复发鼻咽癌大分割与常规分割三维适形放疗对比分析
|
摘要
目的复发鼻咽癌再程放疗困难重重,再程放疗后晚期放射损伤发生率高,且5年生存率低。本研究对比分析大分割与常规分割三维适形放疗治疗鼻咽复发鼻咽癌的放射损伤反应、生活质量影响及疗效。方法回顾性分析中国人民解放军联勤保障部队第九二一医院肿瘤科2008-11-06-2012-10-25收治的复发鼻咽癌患者117例,按治疗情况分成鼻咽癌复发常规分割适形放疗组(对照组59例)和鼻咽癌复发大分割适形放疗组(研究组58例),对照组为常规分割,5次/周,2Gy/次,共30～35次,总量60～70Gy/6～7周。研究组为大分割,5次/周,3Gy/次,共17～20次,总量51～60Gy/4周,观察放射损伤反应、生活质量影响、近期疗效、远期疗效等。结果两组患者近期放射损伤反应如口干(χ~2=1.029,P=0.310)、颌面部皮肤反应(χ~2=1.239,P=0.266)、乏力(χ~2=0.210,P=0.646)发生率差异均无统计学意义。研究组口腔黏膜反应(46.6%)明显比对照组(25.4%)高,χ~2=5.674;P=0.017;两组患者远期放射损伤如口干(χ~2=0.364,P=0.546)、颌面部肌肉纤维化(χ~2=0.010,P=0.919)、放射性脑病(χ~2=1.143,P=0.285)发生率差异均无统计学意义。研究组耳聋(χ~2=4.414,P=0.043)、张口困难(χ~2=4.499,P=0.034)明显比对照组高;两组鼻咽癌患者生活质量评价(KPS评分、体质量变化)治疗前与治疗结束时、治疗结束时与治疗后3个月对比,均P>0.05;3个月后局部控制率(tumor control probability,TCP)对照组为54.2%(32/59),研究组为69.0%(40/58),差异无统计学意义,χ~2=2.681,P=0.102;6个月后对照组TCP为62.7%(37/59),研究组为79.3%(46/58),差异有统计学意义,χ~2=3.909,P=0.048;9个月后对照组TCP为67.8%(40/59),研究组为84.5%(49/58),差异有统计学意义,χ~2=4.473,P=0.034;12个月后对照组TCP为69.5%(41/59),研究组为87.9%(51/58),差异有统计学意义,χ~2=5.919,P=0.015。对照组1年生存率(overallsurvival,OS)为94.9%(56/59),研究组为96.6%(56/58),差异无统计学意义,χ~2=1.191,P=0.662;2年对照组OS为71.2%(42/59),研究组为81.0%(47/58),差异无统计学意义,χ~2=1.558,P=0.212;3年对照组OS为50.8%(30/59),研究组为69.0%(40/58),差异有统计学意义,χ~2=3.995,P=0.046;4年对照组OS为39.0%(23/59),研究组为58.6%(34/58),差异有统计学意义,χ~2=4.515,P=0.034;5年对照组OS为32.2%(19/59),研究组为51.7%(30/58),差异有统计学意义,χ~2=4.579,P=0.032。结论复发鼻咽癌治疗中,大分割三维适形放疗比常规分割放疗疗程有明显缩短,从而降低了部分放射损伤反应,对生活质量影响较小,能明显提高肿瘤的TCP,近期疗效和远期疗效较好。
OBJECTIVE Recurrent nasopharyngeal carcinoma is difficult to undergo radiotherapy,the incidence of late radiation injury after re-radiation is high,and the 5-year survival rate is low.This study compared the effects of large segmentation and conventional segmentation of three-dimensional conformal radiotherapy on radiation injury response,quality of life and efficacy of nasopharyngeal recurrent nasopharyngeal carcinoma.METHODS A retrospective analysis of117 cases of recurrent nasopharyngeal carcinoma patients admitted to the Department of Oncology,The No.921 Hospital of PLA Joint Logistics Support Force,2008-11-06-2012-10-25,according to the treatment situation,resection of nasopharyngeal carcinoma recurrent conventional conformal radiotherapy Group(control group)and nasopharyngeal carcinoma recurrence large-segment conformal radiotherapy group(study group),control group was routinely divided,5 times/week,2 Gy/time,a total of 30-35 times,the total amount of 60-70 Gy/6-7 weeks.The study group consisted of large segmentation,5 times/week,3 Gy/time,a total of 17 to 20 