食管癌同步放化療課件

陜西腫瘤放療年會2008年12月

SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY食管癌同步放化療

馬紅兵王西京任宏濤王寶峰食管癌同步放化療概述藥物臨床進展

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY食管癌同步放化療Cancerstatistics,2008.CACancerJClin.2008Mar-Apr;58(2):71-96.Epub2008Feb20

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY食管癌同步放化療2004年全國40個觀察點統(tǒng)計分析，食管癌發(fā)病率居第四位。全世界每年新發(fā)食管癌病例約３０萬;我國的食管癌發(fā)病率居世界之首，發(fā)病人數(shù)占世界發(fā)病總數(shù)的60%,13/10萬/年，男性的發(fā)病率是女性的二倍。

。接受手術的5年生存率為15%～39%而接受放療者為8%～15%

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY概述我國食管癌食管癌同步放化療

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITYSurgicalOncologyRadiationOncologyMedicalOncologyBiologicalandTargetTherapyThetraditionalChinesemedicine治療手段概述食管癌同步放化療

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY目前，食管癌還是一個需多學科部門聯(lián)合綜合治療以提高臨床療效的惡性腫瘤。放射治療局部病變

藥物治療微小轉移腫瘤治愈一個美好的設想：概述食管癌同步放化療近年，綜合治療顯示優(yōu)勢－－－先進的放療技術＋新的化療藥物精確放療、藥物、生物靶向治療－－－－腫瘤綜合治療的希望

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY概述食管癌同步放化療離體細胞研究、分子生物學機制的研究有助于闡明綜合治療的生物學機制，對探討臨床最佳綜合治療方案有著重要的意義。

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY機制概述食管癌同步放化療SpatialcooperationTemporalcooperationSelectingtoxicitydependingoncellcyclephaseDecreaseintumormassandreoxygenationSelectingtoxicityforhypoxiccellsCytokineticcooperationDNAdamageCellapoptosis

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY機制概述食管癌同步放化療藥物

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY食管癌同步放化療一線藥物（90年代以前的）順鉑、5－Fu、阿霉素

二線藥物（90年代以后）泰素、泰索蒂、諾維本、健擇、半合成的喜樹堿衍生物、新一代鉑類生物靶向藥物

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY藥物食管癌同步放化療

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY5－Fu抗代謝藥2.在體內轉變?yōu)?－氟尿嘧啶脫氧核苷抑制胸腺嘧啶核甙合成酶，影響DNA的生物合成3、能摻入RNA中干擾蛋白質合成4.對有氧和乏氧細胞有相同的殺傷作用藥物食管癌同步放化療5－Fu增敏機制作用于放射抗拒的S期細胞干擾S期調控點實驗室證實，放療期間持續(xù)給藥可以增敏

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY藥物食管癌同步放化療

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY甲酰四氫葉酸順鉑加強5－Fu生化調節(jié)機制4用藥時間放療后5min－8h5用藥量200－375mg/m25－Fu特點：藥物食管癌同步放化療特點：吸收后在體內逐漸變?yōu)榉蜞奏ざ鹱饔闷渥饔脵C理與氟尿嘧啶相同，在體內能干擾、阻斷DNA、RNA及蛋白質的合成其毒性只有氟尿嘧啶的1/4～1/7

化療指數(shù)為氟尿嘧啶的2倍血液中半衰期為5h

用藥量，一般500－1000mg/day慢性毒性試驗中未見到嚴重的骨髓抑制，對免疫的影響較為輕微。

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY新一代替加氟

TegafurInjection

藥物食管癌同步放化療卡莫氟(Carmofure)特點：不需經(jīng)過肝臟的藥物代謝而釋放出5-Fu在血液、淋巴液、腹腔積液以及腫瘤組織中保持高濃度。

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY藥物食管癌同步放化療卡培他濱(Caoecitabine)希羅達由于最后催化后形成5-Fu的胸苷磷酸化酶在瘤組織中的濃度為正常組織中的4倍，口服后瘤組織中的5-Fu濃度是靜脈給予相同劑量的127倍。

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY藥物食管癌同步放化療

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY順鉑Cisplatin,PDD，DDP

1鉑的金屬絡合物，作用似烷化劑2主要作用靶點為DNA作用于DNA鏈間及鏈內交鏈，形成DDP～DNA復合物干擾DNA復制，或與核蛋白及胞漿蛋白結合。3屬周期非特異性藥藥物食管癌同步放化療用藥量順鉑的抗腫瘤作用

