中段食管癌根治性放疗方法剂量学和放射性心脏损伤预测对照分析
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摘要
目的食管癌是我国高发肿瘤之一,放射治疗是食管癌的主要治疗方式,放疗所致的心血管并发症已成为胸部肿瘤放疗后的首位非肿瘤致死原因。因此,降低放射性心脏损伤的风险尤为重要。本研究通过对比螺旋断层放射治疗(tomotherapy,TOMO)、调强放射治疗(intensity-modulated radiotherapy,IMRT)及容积弧形调强放射治疗(volumetric modulated arc therapy,VMAT)在中段食管癌放疗中的剂量学特点,预测放射性心脏损伤风险,为临床治疗的选择提供参考。方法选取重庆市肿瘤医院2015-05-11-2017-04-05收治的10例经病理及影像学检查确诊的中段食管癌患者,在其CT模拟定位图像勾画靶区及正常器官,分别设计IMRT、VMAT和TOMO计划。评估不同计划靶体积(planning target volume,PTV)及危及器官的剂量学参数,并通过拟合剂量-反应曲线预测放射性心脏损伤风险。采用SPSS 22.0对资料进行统计学分析。结果对于大体肿瘤计划靶区(plan gross tumor volume,PGTV)、TOMO计划Dmax(67.37Gy)及Dmin(62.80Gy)与IMRT(Dmax=67.58Gy,Dmin=62.02Gy)和VMAT(Dmax=67.71Gy,Dmin=62.05Gy)相比差异有统计学意义(F=9.56,P<0.001;F=6.50,P=0.005)。TOMO的均匀性指数(homogeneity index,HI=0.06)及适形性指数(conformity index,95%CI:0.71)与IMRT(HI=0.09;95%CI:0.64)及VMAT(HI=0.09;95%CI:0.59)相比差异有统计学意义(FHI=12.32 PHI=0.001;F95%CI=7.40 P95%CI=0.003)。TOMO双肺V20与IMRT及VMAT相比差异有统计学意义(TOMO∶IMRT∶VMAT=24.76∶31.46∶31.44,F=9.79,P=0.001)。VMAT计划发生放射性心脏损伤的绝对超额风险(absolute excess risk,AER)最低,AERVMAT=10.66∶AERIMRT=18.07∶AERTOMO=13.79,F=14.69,P<0.001。结论 VMAT虽能降低放射性心脏损伤的风险,但双肺剂量显著增加,TOMO在降低双肺受照剂量的同时也能降低发生放射性心脏损伤的风险,TOMO放疗计划仍具有优势。
OBJECTIVE Esophageal cancer is one of the most common tumors in China.Most patients with esophageal cancer need radiotherapy in the course of treatment.Cardiovascular complications caused by radiotherapy is the first non-tumor cause of death after radiotherapy for chest tumors.So,reducing radiation-induced heart disease is particularly important.By comparing dosimetric characteristics of three kinds of radiation techniques(helical tomotherapy(TOMO),intensity-modulated radiotherapy(IMRT)and Volumetric Modulated Arc Therapy(VMAT))for patients with middle esophageal carcinoma,this study predict the risk of Radiation-induced heart disease(RIHD),to provide reference for the choice of clinical treatment.METHODS A total of 10 patients with middle esophageal carcinoma were diagnosed by pathology and imaging from May 11 th 2015 to April 5 th 2017 in radiotherapy unit of Chongqing Cancer Hospital.The target volume and organs at risk(OARs)were contoured in CT image.Moreover,IMRT,VMAT and TOMO plans were designed respectively.We evaluated the planning target volume(PTV)and OARs by the dosimetric parameters,and predicted the risk of RIHD by fitting dose response curve.SPSS 22.0 was used for statistical analysis.RESULTS For PGTV,TOMO plan(Dmax=67.37 Gy,Dmin=62.80 Gy)showed statistical significance F=9.56 P<0.001;F=6.50,P=0.005)compared to IMRT(Dmax=67.58 Gy;Dmin=62.02 Gy)and VMAT(Dmax=67.71 Gy;Dmin=62.05 Gy).The homogeneity index(HI=0.06)and conformity index(95%CI:0.71)of TOMO showed statistical significance(FHI=12.32 PHI=0.001,F95%CI=7.40 P95%CI:0.003)compared to IMRT(HI=0.09;95%CI=0.64)and VMAT(HI=0.09;95%CI:0.59).The difference of V20 showed statistical significance(TOMO/IMRT/VMAT=24.76/31.46/31.44,F=9.79,P=0.001)of lungs in TOMO,IMRT and VMAT plans.The risk of RIHD was the lowest in VMAT plan(AER:VMAT/IMRT/TOMO=10.66/18.07/13.79,F=14.69,P<0.001).CONCLUSIONS VMAT reduced the risk of radiation-induced cardiac injury but increased the radiation dose in dual lungs.TOMO can reduce the risk of radiation induced heart injury and the radiation dose of dual lung.TOMO still has its advantage.
