非小细胞肺癌的放射治疗课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,二级,三级,四级,五级,*,PPT,学习交流,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,二级,三级,四级,五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,二级,三级,四级,五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,二级,三级,四级,五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,二级,三级,四级,五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,二级,三级,四级,五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,二级,三级,四级,五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,二级,三级,四级,五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,二级,三级,四级,五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,二级,三级,四级,五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,二级,三级,四级,五级,*,*,非小细胞肺癌,-,放射治疗,1,PPT,学习交流,非小细胞肺癌1PPT学习交流,Lung Cancer Screening,From Presentation at: 2011 ASCO Annual Meeting,2,PPT,学习交流,Lung Cancer ScreeningFrom Pres,SBRT vs.,手术,SBRT,靶区勾画,SBRT,毒副反应,I,期,NSCLC-,放射治疗,3,PPT,学习交流,SBRT vs. 手术I期NSCLC-放射治疗3PPT学习,SBRT-Inoperable stage I NSCLC,SBRT,是无法耐受手术的外周型,I,期,NSCLC,的首选治疗,JAMA. 2010;303:1070-6,.,Phase II trial of SBRT for medically inoperable stage I/II NSCLC-RTOG 0236,55 patients,T 5 cm, N0, M0,20 Gy in 3 fractions,over 1.5 to 2 weeks,Results,3-year primary tumor control rate: 97.6%,Disease-free survival at 3 years: 48.3%,Overall survival,at 3 years:,55.8%,Median overall survival: 48.1 months,4,PPT,学习交流,SBRT-Inoperable stage I NSCLCS,2012,5,PPT,学习交流,20125PPT学习交流,2012,6,PPT,学习交流,20126PPT学习交流,2012,7,PPT,学习交流,20127PPT学习交流,2012,8,PPT,学习交流,20128PPT学习交流,9,PPT,学习交流,9PPT学习交流,SBRT vs 3DCRT,10,PPT,学习交流,SBRT vs 3DCRT 10PPT学习交流,SBRT-Operable stage I NSCLC,Int J Radiat Oncol Biol Phys.2011;81:1352-8,.,SBRT is safe and promising treatment,for operable Stage I NSCLC,The survival rate for SBRT is potentially,comparable to that for surgery,Retrospective Analysis,11,PPT,学习交流,SBRT-Operable stage I NSCLCInt,SBRT VS.Surgery Trials,Closed prematurely,Slowly accruing,12,PPT,学习交流,SBRT VS.Surgery TrialsClosed p,SBRT vs Surgery,RTOG foundation study 3502 is kicking off soon,中方,PI,于金明 ，山东省肿瘤防治研究院,美国,PI,Feng-Ming (Spring) Kong,，美国密西根大学肿瘤中心,A Randomized Trial in Patients with Operable Stage I Non-Small Cell Lung Cancer:Radical Resection Vs Ablative Stereotacitic Radiotherapy(POSITLV),13,PPT,学习交流,SBRT vs Surgery RTOG foundat,I,期,NSCLC-,中心型,中心型,NSCLC,（距离支气管树,2cm,内）可能对临近气管、食管及大血管造成损伤,RTOG 0813 