食管癌大小野高低剂量

食管癌根治性放化疗大野vs小野60Gyvs50Gy杭州市肿瘤医院梁晓东1.valueofENI背景•食管癌易发生区域淋巴结转移。•临床N0患者手术后发现淋巴结转移率较高。HiroshiAkiyamaannalsofsurgery1994•三野清扫可提高OS。•区域淋巴结的积极治疗可望提高OS。TingYe荟萃分析（AnnThoracSurg2013;96）背景•基于RTOG8501研究，CCRT成为标准的非手术治疗。ENI可能提高局部区域控制率•85-01研究采用了ENI，局部区域失败率44.3%RTOG94-05标准组（未采用ENI）为55%。whichisbetter？•ENIvsnoENI•pubMED数据库搜索。•根治性同步放化疗的研究。•除外联合手术、联合靶向治疗；非英文文献；非全文发表。•共入组14个研究975例患者。characteristicofpatientsauthornumbertimeagemalefemalesqumousadenoYasumasa912001-200663(45-74)829901Elizabeth3259(38-73)266Takeshi251998-2002223Herskovic611986-19904912529Kato512006-200864(20-70)456501OhtsuA541992-1997≤75522540WangD682004-201163(40-75)5810680OnozawaM1021999-200164(39-75)85171020Ishikura1391992-199962(38-75)12118HironakaS531992-199964(38-75)458530KatoK762000-200261(39-70)688al-SarrafM691986-199064(30-85)56135514YamashitaH1262000-200967(42-85)115151260AraujoCM281982-198553(30-69)253280AcutetoxicitiestotaldoseLeukopeniaAnemiaThrombocytopeniaEsophagitisinfection/feverNausea/vomitingradiationpneumonitis(Gy)(%)(%)(%)(%)(%)(%)(%)Nishimura6048.90%5.40%4.30%20.70%9.80%4.30%Takeshi6380%28%56%24%8%8%OhtsuA6024%27.80%16.70%15%6%2%WangD59.632.40%7.40%10.30%26.40%Ishikura6043.20%23%18%10%2%4%HironakaS6050.90%15.10%5.70%KatoK6043.40%22.40%5.30%17%13.20%17.10%Yamashita5073%30.10%35.70%25.40%7.10%Elizabeth5021.9%*28.10%12.50%34.40%18.80%28.10%KatoK5082.40%23.50%19.60%35%20%18%Latetoxicitiesofgrade3orgreaterauthornumberEsophagusheartlungpleuralgastrointestinal(%)(%)(%)(%)hemorrhage(%)Nishimura912.26.61.14.4Kato513.95.92WangD684.41.5Hironaka537.55.79.4KatoK7613.215.83.9Yamashita12611.6esophagus:dysphagia,stenosis,fistula;heart:pericarditis,pericardialeffusion,cardiactamponade;treatmentrelateddeathnumbertotaldeathpneumonitisesophagusUpper-gastrointestinalpericarditispleuraleffusioninfarctionrenalfailureneutropenicothersratefistulahemorrhagesepsis(%)(%)(%)(%)(%)(%)(%)(%)(%)(%)Elizabeth3212.50%3.10%3.10%6.30%Takeshi258%8%Herskovic611.60%1.60%OhtsuA547.40%1.90%3.70%1.90%WangD687.40%2.90%4.40%KatoK765.30%2.60%1.30%1.30%al-Sarraf691.40%1.40%YamashitaH1263.20%2.40%0.80%others4640.00%intotal9752.60%0.80%0.60%0.40%0.10%0.10%0.10%0.10%0.10%0.20%failurepatternofENIauthornumberLRFR1LRFR2(%)(%)Takeshi2556Herskovic6139.344.3Kato5127.535.3Ohtsu5435.257.4Wang6826.529.4Onozawa10252Ishikura13954.756.1Hironaka5335.9Kato7634.2al-Sarraf6947.858Yamashita12647Araujo2861Intotal82745.652.3LRFR1:theincidenceoflocalregionalfailurewithoutdistantfailure;LRFR2:theincidenceoflocalregionalfailurebothwithandwithoutdistantfailure.SurvivaloutcomeOverallsurvivalstudieswithavailabledatamean±SD(%)median(range)(%)1-year762.5±15.459(41-88)2-year841.5±8.141(31-56)3-year1140.7±11.543(26-64)5-year829.2±9.927.5(14-46)SD=standarddeviation结论•ENI可行，急性和晚期毒性可耐受，未增加治疗相关死亡率。•ENI局部区域控制率高于不做ENI的9405研究。•ENI未能显著改善OS。（更强的全身治疗情况下，局控的改善有望转化成OS的获益）•8501研究ENI的剂量为30Gy，局部区域控制率与40-50Gy的ENI相似，30Gy的预防剂量可能已经足够。2.60Gyvs50Gy背景•RTOG9405研究显示，64Gy与50Gy相比不能进一步提高局部控制率或OS。背景•RTOG94-05是唯一一个已发表的Ⅲ期研究。•该研究在中期分析后终止。•MST、2yOS、LCR均无统计学差异。•高剂量组治疗相关死亡率高（11vs.2），但高剂量组7/11例患者放疗剂量≤50.4Gy。•高剂量并非是治疗相关死亡率高的原因，放疗至50Gy后再随机分组更合理。•50Gy同步放化疗是欧美的标准治疗。•而在亚洲，更多机构采用60Gy的放疗剂量，全球并无公认的剂量标准。方法•pubMED数据库搜索。•根治性同步放化疗的研究。•除外联合手术、联合靶向治疗；非英文文献；非全文发表定义•高剂量：≥59Gy•标准剂量：50-54Gy•高剂量组：12个研究734例患者•标准剂量组：14个研究1173例患者有效率GyStudieswithavailabledatasampleCR卡方p50Gy10405184(45.4%).14560Gy10739369(49.9%)GyStudieswithavailabledatasampleCR+PR卡方p50Gy10311227(73.0%).00060Gy10370324(87.6%)局部区域失败率GyStudieswithavailabledatasamplelocalregionalfailure卡方p50Gy8444177（39.9%）0.19460Gy6604265（43.9%）OSOverallSurvivalStudieswithavailabledatasampleMean±SDMedian(range)1-years9126568.72±12.4865（52-88.2）2-years1168546.79±13.2445.9（31-76）3-years1063639.26±13.7735（25-63.8）5-years1081628.3±8.9226（14-46）OS（60vs.50）OverallSurvivalGyStudieswithavailabledatasampleMean±SDMedian(range)T-TESTpvalue1-years50Gy838268.24±12.7964.30（52-88.2）0.83260Gy312366.47±8.3965.00(59-76)2-years50Gy846944.59±15.1439（27.9-52.8）0.75460Gy854146.83±12.7549.95(31-70.70)3-years50Gy1163638.22±13.5130（25-63.8）0.55060Gy869841.18±7.3843（25-49）5-years50Gy422020.50±6.421(14-26)0.06460Gy759631.04±8.6429（22.7-46）不良反应GyStudieswithavailabledatasample放射性食管炎卡方p50Gy1046786（18.4%）0.96160Gy10626116（18.5%）结论•60Gy与50Gy耐受性可，不良反应相当。•CR率两组无显著差异，60Gy组ORR显著提高。•局部区域控制率两组无显著差异。•1-3年OS两组无显著差异。•60Gy组5年OS有改善趋势（p=0.064）。