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY濃度依賴性時間依賴性順鉑小劑量長期用藥抑制腫瘤細胞對放療所致亞致死性損傷修復抑制和潛在致死性損傷的修復藥物順鉑最低臨床應用劑量6mg/m2/d食管癌同步放化療順鉑與放療的相互作用陽離子與DNA鏈堿基作用改變DNA修復輻射增加DNA單鏈的修復

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY藥物食管癌同步放化療

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY5－Fu順鉑二者對放射增敏有協(xié)同作用增敏效果與給藥時間有關順鉑在放療前1－6h5－Fu持續(xù)給藥增敏效果最佳藥物食管癌同步放化療卡鉑Carboplatin在乏氧的條件下卡鉑的增敏作用高于順鉑奧沙利鉑（樂沙定,草酸鉑）L-OHP復合體DDP復合體靶分子和作用機制不同抗瘤譜不同萘達鉑

腎毒性、胃腸道反應及骨髓抑制均較DDP輕

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY藥物食管癌同步放化療

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY紫杉類醇藥物(taxanes)

泰素、紫素、特素、紫脘素，Paclitaxel,Taxol,PTX機制使微管不可逆的聚集－－－干擾細胞的有絲分裂主要作用于G2晚期和M期，具有顯著的放射增敏作用

藥物食管癌同步放化療

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY是微管解聚抑制劑，其作用于微管/微管蛋白系統(tǒng)，通過促進微管雙聚體裝配成微管，且通過防止去多聚化過程而使微管穩(wěn)定，阻滯細胞于G2和M期，從而抑制癌細胞的有絲分裂和增殖。多西紫杉醇泰索帝、多西他賽、Docetaxel/TXT機制特點穩(wěn)定微管的作用比紫杉醇強2倍藥物食管癌同步放化療

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY健擇gemcitabinehydrochloride,鹽酸吉西他濱細胞周期特異性抗代謝類藥物

作用于DNA合成期（S期）的腫瘤細胞在一定的條件下，可以阻止G1期向S期的進展藥物食管癌同步放化療分子靶向藥物EGFRI

(EGFR抑制劑）放射－－激活EGFR 抗拒放射EGFRI－－增加腫瘤細胞的放射敏感性機制①阻止細胞進入S期②增加放射誘導的細胞凋亡③抑制放射誘導的EGFR磷酸化④抑制放射損傷的修復

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY藥物食管癌同步放化療臨床進展

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY臨床進展食管癌同步放化療NEnglJMed.1992Jun11;326(24):1629-31.（RTOG－－8501）Combinedchemotherapyandradiotherapycomparedwithradiotherapyaloneinpatientswithcanceroftheesophagus.

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITYMETHODS.ThisphaseIIIprospective,randomized,andstratifiedtrialwasundertakentoevaluatetheefficacyoffourcoursesofcombinedfluorouracil(1000mgpersquaremeterofbody-surfaceareadailyforfourdays)andcisplatin(75mgpersquaremeteronthefirstday)plus5000cGyofradiationtherapy,ascomparedwith6400cGyofradiationtherapyalone,inpatientswithsquamous-cellcarcinomaoradenocarcinomaofthethoracicesophagus.RESULTS.Themediansurvivalwas8.9monthsintheradiation-treatedpatients,ascomparedwith12.5monthsinthepatientstreatedwithchemotherapyandradiationtherapy.Intheformergroup,thesurvivalratesat12and24monthswere33percentand10percent,respectively,whereastheywere50percentand38percentinthepatientsreceivingcombinedtherapy(Plessthan0.001).Sevenpatientsintheradiotherapygroupand25inthecombined-therapygroupwerealiveatthetimeoftheanalysis.

Severeandlife-threateningsideeffectsoccurredin44percentand20percent,respectively,ofthepatientswhoreceivedcombinedtherapy,ascomparedwith25percentand3percentofthosetreatedwithradiationalone.食管癌同步放化療RTOG85-01隨機對照試驗首次證明同步放化療生存期明顯優(yōu)于單純放療這一篇文章被認為是食管癌非手術治療中，具有里程碑意義的重要論文。本文的發(fā)表使得同期放化療成為食管癌的標準治療方案。同步放化療已被美國NCCN推薦治療不可切除的食管癌患者。

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY食管癌同步放化療1:JAMA.1999May5;281(17):1623-7.Chemoradiotherapyoflocallyadvancedesophagealcancer:long-termfollow-upofaprospectiverandomizedtrial(RTOG85-01).RadiationTherapyOncologyGroup.

