非小细胞肺癌放射治疗进展王绿化(与“放射治疗”有关优秀)课件

1、1肺癌的放射治疗进展第1页，共100页。2影像技术和计算机技术的进步为精确放射治疗的实现提供可能第2页，共100页。3第3页，共100页。4第4页，共100页。5屏气技术举例: Elekta ABC第5页，共100页。6四维CT影像技术呼气吸气螺旋开始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床位第6页，共100页。7影像引导放射治疗技术IGRT 40对叶片MLCKV级X射线球管KV级探测器阵列MV级探测器阵列第7页，共100页。8在线校正影像匹配第8页，共100页。9一、放射治疗在肺癌治疗中的地位二、早期NSCL的放射治疗三、局部晚期NSCL的放疗/化疗 综合治疗 四、3DC

2、RT提高NSCLC的生存率五、术后放射治疗第9页，共100页。10一、放射治疗在肺癌治疗中的地位应用循证医学的方法评价放射治疗在肺癌治疗中的地位。第10页，共100页。11第11页，共100页。12RT 在 SCLC治疗中的地位53.6%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）第12页，共100页。13 RT 在 NSCLC 治疗中的地位64.3%4.7% of NSCLC

3、cases require RT.45.9%4.3% in their initial treatment.18.3%1.8% later in the couse of the illness第13页，共100页。14二、早期非小细胞肺癌的放射治疗 放射治疗能够使 早期NSCLC获得治愈 第14页，共100页。15Japanese StudiesI期NSCLC大剂量分割SRT获得满意的局部控制率Institute Dose/fx/OTT LC/Follow-upUematsu 50-60/5-10/5d 94% (47/50) 36MKyoto 48Gy/4fr/12d 96% (49/51

4、) 20M Arimoto 60Gy/8fr/11d 92% (22/24) 24MOnimaru 60Gy/8fr/11d: 88% (50/57) 18M Nagata Y, Kyoto Univ, IASLC, 2004第15页，共100页。16Summary of Japanese StudiesTotal cases： 281Age: 39-92 (median 76) yearsPulmonary disease: Positive:172, Negative:109Histology: Sqamous:122Adeno:131,Others:28Stage: IA:178, IB

5、:103Tumor diameter: 7-58 (median 23) mmMedical Operability: Inoperable:177, Operable: 104Onishi H, ASCO 2004第16页，共100页。17Local Control and ComplicationFollow-up period 2-128 (median 30) monthsLocal responseCR 26.9%PR 59.1%NC 14.0%Pneumonitis (NCI-CTC)Grade 0 : 33.7%Grade 1 : 59.9%Grade 2 : 4.0%Grade

6、 3 : 1.2%Grage 4 : 1.2%Esophagitis (Grade 3)1.2%Pleural effusion (transient)1.6%Rib fracture1.2%Bone marrow suppression0.0%Onishi H, ASCO 2004第17页，共100页。18Local Failure RatesTotal cases38/281 (13.5%) BED 100 Gy17/211 (8.1%)Stage IA17/177 (9.6%) BED 100 Gy 9/136 (6.6%)Stage IB21/102 (20.6%) BED 100 G

7、y 8/73 (11.0%)Adenocarcinoma17/122 (14.0%)Squamous cell ca.18/131 (13.7%)Onishi H, ASCO 2004第18页，共100页。19Mountain *JCOG*JNCCH*Stage IAStage IB67%57%80%63%74%53%STI*90% 84%* Surgery * Stereotactic IrradiationComparison of 5-Yr Overall Survival Between Surgery & STISurvival curves of operable pts irra

8、diated with BED of 100 Gy or more according to Stagestage IA (n=47)stage IB (n=16)p = 0.2Overall SurvivalTime (years)Summary of Japanese StudiesOnishi H, ASCO 2004第19页，共100页。20I期非小细胞肺癌立体定向放射治疗或楔形切除后的转归SRBT (n=55)楔形切除 (n=69)P肺功能（FEV-1）1.39 (0.86-2.37)1.31(0.52-3.0)NSCharlson合并症指数 3(1-4)4(3-6)0.01年龄74