times,the total amount of 51-60 Gy/4 weeks,observed radiation damage response,quality of life effects,short-term efficacy,long-term efficacy.RESULTS The incidence of recent radiation injury in the two groups was as follows:dry mouth(χ~2=1.029,P=0.310),maxillofacial skin reaction(χ~2=1.239,P=0.266),and fatigue(χ~2=0.210,P=0.646).The oral mucosal response of the study group(46.6%)was significantly higher than that of the control group(25.4%,χ~2=5.674;P=0.017);the long-term radiation damage of the two groups was dry mouth(χ~2=0.364,P=0.546),maxillofacial muscle fibrosis(χ~2=0.010,P=0.919)and radiation encephalopathy(χ~2=1.143,P=0.285).The study group had deafness(χ~2=4.414,P=0.043)and difficulty in opening mouth(χ~2=4.499,P=0.034),which was significantly higher than that of the control group.After 3 months,the local control rate(TCP)was 54.2%(32/59),and the study group was 69.0%(40/58),the difference was not statistically significant(χ~2=2.681,P=0.102);TCP was 62.7%(37/59)after 6 months in the control group,and 79.3%(46/58)in the study group(χ~2=3.909,P=0.048);TCP was 67.8%(40/59)after 9 months in the control group and 84.5%(49/58)in the study group(χ~2=4.473,P=0.034);TCP was 69.5%(41/59)after 12 months in the control group and 87.9%(51/58)in the study group(χ~2=5.919,P=0.015).The 1-year OS rate of the control group was 94.9%(56/59),and that of the study group was 96.6%(56/58),the difference was not statistically significant(χ~2=1.191,P=0.662);the 2-year OS rate of the control group was 71.2%(42/59),that of the study group was 81.0%(47/58),and the difference was not statistically significant(χ~2=1.558,P=0.212);the 3-year OS rate of the control group was 50.8%(30/59),that of the study group was 69.0%(40/58),the difference was statistically significant(χ~2=3.995,P=0.046);the 4-year OS rate of the control group 39.0%(23/59),that of the study group was 58.6%(34/58),and the difference was statistically significant(χ~2=4.515,P=0.034);the 5-year OS rate of the control group was 32.2%(19/59),that of the study group was 51.7%(30/58),the difference was statistically significant(χ~2=4.579,P=0.032).CONCLUSIONS In the treatment of nasopharyngeal recurrent nasopharyngeal carcinoma,the large-segment three-dimensional conformal radiotherapy is significantly shorter than the conventional segmentation radiotherapy.Thereby reducing part of the radiation damage response,the impact on the quality of life is small,can significantly improve the tumor TCP,the short-term efficacy and long-term efficacy is better.