OBJECTIVE Esophageal cancer is one of the most common tumors in China.Most patients with esophageal cancer need radiotherapy in the course of treatment.Cardiovascular complications caused by radiotherapy is the first non-tumor cause of death after radiotherapy for chest tumors.So,reducing radiation-induced heart disease is particularly important.By comparing dosimetric characteristics of three kinds of radiation techniques(helical tomotherapy(TOMO),intensity-modulated radiotherapy(IMRT)and Volumetric Modulated Arc Therapy(VMAT))for patients with middle esophageal carcinoma,this study predict the risk of Radiation-induced heart disease(RIHD),to provide reference for the choice of clinical treatment.METHODS A total of 10 patients with middle esophageal carcinoma were diagnosed by pathology and imaging from May 11 th 2015 to April 5 th 2017 in radiotherapy unit of Chongqing Cancer Hospital.The target volume and organs at risk(OARs)were contoured in CT image.Moreover,IMRT,VMAT and TOMO plans were designed respectively.We evaluated the planning target volume(PTV)and OARs by the dosimetric parameters,and predicted the risk of RIHD by fitting dose response curve.SPSS 22.0 was used for statistical analysis.RESULTS For PGTV,TOMO plan(Dmax=67.37 Gy,Dmin=62.80 Gy)showed statistical significance F=9.56 P<0.001;F=6.50,P=0.005)compared to IMRT(Dmax=67.58 Gy;Dmin=62.02 Gy)and VMAT(Dmax=67.71 Gy;Dmin=62.05 Gy).The homogeneity index(HI=0.06)and conformity index(95%CI:0.71)of TOMO showed statistical significance(FHI=12.32 PHI=0.001,F95%CI=7.40 P95%CI:0.003)compared to IMRT(HI=0.09;95%CI=0.64)and VMAT(HI=0.09;95%CI:0.59).The difference of V20 showed statistical significance(TOMO/IMRT/VMAT=24.76/31.46/31.44,F=9.79,P=0.001)of lungs in TOMO,IMRT and VMAT plans.The risk of RIHD was the lowest in VMAT plan(AER:VMAT/IMRT/TOMO=10.66/18.07/13.79,F=14.69,P<0.001).CONCLUSIONS VMAT reduced the risk of radiation-induced cardiac injury but increased the radiation dose in dual lungs.TOMO can reduce the risk of radiation induced heart injury and the radiation dose of dual lung.TOMO still has its advantage.
引文
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[10]武瑞凤,苏晋生,宋建波,等.首过灌注及心肌活性分析实验犬放射性心脏损伤的实验研究[J].中国现代药物应用,2014,8(8):241-242.
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[12]Schultzhector S,Trott KR.Radiation-induced cardiovascular diseases:is the epidemiologic evidence compatible with the radiobiologic data?[J].Int J Radiat Oncol Biol Phys,2007,67(1):10-18.
[13]Ramyar A,Shafiei M,Moazzami K,et al.Severe valvular toxicity and pericarditis early after radiation therapy in a patient treated for Hodgkin's lymphoma[J].Turk J Pediatr,2010,52(4):423.
[14]Stewart FA.Mechanisms and dose-response relationships for radiation-induced cardiovascular disease[J].Ann ICRP,2012,41(3-4):72-79.
[15]Little MP,Gola A,Tzoulaki I.A model of cardiovascular disease giving aplausible mechanism for the effect of fractionated low-dose ionizing radiation exposure[EB/OL].PLoS Comput Biol,2009,5(10):e1000539[2017-08-06].http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1000539.
[16]Heidenreich PA,Schnittger I,Strauss HW,et al.Screening for coronary artery disease after mediastinal irradiation for Hodgkin’s disease[J].J Clin Oncol,2007,25(1):43-49.
[17]Nagykálnai T,Nagy AC,Landherr L.Postoperative radiotherapy of breast cancer and cardiotoxicity[J].Orv Hetil,2014,155(23):897-902.
[18]Schellong G,Riepenhausen M,Bruch C,et al.Late valvular and other cardiac diseases after different doses of mediastinal radiotherapy for Hodgkin disease in children and dolescents:Report from the longitudinal GPOH follow-up project of the German-Austrian DAL-HD studies[J].Pediatr Blood Cancer,2010,55(6):1145.
[19]Wang K,Eblan MJ,Deal AM,et al.Cardiac toxicity after radiotherapy for stageⅢnon-small-cell lung cancer:Pooled analysis of dose-escalation trials delivering 70to 90Gy[J].J Clin Oncol,2017,35(13):1387-1394.
[20]Maraldo MV,Brodin NP,Vogelius IR,et al.Risk of developing cardiovascular disease after involved node radiotherapy versus mantle field for Hodgkin lymphoma[J].Int J Radiat Oncol Biol Phys,2012,83(4):1232.
