非小细胞肺癌放射治疗进展课件.ppt

1、非小细胞肺癌放射治非小细胞肺癌放射治疗进展疗进展2020/11/1422020/11/1432020/11/1442020/11/145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2020/11/146 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2020/11/1472020/11/148一、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、四、3DCRT提高提高NSCLC的生存率的生存率五、术后

2、放射治疗五、术后放射治疗2020/11/149l应用循证医学的方法评价放射治疗在肺癌治疗中的地位。2020/11/14102020/11/1411l53.6%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）2020/11/1412l64.3%4.7%of NSCLC cases require RT.45.9%4.3%in their initial treatment.18.3%1.8%l

3、ater in the couse of the illness2020/11/1413放射治疗能够使 早期NSCLC获得治愈 2020/11/1414Institute 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,Kyoto Univ,IASLC,20042020/11/1415lTotal case

4、s：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 20042020/11/1416lFollow-up period 2-128(median 30)monthslLocal respon

5、seCR 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 20042020/11/1417lTotal cases38/281(13.5%)BED 100 Gy17/211(8.1%)lStage IA17

6、/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 20042020/11/1418Mountain*JCOG*JNCCH*Stage IAStage IB67%57%80%63%74%53%STI*90%84%*Surgery*Stereotactic IrradiationComparison of 5-Yr Overall Survival Be

7、tween 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 20042020/11/1419SRBT(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

8、年龄年龄74(69-78)78(55-89)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 2001,2003RANDOMIZE2020/11/1434二二.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

9、 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)2020/11/14352020/11/14362020/11/14372020/11/1438？诱导化疗？诱导化疗?巩固化疗巩固化疗2020/11/1439诱导化疗诱导化疗2020/11/1440J Clin On

10、col.2007 May 1;25(13):1698-704.Epub 2007Apr 2020/11/1441lJuly 1998 and was closed in May 2002,Totally 366 patients registered2020/11/14422020/11/14432020/11/1444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

11、 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 chemoradiotherapy is current standard therapy for unresectable stage IIIB NSCLC2020/11/1445Study CTRT99/97 by the Bronchial Carcinoma Therapy GroupPC x 3诱导化疗诱导化疗RandomizeRT aloneRT+Paclitaxel 60mg/m2 weekly2020/11/1446paclitaxel 200 mg/m2 carboplatin AUC=

12、6every 3 weeks X 2 cyclespaclitaxel 60 mg/m2 weeklyRadiotherapy alone2020/11/14472020/11/14482020/11/1449巩固化疗巩固化疗2020/11/1450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 2020/11/14512

13、020/11/1452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)8326(18-35)*54%(43-65)*37%(22-52)*95%CI2020/11/1453Concurrent Chemo/RadioDDP+Vp16/RTConsolidation ChemoDocetaxel MaintenanceGEFITINIB orPLACEBO2020/11/14542020/11/1455巩固化疗巩固化疗Results of ASCO 2

14、0072020/11/1456HOG 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)Stratificationat randomization PS 0-1 vs 2 IIIA vs IIIB CR vs non-CR Inclusion at baseline Unresectable stag

15、e 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:OSSecondary endpoints:PFS,toxicity2020/11/1457HOG LUN 01-24:OS(ITT)Randomized Patients(n=147)Hanna et al.ASCO 2

16、007: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%2020/11/1458Comparison of Grade 3-5 ToxicitiesToxicitySWOG 9504SWOG 0023HOG 01-24Febrile Neutropenia l l PE/XRT l l D

17、ocetaxel 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”2020/11/1459 The MST with EP/XRT was higher than historical controls;Consolidation D does not further improve survival,is associated with significant toxici

18、ty including an increased rate of hospitalization and premature death,And should no longer be used for pts with unresectable stage III NSCLCConclusions2020/11/1460术前同时化放疗的临床研究术前同时化放疗的临床研究2020/11/14612020/11/1462CT/RT/S 145/202CT/RT 155/194Logrank p=0.24危险比危险比=0.87(0.70,1.10)存活率存活率%0255075100从随机分组开始后

19、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 7014.2020/11/1463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 2005.Abstract 7014.2020/11/1464Logrank p=0.00

20、2CT/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 7014.2020/11/14652020/11/1466 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？2020/11/14672020/11/

21、14682020/11/14692020/11/14702020/11/1471New data supports PORT in N2 cases2020/11/1472l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,2005.47:81-32020/11/1473SEER 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

22、 J Clin Oncol,2006.24:2998-3006 预后多因素分析预后多因素分析HR95%CI Polder age1.0251.022-1.0280.0001T3-4 disease1.2881.117-1.4840.0005N2 nodal disease1.2811.101-1.4900.0014greater number of involved lymph nodes1.0431.027-1.0600.0001PORT1.0480.987-1.1130.12692020/11/1474N0N1N2SSRSSRSSR5yOS41%31%34%30%20%27%DSS53%3

23、9%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DSSN0N1N22020/11/1475New 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 Grodzk

24、i,A Le Groumelec,D Aubert,J Gasmi,JY Douillard on behalf of the djuvant avelbine nternational rial ssociation2020/11/1476Seq=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