9、 (69-78)78 (55-89) RT (60 Gy, 2Gy QD) day 50 同步: PV/RT (60 Gy, 2Gy QD) day 1 同步/HFRT: PE/HFRT (69.2 Gy, 1.2Gy BID) day 1PV: 顺铂/长春花碱PE: 顺铂/oral 足叶乙甙RT: 放疗; QD: 每日一次; HFRT: 超分隔放疗Curran: ASCO, 2000; updated IASLC 2000; ASTRO 2001,2003RANDOMIZE第34页，共100页。二.同时化放疗 vs 序贯化放疗(2) SEQ CON-QD CON-BID 中位生存期： 14.

10、6 17 15.6（月） 4 年生存率： 12% 21% 17% p=0.046 G3急性和晚期非血液系统毒性： 30%，48%，62% 和 14%，15%，16%。Curran W et al. Pro. Am Soc Clin Oncol. J. Clin. Oncol. 2003; (abstract 2499) 第35页，共100页。第36页，共100页。第37页，共100页。结论：同步放化疗优于序贯放化疗，但是，急性毒性反应增加第38页，共100页。同步放化疗？诱导化疗 ? 巩固化疗第39页，共100页。同步放化疗诱导化疗第40页，共100页。Induction Chemothera

11、py Followed by Chemoradiotherapy With Chemoradio-therapy Alone for Regionally Advanced Unresectable StageIII NonSmall-CellLung:Cancer and Leukemia GroupBCALGB 39801J Clin Oncol. 2007 May 1;25(13):1698-704. Epub 2007Apr 第41页，共100页。CALGB 39801 study designJuly 1998 and was closed in May 2002, Totally

12、366 patients registered第42页，共100页。Survival intent to treat第43页，共100页。Survival of eligible patients with a weight loss of 5%第44页，共100页。Discussion 增加毒性 induction chemotherapy increases neutropenia and overall maximal toxicity 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 Concom

13、itant chemoradiotherapy is current standard therapy for unresectable stage IIIB NSCLC第45页，共100页。Albain et al.Japanese StudiesI期NSCLC大剂量分割SRT获得满意的局部控制率随访资料IIIA vs IIIB7% of NSCLC cases require RT.第30页，共100页。 PE/XRTPR 59.BED 100 Gy17/211 (8.Grills et al:Stage IB21/102 (20.Local responseCR 26.第81页，共100

14、页。Simultaneous Chemoradiotherapy Compared With Radiotherapy Alone After Induction Chemotherapy in Inoperable Stage IIIA or IIIB NonSmall-Cell Lung Cancer:Study CTRT99/97 by the Bronchial Carcinoma Therapy GroupRudolf M. Huber, Michael Flentje, Michael Schmidt, Barbara Pllinger, Helga Gosse, Jochen W

15、illner, and Kurt UlmPC x 3诱导化疗RandomizeRT aloneRT+ Paclitaxel 60mg/m2 weekly第46页，共100页。paclitaxel 200 mg/m2 carboplatin AUC=6every 3 weeks X 2 cyclespaclitaxel 60 mg/m2 weeklyRadiotherapy alone第47页，共100页。第48页，共100页。Survival after induction chemotherapy for patients with complete or partial response第

16、49页，共100页。同步放化疗巩固化疗第50页，共100页。SWOG 9504: 同步放化疗后应用泰索帝 巩固化疗治疗IIIb 期NSCLC顺铂/VP-16 X XRT泰索帝 X X X 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 (2Gy/fx)泰索帝: 75mg/m2 cycle 1 - 100mg/m2 cycle 2-3 第51页，共100页。SWOG 9504: 总生存%020406080100%012243648入组时间（月） N Events中位生存83

17、45 26月2 年生存率: 54%3 年生存率: 37%第52页，共100页。 SWOG 9504 和 SWOG 9019比较研究病例MST(月)2 年生存3 年生存S9019(PE/RT PE)5015(10-22)* 34%(21- 47)* 17%(7-27)*S9504(PE/RT 泰索帝)8326(18-35)*54%(43-65)*37%(22-52)*95% CI第53页，共100页。SWAG 0023Concurrent Chemo/RadioDDP+Vp16/RTConsolidation ChemoDocetaxel MaintenanceGEFITINIB orPLACE