OBJECTIVE Recurrent nasopharyngeal carcinoma is difficult to undergo radiotherapy,the incidence of late radiation injury after re-radiation is high,and the 5-year survival rate is low.This study compared the effects of large segmentation and conventional segmentation of three-dimensional conformal radiotherapy on radiation injury response,quality of life and efficacy of nasopharyngeal recurrent nasopharyngeal carcinoma.METHODS A retrospective analysis of117 cases of recurrent nasopharyngeal carcinoma patients admitted to the Department of Oncology,The No.921 Hospital of PLA Joint Logistics Support Force,2008-11-06-2012-10-25,according to the treatment situation,resection of nasopharyngeal carcinoma recurrent conventional conformal radiotherapy Group(control group)and nasopharyngeal carcinoma recurrence large-segment conformal radiotherapy group(study group),control group was routinely divided,5 times/week,2 Gy/time,a total of 30-35 times,the total amount of 60-70 Gy/6-7 weeks.The study group consisted of large segmentation,5 times/week,3 Gy/time,a total of 17 to 20 times,the total amount of 51-60 Gy/4 weeks,observed radiation damage response,quality of life effects,short-term efficacy,long-term efficacy.RESULTS The incidence of recent radiation injury in the two groups was as follows:dry mouth(χ~2=1.029,P=0.310),maxillofacial skin reaction(χ~2=1.239,P=0.266),and fatigue(χ~2=0.210,P=0.646).The oral mucosal response of the study group(46.6%)was significantly higher than that of the control group(25.4%,χ~2=5.674;P=0.017);the long-term radiation damage of the two groups was dry mouth(χ~2=0.364,P=0.546),maxillofacial muscle fibrosis(χ~2=0.010,P=0.919)and radiation encephalopathy(χ~2=1.143,P=0.285).The study group had deafness(χ~2=4.414,P=0.043)and difficulty in opening mouth(χ~2=4.499,P=0.034),which was significantly higher than that of the control group.After 3 months,the local control rate(TCP)was 54.2%(32/59),and the study group was 69.0%(40/58),the difference was not statistically significant(χ~2=2.681,P=0.102);TCP was 62.7%(37/59)after 6 months in the control group,and 79.3%(46/58)in the study group(χ~2=3.909,P=0.048);TCP was 67.8%(40/59)after 9 months in the control group and 84.5%(49/58)in the study group(χ~2=4.473,P=0.034);TCP was 69.5%(41/59)after 12 months in the control group and 87.9%(51/58)in the study group(χ~2=5.919,P=0.015).The 1-year OS rate of the control group was 94.9%(56/59),and that of the study group was 96.6%(56/58),the difference was not statistically significant(χ~2=1.191,P=0.662);the 2-year OS rate of the control group was 71.2%(42/59),that of the study group was 81.0%(47/58),and the difference was not statistically significant(χ~2=1.558,P=0.212);the 3-year OS rate of the control group was 50.8%(30/59),that of the study group was 69.0%(40/58),the difference was statistically significant(χ~2=3.995,P=0.046);the 4-year OS rate of the control group 39.0%(23/59),that of the study group was 58.6%(34/58),and the difference was statistically significant(χ~2=4.515,P=0.034);the 5-year OS rate of the control group was 32.2%(19/59),that of the study group was 51.7%(30/58),the difference was statistically significant(χ~2=4.579,P=0.032).CONCLUSIONS In the treatment of nasopharyngeal recurrent nasopharyngeal carcinoma,the large-segment three-dimensional conformal radiotherapy is significantly shorter than the conventional segmentation radiotherapy.Thereby reducing part of the radiation damage response,the impact on the quality of life is small,can significantly improve the tumor TCP,the short-term efficacy and long-term efficacy is better.
引文
[1]Chen X,Lei H,Liang Z,et al.Intensity-modulated radiotherapy controls nasopharyngeal carcinoma distant metastasis and improves survival of patients[J].Springerplus,2016,5(1):1459.
[2]Vazquez A,Khan MN,Govindaraj S,et al.Nasopharyngeal squamous cell carcinoma:a comparative analysis of keratinizing and nonkeratinizing subtypes[J].Int Forum Allergy Rhinol,2014,4(8):675-683.
[3]Twu CW,Wang WY,Chen CC,et al.Metronomic adjuvant chemotherapy improves treatment outcome in nasopharyngeal carcinoma patients with postradiation persistently detectable plasma Epstein-Barr virus deoxyribonucleic acid[J].Int J Radiat Oncol Biol Phys,2014,89(1):21-29.
[4]Zhao L,Tang M,Hu Z,et al.miR-504mediated down-regulation of nuclear respiratory factor 1leads to radio-resistance in nasopharyngeal carcinoma[J].Oncotarget,2015,6(18):15995-16018.
[5]Lu J,Tang M,Li H,et al.EBV-LMP1suppresses the DNA damage response through DNA-PK/AMPK signaling to promote radioresistance in nasopharyngeal carcinoma[J].Cancer Lett,2016,380(1):191-200.
[6]Ren JH,Dai XF,Yan GL,et al.Acute oral mucositis in nasopharyngeal carcinoma patients treated with radiotherapy:association with genetic polymorphism in DNA DSB repair genes[J].Int JRadiat Biol,2014,90(3):256-261.
