非小細胞肺癌放射治療進展課件

1、非小細胞肺癌放射治療進展非小細胞肺癌放射治療進展非小細胞肺癌放射治療進展影像技術和計算機技術的進步為精確放射治療的實現(xiàn)提供可能2020/11/142非小細胞肺癌放射治療進展非小細胞肺癌放射治療進展非小細胞肺癌影像技術和計算機技術的進步為精確放射治療的實現(xiàn)提供可能2020/11/142影像技術和計算機技術的進步為精確放射治療的實現(xiàn)提供可能202020/11/1432020/11/1432020/11/1442020/11/144屏氣技術舉例: Elekta ABC2020/11/145屏氣技術舉例: Elekta ABC2020/11/145四維CT影像技術呼氣吸氣螺旋開始時相由吸轉呼呼氣末由呼

2、轉吸由吸轉呼呼氣吸氣螺旋開始呼吸曲線床位2020/11/146四維CT影像技術呼氣吸氣螺旋開始時相由吸轉呼呼氣末由呼轉吸由影像引導放射治療技術IGRT 40對葉片MLCKV級X射線球管KV級探測器陣列MV級探測器陣列2020/11/147影像引導放射治療技術IGRT 40對葉片MLCKV級X射線在線校正影像匹配2020/11/148在線校正影像匹配2020/11/148一、放射治療在肺癌治療中的地位二、早期NSCL的放射治療三、局部晚期NSCL的放療/化療 綜合治療 四、3DCRT提高NSCLC的生存率五、術后放射治療2020/11/149一、放射治療在肺癌治療中的地位2020/11/149一

3、、放射治療在肺癌治療中的地位應用循證醫(yī)學的方法評價放射治療在肺癌治療中的地位。2020/11/1410一、放射治療在肺癌治療中的地位應用循證醫(yī)學的方法評價放射治療2020/11/14112020/11/1411RT 在 SCLC治療中的地位53.6%3.3% SCLC 病例在其疾病的不同時期需要接受放射治療 45.4%4.3% 為首程治療 （in the initial treatment）. 8.2%1.5% 為復發(fā)和進展病例的治療（later for recurrence or progression）2020/11/1412RT 在 SCLC治療中的地位53.6%3.3% SCLC RT

4、 在 NSCLC 治療中的地位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 治療中的地位64.3%4.7% o二、早期非小細胞肺癌的放射治療 放射治療能夠使 早期NSCLC獲得治愈 2020/11/1414二、早期非小細胞肺癌的放射治療 放射治療能夠使2020/11Japanese StudiesI期NSCLC大劑量分割SRT獲得滿意的局部控制率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大劑量分割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期非小細胞肺癌立體定向放射治療或楔形切除后的轉歸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合并癥指數(shù) 3(1-4)4(3-6)0.01年齡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: 順鉑/長春花堿PE: 順鉑/oral 足葉乙甙RT: 放療; QD: 每日一次; HFRT: 超分隔放療Curran: ASCO, 2000; updated IASLC 2000; ASTRO 2001,2003RANDOMIZE2020/11/1434RTOG 9410:III期NSCLC 同步放化療 vs 二.同時化放療 vs 序貫化放療(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統(tǒng)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.同時化放療 vs 序貫化放療(2) 2020/11/142020/11/14362020/11/14362020/11/14372020/11/1437結論：同步放化療優(yōu)于序貫放化療，但是，急性毒性反應增加2020/11/1438結論：同步放化療優(yōu)于序貫放化療，但是，急性毒性反應增加2同步放化療？誘導化療 ? 鞏固化療20

13、20/11/1439同步放化療？誘導化療 ? 鞏固化療2020/11/1439同步放化療誘導化療2020/11/1440同步放化療誘導化療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 沒有生存優(yōu)勢 No survival benefit over concurrent therapy alone同期放化療是標準的治療模式 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誘導化療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同步放化療鞏固化療2020/11/1450同步放化療鞏固化療2020/11/1450SWOG 9504: 同步放化療后應用泰索帝 鞏固化療治療IIIb 期NSCLC順鉑/VP-16 X XRT泰索帝 X X X 順鉑 50mg/m2 d 1, 8, 29, 36 VP-

19、16 50mg/m2 d1-5, 29-33RT: 61 Gy: 45Gy(1.8Gy/fx), 16Gy 縮野 (2Gy/fx)泰索帝: 75mg/m2 cycle 1 - 100mg/m2 cycle 2-3 2020/11/1451SWOG 9504: 同步放化療后應用泰索帝 SWOG 9504: 總生存%020406080100%012243648入組時間（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: 總生存%02040608010 SWOG 9504 和 SWOG 9019比較研究病例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比較研究病例MSSWAG 0023Concurrent Chemo/RadioDDP+Vp16/RTConsolidation ChemoDocetaxel MaintenanceGEFITINIB orPLACEBO2020/11/1454SWAG 0023Concurrent Chemo/R