I/II,期研究剂量爬坡,(50Gy/5f,）研究适合中心型,NSCLC,的分割模式及最大耐受剂量,14,PPT,学习交流,I期NSCLC-中心型中心型NSCLC（距离支气管树2cm内,靶区勾画,-SBRT,GTV,在肺窗进行勾画，纵膈窗可区分邻近血管或胸壁结构,GTV,不外扩，,GTV=CTV,GTV,在水平面上外扩,0.5cm,，在头尾方向外扩,1cm,为,PTV,4D CT,设备的中心使用呼气或吸气图像或最大密度投影,(MIP),时可能会产生一个内靶区（,IGTV,）,无,4D-CT,，,GTV,勾画应建立在慢,CT,扫描的基础上,PTV= IGTV+,摆位 误差,(,根据各肿瘤中心而定）,15,PPT,学习交流,靶区勾画-SBRTGTV在肺窗进行勾画，纵膈窗可区分邻近血管,SBRT,毒副反应,55 inoperable patients with T1-2N0M0 peripheral NSCLC,RT,：,20Gy3,（,RTOG 0236,）,Logistic regression to investigate relationship between Pulmonary Function(PF) and pulmonary toxicity.,Cox proportional hazards models to evaluated between PF test and OS,2012,16,PPT,学习交流,SBRT毒副反应55 inoperable patients,Results&Conclusions,Baseline PF was not predictive of radiation pneumonitis or any pulmonary toxicity following SBRT,There did not appear to be a relationship between the occurrence of radiation pneumonitis and normal lung tissue dose,Poor baseline PF alone did not appear to predict decreased OS,Poor baseline PF alone within the range defining trial eligibility should not be used to exclude early stage NSCLC pts from SBRT,17,PPT,学习交流,Results&ConclusionsBaseline PF,II,期,NSCLC-,放射治疗,18,PPT,学习交流,II期NSCLC-放射治疗18PPT学习交流,II,期,NSCLC,II,期,NSCLC,术后不推荐给予术后放疗,不可手术切除或患者，首选治疗为根治性放疗,同步放化疗的应用尚无明确定论,不可手术患者，根治性同步放化疗,(60-74Gy),，,5,年,OS 15-23%,肺上沟瘤易侵犯临近结构如臂丛、胸膜或肋骨，通常分期为,T3-T4,同步放化疗联合手术是可切除肺上沟瘤的首选治疗，,45Gy,常规分割，,5,年生存率,44-59%,19,PPT,学习交流,II期NSCLC19PPT学习交流,术后放疗的价值,术后化放疗顺序,术后靶区的勾画,A,期,NSCLC-,放射治疗,20,PPT,学习交流,术后放疗的价值A期NSCLC-放射治疗20PPT学习交流,A,期,NSCLC,A,期,NSCLC,单纯完全切除术后,5,年生存率约为,20-35%,，术后复发率、死亡率高,术后辅助化疗已有,I,类循证证据显示其明确的临床获益,A,期,NSCLC,包括,T1-4,或,N0-3,，异质性很大，对于,A(N2,),患者，仅行手术,/,化疗的局部复发率达,30%-60%,对于切除状态不完全或不确定的,A(N2,),患者，需要进行术后辅助放疗和化疗,手术完全切除后是否需要辅助辅助放疗是目前争论的焦点,21,PPT,学习交流,A期NSCLCA期NSCLC单纯完全切除术后5年生存率约,IIIa,不同预后亚群及治疗选择,Ruckdeschel,将,N2,分为四种预后显著不同亚型,22,PPT,学习交流,IIIa不同预后亚群及治疗选择Ruckdeschel 将N2,A-,术后放疗,: Evidence-Based,23,PPT,学习交流,A-术后放疗 : Evidence-Based23PPT学,术后放疗,Meta,分析结果及缺陷,结论：,术后放疗对生存率的降低与分期相 关。,I,、,期明显，,期病例术后放疗对生存率没有明显影响,缺陷：,3/9,随机研究是未发表资料,每组样本量偏小,时间跨度大,分期不明确,入选标准差异大,放疗技术特点：,大多数接受,Co,60,线照射,部分患者采用单野照射,4/9,个临床试验的单次剂量,2Gy,4/9,个研究的总剂量,=60Gy,24,PPT,学习交流,术后放疗Meta分析结果及缺陷结论：术后放疗对生存率的降低,该,Meta,分析，入组了自,1965,年以来符合标准的手术联合化疗放疗,13,项临床研究,9,项临床试验采用先化疗后放疗模式,4,项临床试验采用同步放化疗模式,序贯化、放疗和同步放化疗之间无显著性差异（,P=0.28,）,A,术后化疗、放疗顺序,25,PPT,学习交流,该Meta分析，入组了自1965年以来符合标准的手术联合化疗,2013 NCCN,：化疗、放疗顺序尚无定论，但可优先选择先化疗后放疗模式,关于,a,完全切除术后辅助化疗、放疗顺序有待随机临床试验证明,A,术后化疗、放疗顺序,26,PPT,学习交流,2013 NCCN ：化疗、放疗顺序尚无定论，但可优先选择先,A,术后放疗靶区,目前术后放疗靶区勾画各肿瘤中心存在分歧,荷兰研究分析了来自不同肿瘤中心的,17,位胸部肿瘤放疗专家勾画,A,（,N2,）,NSCLC,术后靶区,:,不同医生之间术后放疗靶区勾画存在着较大差异,前瞻性临床试验的研究方案统一确定的靶区勾画能降低这种差异,Int