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITYPATIENTS:Patientshadsquamouscelloradenocarcinomaoftheesophagus,T1-3N0-1M0(Ⅲstage),adequaterenalandbonemarrowreserve,andaKarnofskyscoreofatleast50.

MethodsInterventionsCombinedmodalitytherapy(n=134):50Gyin25fractionsover5weeks,pluscisplatin75mg/m2intravenouslyonthefirstdayofweeks1,5,8,and11,andfluorouracil,1g/m2perdaybycontinuousinfusiononthefirst4daysofweeks1,5,8,and11.Intherandomizedstudy,combinedtherapywascomparedwithRTonly(n=62):64Gyin32fractionsover6.4weeks.RESULTS:at5yearsoffollow-uptheoverallsurvivalforcombinedtherapywas26%(95%confidenceinterval[CI],15%-37%)comparedwith0%followingRT.Inthesucceedingnonrandomizedpart,combinedtherapyproduceda5-yearoverallsurvivalof14%(95%CI,6%-23%).Severeacutetoxiceffectsalsoweregreaterinthecombinedtherapygroups.Therewerenosignificantdifferencesinseverelatetoxiceffectsbetweenthegroups.CONCLUSION:

Combinedtherapyincreasesthesurvivalofpatientswhohavesquamouscelloradenocarcinomaoftheesophagus,T1-3N0-1M0,comparedwithRTalone.1級NCCN食管癌同步放化療JClinOncol.2002Mar1;20(5):1167-74.INT0123(RadiationTherapyOncologyGroup94-05)phaseIIItrialofcombined-modalitytherapyforesophagealcancer:high-doseversusstandard-doseradiationtherapy.

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITYPURPOSE:Tocomparethelocal/regionalcontrol,survival,andtoxicityofcombined-modalitytherapyusinghigh-dose(64.8Gy)versusstandard-dose(50.4Gy)radiationtherapyforthetreatmentofpatientswithesophagealcancer.PATIENTSANDMETHODS:Atotalof236patientswithclinicalstageT1toT4,N0/1,M0squamouscellcarcinomaoradenocarcinomafourmonthlycyclesoffluorouracil(5-FU)(1,000mg/m(2)/24hoursfor4days)andcisplatin(75mg/m(2)bolusday1)withconcurrent64.8Gyversusthesamechemotherapyschedulebutwithconcurrent50.4Gy.

Thetrialwasstoppedafteraninterimanalysis.RESULTS:Forthe218eligiblepatients,therewasnosignificantdifferenceinmediansurvival(13.0v18.1months),2-yearsurvival(31%v40%),orlocal/regionalfailureandlocal/regionalpersistenceofdisease(56%v52%)betweenthehigh-doseandstandard-dosearms.

CONCLUSION:Thehigherradiationdosedidnotincreasesurvivalorlocal/regionalcontrol.RTOG9405食管癌同步放化療RTOG0113.試驗fluorouracil,cisplatin,andpaclitaxel誘導化療然后fluorouracil＋paclitaxel＋50.4GyRT(armA)(37/41)paclitaxelpluscisplatin誘導化療然后fluorouracil＋paclitaxel＋50.4GyRT(armB)(35/43).結果中位生存時間28.7months(armA)，14.9months(armB)1年生存率75.7%(armA)，2年生存率56%(armA)37%(armB)3級毒性(armA=54%,armB=43%)4級毒性(armA=27%,armB=40%)死亡(armA=3%,armB=6%)但沒有達到77.5%目標.