[21]Darby SC,Ewertz M,Mcgale P,et al.Risk of ischemic heart disease in women after radiotherapy for breast cancer[J].N Engl J Med,2013,368(11):987-998.
[2]李多杰,李红伟,崔珍,等.食管癌调强放疗累及野照射的同期对照研究[J].实用医学杂志,2016,32(11):1799-1802.
[3]Dogan SM,Bilici HM,Bakkal H,et al.The effect of radiotherapy on cardiac function[J].Coron Artery Dis,2012,23(3):146-154.
[4]Feng M,Moran JM,Koelling T,et al.Development and validation of a heart atlas to study cardiac exposure to radiation following treatment for breast cancer[J].Int J Radiat Oncol Biol Phys,2011,79(1):10-18.
[5]Feuvret L,Noёl G,Nauraye C,et al.Conformal index and radiotherapy[J].Cancer Radiother,2004,8(2):108.
[6]Yim J,Suttie C,Bromley R,et al.Intensity modulated radiotherapy and 3Dconformal radiotherapy for whole breast irradiation:a comparative dosimetric study and introduction of a novel qualitative index for plan evaluation,the normal tissue index[J].J Med Radiat Sci,2015,62(3):184-191.
[7]Schellong G,Riepenhausen M,Bruch C,et al.Late valvular and other cardiac diseases after different doses of mediastinal radiotherapy for hodgkin disease in children and adolescents:Report from the longitudinal GPOH follow-up project of the GermanAustrian DAL-HD studies[J].Pediatr Blood Cancer,2010,55(6):1145-1152.
[8]Filippi AR,Ragona R,Piva C,et al.Optimized volumetric modulated arc therapy versus 3D-CRT for early stage mediastinal Hodgkin lymphoma without axillary involvement:a comparison of second cancers and heart disease risk[J].Int J Radiat Oncol Biol Phys,2015,92(1):161.
[9]赖霄晶,谷庆,杨双燕,等.食管癌螺旋断层放疗及三维适形调强放疗计划剂量学研究[J].中华肿瘤防治杂志,2017,24(10):696-702.
[10]武瑞凤,苏晋生,宋建波,等.首过灌注及心肌活性分析实验犬放射性心脏损伤的实验研究[J].中国现代药物应用,2014,8(8):241-242.
[11]Aleman BM,Moser EC,Nuver J,et al.Cardiovascular disease after cancer therapy[J].EJC Suppl,2014,12(1):18.
[12]Schultzhector S,Trott KR.Radiation-induced cardiovascular diseases:is the epidemiologic evidence compatible with the radiobiologic data?[J].Int J Radiat Oncol Biol Phys,2007,67(1):10-18.
[13]Ramyar A,Shafiei M,Moazzami K,et al.Severe valvular toxicity and pericarditis early after radiation therapy in a patient treated for Hodgkin's lymphoma[J].Turk J Pediatr,2010,52(4):423.
[14]Stewart FA.Mechanisms and dose-response relationships for radiation-induced cardiovascular disease[J].Ann ICRP,2012,41(3-4):72-79.
[15]Little MP,Gola A,Tzoulaki I.A model of cardiovascular disease giving aplausible mechanism for the effect of fractionated low-dose ionizing radiation exposure[EB/OL].PLoS Comput Biol,2009,5(10):e1000539[2017-08-06].http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1000539.
[16]Heidenreich PA,Schnittger I,Strauss HW,et al.Screening for coronary artery disease after mediastinal irradiation for Hodgkin’s disease[J].J Clin Oncol,2007,25(1):43-49.
[17]Nagykálnai T,Nagy AC,Landherr L.Postoperative radiotherapy of breast cancer and cardiotoxicity[J].Orv Hetil,2014,155(23):897-902.
[18]Schellong G,Riepenhausen M,Bruch C,et al.Late valvular and other cardiac diseases after different doses of mediastinal radiotherapy for Hodgkin disease in children and dolescents:Report from the longitudinal GPOH follow-up project of the German-Austrian DAL-HD studies[J].Pediatr Blood Cancer,2010,55(6):1145.
[19]Wang K,Eblan MJ,Deal AM,et al.Cardiac toxicity after radiotherapy for stageⅢnon-small-cell lung cancer:Pooled analysis of dose-escalation trials delivering 70to 90Gy[J].J Clin Oncol,2017,35(13):1387-1394.
[20]Maraldo MV,Brodin NP,Vogelius IR,et al.Risk of developing cardiovascular disease after involved node radiotherapy versus mantle field for Hodgkin lymphoma[J].Int J Radiat Oncol Biol Phys,2012,83(4):1232.
[21]Darby SC,Ewertz M,Mcgale P,et al.Risk of ischemic heart disease in women after radiotherapy for breast cancer[J].N Engl J Med,2013,368(11):987-998.