Ⅲ+Ⅳ期非小细胞肺癌调强放疗剂量学参数预测有症状放射性肺炎的临床研究
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摘要
目的:探讨接受调强放疗(intensity modulated radiotherapy,IMRT)的Ⅲ、Ⅳ期非小细胞肺癌(nonsmall-cell lung cancer,NSCLC)患者正常肺组织剂量-体积参数对有症状放射性肺炎(≥2级,radiation pneumonitis,RP)的预测作用。方法 :回顾性分析53例接受调强放疗的Ⅲ、Ⅳ期NSCLC患者临床资料,记录剂量-体积参数V5、V20、平均肺剂量(MLD)及≥2级RP发生率。肺损伤评估根据CTCAE4.0标准。单因素及多因素分析各个剂量学参数与≥2级RP之间的关系,并采用ROC曲线分析各剂量参数的敏感性、特异性对预测≥2级RP的价值。结果:53例患者中2级RP发生率为9.43%(5/53),3级RP发生率为5.66%(3/53),4级RP发生率为3.77%(2/53),≥2级RP总发生率为18.87%(10/53)。经Spearman等级相关分析,V5、V20、MLD均与≥2级RP的发生相关(r=0.485、0.404、0.404,P=0.000、0.003、0.003)。单因素分析发现V5、V20、MLD与≥2级RP的发生有相关性(t=-4.588、-2.433、-2.845,P=0.000、0.019、0.006)。经单因素分析中有意义的参数,再次进行多因素分析显示:V5是≥2级RP发生的独立影响因素(P=0.03)。经ROC曲线分析,V5预测≥2级RP有统计学意义(P<0.05),其曲线下面积为0.862,敏感性和特异性分别为1.00、0.442。当V5临界值为43.65%时≥2级RP发生率分别为7.14%、32%。结论:剂量-体积参数V5、V20、MLD与≥2级RP相关,其中V5是独立预测因素。
Objective: To determine lung dosimetric constraints that correlated with symptomatic radiation pneumonitis( ≥2 grade) in stage Ⅲ and Ⅳ non- small cell lung cancer patients treated with intensity modulated radiotherapy( IMRT). Methods: 53 NSCLC patients were treated with IMRT. Several dosimetric factors and ≥2 grade RP incidence were recorded and analyzed. Radiation induced lung injury was evaluated according to the standard CTCAE4. 0.Univariate and multivariate analyses were performed to assess the relationship between dosimetric factors and ≥ 2grade RP. The ROC curve was used to explore the predictive sensitivity( SEN) and specificity( SPE) for potential DVH parameters associated with ≥2 grade RP. Results:The morbidity of ≥2 grade RP was 18. 87 %,and grade of 2,3,and 4 were 9. 43 %,5. 66 %,3. 77 %,respectively. According to Spearman rank correlation analyses,V5,V20,MLD were the prognostic factors associated with RP of grade 2 or greater( r = 0. 485,0. 404,0. 404,P = 0. 000,0. 003,0. 003). According to univariate analyses,V5,V20,MLD were significantly related to RP of grade 2 or greater( t =- 4. 588,- 2. 433,- 2. 845,P = 0. 000,0. 019,0. 006). According to multivariate analyses,V5 was the only factor associated with RP of grade 2 or greater( P = 0. 03). According to ROC curve analyses,V5 was valuable in predicting RP of grade 2 or greater. If predictive cut- off values was established as follows: V5= 0. 862,the parameters could provide predictive SEN,SPE were 1. 00 and 0. 442. And RP incidence of grade 2 or greater were 7. 14 % and 32 % in patients with a V5 of < 43. 65 % and ≥43. 65 %,respectively. Conclusion:Dosimetric factors are associated with RP of grade 2 or greater,and the incidence and grade of RP are significantly related to the V5 value.
Objective: To determine lung dosimetric constraints that correlated with symptomatic radiation pneumonitis( ≥2 grade) in stage Ⅲ and Ⅳ non- small cell lung cancer patients treated with intensity modulated radiotherapy( IMRT). Methods: 53 NSCLC patients were treated with IMRT. Several dosimetric factors and ≥2 grade RP incidence were recorded and analyzed. Radiation induced lung injury was evaluated according to the standard CTCAE4. 0.Univariate and multivariate analyses were performed to assess the relationship between dosimetric factors and ≥ 2grade RP. The ROC curve was used to explore the predictive sensitivity( SEN) and specificity( SPE) for potential DVH parameters associated with ≥2 grade RP. Results:The morbidity of ≥2 grade RP was 18. 87 %,and grade of 2,3,and 4 were 9. 43 %,5. 66 %,3. 77 %,respectively. According to Spearman rank correlation analyses,V5,V20,MLD were the prognostic factors associated with RP of grade 2 or greater( r = 0. 485,0. 404,0. 404,P = 0. 000,0. 003,0. 003). According to univariate analyses,V5,V20,MLD were significantly related to RP of grade 2 or greater( t =- 4. 588,- 2. 433,- 2. 845,P = 0. 000,0. 019,0. 006). According to multivariate analyses,V5 was the only factor associated with RP of grade 2 or greater( P = 0. 03). According to ROC curve analyses,V5 was valuable in predicting RP of grade 2 or greater. If predictive cut- off values was established as follows: V5= 0. 862,the parameters could provide predictive SEN,SPE were 1. 00 and 0. 442. And RP incidence of grade 2 or greater were 7. 14 % and 32 % in patients with a V5 of < 43. 65 % and ≥43. 65 %,respectively. Conclusion:Dosimetric factors are associated with RP of grade 2 or greater,and the incidence and grade of RP are significantly related to the V5 value.