J Radiat Oncol Biol Phys, 2010, 76:1106-1113,.,27,PPT,学习交流,A术后放疗靶区目前术后放疗靶区勾画各肿瘤中心存在分歧Int,A,术后放疗靶区,Handbook of Evidence Based Radiation Oncology Second Edition,28,PPT,学习交流,A术后放疗靶区Handbook of Evidence B,同步化疗方案,同步放疗剂量,放疗靶区勾画,靶向联合放疗,B,期,NSCLC-,放射治疗,29,PPT,学习交流,同步化疗方案B期NSCLC-放射治疗29PPT学习交流,同步化疗方案,同步放化疗为首选标准治疗,同步放化疗优于序贯放化疗和单纯放疗,同步化疗方案：,2013NCCN,增加了培美曲塞联合顺铂或卡铂方案,同步化疗方案之间目前无孰优孰劣,顺铂为主的同步化疗方案优于卡铂（,王绿化等，,III,期临床试验,-NCT01494558,待发表,）,30,PPT,学习交流,同步化疗方案同步放化疗为首选标准治疗30PPT学习交流,同步放疗剂量,Carbo/Taxol Weekly,Radiation to 60Gy,Carbo/Taxol,2-3 wk cycles,Stage III NSCLC,N=512 pts,Carbo/Taxol Weekly,+Weekly Erbitux,Radiation to 60Gy,Carbo/Taxol,2-3 wk cycles,+Weekly Erbitux,Carbo/Taxol Weekly,Radiation to 74Gy,Carbo/Taxol,2-3 wk cycles,Carbo/Taxol Weekly,+Weekly Erbitux,Radiation to 74Gy,Carbo/Taxol,2-3 wk cycles,+Weekly Erbitux,Jeffery Bradley et al. 2011 ASTRO Annual Meeting,31,PPT,学习交流,同步放疗剂量Carbo/Taxol WeeklyCarbo/,Overall survival,根治性放化疗通常推荐的放疗剂量仍是,60Gy,32,PPT,学习交流,Overall survival根治性放化疗通常推荐的放疗剂,放疗靶区勾画,-IFI,STDF,IF,Stage III NSCLC: ChT/RT; 200 Pts Randomized,Am J Cli Oncol 2007;30:239-244,33,PPT,学习交流,放疗靶区勾画-IFISTDFIFStage III NSCL,放疗靶区勾画,-IFI,NSCLC,累及野照射较预防照射提高了疗效并降低了放射损伤,2,年生存率由常规放疗的,25.6%,提高到,39.4%,放射性肺损伤由常规放疗的,29%,降低到,17%,预防照射,累及野照射,34,PPT,学习交流,放疗靶区勾画-IFINSCLC累及野照射较预防照射提高了疗效,美国国家癌症治疗协作网最新修订的,肿瘤治疗指南,采用了我们的研究：将肺癌放疗靶区的定义由预防性淋巴结照射改为累及野照射,美国,RTOG,-,0617,临床试验,的参照,35,PPT,学习交流,美国国家癌症治疗协作网最新修订的肿瘤治疗指南采用了我们的,The Phase II Trial Of Erlotinib-RT After Chemo-RT For Patients With Stage III Non-Small Cell Lung Cancer Has Shown A Favorable Response,NCI Trial Identifier: NCI-2012-01761,Ritsuko Komaki, M.D. FACR, FASTRO,The University of Texas MD Anderson Cancer,Center, Houston, TX,靶向联合放疗,-Erlotinib,2012,36,PPT,学习交流,The Phase II Trial Of Erlotini,ConsolidationChemotherapy,(Every 3 weeks; Two cycles,Paclitaxel:200mg/m,2,Carboplatin: AUC=6,Concurrent ChemoRT,+ Tarceva(150mg PO),48 Stage III,NSCLC,2012,37,PPT,学习交流,ConsolidationChemotherapyConcu,ResultsTumor Responses by RECIST 3.0,*,One patient was not evaluable for tumor response due to no follow-up image p=0.07,2012,38,PPT,学习交流,ResultsTumor Responses by REC,2012,39,PPT,学习交流,201239PPT学习交流,Conclusions,Chemoradiotherapy F/B erlotinib/RT well tolerated,Excellent 2-year OS 67.7% and median survival time 34.1 months,Grade 3 pneumonitis rate was 6.5%,Erlotinib seemed to demonstrate a radiosensitization effect in combination with chemoradiotherapy,EGFR mutated