18、BO第54页，共100页。第55页，共100页。同步放化疗巩固化疗Results of ASCO 2007第56页，共100页。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)Stratificationat randomization PS 0-1 vs 2 IIIA vs IIIB

19、 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: OSSecondary endpoints: PFS, toxicity第57页，共100页。HOG LUN 0

20、1-24: 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%第58页，共100页。Comparison of Grade 3-5 ToxicitiesToxicitySWO

21、G 9504SWOG 0023HOG 01-24Febrile Neutropenia PE/XRT 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” 第59页，共100页。Hog LUGN o1-20/USO-023 The MST with EP/XRT was higher than historical controls; Consoli

22、dation D does 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 NSCLCConclusions第60页，共100页。61术前同时化放疗的临床研究第61页，共100页。62可手术（Operable） A(N2) 放/化疗 vs 放

23、化疗+手术 RTOG 93-09 INT：0139 第62页，共100页。63CT/RT/S 145/202CT/RT 155/194Logrank p=0.24危险比 = 0.87 (0.70, 1.10)存活率%0255075100从随机分组开始后的月数01224364860死亡/总数INT0139试验: 总生存中位FU 81 个月Albain et al. ASCO 2005. Abstract 7014.第63页，共100页。64随机分组后的月数 MS3 yr OS5 yr OS19月 36% 22%CT/RT/SCT/RT存活率%025507510001224364860/29月 4

24、5% 24%死亡/总计CT/RT/S38/51CT/RT42/51Log rank p=NSINT0139试验: 肺切除亚组和相应化疗/放疗亚组的总生存的比较Albain et al. ASCO 2005. Abstract 7014.第64页，共100页。65Logrank p=0.002CT/RT/S 57/90CT/RT 74/90死亡/总计存活率%0255075100随机分组后的月数01224364860/MS 34月 22 月5 yr OS 36% 18%CT/RT/SCT/RTINT0139试验: 肺叶切除亚组和相应化疗/放疗亚组的总生存的比较Albain et al. ASCO

25、2005. Abstract 7014.第65页，共100页。66第66页，共100页。67 EORTC 08941 A：Unresectable pN2不能手术的ApN2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？第67页，共100页。68第68页，共100页。69第69页，共100页。70第70页，共100页。71第71页，共100页。* SurgerySecondary endpoints: PFS, toxicity序贯: PV - RT (60 Gy, 2Gy QD) day 50BED 100 Gy 8/73 (11.Local Failure RatesCT/RT C

26、oncurrentRT would be recommended.CR+PR vs SD+PD第50页，共100页。第70页，共100页。Japanese StudiesI期NSCLC大剂量分割SRT获得满意的局部控制率Log rank p=NS可手术（Operable） A(N2) 放/化疗 vs 放化疗+手术 RTOG 93-09 INT：013972四、NSCLC术后放射治疗New data supports PORT in N2 cases第72页，共100页。731998 PORT死亡风险增加 21%2年OS 下降7 55% -48%pN0 pN1 有害pN2 降低局部复发 对OS无

27、明确结论PORT Meta-analysis Lancet, 1998. 352: 257-63Update of PORT Lung Cancer, 2005. 47: 81-3第73页，共100页。74New Data 1回顾分析PORTSEER 1988年2001年、期NSCLC 7465例根治性术后PORT 3508例（47%）SEER J Clin Oncol, 2006. 24: 2998-3006 预后多因素分析HR95% CI Polder age1.0251.022-1.0280.0001T3-4 disease1.2881.117-1.4840.0005N2 nodal d

28、isease1.2811.101-1.4900.0014greater number of involved lymph nodes1.0431.027-1.0600.0001PORT1.0480.987-1.1130.1269第74页，共100页。75PORT在N2中的作用N0N1N2SSRSSRSSR5yOS41%31%34%30%20%27%DSS53%39%44%38%27%36%P0.04350.01960.0077PORT既能够提高OS也能够提高DSSN0N1N2第75页，共100页。76New Data 2Results from ANITA: Phase III Adjuvan