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITYJClinOncol.2008Oct1;26(28):4551-6.Epub2008Jun23

PhaseIIrandomizedtrialoftwononoperativeregimensofinductionchemotherapyfollowedbychemoradiationinpatientswithlocalizedcarcinomaoftheesophagus:RTOG0113.食管癌同步放化療第49屆ASTRO年會

RTOG0246試驗初步結果:根治性放化療聯(lián)合選擇性手術挽救治療局部晚期食管癌可行

RTOG0246試驗(2003年9月5日-2006年3月17日),先給予以紫杉醇為基礎的誘導化療然后采用以紫杉醇為基礎的同步放化療聯(lián)合選擇性手術治療可以切除的局部晚期食管癌初步結果：研究納入43例無轉移食管癌患者,其中40例可分析,治療前分期為T3-4N1。結果顯示,40例完成了誘導化療,37例完成同步放化療,發(fā)生Ⅲ度、Ⅳ度血液學毒性及Ⅲ度非血液學毒性的患者分別有28例、7例和7例。18例接受了手術,其中17例經(jīng)胸腹CT、超聲內鏡或PET證實為復發(fā)或殘留,1例為患者自己選擇了手術。剩余22例沒有接受手術的患者中,15例未復發(fā),1例為醫(yī)學原因不能手術,3例轉移,3例死亡。預計1年總生存(OS)率為72%,預計1年無病生存(DFS)率為39%。這項多中心前瞻性Ⅱ期研究提示,根治性放化療聯(lián)合選擇性外科手術挽救治療局部晚期食管癌是可行的

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY食管癌同步放化療OBJECTIVE:評價大野加局部小野推高劑量照射聯(lián)合同期放化療治療胸部食管癌的可行性。.

METHODS:病人：T1-4N0-1M0(UICC1997)胸部鱗狀細胞食管癌.

大野：鎖骨上窩至縱隔39.6Gy

小野：推量至66.6Gy(1.8Gy/day,5/week).2小時cisplatin(80mg/m(2)onday連續(xù)5-fluorouracil(800mg/m(2)/dayondays2-6)every3-4weeks,fortwocycles.RESULTS:30例(stageI,3;stageII,11;stageIII,16)納入觀察.21例(70%)完成計劃.>or=70years老年病人,4/6退出.3級(NCI-CTC)毒性反應20(67%)例，4級毒性反應3(10%)例.主要表現(xiàn)為血液、消化道和肺損傷.沒有5級毒性反應.中位生存期27months(range:9-49months).

平均生存時間21months.1-、2-year生存率是65%and49%.食管狹窄(grade1-2:RTOG)was21%.沒有食管穿孔.結論：大野加局部小野推高劑量照射聯(lián)合同期放化療治療胸部食管癌的可行。

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY1:JpnJClinOncol.2001Aug;31(8):375-81.LinksConcurrentchemoradiotherapyforsquamouscellcarcinomaofthoracicesophagus:feasibilityandoutcomeoflargeregionalfieldandhigh-doseexternalbeamboostirradiation.食管癌同步放化療復旦大學附屬腫瘤醫(yī)院后程加速超分割(LCAF)與聯(lián)合同步化療(LCAF+CT)治療原發(fā)性食管癌的Ⅲ期隨機對照研究(患者111名)先予常規(guī)放療DT41.4Gy/23f,4～5W,(1.8Gy/次,1次/天)縮野行加速超分割,DT27Gy/18次(1.5Gy/次,2次/日)累積放療總量6814Gy/41f,44d完成。54例患者FP方案化療4個周期(順鉑25mg/m2,d1～d3,5-FU600mg/m2,d1～d3,28天為1周期)

中位生存期:30.8月vs.23.9月(LCAF+CTvs.LCAF)

LCAF+CT組與LCAF組1、3、5年生存率分別為67%、44%、40%,77%、39%、28%,(P=0.310)

結論：認為后程加速超分割結合同步化療有延長生存期的趨勢。

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITYZhaoKL,ShiXH,JiangG,etal.Latecourseacceleratedhyperfractionatedradiotherapyplusconcurrentchemotherapyforsquamouscellcarcinomaoftheesophagus:aphaseⅢrandomizedstudy[J].IntJRadiatOncolBiolPhys,2005,62(4):1014-1020.食管癌同步放化療

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY目的：評價聯(lián)合放療和化療與單獨放療治療局部食管癌的療效，從總生存率、cause-specific生存、局部復發(fā)、吞咽困難緩解、生活質量以及急性和慢性毒性反應方面予以評估。藥物為cisplatinor5-fluorouracil