21、adi2020/11/14552020/11/1455同步放化療鞏固化療Results of ASCO 20072020/11/1456同步放化療鞏固化療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術前同時化放療的臨床研究2020/11/1461術前同時化放療的臨床研究2020/11/1461可手術（Operable） A(N2) 放/化療 vs 放化療+手術 RTOG 93-09 INT：0139 2020/11/1462可手術（Operable） A(N2) 放/化CT/RT/S 145/202CT/RT 155/194Logrank p=0.24危險比 = 0.87 (0.70, 1.1

27、0)存活率%0255075100從隨機分組開始后的月數(shù)01224364860死亡/總數(shù)INT0139試驗: 總生存中位FU 81 個月Albain et al. ASCO 2005. Abstract 7014.2020/11/1463CT/RT/S 145/202Logrank p=0隨機分組后的月數(shù) MS3 yr OS5 yr OS19月 36% 22%CT/RT/SCT/RT存活率%025507510001224364860/29月 45% 24%死亡/總計CT/RT/S38/51CT/RT42/51Log rank p=NSINT0139試驗: 肺切除亞組和相應化療/放療亞組的總生存的

28、比較Albain et al. ASCO 2005. Abstract 7014.2020/11/1464隨機分組后的月數(shù) MS19月CT/RT/SCT/RT存活Logrank p=0.002CT/RT/S 57/90CT/RT 74/90死亡/總計存活率%0255075100隨機分組后的月數(shù)01224364860/MS 34月 22 月5 yr OS 36% 18%CT/RT/SCT/RTINT0139試驗: 肺葉切除亞組和相應化療/放療亞組的總生存的比較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不能手術的ApN2病例通過誘導化療后成為可手術病例是選擇手術還是選擇放療？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術后放射治療New data supports PORT in N2 cases2020/11/1472四、NSCLC術后放射治療New d

30、ata supports1998 PORT死亡風險增加 21%2年OS 下降7 55% -48%pN0 pN1 有害pN2 降低局部復發(fā) 對OS無明確結論PORT Meta-analysis Lancet, 1998. 352: 257-63Update of PORT Lung Cancer, 2005. 47: 81-32020/11/14731998 PORT死亡風險增加 21%PORT Meta-aNew Data 1回顧分析PORTSEER 1988年2001年、期NSCLC 7465例根治性術后PORT 3508例（47%）SEER J Clin Oncol, 2006. 24:

31、2998-3006 預后多因素分析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回顧分析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既能夠提高OS也能夠提高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具備完整治療信息 一般臨床資料 術中所見及術后病理 治療模式及參數(shù) 隨訪資料2020/11/1479New Data 3 from Cancer Hospit材料與方法排除標準T4N2者pN3病例及N分期不明者手術后3個月內死亡的患者手術后3個月內腫瘤進展者單純探查術或縱隔鏡活檢術2020/11/1480材料與方法排除標準T4N2者2020/11/1480材料與方法全組例數(shù)PORT無PORT術式肺葉切除19784113全肺切除241212清掃淋巴結數(shù)目總數(shù)（枚）1-603-601-60中位數(shù)（枚）2119222020/11/1481材料與方法全組例數(shù)

36、PORT無PORT術式肺葉切除197841OS例數(shù)MST(月)1年3年5年2P值無PORT 12531.977.645.430.65.2350.046PORT 9643.994.859.134.3生存率 2020/11/1482OS例數(shù)MST(月)1年3年5年2P值無PORT 1253DFS 1年3年5年2P值無PORT 56.428.216.56.8910.009PORT 76.139.832.1DFS2020/11/1483DFS 1年3年5年2P值無PORT 56.428.216治療模式與生存率 項目例數(shù)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治療模式與生存率 項目例數(shù)MST(月)1年OS3年OS5年O非腫瘤死亡項目 例數(shù)無術后放療術后放療組 心功能衰竭10心肌梗死10小腦萎縮10急性胰腺炎10膿胸10腦血管意外11肺部感染21氣管食管瘺01肺栓塞01不明原因消瘦01死亡原因不明22合計107有無術后放療組的非腫瘤死亡率并無差異（p=0.493） 2020/11/1485非腫瘤死亡項目 例數(shù)無術后放療術后放療組 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的結果醫(yī)科院腫瘤醫(yī)院的結果完全切除的AN2 NCSLC推薦術后化療+放療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能夠提高NSCLC的治療療效 2020/11/14883DCRT能夠提高NSCLC的治療療效 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 常規(guī)放療 中國醫(yī)學科學院腫瘤醫(yī)院 2001-20062020/11/14913 DCRT vs 常規(guī)放療 中國醫(yī)學科學院腫瘤醫(yī)院期NSCLC適形放療 vs 常規(guī)放療2020/11/1492期NSCLC適形放療 vs 常規(guī)放療2020/11/1局部晚期NSCLC（A/B）3DCRT vs 常規(guī)放療分組例數(shù)1年3年5年MST常規(guī)放療27561.013.88.015.63-DCRT21873.326.114.420.15年