25、IA37_1=IV VRL+CDDP radio=NOIA37_1=IV VRL+CDDP radio=YESCensored IA37_1=IV VRL+CDDP radio=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.2020/11/14

26、77CT RTCTRTOBS0.000.250.500.751.00DURATION OF SURVIVAL(MONTHS)020406080100120CT&RT is the bestRT is better than OBS 2020/11/14782003.01.01-2005.12.30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2020/11/1479T4N2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

27、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2020/11/1480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）1-603-601-60中位数（枚）中位数（枚）2119222020/11/1481OS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 PO

28、RTPORT 2=5.235 P=0.046时间（月）生存率（%）2020/11/1482DFS 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（%）无病生存率（%）2020/11/148301224364860728496020406080100S+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%

29、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%2020/11/1484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）2020/11/1

30、485S+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推荐术后化疗推荐术后化疗+放疗放疗2020/11/14861.00.80.60.40.20.01-S peci fi ci ty1-S peci fi ci ty1.00.80.6

31、0.40.20.0S ensi ti vi tyS ensi ti vi tyAbsolute Volume of lung received 30GyRP(%)340 cm329.2(7/24)340 cm32.5(1/40)Ji Wei et al:ASTRO meeting 2008 BostonConclusion：It was safe for patients with NSCLC to receive postoperative 3DCRT，if irradiation dose to lung tissue was well defined.2020/11/14872020/1

32、1/14883D vs 2D in MEDICALLY INOPERABLE STAGE I NONSMALL-CELL LUNG CANCER(a)Overall survival(b)Disease-specific survival2020/11/14893D vs 2D in MEDICALLY INOPERABLE STAGE I NONSMALL-CELL LUNG CANCERLocal-regional control2020/11/14902020/11/14912020/11/149201224364860728496 108 1200204060801003-D2-DP=

33、0.002MonthsOS(%)分组分组例数例数1 1年年3 3年年5 5年年MSTMST常规放疗常规放疗27561.061.013.813.88.08.015.615.63-DCRT3-DCRT21873.373.326.126.114.414.420.120.15 5年年OS 6.4%OS 6.4%MST 4.5MST 4.5月月2020/11/149301224364860728496 108 1200204060801003-D2-DP=0.000MonthsCSS(%)分组分组例数例数1 1年年3 3年年5 5年年常规放疗常规放疗27565.165.116.716.711.211.2

34、3-DCRT3-DCRT21879.079.033.333.320.820.82020/11/1494变量变量单因素单因素多因素多因素危险比危险比P P 值值危险比危险比P P 值值70 vs 7070 vs 70岁岁1.0351.0350.7440.744-女性女性 vs vs 男性男性1.0751.0750.5520.552-体重下降体重下降(5%vs 5%)5%vs 5%)1.1221.1220.3700.370-吸烟吸烟(无无 vs vs 有有)1.0741.0740.5220.522-KPS(80 vs KPS(80 vs 80)80)1.6711.6710.0000.0001.56

35、31.5630.0010.001IIIa vs IIIbIIIa vs IIIb1.2641.2640.0310.0311.2161.2160.0890.089非鳞癌非鳞癌 vs vs 鳞癌鳞癌1.0511.0510.6190.619-Hb(120 vs Hb(120 vs 120 g/L)120 g/L)1.6251.6250.0000.0001.4221.4220.0080.008化学治疗化学治疗 (无无 vs vs 有有)0.8660.8660.1380.138-50-60 vs 60 vs 50-60 vs 60 vs 60 Gy60 Gy0.7850.7850.0010.0010.8

36、520.8520.0460.046常规放疗常规放疗vs vs 三维适形三维适形0.7370.7370.0020.0020.7620.7620.0090.009CR+PR vs SD+PDCR+PR vs SD+PD1.6071.6070.0000.0001.5711.5710.0010.0012020/11/14952 D3 DX2P值值例数（比例例数（比例%）例数（比例例数（比例%）食管炎2级135（61.9）180（65.5）0.6560.4502疾83（38.1）95（34.5）放射性放射性肺炎肺炎2级级148（67.9）202（73.5)1.8290.1942疾疾70（32.1）73(

37、26.5)食管炎3级207（95.0）264（96.0）0.3120.6623疾11（5.0）11（4.0）放射性肺炎3级192(88.5)251(91.3)1.0550.3633疾25(11.5)24(8.7)2020/11/1496与常规放射治疗技术相比与常规放射治疗技术相比3DCRT 能够提能够提高高NSCLC的生存率的生存率推荐推荐3DCRT作为非小细胞肺癌的标准治作为非小细胞肺癌的标准治疗技术疗技术2020/11/14971、Combined Treatment：Concurrent Chemoradiotherapy同时放化疗中化疗方案的选择同时放化疗中化疗方案的选择诱导化疗或巩固化疗的必要性和化疗方案诱导化疗或巩固化疗的必要性和化疗方案放射治疗与生物靶向治疗的联合应用放射治疗与生物靶向治疗的联合应用2020/11/14982、New Radiation Techniques:3DRT，IMRT,IGRT,4D RT3、Normal Tissue Protection：Radiation Pneumonitis and Esophagitis 2020/11/14992020/11/14100谢谢大家！