方法：檢索相關的MeSH主題詞、Cochrane圖書館、國際腫瘤文獻文摘數(shù)據(jù)庫（CancerLIT）、聯(lián)機醫(yī)學文獻分析與檢索系統(tǒng)（MEDLINE）,醫(yī)學文摘數(shù)據(jù)庫（EMBASE）主要結果：19個隨機試驗被納入，11個聯(lián)合放化療和8個續(xù)貫放化療聯(lián)合放化療死亡風險比(HR)0.73(95%(CI)0.64to0.84)，明顯下降.絕對生存受益率為1年9%(95%CI5to12%)，2年4%(95%CI3to6%)，局部復發(fā)率（NNT需治數(shù)為9）為12%，(95%CI3to22%)單放組為68%.嚴重毒性和生命威脅毒性（NNH致成危害需要的人數(shù)為6）較顯著。續(xù)貫放化療對于局部控制和生存率方面沒有益處。結論：對于非手術的局部食管癌病人，相對單純放療同步放化療應該優(yōu)選，但有毒性風險。CochraneDatabaseSystRev食管癌同步放化療CONCLUSIONS:

Basedontheavailabledata,whenanon-operativeapproachisselectedthenconcomitantRTCTissuperiortoRTaloneforpatientswithlocalizedesophagealcancerbutwithsignificanttoxicities.Inpatientswhoareingoodgeneralcondition,andtheriskbenefithasbeenthoroughlydiscussedwiththepatient,concomitantRTCTshouldbeconsideredforthemanagementofesophagealcancercomparedwithradiotherapyalone.

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITYCochraneDatabaseSystRev.2001;(2):CD002092.Combinedchemotherapyandradiotherapy(withoutsurgery)comparedwithradiotherapyaloneinlocalizedcarcinomaoftheesophagus.

CochraneDatabaseSystRev.2003;(1):CD002092.Combinedchemotherapyandradiotherapy(withoutsurgery)comparedwithradiotherapyaloneinlocalizedcarcinomaoftheesophagus.

1:CochraneDatabaseSystRev.2006Jan25;(1):CD002092.Combinedchemotherapyandradiotherapy(withoutsurgery)comparedwithradiotherapyaloneinlocalizedcarcinomaoftheesophagus.

WongR,MalthanerR.食管癌同步放化療Philip進行多中心前瞻隨機試驗比較了標準食管癌切除術與放化療的療效。80例患者中36例接受了同步放化療化療采用連續(xù)灌注5-FU(200mg/m2,d1～d42)、順鉑(60mg/m2,d1、d22),對腫瘤區(qū)和區(qū)域淋巴結同時照射,總劑量50～60Gy44例接受標準手術,手術死亡率618%,術后并發(fā)癥發(fā)生率達38.6%。放化組與手術組的早期生存率沒有區(qū)別,2年生存率分別為58.3%、54.5%。提示同步放化療與手術治療療效相當,該試驗還提示手術組縱隔復發(fā)率高于放化組,而放化組則在頸部及腹部復發(fā)率偏高。

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITYChiuPW,ChanAC,LeungSF,etal.Multicenterprospectiverandomizedtrialcomparingstandardesophagectomywithchemoradiotherapyfortreatmentofsquamousesophagealcancer:earlyresultsfromthechineseuniversityresearchgroupforesophagealcancer[J].GastrointestSurg,2005,9(6):794-802.食管癌同步放化療同步放化療后是否可以延緩手術,也是目前研究的熱點－－法國Bedenne法國Bedenne－－－FFCD9102試驗,EligiblepatientshadoperableT3N0-1M0thoracicesophagealcancer.Patientsreceivedtwocyclesoffluorouracil(FU)andcisplatin(days1to5and22to26)andeitherconventional(46Gyin4.5weeks)orsplit-course(15Gy,days1to5and22to26)concomitantradiotherapy.

然后randomlyassignedtosurgery(armA)orcontinuationofchemoradiation(armB;threecyclesofFU/cisplatinandeitherconventional[20Gy]orsplit-course[15Gy]radiotherapy).

在該試驗中444例患者接受了放化療,其中259例患者接受了進一步的手術切除,其余患者接受進一步放化療單純放化療與手術組2年生存率分別為40%和34%,治療相關致死率分別為1%和9%CONCLUSION:

Ourdatasuggestthat,inpatientswithlocallyadvancedthoracicesophagealcancers,whorespondtochemoradiation,thereisnobenefitfortheadditionofsurgeryafterchemoradiationcomparedwiththecontinuationofadditionalchemoradiation.

