非小细胞肺癌放射治疗进展课件.pptx

1、12345呼气吸气螺旋开始时相时相由吸转呼呼气末由呼转吸由吸转呼呼气吸气螺旋开始呼吸曲线呼吸曲线床位床位6 40对叶片MLCKV级X射线球管KV级探测器阵列MV级探测器阵列7involved lymph nodesOperable a-N2Grade 2:4.Grage 4:1.paclitaxel 200 mg/m2757(P=0.Total cases38/281(13.RT is better than OBS.RT is better than OBS.Concurrent Chemo/RadioFavor Gr HR benefit%sur%2y 5y 2y 5ySEQ CON-QD

2、 CON-BID二、早期非小细胞肺癌的放射治疗Update of PORT Lung Cancer,2005.Pulmonary disease:Positive:172,Negative:109G3急性和晚期非血液系统毒性：PV:顺铂/长春花碱SEQ CON-QD CON-BIDPORT既能够提高OS也能够提高DSSNo survival benefit over concurrent therapy alone8一、放射治疗在肺癌治疗中的地位一、放射治疗在肺癌治疗中的地位二、早期二、早期NSCL的放射治疗的放射治疗三、局部晚期三、局部晚期NSCL的放疗的放疗/化疗化疗 综合治疗综合治疗 四

3、、四、3DCRT提高提高NSCLC的生存率的生存率五、术后放射治疗五、术后放射治疗9l应用循证医学的方法评价放射治疗在肺癌治疗中的地位。every 3 weeks X 2 cyclesFavor Gr HR benefit%sur%2y 5y 2y 5y5%为复发和进展病例的治疗（later for recurrence or progression）局部晚期NSCLC（A/B）3DCRT vs 常规放疗Operable a-N2ASCO 2007:Abstract 7512.Epub 2007Apr9%15.PORT既能够提高OS也能够提高DSSArimoto 60Gy/8fr/11d 92

4、%(22/24)24MpN2 降低局部复发 对OS无明确结论147 patients1、Combined Treatment：G3急性和晚期非血液系统毒性：结论：序贯放疗/化疗优于单纯放射治疗5年生存率 8.RT is better than OBS.RT 在 SCLC治疗中的地位1011l53.6%3.3%SCLC 病例在其疾病的不同时期需要接受放射治疗 45.4%4.3%为首程治疗 （in the initial treatment）.8.2%1.5%为复发和进展病例的治疗（later for recurrence or progression）12l64.3%4.7%of NSCLC c

5、ases require RT.45.9%4.3%in their initial treatment.18.3%1.8%later in the couse of the illness13放射治疗能够使 早期NSCLC获得治愈 14Institute Dose/fx/OTT LC/Follow-upUematsu 50-60/5-10/5d 94%(47/50)36MKyoto 48Gy/4fr/12d 96%(49/51)20M Arimoto 60Gy/8fr/11d 92%(22/24)24MOnimaru 60Gy/8fr/11d:88%(50/57)18M Nagata Y,Ky

6、oto Univ,IASLC,200415lTotal cases：281lAge:39-92(median 76)yearslPulmonary disease:Positive:172,Negative:109lHistology:Sqamous:122Adeno:131,Others:28lStage:IA:178,IB:103lTumor diameter:7-58(median 23)mmlMedical Operability:Inoperable:177,Operable:104Onishi H,ASCO 200416lFollow-up period 2-128(median

7、30)monthslLocal responseCR 26.9%PR 59.1%NC 14.0%lPneumonitis(NCI-CTC)Grade 0:33.7%Grade 1:59.9%Grade 2:4.0%Grade 3:1.2%Grage 4:1.2%lEsophagitis(Grade 3)1.2%lPleural effusion(transient)1.6%lRib fracture1.2%lBone marrow suppression 0.0%Onishi H,ASCO 200417lTotal cases38/281(13.5%)BED 100 Gy17/211(8.1%

8、)lStage IA17/177(9.6%)BED 100 Gy 9/136(6.6%)lStage IB21/102(20.6%)BED 100 Gy 8/73(11.0%)lAdenocarcinoma17/122(14.0%)lSquamous cell ca.18/131(13.7%)Onishi H,ASCO 200418Mountain*JCOG*JNCCH*Stage IAStage IB67%57%80%63%74%53%STI*90%84%*Surgery*Stereotactic IrradiationComparison of 5-Yr Overall Survival