[7]Oechsner M,Bratengeier K,Gainey M,et al.Proposals for a IC-RU-50/62-Consistent Dose Prescription Suited for IMRT Radiation Techniques[M]//World Congress on Medical Physics and Biomedical Engineering.Munich:Germany.Springer Berlin Heidelberg,2009:425-428.
[8]Lee N,Harris J,Garden AS,et al.Intensity-modulated radiation therapy with or without chemotherapy for nasopharyngeal carcinoma:radiation therapy oncology group phaseⅡtrial 0225[J].JClin Oncol,2009,27(22):3684-3690.
[9]龙斌,刘利民,周光华,等.大分割伽马刀与大分割适形再程放疗治疗局部复发鼻咽癌的对比研究[J].中国医师进修杂志,2018,41(9):779-786.
[10]孙燕.临床肿瘤学高级教程[M].北京:人民军医出版社,2011:117-118.
[11]吴立洲,王丽君,黄生富,等.鼻咽癌调强放疗后局部复发的临床分析[J].肿瘤学杂志,2015,21(3):179-184.
[12]金雯雯,王业涛,王力,等.EBV-DNA阳性对鼻咽癌放疗后复发转移影响的探讨[J].中华肿瘤防治杂志,2017,24(20):1473-1475.
[13]张慧慧,张献文,江浩.局部复发鼻咽癌再程调强放射治疗的疗效及预后分析[J].上海交通大学学报:医学版,2018,38(6):662-669.
[14]Moon SH,Cho KH,Lee CG,et al.IMRT vs.2D-radiotherapy or3D-conformal radiotherapy of nasopharyngeal carcinoma:Survival outcome in a Korean multi-institutional retrospective study(KROG 11-06)[J].Strahlenther Onkol,2016,192(6):377-385.
[15]中国抗癌协会鼻咽癌专业委员会,李金高,陈晓钟,等.鼻咽癌复发、转移诊断专家共识[J].中华放射肿瘤学杂志,2018,27(1):7-15.
[16]中国抗癌协会鼻咽癌专业委员会,林少俊,陈晓钟,等.复发鼻咽癌治疗专家共识[J].中华放射肿瘤学杂志,2018,27(1):16-22.
[17]张超,罗希,林立平,等.先大分割后常规分割放疗联合同期化疗治疗晚期中央型非小细胞肺癌疗效及生物效应剂量探讨[J].肿瘤学杂志,2017,23(8):686-691.
[18]刘军华.大分割放疗联合替莫唑胺治疗大体积脑转移瘤的效果观察[J].实用癌症杂志,2017,32(11):1814-1816.
[19]Nguyen NA,Isfahanian N,Pond G,et al.A novel neoadjuvant therapy for operable locally Invasive non-Small-Cell lung cancer.phase i study of neoadjuvant stereotactic body radiotherapy.LINNEARRE I(NCT02433574)[J].Clin Lung Cancer,2017,18(4):436-440.
[20]郝福荣,吕春燕,刘杰,等.乳腺癌保留乳房术后大分割调强放疗初步临床观察[J].中华肿瘤防治杂志,2013,20(24):1912-1916.
[21]Deantonio L,Cozzi S,Tunesi S,et al.Hypofractionated radiation therapy for breast cancer:long-term results in a series of 85patients[J].Tumori,2016,102(4):398-403.
[22]汤轶强,黄敏,叶新芊,等.三维适形放射治疗鼻咽癌后程大分割的剂量学研究[J].实用癌症杂志,2009,24(3):288-290.
[23]Han F,Zhao C,Huang SM,et al.Long-term outcomes and prognostic factors of re-irradiation for locally recurrent nasopharyngeal carcinoma using intensity-modulated radiotherapy[J].Clin Oncol(R Coll Radiol),2012,24(8):569-576.
[24]马涛,刘斌,刘丽霞,等.局部复发鼻咽癌调强放疗的临床结果和预后因素分析[J].河北医药,2016,38(14):2185-2187.
[25]Chen HY,Ma XM,Ye M,et al.Effectiveness and toxicities of intensity-modulated radiotherapy for patients with locally recurrent nasopharyngeal carcinoma[J].PLoS One,2013,8(9):e73918.
