Application Of Comformal Radiation Therapy (Three-Dimensional Conformal Radiation Therapy And Intensity Modulated Radiation Therapy) In Non-Small Cell Lung Cancer

1.A phaseⅠ/Ⅱdose escalation trial in non-small cell lung cancer using hypofractionated three-dimensional conformal radiation therapyPurpose:To prospectively assess the feasibility and efficacy of a hypofractionated regimen using three-dimensional conformal radiation therapy(3DCRT) in patients with non-small-cell lung cancer(NSCLC). Materials/Methods:The main eligibility criteria of the trial were: pathologically proved stage 1b-Ⅲb medically inoperable or surgically unresectable NSCLC,Karnofsky performance(KPS)≥70,weight loss＜5%within 6 months and no thoracic radiotherapy before enrollment.The 3DCRT technique was used and no elective nodal irradiation was given. Patients were treated 50Gy/20 fractions with 5 days a week,then doses were delivered at 3Gy per fraction,total radiation dose escalated from 65Gy to 71Gy.Chemotherapy using a third generation agent combined with cisplatin or carboplatin were given sequentially.Toxicity was scored according Common Terminology Criteria for Adverse Events version 3.0, dose-limiting toxicities were defined as≥grade 3 radiotherapy related pulmonary,esophagus,heart or spinal cord toxicities. Results:Form Apr.2006 to Jan.2008,30 patients had been enrolled and completed planning treatment.One had stageⅠ,five had stageⅡ,12 had stageⅢa,11 had stageⅢb,one patient with stageⅣwas inadventently enrolled and was included in the toxicity anaysis.There were 19 patients received 65Gy and 11 received 68Gy.All patients had completed 2 cycles induction chemotherapy and 16,11 and 3 patients had received 2 cycles, 1 cycle and 0 cycle consolidation chemotherapy.All of the chemotherapy regiments were navelbine plus cisplatin or carboplatin.No patients developed grade 3 or worse radiation related toxicity.The median follow-up time was 11(5-23) months for all patients,16(6-23) months for group 1(65Gy) and 9(5-11) months for group 2(68Gy).Radiation pneumonitis were observed in 19 patients,where 9 of grade 1 and 10 of grade 2.Pulmonary fibrosis were occurred in 11 patients,all of which were grade 1.Three patients developed grade 1-2 atelectasis between 2-4 months after completion of radiotheray,two of them had been confirmed to due to bronchus excretion by tracheoscope examination and one was comfirmed to have no tumor progression by 9 months follow-up.20 patients developed radiation esophagitis including 13 with grade 1 and 7 with grade 2.At present,13 patients had experienced treatment failure including 5 with isolated distant metastasis,2 with local failure inside PTV,4 with local failure both inside and outside PTV,2 patients with local and distant failure.Because of limited follow-up time,we just analysed the survival status for the patients of group 1(received 65Gy), one year overall survial,progression-free survival,localreginal progression-free and distant-free survival was 77.8%,40.6%,50.3%and 63.3%respectively.Conclusions:Hypofractionated radiotherapy using 3DCRT in NSCLC is feasibility,however more data are needed to comfirm its outcomes. 2.The Dosimetric Study in Intensity Modulated Radiation Therapy for Non-Small Cell Lung CancerPurpose:To investigate whether the technique of intensity modulated radiation therapy(IMRT) could reduce dose to normal lungs compared with three-dimensional conformal radiotherapy(3DCRT) for non-small cell lung cancer(NSCLC),and the impact of different beams' set-up methods to the qulity of IMRT.Materials and Methods:We selected the patients with stageⅠ-ⅢNSCLC who had received 3DCRT with ELEKTA Snergy LA(1cm MLCs' width) between 2006 and 2007 in our hospital.The eligibity criteria including:total radiation dose was 65Gy;prescription dose should cover more than 95%of the PTV,≥99%of the PTV received≥95% of the prescribed dose,no more than 20%of the PTV could receive≥110%of the prescribed dose;the maximum dose to spinal cord could not exceed 45Gy,V55 of esophagus≤30%and mean esophageal dose≤34Gy,V40 of heart≤50%.Step and shoot was used as our IMRT technique.Three IMRT plans will be designed for each case:IMRT-7 which uses nine equal-spaced beams including 0°,51°,102°,153°,204°, 255°,306°;IMRT-5 with five equal-spaced beams including 0°,72°,144°, 216°,288°;and IMRT-5m which is created from IMRT-7 but excluded 2 fields(51°,102°will be omitted if lesion in the right lung,255°,306°will be excluded if lesion in the left lung).There were two more dose specifications than 3DCRT for the target when planning IMRT:a contiguous volume of no more than 2 cm~3 inside the PTV exceeds 120% of the prescribed dose;no more than 1 cm~3 of contiguous tissue outside the PTV receives≥110%of the prescribed dose.Dose constrains of IMRT for the critical structures were the same as 3DCRT except for lung, which V5-V60 in IMRT should be lower than 3DCRT of the same patient. The prescripation dose for IMRT start from 65Gy,then will be escalated or decreased step by step by 2Gy once a time until the best plan was obtained.The parameters being compared between plans include conformity index(CI),heterogeneity index(HI),V5-V60(in increments of 5 Gy) of lung,mean lung dose(MLD),normal tissue complication probability(NTCP) for lung,V55 and mean dose of esophagus, maximum dose to spinal cord,V40 of heart,total monitor units(MUs), and the prescripation dose of best plan.Statistical analysis is performed using paired student's t-test.Results:21 patients were enrolled in this study.Compared to 3DCRT,all the three types of IMRTs significantly decreased the V5-V60 of lung, MLD and NTCP.For IMRTs,we found IMRT-5m has lower V5-V25 than the other two;there was no major difference in V30-V40;for V45-V60,IMRT-5 was the worst,IMRT-7 and IMRT-5m were similar. Doses to esophagus and heart were smaller in IMRTs than 3DCRT and similar among IMRTs.The maximum dose to spinal cord was minorly increased by IMRTs,but the defference between 3DCRT and IMRTs did not reach statistically significance except for IMRT-5.IMRTs could increase prescription dose by 5.1Gy(SD=4.6Gy) for IMRT-7,3.1Gy (SD=5.3Gy) for IMRT-5,and 5.5Gy(SD=4.8Gy) for IMRT-5m.The target comformity was higher in IMRTs while heterogeneity was greater. Total MUs of IMRTs were more than 3DCRT,but no significant difference was found between IMRTs.Conclusions:IMRT can reduce the dose to normal lungs in NSCLC so that potentially decrease the risk of radiation lung injury.Use fewer beams and modified beam angles could result in similar,even better plan quality.