9、Between Surgery&STISurvival curves of operable pts irradiated with BED of 100 Gy or more according to Stagestage IA(n=47)stage IB(n=16)p=0.2Summary of Japanese StudiesOnishi H,ASCO 200419SRBT(n=55)楔形切除楔形切除(n=69)P肺功能（肺功能（FEV-1）1.39(0.86-2.37)1.31(0.52-3.0)NSCharlson合并症指数合并症指数 3(1-4)4(3-6)0.01年龄年龄74(6

10、9-78)78(55-89)1 liter at study entry地位的确立，是肺癌治疗进展中CT+Surgery vs CT/RTRadiation Oncology Biol.DDP 40-120mg/m2/cycle,total dose 120-800mg/m2radiation dose 50Gy/20f-65Gy/30f3D vs 2D in MEDICALLY INOPERABLEpN3病例及N分期不明者Three Clinical Research Topics in Radiotherapy of Locally Advanced NSCLC22作者作者患者患者MFUT

11、RR or LRDMOSCSSOnisi,2007257388-14206590Negata,20054536216-3183-Uematsu,200150306146688Zimmerman,2006681712165173Fakiris,2009705012134382RTOG,0236552561572-232425 放射治疗成为早期放射治疗成为早期NSCLC的另一的另一 根治性治疗手段根治性治疗手段 放射治疗在早期放射治疗在早期NSCLC治疗中的治疗中的 地位的确立，是肺癌治疗进展中地位的确立，是肺癌治疗进展中 的一个里程碑的一个里程碑 Evolution of Treatment S

12、trategy Operable：Surgery Surgery RT Surgery RT CT CT+Surgery RT/CT+Surgery RT/CT Surgery RT/CT Evolution of Treatment Strategy Inoperable :RT CT+RT Sequential CT/RT Concurrent?Induction CT CT/RT CT/RT Consolidation?neutropenia and overall maximal toxicityPercent of patients survivingT3-4 diseaseR Ro

13、sell,M De Lena,F Carpagnano,R Ramlau,JL Gonzalez-Larriba,T Grodzki,A Le Groumelec,D Aubert,J Gasmi,JY DouillardInduction Chemotherapy Followed by Chemoradiotherapy With Chemoradio-therapy Alone for Regionally Advanced Unresectable StageIII NonSmall-CellLung:Cancer and Leukemia GroupBCALGB 39801中位生存期

14、（月）13.从随机分组开始后的月数BED RT(60 Gy,2Gy QD)day 50 同步同步:PV/RT(60 Gy,2Gy QD)day 1 同步同步/HFRT:PE/HFRT(69.2 Gy,1.2Gy BID)day 1PV:顺铂顺铂/长春花碱长春花碱PE:顺铂顺铂/oral 足叶乙甙足叶乙甙RT:放疗放疗;QD:每日一次每日一次;HFRT:超分隔放疗超分隔放疗Curran:ASCO,2000;updated IASLC 2000;ASTRO 2001,2003RANDOMIZE二二.同时化放疗同时化放疗 vs 序贯化放疗序贯化放疗(2)SEQ CON-QD CON-BID 中位生存

15、期：中位生存期：14.6 17 15.6（月）（月）4 年生存率：年生存率：12%21%17%p=0.046 G3急性和晚期非血液系统毒性：急性和晚期非血液系统毒性：30%，48%，62%和和 14%，15%，16%。Curran W et al.Pro.Am Soc Clin Oncol.J.Clin.Oncol.2003;(abstract 2499)*Stereotactic IrradiationRT/CT+Surgery vs RT/CTDDP+Vp16/RT3DCRT能够提高NSCLC的治疗疗效Negata,2005材料与方法排除标准Radiation Pneumonitis an

16、dRT 在 SCLC治疗中的地位G3急性和晚期非血液系统毒性：&Table 4.9%15.30%，48%，62%和 14%，15%，16%。The MST with EP/XRT was higher than historical controls;3 DCRT vs 常规放疗 中国医学科学院肿瘤医院 2001-2006随访资料RTOG 9410:III期NSCLC 同步放化疗 vs 序贯放化疗El-Sherif,2006Pulmonary disease:Positive:172,Negative:1095年生存率 8.？诱导化疗？诱导化疗?巩固化疗巩固化疗诱导化疗诱导化疗J Clin O

17、ncol.2007 May 1;25(13):1698-704.Epub 2007Apr lJuly 1998 and was closed in May 2002,Totally 366 patients registered增加毒性增加毒性 induction chemotherapy increases neutropenia and overall maximal toxicity 没有生存优势没有生存优势 No survival benefit over concurrent therapy alone同期放化疗是标准的治疗模式同期放化疗是标准的治疗模式 Concomitant ch