引文
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[7]Kim M.Factors predicting radiation pneumonitis in locally advanced non-small cell lung cancer[J].Radiat Oncol J,2011,29(3):181-190.
[8]Bradley JD,Hope A,El Naqal,et al.A nomogram to predict radiation pneumonitis,derived from a combined analysis of rtog9311 and institutional data[J].Int J Radiat Oncol Biol Phys,2007,69(4):985-992.
[9]Fox AM,Dosoretz AP,Manch PM,et al.Predictive factors for radiation pneumonitis in Hodskin lymphoma patients receiving combined-modality therapy[J].Int J Radiat Oncol Biol Phys,2012,83(1):277-283.
[10]Jin H,Tucker SL,Liu HH,et al.Dose-volume thresholds and smoking status for the risk of treatment related pneumonitis in inoperable non-small cell lung cancer treated with definitive radiotherapy[J].Radiother Oncol,2008,91(3):427-432.
[11]Barriger RB,Fakiris AJ,Hanna N,et al.Dose-volume analysis of radiation pneumonitis in non-small-cell lung cancer patients treated with concurrent cisplatinum and etoposide with or without consolidation docetaxel[J].Int J Radiat Oncol Biol Phys,2010,78(5):1381-1386.
[12]Han S,Gu F,Lin G,et al.Analysis of clinical and dosimetric factors influencing radiation-induced lung injury in patients with lung cancer[J].J Cancer,2015,6(11):1172-1178.
[13]Weili Wang,Yaping Xu,Matthew Schipper,et al.Effect of normal lung definition on lung dosimetry and lung toxicity prediction in radiation therapy treatment planning[J].Int J Radiat Oncol Biol Phys,2013,86(5):956-963.
[14]Zhang XJ,Sun JG,Sun J,et al.Prediction of radiation pneumonitis in lung cancer patients:A systematic review[J].J Cancer Res Clin Oncol,2012,138(12):2103-2106.
[15]Ramella S,Trodella L,Mineo TC,et al.Adding ipsilateral V20and V30to conventional dosimetric constraints predicts radiation pneumonitis in stageⅢa-bNSCLC treated with combined-modality therapy[J].Int J Radiat Oncol Biol Phys,2010,76(1):110-115.
[16]Rodrigues G,Lock M,D'souza D,et al.Prediction of radiation pneumonitis by dose-volume histogram parameters in lung cancer-a systematic review[J].Radiother Oncol,2004,71(2):127-138.
[17]Sue S Yom,Zhongxing Liao,H Helen Liu,et al.Initial evaluation of treatment-related pneumonitis in advanced-stage non-small-cell lung cancer patients treated with concurrent chemotherapy and intensity-modulated radiotherapy[J].Int J Radiat Oncol Biol Phys,2007,68(1):94-102.
[18]John M,Schallenkamp,Robert C Miller,et al.Incidence of radiation pneumonitis after thoracic irradiation:Dose-volum correlates[J].Int J Radiation Oncology Biol Phys,2007,67(2):410-416.
[19]Sura S,Gupta V,Yorke E,et al.Intensity-modulated radiation therapy(IMRT)for inoperable non-small cell lung cancer:The Memorial Sloan-Kettering Cancer Center(MSKCC)experience[J].Radiother Oncol,2008,87(1):17-23.
[20]Novakova-Jiresova A,Van Luijk P,Van Goor H,et al.Changes in injury expression after graded volume irradiation of the rat lung[J].Int J Radiat Oncol Biol Phys,2007,67(5):1510-1518.
[21]Wang S,Liao Z,Wei X,et al.Analysis of clinical an dosimetric factors associated with treatment-related pneumonitis(TRP)in patients with non-small-cell lung cancer(NSCLC)treated with concurrent chemotherapy and three-dimensional conformal radiotherapy(3 D-CRT)[J].Int J Radiat Oncol Biol Phys,2006,66(5):1399-1407.
[22]Yorke ED,Lackson A,Rosenzweig KE,et al.Correlation of dosimetric factors and radiation pneumonitis for non-small-cell lung cancer patients in a recently completed dose escalation study[J].J Radiat Oncol Biol Phys,2005,63(3):672-682.
[2]Wang LH,Fu XL,Chen M,et al.The diagnosis and treatment of radiation lung injury[J].Chin J Radiation Oncol,2015,24(1):4-9.[王绿化,傅小龙,陈明,等.放射性肺损伤的诊断及治疗[J].中华放射肿瘤学杂志,2015,24(1):4-9.]
