非小细胞肺癌放射治疗进展课件

1、非小细胞肺癌放射治疗进展非小细胞肺癌放射治疗进展非小细胞肺癌放射治疗进展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2020/11/142非小细胞肺癌放射治疗进展非小细胞肺癌放射治疗进展非小细胞肺癌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2020/11/142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202020/11/1432020/11/1432020/11/1442020/11/144屏气技术举例: Elekta ABC2020/11/145屏气技术举例: Elekta ABC2020/11/145四维CT影像技术呼气吸气螺旋开始时相由吸转呼呼气末由呼

2、转吸由吸转呼呼气吸气螺旋开始呼吸曲线床位2020/11/146四维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2020/11/147影像引导放射治疗技术IGRT 40对叶片MLCKV级X射线在线校正影像匹配2020/11/148在线校正影像匹配2020/11/148一、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、3DCRT提高NSCLC的生存率五、术后放射治疗2020/11/149一、放射治疗在肺癌治疗中的地位2020/11/149一

3、、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。2020/11/1410一、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2020/11/14112020/11/1411RT 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）2020/11/1412RT 在 SCLC治疗中的地位53.6%3.3% SCLC RT

4、 在 NSCLC 治疗中的地位64.3%4.7% of NSCLC cases require RT.45.9%4.3% in their initial treatment.18.3%1.8% later in the couse of the illness2020/11/1413 RT 在 NSCLC 治疗中的地位64.3%4.7% o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 2020/11/1414二、早期非小细胞肺癌的放射治疗 放射治疗能够使2020/11Japanese StudiesI期NSCLC大剂量分割SRT获得满意的局部控制率Institute

5、 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, 20042020/11/1415Japanese StudiesI期NSCLC大剂量分割SSummary of Japanese StudiesTotal cases： 281Age: 39-92 (

6、median 76) yearsPulmonary disease: Positive:172, Negative:109Histology: Sqamous:122Adeno:131,Others:28Stage: IA:178, IB:103Tumor diameter: 7-58 (median 23) mmMedical Operability: Inoperable:177, Operable: 104Onishi H, ASCO 20042020/11/1416Summary of Japanese StudiesTLocal Control and ComplicationFol

7、low-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 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 20042020/11/1417

8、Local Control and ComplicationLocal 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 Gy 8/73 (11.0%)Adenocarcinoma17/122 (14.0%)Squamous cell ca.18/131 (13.7%)Onishi H, ASCO 20042020/11/1418Local Failure RatesTo

9、tal casesMountain *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 irradiated with BED of 100 Gy or more according to Stagestage IA (n=47)stage IB (n=16)p = 0.2Overall

10、 SurvivalTime (years)Summary of Japanese StudiesOnishi H, ASCO 20042020/11/1419Mountain *JCOG*JNCCH*Stage IA6I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 (69-78)78 (55-89) RT (60 Gy, 2Gy QD) day 50 同步: PV/RT (60 Gy, 2Gy

11、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 2001,2003RANDOMIZE2020/11/1434RTOG 9410:III期NSCLC 同步放化疗 vs 二.同时化放疗 vs 序贯化放疗(2) SEQ CON-QD CON-BID 中位生存期： 14.6 17 15.6（月） 4 年生存率： 12% 21% 17% p=0.

12、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) 2020/11/1435二.同时化放疗 vs 序贯化放疗(2) 2020/11/142020/11/14362020/11/14362020/11/14372020/11/1437结论：同步放化疗优于序贯放化疗，但是，急性毒性反应增加2020/11/1438结论：同步放化疗优于序贯放化疗，但是，急性毒性反应增加2同步放化疗？诱导化疗 ? 巩固化疗20

13、20/11/1439同步放化疗？诱导化疗 ? 巩固化疗2020/11/1439同步放化疗诱导化疗2020/11/1440同步放化疗诱导化疗2020/11/1440Induction Chemotherapy 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):169

14、8-704. Epub 2007Apr 2020/11/1441Induction Chemotherapy FolloweCALGB 39801 study designJuly 1998 and was closed in May 2002, Totally 366 patients registered2020/11/1442CALGB 39801 study designJuly 1Survival intent to treat2020/11/1443Survival intent to treat2020/1Survival of eligible patients with a