[26]Xiao W,Liu S,Tian Y,et al.Prognostic significance of tumor volume in locally recurrent nasopharyngeal carcinoma treated with salvage Intensity-modulated radiotherapy[J].PLoS One,2015,10(4):e0125351.
[27]肖绍文,李运华,蒋静,等.局部复发老年鼻咽癌再程调强放射治疗的效果[J].中国老年学杂志,2016,36(12):2931-2933.
[28]Chan OS,Sze HC,Lee MC et al.Reirradiation with intensity‐modulated radiotherapy for locally recurrent T3to T4nasopharyngeal carcinoma[J].Head Neck,2017,39(3):533-540.
[29]Kong L,Wang L,Shen C,et al.Salvage intensity modulated radiation therapy(IMRT)for locally recurrent nasopharyngeal cancer after definitive IMRT:treatment outcomes of a clinically distinct condition in the modern era[J].Int J Radiat Oncol Biol Phys,2016,6(2S):E329.
[30]Schr9der C,Engenhart-Cabillic R,Vorwerk H,et al.Changes in pulmonary function and influencing factors after high-dose intrathoracic radio(chemo)therapy[J].Strahlenther Onkol,2017,193(2):125-131.
[31]龙斌,周光华,苏加利,等.前程常规分割联合后程大分割适形放疗鼻咽癌的临床分析[J].实用医学杂志,2018,34(19):3250-3254.
[2]Vazquez A,Khan MN,Govindaraj S,et al.Nasopharyngeal squamous cell carcinoma:a comparative analysis of keratinizing and nonkeratinizing subtypes[J].Int Forum Allergy Rhinol,2014,4(8):675-683.
[3]Twu CW,Wang WY,Chen CC,et al.Metronomic adjuvant chemotherapy improves treatment outcome in nasopharyngeal carcinoma patients with postradiation persistently detectable plasma Epstein-Barr virus deoxyribonucleic acid[J].Int J Radiat Oncol Biol Phys,2014,89(1):21-29.
[4]Zhao L,Tang M,Hu Z,et al.miR-504mediated down-regulation of nuclear respiratory factor 1leads to radio-resistance in nasopharyngeal carcinoma[J].Oncotarget,2015,6(18):15995-16018.
[5]Lu J,Tang M,Li H,et al.EBV-LMP1suppresses the DNA damage response through DNA-PK/AMPK signaling to promote radioresistance in nasopharyngeal carcinoma[J].Cancer Lett,2016,380(1):191-200.
[6]Ren JH,Dai XF,Yan GL,et al.Acute oral mucositis in nasopharyngeal carcinoma patients treated with radiotherapy:association with genetic polymorphism in DNA DSB repair genes[J].Int JRadiat Biol,2014,90(3):256-261.
[7]Oechsner M,Bratengeier K,Gainey M,et al.Proposals for a IC-RU-50/62-Consistent Dose Prescription Suited for IMRT Radiation Techniques[M]//World Congress on Medical Physics and Biomedical Engineering.Munich:Germany.Springer Berlin Heidelberg,2009:425-428.
[8]Lee N,Harris J,Garden AS,et al.Intensity-modulated radiation therapy with or without chemotherapy for nasopharyngeal carcinoma:radiation therapy oncology group phaseⅡtrial 0225[J].JClin Oncol,2009,27(22):3684-3690.
[9]龙斌,刘利民,周光华,等.大分割伽马刀与大分割适形再程放疗治疗局部复发鼻咽癌的对比研究[J].中国医师进修杂志,2018,41(9):779-786.
[10]孙燕.临床肿瘤学高级教程[M].北京:人民军医出版社,2011:117-118.
[11]吴立洲,王丽君,黄生富,等.鼻咽癌调强放疗后局部复发的临床分析[J].肿瘤学杂志,2015,21(3):179-184.
[12]金雯雯,王业涛,王力,等.EBV-DNA阳性对鼻咽癌放疗后复发转移影响的探讨[J].中华肿瘤防治杂志,2017,24(20):1473-1475.
[13]张慧慧,张献文,江浩.局部复发鼻咽癌再程调强放射治疗的疗效及预后分析[J].上海交通大学学报:医学版,2018,38(6):662-669.