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY

BedenneL,MichelP,BoucheO,etal.Chemoradiationfollowedbysurgerycomparedwithchemoradiationaloneinsquamouscanceroftheesophagus:FFCD9102[J].JClinOncol,2007,25(10):1160-1168.食管癌同步放化療日本Yamada對早期(I期)食管癌同步放化療的可行性進行研究63例患者,其中T1a(粘膜癌)有23例,T1b(粘膜下癌)40例放療外照射55～60Gy/50～60d,同步1～3周期FP方案化療,隨后腔內照射10～12Gy/2～3次。5年總生存率及無疾病生存率分別為66.4%和63.7%;T1a、T1b5年無疾病生存率分別為84.4%、50.5%作者認為同步放化療對I期食管癌的器官保存率為89.2%,長期生存率與手術相當。

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITYYamadaK,MurakamiM,OkamotoY,etal.TreatmentresultsofchemoradiotherapyforclinicalstageI(T1N0M0)esophagealcarcinoma[J].IntJRadiatOncolBiolPhys,2006,64(4):1106-1111.食管癌同步放化療同步放化療后手術:術后病理完全緩解是提高生存率的唯一因素

美國馬里蘭醫(yī)學中心報告術前采用同步放化療(放療劑量為50.4Gy,化療方案為順鉑+5-氟尿嘧啶,放療中進行2個周期的化療),中位時間間隔7周后手術。

多因素分析顯示,T分期、病變長度、組織學及手術時間間隔對OS率沒有影響,只有術后病理完全緩解(pCR)是唯一可以提高生存率的因素。而組織學是唯一可以預測術后病理結果的因素,鱗癌比腺癌有更高的術后pCR率(56%對35%)。腺癌中,淋巴結陰性者和陽性者的pCR率分別為45%和28%(P=0.049),因此,淋巴結狀態(tài)也是預測術后病理結果的指標之一。術后病理殘存腫瘤組的3年OS率也達到了36%(RTOG8501試驗的3年OS率為30%)。

對Ⅳ期食管癌進行了分層研究,Ⅳ期包括M1a(有腹腔淋巴結轉移)和M1b(有其他部位淋巴結轉移,但不包括結外轉移)。Ⅳ期(27例)和Ⅲ期的OS相比,無顯著差異(25.2個月對27個月)。此外,這組Ⅳ期病例中,61%的受累淋巴結沒有在術前通過PET或CT檢測出來,因此,術前精確辨別M1a和M1b的淋巴結病變將會進一步指導放療,提高可手術、無結外轉移的Ⅳa和Ⅳb患者的療效。

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY第49屆ASTRO年會報道(三)食管癌放療進展北京醫(yī)院放療科

高鴻李高峰

食管癌同步放化療

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY英國的Geh系統(tǒng)評價了1980～2001年的相關資料對26個隨機對照試驗的1335位患者進行系統(tǒng)評價,其中311例患者(24%)取得pCRpCR的發(fā)生率與放療(P=0.006)、5-FU(P=0.003)、順鉑(P=0.018)劑量增加有關而絲裂霉素C的同步化療不影響pCR同時放射治療時間及中位年齡的增長減少了pCR食管癌α/β估計值約為4.9Gy,在放療增敏中,1g/m2的5-FU相當于放療劑量1.9Gy(95%CI:0.8～5.2Gy),100mg/m2的順鉑為7.2Gy(95%CI:2.1～28Gy)結論認為放射、5-FU、順鉑的劑量與pCR存在劑量反應關系。

GehJI,BondSJ,BentzenSM,etal.Systematicoverviewofpreoperative(neoadjuvant)chemoradiotherapytrialsinoesophagealcancer:evidenceofaradiationandchemotherapydoseresponse[J].RadiotherOncol,2006,78(3):236-244.食管癌同步放化療JClinOncol.2002Jun15;20(12):2844-50

Oxaliplatinincombinationwithprotracted-infusionfluorouracilandradiation:reportofaclinicaltrialforpatientswithesophagealcancer.

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITYCONCLUSION:OXP85mg/m(2)ondays1,15,and29administeredwithPI5-FUandXRTissafe,tolerable,andseemseffectiveagainstprimaryesophagealcarcinoma

.TheroleofOXPinmultimodalityregimensagainstesophagealcarcinomadeservesfurtherevaluation.