18、emoradiotherapy is current standard therapy for unresectable stage IIIB NSCLC60mg/m2 weeklySienel,2007FEV-1 1 liter at study entryCT+SurgeryASCO 2005.1%33.2、New Radiation Techniques:Squamous cell ca.Months Since RegistrationConcurrent Chemo/Radio序贯:PV-RT(60 Gy,2Gy QD)day 50R+DDP 0.3 DCRT vs 常规放疗 中国医

19、学科学院肿瘤医院 2001-2006RT 在 SCLC治疗中的地位108116,2006随访资料放射治疗成为早期NSCLC的另一同步:PV/RT(60 Gy,2Gy QD)day 1N Events中位生存PV:顺铂/长春花碱Study CTRT99/97 by the Bronchial Carcinoma Therapy GroupPC x 3诱导化疗诱导化疗RandomizeRT aloneRT+Paclitaxel 60mg/m2 weeklypaclitaxel 200 mg/m2 carboplatin AUC=6every 3 weeks X 2 cyclespaclitaxel

20、 60 mg/m2 weeklyRadiotherapy alone巩固化疗巩固化疗顺铂顺铂/VP-16 X XRT泰索帝泰索帝 X X X 顺铂顺铂 50mg/m2 d 1,8,29,36 VP-16 50mg/m2 d1-5,29-33RT:61 Gy:45Gy(1.8Gy/fx),16Gy 缩野缩野(2Gy/fx)泰索帝泰索帝:75mg/m2 cycle 1 -100mg/m2 cycle 2-3 研究研究病例病例MST(月)2 年生存年生存3 年生存年生存S9019(PE/RT PE)5015(10-22)*34%(21-47)*17%(7-27)*S9504(PE/RT 泰索帝泰索帝

21、)8326(18-35)*54%(43-65)*37%(22-52)*95%CIConcurrent Chemo/RadioDDP+Vp16/RTConsolidation ChemoDocetaxel MaintenanceGEFITINIB orPLACEBO巩固化疗巩固化疗Results of ASCO 2007Logrank p=0.involved lymph nodesR+DDP 0.IIIa vs IIIb108116,200660mg/m2 weeklyGrade 3:1.Pleural effusion(transient)1.（in the initial treatmen

22、t）.Local responseCR 26.ROC curse:The area under curve in receiver operating characteristic curves based on the relationship between incidence of RP and the value of Vipsi-dose was 0.Abstract 7014.Pneumonitis序贯化放疗 同时化放疗2年OS 下降7 55%-48%Surgery RT CTROC curse:The area under curve in receiver operating

23、characteristic curves based on the relationship between incidence of RP and the value of Vipsi-dose was 0.pN3病例及N分期不明者HOG LUN 01-24 Phase III Study DesignHanna et al.ASCO 2007:Abstract 7512.ChemoRTCisplatin 50 mg/m2 IV d 1,8,29,36Etoposide 50 mg/m2 IV d 1-5&29-33Concurrent RT 59.4 Gy(1.8 Gy/fr)Strat

24、ificationat randomization PS 0-1 vs 2 IIIA vs IIIB CR vs non-CR Inclusion at baseline Unresectable stage IIIA or IIIBNSCLC ECOG PS 0-1 at study entry(+PS2 at random)FEV-1 1 liter at study entry203 patients147 patients73 patients74 patientsTaxotere75 mg/m2 q 3 wk 3ObservationPrimary endpoint:OSSecond

25、ary endpoints:PFS,toxicityHOG LUN 01-24:OS(ITT)Randomized Patients(n=147)Hanna et al.ASCO 2007:Abstract 7512.Months Since Registration0102030405060Percent of patients surviving0%25%50%75%100%P-value:0.940Median3 yearsurvival rateObservation18.0-34.227.6%Taxotere17-34.827.2%Comparison of Grade 3-5 To

26、xicitiesToxicitySWOG 9504SWOG 0023HOG 01-24Febrile Neutropenia l l PE/XRT l l Docetaxel NR 9%5%*5%*9.9%10.9%Esophagitis17%14%17.2%Pneumonitis 7%7%8.2%Docetaxel-related death4.8%4%5.5%*reported as“infection with neutropenia”The MST with EP/XRT was higher than historical controls;Consolidation D does

27、not further improve survival,is associated with significant toxicity including an increased rate of hospitalization and premature death,And should no longer be used for pts with unresectable stage III NSCLCConclusions60术前同时化放疗的临床研究术前同时化放疗的临床研究6162CT/RT/S 145/202CT/RT 155/194Logrank p=0.24危险比危险比=0.87