29、t 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 Adjuvant Navelbine International Trial Association第76

30、页，共100页。77CT RTCTRTOBSPORT in N1 PatientsRT is better than OBS. For patient who can not tolerate CT, RT would be recommended. 第77页，共100页。CT RTCTRTOBSPORT in N2 Patients0.000.250.500.751.00DURATION OF SURVIVAL (MONTHS)020406080100120CT & RT is the bestRT is better than OBS 第78页，共100页。79New Data 3 fro

31、m Cancer Hospital & Institute of CAMS根治性切除NSCLCT1-3,N2具备完整治疗信息 一般临床资料 术中所见及术后病理 治疗模式及参数 随访资料第79页，共100页。80材料与方法排除标准T4N2者pN3病例及N分期不明者手术后3个月内死亡的患者手术后3个月内肿瘤进展者单纯探查术或纵隔镜活检术第80页，共100页。81材料与方法全组例数PORT无PORT术式肺叶切除19784113全肺切除241212清扫淋巴结数目总数（枚）1-603-601-60中位数（枚）211922第81页，共100页。OS例数MST(月)1年3年5年2P值无PORT 12531.

32、977.645.430.65.2350.046PORT 9643.994.859.134.3生存率 第82页，共100页。DFS 1年3年5年2P值无PORT 56.428.216.56.8910.009PORT 76.139.832.1DFS第83页，共100页。治疗模式与生存率 项目例数MST(月)1年OS3年OS5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%第84页，共100页。非肿瘤死亡项目 例数无术后放疗术后放疗组 心功能衰竭10

33、心肌梗死10小脑萎缩10急性胰腺炎10脓胸10脑血管意外11肺部感染21气管食管瘘01肺栓塞01不明原因消瘦01死亡原因不明22合计107有无术后放疗组的非肿瘤死亡率并无差异（p=0.493） 第85页，共100页。S+C+R S+CS+RS5yOS47.0%34.0 %21.3 %16.6 %5yOS38.2%31.9% 33.7 %23.1 %MST（M）47.423.822.712.7MST（M）48.333.138.321.6ANITA的结果医科院肿瘤医院的结果完全切除的AN2 NCSLC推荐术后化疗+放疗第86页，共100页。87Absolute Volume of lung rec

34、eived 30GyRP (%)NO RP(%)P 340 cm329.2 (7/24)70.8 (17/24)0.003340 cm32.5(1/40)97.5 (39/40) PORT can be safely used with 3DCRTGraph 1. & Table 4. 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 wa

35、s 0.757 (P = 0.020). Graph 1. & Table 4. 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 0.757 (P = 0.020). Graph 1. & Table 4. ROC curse: The area under curve in receiver operating characte

36、ristic curves based on the relationship between incidence of RP and the value of Vipsi-dose was 0.757 (P = 0.020). Graph 1. & Table 4. 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 0.757 (

37、P = 0.020). 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. 第87页，共100页。883DCRT能够提高NSCLC的治疗疗效 第88页，共100页。89Int. J. Radiation Oncology Biol. Phys., Vol. 66, No. 1, pp. 108116, 200

38、63D vs 2D in MEDICALLY INOPERABLE STAGE I NONSMALL-CELL LUNG CANCER(a) Overall survival(b) Disease-specific survival第89页，共100页。90Int. J. Radiation Oncology Biol. Phys., Vol. 66, No. 1, pp. 108116, 20063D vs 2D in MEDICALLY INOPERABLE STAGE I NONSMALL-CELL LUNG CANCERLocal-regional control第90页，共100页。913 DCRT vs 常规放疗 中国医学科学院肿瘤医院 2001-2006第91页，共100页。92期NSCLC适形放疗 vs 常规放疗第92页，共100页。93局部晚期NSCLC（A/B）3DCRT vs 常规放疗分组例数1年3年5年MST常规放疗2