobiological theory,increase of fraction dose can significantly aggravated the radiation injury to late response organ such as the heart.During the past time,we have not considered heart as radiation-sensitive organs,and ignored the radiation protection of the heart in course of radiotherapy. But because of long-time observation,as well as advances in detection methods, radiation heart injuries cases have been reported more frequently than before, including pericardial disease,myocardial fibrosis,coronary arterial disease,heart valve disease and cardiac conduction system injury.We come to the conclusion of radiation heart injury almost from previous observation to patients with lymphoma and breast cancer receiving conventional radiotherapy.Because clinical symptoms was not obvious in most cases,radiation heart injury has not gained due attention in course of 3DCRT for NSCLC.In this study,we applied the indexes of Troponin I(cTnI) in blood,24-hour ambulatory electrocardiography(24-AECG),CT,single photon emission computerized tomography(SPECT) myocardial perfusion imaging and color Doppler echocardiography(CDE) to improve specificity and sensitivity of the detection and seek for effective prediction of radiation-induced myocardial fibrosis.It is significant for achieving prediction and prevention of radiation heart injury.By comparing efficacy of High-dose conventional fractionation(HF) and conventional fractionation(CF) in the three-dimensional conformal radiotherapy (3DCRT) for NSCLC and side-effect on heart,we try to wonder the rationality of High-dose Conventional Fractionation in 3DCRT for Non-small-cell lung cancer.Objective:To compare the side-effect of High-dose conventional fractionation(HF) and conventional fractionation(CF) in the three-dimensional conformal radiotherapy(3DCRT) for non-small-cell lung cancer(NSCLC) on the heart,and explore effective prediction on radiation-induced myocardial fibrosis.Methods From April 2004 to January 2008,a total of 85 patients with stageⅠ～ⅢNSCLC were randomized into HF group and CF group,with 39 patients in HF group by 4Gy/f,64Gy/16f/22d and 46 patients in CF group by 2Gy/f,64Gy/16f/44d.Troponin I(cTnI) in blood was all detected before radiotherapy,at dose of 40Gy,at end of the radiotherapy and one month after radiotherapy.24-hour ambulatory electrocardiography(24h-AECG) was underdone at end of radiotherapy.Evaluate radiation-induced pericardium injury via CT.One year later,patients underwent single photon emission computerized tomography(SPECT) myocardial perfusion imaging and color Doppler echocardiography(CDE) test.Results:78 of 85 patients completed radiation treatment.Follow-up time was 12 months.Complete remission(CR) rate and local control rate in group HF was respectively 60.0%and 97.1%,while those in group CF was respectively 41.9% and 79.1%.Overall survival rate and disease-free survival rate in group HF was respectively 85.7%and 65.7%at 1 year,while those in group CF was respectively 81.3%and 58.1%at 1 year.Late radiation-induced lung injury rate and late radiation esophageal injury rate was respectively 57.1%and 17.1%in HF group with 53.5%and 18.6%in CF group.The incidence of Grade≥3 acute and late radiation injury was not observed in the both groups.The serum catnip level in HF group was significantly higher than CF group at dose of 40Gy and end of the radiotherapy.The difference in results of 24h-AECG,SPECT,CDE and incidence of radiation pericardium injury between the two groups were not statistically significant.The serum cTnI level at dose of 40Gy,V₃₀,and V₄₀ were independent risk factor for radiation-induced myocardial fibrosis.Conclusions:During 1 year observation,HF 3DCRT is superior to CF 3DCRT for NSCLC with tumor of≤3cm in recent treatment efficacy without increasing lung and esophageal toxicity significantly.However,there is no advantage of HF 3DCRT over CF 3DCRT in patients with tumor of 3～5cm.HF has not increased incidence of the radiation-induced heart complication,but Long-term effect is unknown.Long-term follow-up is needed.DVH combined with cTnI serum concentration could improve the sensitivity and specificity for identification of radiation-induced myocardial fibrosis.