[3]National Cancer Institute.Cancer Therapy Evaluation Program[DB/OL].[2009-05-28].http://ctep.cancer.gov/reporting/ctc.html.
[4]Zhao NQ.Clinical medical research design and data analysis[M].Shanghai:Fudan University Press,2005:241-252.[赵耐清.临床医学研究设计和数据分析[M].上海:上海复旦大学出版社,2005:241-252.]
[5]Bradley J,Graham MV,Winter K,et al.Toxicity and outcome results of RTOG 9311:A phaseⅠ-Ⅱdose-escalation study using three-dimensional conformal radiotherapy in patients with inoperable non-small-cell lung carcinoma[J].Int J Radiat Oncol Biol Phys,2005,61(2):318-328.
[6]Kimura T.Radiation pneumonitis in patients with lung and mediastinal tumours:A retrospective study of risk factors focused on pulmonary emphysema[J].Br J Radiol,2012,85(10):135-141.
[7]Kim M.Factors predicting radiation pneumonitis in locally advanced non-small cell lung cancer[J].Radiat Oncol J,2011,29(3):181-190.
[8]Bradley JD,Hope A,El Naqal,et al.A nomogram to predict radiation pneumonitis,derived from a combined analysis of rtog9311 and institutional data[J].Int J Radiat Oncol Biol Phys,2007,69(4):985-992.
[9]Fox AM,Dosoretz AP,Manch PM,et al.Predictive factors for radiation pneumonitis in Hodskin lymphoma patients receiving combined-modality therapy[J].Int J Radiat Oncol Biol Phys,2012,83(1):277-283.
[10]Jin H,Tucker SL,Liu HH,et al.Dose-volume thresholds and smoking status for the risk of treatment related pneumonitis in inoperable non-small cell lung cancer treated with definitive radiotherapy[J].Radiother Oncol,2008,91(3):427-432.
[11]Barriger RB,Fakiris AJ,Hanna N,et al.Dose-volume analysis of radiation pneumonitis in non-small-cell lung cancer patients treated with concurrent cisplatinum and etoposide with or without consolidation docetaxel[J].Int J Radiat Oncol Biol Phys,2010,78(5):1381-1386.
[12]Han S,Gu F,Lin G,et al.Analysis of clinical and dosimetric factors influencing radiation-induced lung injury in patients with lung cancer[J].J Cancer,2015,6(11):1172-1178.
[13]Weili Wang,Yaping Xu,Matthew Schipper,et al.Effect of normal lung definition on lung dosimetry and lung toxicity prediction in radiation therapy treatment planning[J].Int J Radiat Oncol Biol Phys,2013,86(5):956-963.
[14]Zhang XJ,Sun JG,Sun J,et al.Prediction of radiation pneumonitis in lung cancer patients:A systematic review[J].J Cancer Res Clin Oncol,2012,138(12):2103-2106.
[15]Ramella S,Trodella L,Mineo TC,et al.Adding ipsilateral V20and V30to conventional dosimetric constraints predicts radiation pneumonitis in stageⅢa-bNSCLC treated with combined-modality therapy[J].Int J Radiat Oncol Biol Phys,2010,76(1):110-115.
[16]Rodrigues G,Lock M,D'souza D,et al.Prediction of radiation pneumonitis by dose-volume histogram parameters in lung cancer-a systematic review[J].Radiother Oncol,2004,71(2):127-138.
[17]Sue S Yom,Zhongxing Liao,H Helen Liu,et al.Initial evaluation of treatment-related pneumonitis in advanced-stage non-small-cell lung cancer patients treated with concurrent chemotherapy and intensity-modulated radiotherapy[J].Int J Radiat Oncol Biol Phys,2007,68(1):94-102.
[18]John M,Schallenkamp,Robert C Miller,et al.Incidence of radiation pneumonitis after thoracic irradiation:Dose-volum correlates[J].Int J Radiation Oncology Biol Phys,2007,67(2):410-416.
[19]Sura S,Gupta V,Yorke E,et al.Intensity-modulated radiation therapy(IMRT)for inoperable non-small cell lung cancer:The Memorial Sloan-Kettering Cancer Center(MSKCC)experience[J].Radiother Oncol,2008,87(1):17-23.
[20]Novakova-Jiresova A,Van Luijk P,Van Goor H,et al.Changes in injury expression after graded volume irradiation of the rat lung[J].Int J Radiat Oncol Biol Phys,2007,67(5):1510-1518.
[21]Wang S,Liao Z,Wei X,et al.Analysis of clinical an dosimetric factors associated with treatment-related pneumonitis(TRP)in patients with non-small-cell lung cancer(NSCLC)treated with concurrent chemotherapy and three-dimensional conformal radiotherapy(3 D-CRT)[J].Int J Radiat Oncol Biol Phys,2006,66(5):1399-1407.
[22]Yorke ED,Lackson A,Rosenzweig KE,et al.Correlation of dosimetric factors and radiation pneumonitis for non-small-cell lung cancer patients in a recently completed dose escalation study[J].J Radiat Oncol Biol Phys,2005,63(3):672-682.
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