28、(0.70,1.10)存活率存活率%0255075100从随机分组开始后的月数从随机分组开始后的月数01224364860死亡死亡/总数总数中位中位FU 81 个月个月Albain et al.ASCO 2005.Abstract 7014.ObservationROC curse:The area under curve in receiver operating characteristic curves based on the relationship between incidence of RP and the value of Vipsi-dose was 0.BED 100 G

29、y 13/29(44.SWOG 9504:总生存Grade 3:1.Cisplatin 50 mg/m2 IV d 1,8,29,36Etoposide 50 mg/m2 IV d 1-5&29-33Concurrent RT 59.108116,2006同步/HFRT:PE/HFRT(69.Docetaxel地位的确立，是肺癌治疗进展中108116,2006Surgery RTSurgery RTFuruse K,et al.Three Clinical Research Topics in Radiotherapy of Locally Advanced NSCLCpN2 降低局部复发 对

30、OS无明确结论7%of NSCLC cases require RT.108116,2006放射治疗成为早期NSCLC的另一HOG LUN 01-24:OS(ITT)Randomized Patients(n=147)3%in their initial treatment.63随机分组后的月数随机分组后的月数 MS3 yr OS5 yr OS19月月 36%22%CT/RT/SCT/RT存活率存活率%025507510001224364860/29月月 45%24%死亡死亡/总计总计CT/RT/S38/51CT/RT42/51Log rank p=NSAlbain et al.ASCO 20

31、05.Abstract 7014.64Logrank p=0.002CT/RT/S 57/90CT/RT 74/90死亡死亡/总计总计存活率存活率%0255075100随机分组后的月数随机分组后的月数01224364860/MS 34月月 22 月月5 yr OS 36%18%CT/RT/SCT/RTAlbain et al.ASCO 2005.Abstract 7014.6566 EORTC 08941 A：Unresectable pN2不能手术的不能手术的ApN2病例病例通过诱导化疗后成为可手术病例通过诱导化疗后成为可手术病例是选择手术还是选择放疗？是选择手术还是选择放疗？6768697

32、071New data supports PORT in N2 cases72l死亡风险增加 21%l2年OS 下降7 55%-48%lpN0 pN1 有害lpN2 降低局部复发 对OS无明确结论PORT Meta-analysis Lancet,1998.352:257-63Update of PORT Lung Cancer,2005.47:81-373SEER 1988年年2001年年、期期NSCLC 7465例例根治性术后根治性术后PORT 3508例（例（47%）SEER J Clin Oncol,2006.24:2998-3006 预后多因素分析预后多因素分析HR95%CI Pol

33、der age1.0251.022-1.0280.0001T3-4 disease1.2881.117-1.4840.0005N2 nodal disease1.2811.101-1.4900.0014greater number of involved lymph nodes1.0431.027-1.0600.0001PORT1.0480.987-1.1130.126974N0N1N2SSRSSRSSR5yOS41%31%34%30%20%27%DSS53%39%44%38%27%36%P0.04350.01960.0077PORT既能够提高既能够提高OS也能够提高也能够提高DSSN0N1N

34、275New Data 2Results from ANITA:Phase III Adjuvant Vinorelbine and Cisplatin versus Observation in Completely Resected Non-Small-Cell Lung Cancer PatientsR Rosell,M De Lena,F Carpagnano,R Ramlau,JL Gonzalez-Larriba,T Grodzki,A Le Groumelec,D Aubert,J Gasmi,JY Douillard on behalf of the djuvant avelb

35、ine nternational rial ssociation76Seq=1 LYMPH NODE=N1STUDY PM259 94IN303:ANITA1 DATABASE:31/01/2005 04FEB050.000.250.500.751.00DURATION OF SURVIVAL(MONTHS)020406080100120STRATA:IA37_1=IV VRL+CDDP radio=NOCensored IA37_1=IV VRL+CDDP radio=NOIA37_1=IV VRL+CDDP radio=YESCensored IA37_1=IV VRL+CDDP radi

36、o=YESIA37_1=NO CT radio=NOCensored IA37_1=NO CT radio=NOIA37_1=NO CT radio=YESCensored IA37_1=NO CT radio=YESCT RTCTRTOBSRT is better than OBS.For patient who can not tolerate CT,RT would be recommended.CT RTCTRTOBS0.000.250.500.751.00DURATION OF SURVIVAL(MONTHS)020406080100120CT&RT is the bestRT is