[14]Moon SH,Cho KH,Lee CG,et al.IMRT vs.2D-radiotherapy or3D-conformal radiotherapy of nasopharyngeal carcinoma:Survival outcome in a Korean multi-institutional retrospective study(KROG 11-06)[J].Strahlenther Onkol,2016,192(6):377-385.
[15]中国抗癌协会鼻咽癌专业委员会,李金高,陈晓钟,等.鼻咽癌复发、转移诊断专家共识[J].中华放射肿瘤学杂志,2018,27(1):7-15.
[16]中国抗癌协会鼻咽癌专业委员会,林少俊,陈晓钟,等.复发鼻咽癌治疗专家共识[J].中华放射肿瘤学杂志,2018,27(1):16-22.
[17]张超,罗希,林立平,等.先大分割后常规分割放疗联合同期化疗治疗晚期中央型非小细胞肺癌疗效及生物效应剂量探讨[J].肿瘤学杂志,2017,23(8):686-691.
[18]刘军华.大分割放疗联合替莫唑胺治疗大体积脑转移瘤的效果观察[J].实用癌症杂志,2017,32(11):1814-1816.
[19]Nguyen NA,Isfahanian N,Pond G,et al.A novel neoadjuvant therapy for operable locally Invasive non-Small-Cell lung cancer.phase i study of neoadjuvant stereotactic body radiotherapy.LINNEARRE I(NCT02433574)[J].Clin Lung Cancer,2017,18(4):436-440.
[20]郝福荣,吕春燕,刘杰,等.乳腺癌保留乳房术后大分割调强放疗初步临床观察[J].中华肿瘤防治杂志,2013,20(24):1912-1916.
[21]Deantonio L,Cozzi S,Tunesi S,et al.Hypofractionated radiation therapy for breast cancer:long-term results in a series of 85patients[J].Tumori,2016,102(4):398-403.
[22]汤轶强,黄敏,叶新芊,等.三维适形放射治疗鼻咽癌后程大分割的剂量学研究[J].实用癌症杂志,2009,24(3):288-290.
[23]Han F,Zhao C,Huang SM,et al.Long-term outcomes and prognostic factors of re-irradiation for locally recurrent nasopharyngeal carcinoma using intensity-modulated radiotherapy[J].Clin Oncol(R Coll Radiol),2012,24(8):569-576.
[24]马涛,刘斌,刘丽霞,等.局部复发鼻咽癌调强放疗的临床结果和预后因素分析[J].河北医药,2016,38(14):2185-2187.
[25]Chen HY,Ma XM,Ye M,et al.Effectiveness and toxicities of intensity-modulated radiotherapy for patients with locally recurrent nasopharyngeal carcinoma[J].PLoS One,2013,8(9):e73918.
[26]Xiao W,Liu S,Tian Y,et al.Prognostic significance of tumor volume in locally recurrent nasopharyngeal carcinoma treated with salvage Intensity-modulated radiotherapy[J].PLoS One,2015,10(4):e0125351.
[27]肖绍文,李运华,蒋静,等.局部复发老年鼻咽癌再程调强放射治疗的效果[J].中国老年学杂志,2016,36(12):2931-2933.
[28]Chan OS,Sze HC,Lee MC et al.Reirradiation with intensity‐modulated radiotherapy for locally recurrent T3to T4nasopharyngeal carcinoma[J].Head Neck,2017,39(3):533-540.
[29]Kong L,Wang L,Shen C,et al.Salvage intensity modulated radiation therapy(IMRT)for locally recurrent nasopharyngeal cancer after definitive IMRT:treatment outcomes of a clinically distinct condition in the modern era[J].Int J Radiat Oncol Biol Phys,2016,6(2S):E329.
[30]Schr9der C,Engenhart-Cabillic R,Vorwerk H,et al.Changes in pulmonary function and influencing factors after high-dose intrathoracic radio(chemo)therapy[J].Strahlenther Onkol,2017,193(2):125-131.
[31]龙斌,周光华,苏加利,等.前程常规分割联合后程大分割适形放疗鼻咽癌的临床分析[J].实用医学杂志,2018,34(19):3250-3254.