OXP85mg/m2ondays1,15,and29;PI5-FU180mg/m2for24hoursfor35days;XRT1.8Gyin28fractionsstartingonday8；

2B2B級是基于低水平證據(jù)，專家組無統(tǒng)一認識，但爭議不大食管癌同步放化療Active,notrecruitingCombinationChemotherapyFollowedByChemoradiotherapy,WithorWithoutSurgery,inTreatingPatientsWithResectableLocallyAdvancedCanceroftheEsophagusorGastroesophagealJunction

Condition:Esophageal

Cancer

Interventions:Drug:

cisplatin;

Drug:

filgrastim;

Drug:

fluorouracil;

Drug:

paclitaxel;

Drug:

pegfilgrastim;

Procedure:

conventional

surgery;

Procedure:

radiation

therapy

2RecruitingAStudytoEvaluatetheCombinationofCetuximabandChemotherapyasNeoadjuvantTherapyFollowedConcomitantChemoradiotherapyPlusCetuximabinLocoregionalEsophagealCarcinoma

Condition:Esophageal

Carcinoma

Intervention:Drug:cetuximabandchemotherapy(docetaxel,cisplatin,5-fluorouracil)

3TerminatedRCTontheCombinedModalityTreatmentofSquamousCellCarcinomaoftheEsophagus

Conditions:Esophageal

Neoplasms;

Squamous

Cell

Cancer

Interventions:Procedure:transthoracicesophagectomy2-fieldextendedlymphadenectomy;

Drug:neoadjuvantchemotherapy(cisplatin,5-fluorouracil);

Radiation:

neoadjuvant

chemoradiotherapy

4NotyetrecruitingChemotherapyInductionandChemoradiotherapyinPatientsWithEsophagealCarcinoma

Condition:Esophageal

Cancer

Interventions:Drug:

5-FU;

Drug:

Cisplatin;

Drug:

Taxotere;

Biological:

Cetuximab;

Radiation:Radiationduringchemoradio-immunotherapy

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY食管癌同步放化療NotyetrecruitingConcurrentChemoradiotherapyContainingPaclitaxelandCisplatinWith/WithoutTarcevainLocallyAdvancedEsophagealCancer

Condition:Esophageal

Cancer

Interventions:Drug:

Paclitaxel;

Drug:

Cisplatin;

Drug:

Tarceva

7Active,notrecruitingNeoadjuvantDocetaxelandCisplatinPlusChemoradiotherapyChemoradiotherapyFollowedBySurgeryinTreatingPatientsWithLocallyAdvanced,ResectableEsophagealCancer

Condition:Esophageal

Cancer

Interventions:Drug:

cisplatin;

Drug:

docetaxel;

Procedure:

conventional

surgery;

Procedure:

neoadjuvant

therapy;

Procedure:

radiation

therapy

8Active,notrecruitingLow-DoseCDGP/5-FUCombinedWithRadiationforEsophagealCancer

Conditions:Esophageal

Cancer;

Squamous

Cell

Carcinoma

Interventions:Drug:

CDGP/5-FU;

Radiation:

Chemoradiotherapy

9CompletedCCRTWithTwiceWeeklyPaclitaxelandCisplatinFollowedbySurgeryforLocallyAdvancedEsophagealCancer

Condition:Esophageal

Cancer

Intervention:Drug:

Paclitaxel,

Cisplatin,Surgery,

CCRT

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY食管癌同步放化療RecruitingOxaliplatin-BasedChemotherapyandChemoradiotherapyorChemoradiotherapyinEsophagealorGastroesophagealCarcinoma

Conditions:Esophageal

Cancer;

Gastroesophageal

Cancer

Interventions:Drug:

5-Fluorouracil;

Drug:

Oxaliplatin;

Radiation:

Radiation

Therapy

11CompletedMulti-CenterProspectiveRandomizedTrialComparingStandardEsophagectomyAgainstChemo-RadiotherapyforTreatmentofSquamousEsophagealCancer–EarlyResultsFromtheChineseUniversityResearchGroupforEsophagealCancer(CURE)

Condition:Esophageal

Cancer

Interventions:Procedure:

Esophagectomy;

Procedure:

Chemoradiation

12Active,notrecruitingRadiotherapy,CombinationChemotherapy,andGefitinibBeforeandAfterSurgeryinTreatingPatientsWithAdvancedEsophagealorGastroesophagealJunctionCancer