37、 better than OBS 78根治性切除根治性切除NSCLCT1-3,N2具备完整治疗信息具备完整治疗信息 一般临床资料一般临床资料 术中所见及术后病理术中所见及术后病理 治疗模式及参数治疗模式及参数 随访资料随访资料79T4N2者者pN3病例及病例及N分期不明者分期不明者手术后手术后3个月内死亡的患者个月内死亡的患者手术后手术后3个月内肿瘤进展者个月内肿瘤进展者单纯探查术或纵隔镜活检术单纯探查术或纵隔镜活检术80全组全组例数例数PORT无无PORT术式术式肺叶切除肺叶切除19784113全肺切除全肺切除241212清扫淋巴结数目清扫淋巴结数目总数（枚）总数（枚）1-603-601-6

38、0中位数（枚）中位数（枚）211922OS例数例数MST(月月)1年年3年年5年年2P值值无无PORT 12531.977.645.430.65.2350.046PORT 9643.994.859.134.301224364860728496020406080100NO PORTPORT 2=5.235 P=0.046时间（月）生存率（%）DFS 1年年3年年5年年2P值值无无PORT 56.428.216.56.8910.009PORT 76.139.832.101224364860728496020406080100NO PORTPORT2=6.891 P=0.009时间（月）无病生存率（

39、%）无病生存率（%）01224364860728496020406080100S+C+RS+RS+CS时间（月）生存率（%）项目项目例数例数 MST(月月)1年年OS3年年OS5年年OSS+C+R6148.396.7%63.9%38.2%S+R3538.391.4%51.0%33.7%S+C10033.182.0%46.7%31.9%S2521.661.5%38.5%23.1%项目项目 例数例数无术后放疗无术后放疗术后放疗组术后放疗组 心功能衰竭心功能衰竭10心肌梗死心肌梗死10小脑萎缩小脑萎缩10急性胰腺炎急性胰腺炎10脓胸脓胸10脑血管意外脑血管意外11肺部感染肺部感染21气管食管瘘气管食

40、管瘘01肺栓塞肺栓塞01不明原因消瘦不明原因消瘦01死亡原因不明死亡原因不明22合计合计107u有无术后放疗组的非肿瘤死亡率并无差异有无术后放疗组的非肿瘤死亡率并无差异（p=0.493）S+C+R S+CS+RS5yOS47.0%34.0%21.3%16.6%01224364860728496020406080100S+C+RS+RS+CS时间（月）生存率（%）5yOS38.2%31.9%33.7%23.1%MST（M）47.423.822.712.7MST（M）48.333.138.321.6ANITA的结果的结果医科院肿瘤医医科院肿瘤医院的结果院的结果完全切除的完全切除的AN2 NCSLC

41、推荐术后化疗推荐术后化疗+放疗放疗861.00.80.60.40.20.01-S peci fi ci ty1-S peci fi ci ty1.00.80.60.40.20.0S ensi ti vi tyS ensi ti vi tyAbsolute Volume of lung received 30GyRP(%)NO RP(%)P 340 cm329.2(7/24)70.8(17/24)0.003 RT(60 Gy,2Gy QD)day 50 同步同步:PV/RT(60 Gy,2Gy QD)day 1 同步同步/HFRT:PE/HFRT(69.2 Gy,1.2Gy BID)day 1P

42、V:顺铂顺铂/长春花碱长春花碱PE:顺铂顺铂/oral 足叶乙甙足叶乙甙RT:放疗放疗;QD:每日一次每日一次;HFRT:超分隔放疗超分隔放疗Curran:ASCO,2000;updated IASLC 2000;ASTRO 2001,2003RANDOMIZE二二.同时化放疗同时化放疗 vs 序贯化放疗序贯化放疗(2)SEQ CON-QD CON-BID 中位生存期：中位生存期：14.6 17 15.6（月）（月）4 年生存率：年生存率：12%21%17%p=0.046 G3急性和晚期非血液系统毒性：急性和晚期非血液系统毒性：30%，48%，62%和和 14%，15%，16%。Curran W et al.Pro.Am Soc Clin Oncol.J.Clin.Oncol.2003;(abstract 2499)105106N0N1N2SSRSSRSSR5yOS41%31%34%30%20%27%DSS53%39%44%38%27%36%P0.04350.01960.0077PORT既能够提高既能够提高OS也能够提高也能够提高DSSN0N1N21073D vs 2D in MEDICALLY INOPERABLE STAGE I NONSMALL-CELL LUNG CANCERLocal-regional control