15、weight loss of 5%2020/11/1444Survival of eligible patients 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 Concomitant chemoradiotherapy is current standard therapy for unresectable stage

16、IIIB NSCLC2020/11/1445Discussion 增加毒性 induction cheSimultaneous 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

17、 Schmidt, Barbara Pllinger, Helga Gosse, Jochen Willner, and Kurt UlmPC x 3诱导化疗RandomizeRT aloneRT+ Paclitaxel 60mg/m2 weekly2020/11/1446Simultaneous Chemoradiotherapypaclitaxel 200 mg/m2 carboplatin AUC=6every 3 weeks X 2 cyclespaclitaxel 60 mg/m2 weeklyRadiotherapy alone2020/11/1447paclitaxel 200

18、mg/m2 paclitaxe2020/11/14482020/11/1448Survival after induction chemotherapy for patients with complete or partial response2020/11/1449Survival after induction chemo同步放化疗巩固化疗2020/11/1450同步放化疗巩固化疗2020/11/1450SWOG 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-

19、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 2020/11/1451SWOG 9504: 同步放化疗后应用泰索帝 SWOG 9504: 总生存%020406080100%012243648入组时间（月） N Events中位生存8345 26月2 年生存率: 54%3 年生存率: 37%2020/11/1452SWOG 9504: 总生存%02040608010 SWOG 9504 和 SWOG 9019比较研究病例MST(月

20、)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% CI2020/11/1453 SWOG 9504 和 SWOG 9019比较研究病例MSSWAG 0023Concurrent Chemo/RadioDDP+Vp16/RTConsolidation ChemoDocetaxel MaintenanceGEFITINIB orPLACEBO2020/11/1454SWAG 0023Concurrent Chemo/R

21、adi2020/11/14552020/11/1455同步放化疗巩固化疗Results of ASCO 20072020/11/1456同步放化疗巩固化疗Results of ASCO 20072HOG 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 rand

22、omization 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: OSSecondary endpoints:

23、 PFS, toxicity2020/11/1457HOG LUN 01-24 Phase III Study HOG 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-

24、34.827.2%2020/11/1458HOG LUN 01-24: OS (ITT)RandomComparison of Grade 3-5 ToxicitiesToxicitySWOG 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” 202

25、0/11/1459Comparison of Grade 3-5 ToxiciHog LUGN o1-20/USO-023 The MST with EP/XRT was higher than historical controls; Consolidation D does not further improve survival, is associated with significant toxicity including an increased rate of hospitalization and premature death, And should no longer b

26、e used for pts with unresectable stage III NSCLCConclusions2020/11/1460Hog LUGN o1-20/USO-023 The M术前同时化放疗的临床研究2020/11/1461术前同时化放疗的临床研究2020/11/1461可手术（Operable） A(N2) 放/化疗 vs 放化疗+手术 RTOG 93-09 INT：0139 2020/11/1462可手术（Operable） A(N2) 放/化CT/RT/S 145/202CT/RT 155/194Logrank p=0.24危险比 = 0.87 (0.70, 1.1

27、0)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 7014.2020/11/1463CT/RT/S 145/202Logrank p=0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 45% 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

28、比较Albain et al. ASCO 2005. Abstract 7014.2020/11/1464随机分组后的月数 MS19月CT/RT/SCT/RT存活Logrank 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 2005. Abstract 7014.2020/11/1465Logrank p=0.002CT/

29、RT/S 57/2020/11/14662020/11/1466 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？2020/11/1467 EORTC 08941不能手2020/11/14682020/11/14682020/11/14692020/11/14692020/11/14702020/11/14702020/11/14712020/11/1471四、NSCLC术后放射治疗New data supports PORT in N2 cases2020/11/1472四、NSCLC术后放射治疗New d

30、ata supports1998 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无明确结论PORT Meta-analysis Lancet, 1998. 352: 257-63Update of PORT Lung Cancer, 2005. 47: 81-32020/11/14731998 PORT死亡风险增加 21%PORT Meta-aNew 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:

31、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 disease1.2811.101-1.4900.0014greater number of involved lymph nodes1.0431.027-1.0600.0001PORT1.0480.987-1.1130.12692020/11/1474New Data 1回顾分析PORTSEER 1988年PORT在N2中的作用N0N1N2SSRSSRSSR5yOS41%31%34%30%20

32、%27%DSS53%39%44%38%27%36%P0.04350.01960.0077PORT既能够提高OS也能够提高DSSN0N1N22020/11/1475PORT在N2中的作用N0N1N2SSRSSRSSR5yOSNew 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

33、Ramlau, JL Gonzalez-Larriba, T Grodzki, A Le Groumelec, D Aubert, J Gasmi, JY Douillard on behalf of the Adjuvant Navelbine International Trial Association2020/11/1476New Data 2R Rosell, M De Lena,CT RTCTRTOBSPORT in N1 PatientsRT is better than OBS. For patient who can not tolerate CT, RT would be

34、recommended. 2020/11/1477CT RTCTRTOBSPORT in N1 PatientCT RTCTRTOBSPORT in N2 Patients0.000.250.500.751.00DURATION OF SURVIVAL (MONTHS)020406080100120CT & RT is the bestRT is better than OBS 2020/11/1478CT RTCTRTOBSPORT in N2 PatientNew Data 3 from Cancer Hospital & Institute of CAMS2003.01.01-2005.

35、12.30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2020/11/1479New Data 3 from Cancer Hospit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2020/11/1480材料与方法排除标准T4N2者2020/11/1480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）2119222020/11/1481材料与方法全组例数

36、PORT无PORT术式肺叶切除197841OS例数MST(月)1年3年5年2P值无PORT 12531.977.645.430.65.2350.046PORT 9643.994.859.134.3生存率 2020/11/1482OS例数MST(月)1年3年5年2P值无PORT 1253DFS 1年3年5年2P值无PORT 56.428.216.56.8910.009PORT 76.139.832.1DFS2020/11/1483DFS 1年3年5年2P值无PORT 56.428.216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.

37、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治疗模式与生存率 项目例数MST(月)1年OS3年OS5年O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） 2020/11/1485非肿瘤死亡项目 例数无术后放疗术后放疗组 S+C+R S+CS+RS5yOS47.0%34.0

38、%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2020/11/1486S+C+R5yOS5yOSMST（M）MST（M）ANITAAbsolute Volume of lung received 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 safe

39、ly 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 was 0.757 (P = 0.020). Graph 1. & Table 4. ROC curse: The area under curve in receiver operating characteris

40、tic 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 (P =

41、 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). Ji Wei et al: ASTRO meeting 2008 BostonConclusion：It was safe for patients with NSCLC to recei

42、ve postoperative 3DCRT， if irradiation dose to lung tissue was well defined. 2020/11/1487Absolute Volume of lung receiv3DCRT能够提高NSCLC的治疗疗效 2020/11/14883DCRT能够提高NSCLC的治疗疗效 2020/11/1Int. J. Radiation Oncology Biol. Phys., Vol. 66, No. 1, pp. 108116, 20063D vs 2D in MEDICALLY INOPERABLE STAGE I NONSMAL

43、L-CELL LUNG CANCER(a) Overall survival(b) Disease-specific survival2020/11/1489Int. J. Radiation Oncology BioInt. J. Radiation Oncology Biol. Phys., Vol. 66, No. 1, pp. 108116, 20063D vs 2D in MEDICALLY INOPERABLE STAGE I NONSMALL-CELL LUNG CANCERLocal-regional control2020/11/1490Int. J. Radiation Oncology Bio3 DCRT vs 常规放疗 中国医学科学院肿瘤医院 2001-20062020/11/14913 DCRT vs 常规放疗 中国医学科学院肿瘤医院期NSCLC适形放疗 vs 常规放疗2020/11/1492期NSCLC适形放疗 vs 常规放疗2020/11/1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27561.013.88.015.63-DCRT21873.326.114.420.15年