Condition:Esophageal

Cancer

Interventions:Drug:

cisplatin;

Drug:

fluorouracil;

Drug:

gefitinib;

Procedure:

adjuvant

therapy;

Procedure:

conventional

surgery;

Procedure:

neoadjuvant

therapy;

Procedure:

radiation

therapy

13CompletedCombinationChemotherapyPlusRadiationTherapyWithorWithoutFluorouracilinTreatingPatientsWithCanceroftheEsophagusorStomach

Conditions:Esophageal

Cancer;

Gastric

Cancer

Interventions:Drug:

cisplatin;

Drug:

filgrastim;

Drug:

fluorouracil;

Drug:

paclitaxel;

Procedure:

radiation

therapy

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY食管癌同步放化療RecruitingBiologicalFactorsinPredictingResponsetoTreatmentinPatientsWithEsophagealCancerorRectalCancer

Conditions:Colorectal

Cancer;

Esophageal

Cancer

Interventions:Procedure:

biopsy;

Procedure:

endoscopic

biopsy;

Procedure:

gene

expression

analysis;

Procedure:

laboratory

biomarker

analysis;

Procedure:

mutation

analysis;

Procedure:

polymorphism

analysis

15RecruitingCombinationChemotherapy,Surgery,andRadiationTherapyinTreatingPatientsWithLocoregionallyAdvancedCanceroftheEsophagus,GastroesophagealJunction,orStomach

Conditions:Esophageal

Cancer;

Gastric

Cancer

Interventions:Drug:

cisplatin;

Drug:

epirubicin

hydrochloride;

Drug:

fluorouracil;

Drug:

oxaliplatin;

Procedure:

adjuvant

therapy;

Procedure:

neoadjuvant

therapy;

Procedure:

radiation

therapy;

Procedure:

therapeutic

conventional

surgery

16RecruitingAdvancedOesophagealCancerStudytoCompareQualityofLifeandPalliationofDysphagia.

Condition:Esophagus

Cancer

Interventions:Drug:

Cisplatin;

Radiation:

Radiation

therapy;

Drug:

5-Fluorouacil

17RecruitingS-1,Cisplatin,andRadiationTherapyinTreatingPatientsWithStageIIA,StageIII,orStageIVAEsophagealCancerThatCanBeRemovedbySurgery

Condition:Esophageal

Cancer

Interventions:Drug:

S-1;

Drug:

cisplatin;

Procedure:

cytology

specimen

collection

procedure;

Procedure:

endoscopic

biopsy

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY食管癌同步放化療Active,notrecruitingSelectiveDoseEscalationforEsophagealCancer

Condition:Esophageal

Cancer

Intervention:Drug:

carboplatin,

5FU,

Taxol

and

radiation

19Active,notrecruitingIrinotecan,Cisplatin,andRadiationTherapyWithorWithoutCelecoxibinTreatingPatientsWithStageII,StageIII,orStageIVEsophagealCancer

Condition:Esophageal

Cancer

Interventions:Drug:

celecoxib;

Drug:

cisplatin;

Drug:

irinotecan

hydrochloride;

Procedure:TdT-mediateddUTPnickendlabelingassay;

Procedure:

biopsy;

Procedure:

conventional

surgery;

Procedure:

gene

expression

analysis;

Procedure:

immunoenzyme

technique;

Procedure:

immunohistochemistry

staining

method;

Procedure:

immunologic

technique;

Procedure:

laboratory

biomarker

analysis;

Procedure:

neoadjuvant

therapy;

Procedure:

protein

expression

analysis;

Procedure:

radiation

therapy;

Procedure:reversetranscriptase-polymerasechainreaction

20RecruitingPhaseIDoseEscalationofStereotacticRadiosurgicalBoostforLocallyAdvancedEsophagealCancer

Conditions:Esophageal

Neoplasms;

Adenocarcinoma;

Carcinoma,

Squamous

Cell

Interventions:Drug:

Capecitabine

(Xeloda);

Drug:

Oxaliplatin

(Eloxatin);

Procedure:

Radiation

therapy;

Procedure:

Surgery

西安交通大學醫(yī)學院第二附屬醫(yī)院SECONDAFFILIATEDHOSPITALOFMEDICALCOLLEGEOFXI’ANJIAOTONGUNIVERSITY食管癌同步放化療NotyetrecruitingErbituxCombinedWithChemo-Ra