patients might need maintenance EGFR-TKI to reduce DM,Need to validate with a larger number of patients or in a randomized prospective trial,2012,40,PPT,学习交流,ConclusionsChemoradiotherapy,Phase II Study of Nimotuzumab in Combination With Concurrent Chemoradiation Therapy in Patients With Locally Advanced Non-small Cell Lung Cancer,Kinki University Faculty Of medicine, Japan,Shizuoka Cancer Center, Japan,Hyogo Cancer Center, Japan,The Cancer Institute Hospital, Japan,2012,靶向联合放疗,-,Nimotuzumab,41,PPT,学习交流,Phase II Study of Nimotuzumab,Materials/Methods,Multicenter phase II study evaluated tolerability and efficacy of nimotuzumab in combination with concurrent CRT in pts with unresectable locally advanced NSCLC,Pts receive concurrent RT(60Gy/30F) and 4 cycles of Chemo(NP),Nimotuzumab(200mg)was administrated once a week from cycle 1 to 4,2012,42,PPT,学习交流,Materials/MethodsMulticenter,Results,39 pts were eligible from 7 institutions,34 Pts(87%) met criteria for treatment tolerability,grade 3 skin rash,grade 3 radiation pneumonitis or,grade 4 nonhematological toxicity were not observed,The 2 Yr OS rate was 76%;The median PFS was 16.7 months,In-field relapse rates were low for Sq(19%) and non-Sq(13%),2012,43,PPT,学习交流,Results39 pts were eligible fr,Conclusions,Addition of nimotuzumab to concurrent CRT was well tolerated with clinical benefit,The low in field relapse rates may be attributed to radio-sensitizing effect of nimotuzumab,The finds warrant further clinical evaluation in a phase III trial,2012,44,PPT,学习交流,ConclusionsAddition of nimotuz,Meta-analysis of toxicities in Phase I or II trials studying the use of target therapy combined with radiation therapy in patients with locally advanced non-small cell lung cancer,M.Santos , D.Lefeuvre, G.Le Teuff, et al.,Institute Gustave Roussy, Paris, France.,靶向联合放疗,-Meta analysis,2012,45,PPT,学习交流,Meta-analysis of toxicities in,Materials/Methods,Phase I, I/II and II trials published between 2000 and 2011 treated by targeted therapy(TT) with Chemo-RT,Pooled incidence rates of all and specific AEs were estimated,Pooled medians of PFS and OS were studied,2012,46,PPT,学习交流,Materials/MethodsPhase I, I/I,Results,Eight trials(4 phase I, 4 phase II) including 242 pts testing 4 drugs(Bevacizumab, Cetuximab, Erlotinib and Gefitinib),The pooled incidence rates of AE in TT/Chemo-RT was statistically higher than that estimated in Chemo-RT group,Median PFS and OS were 10.0 and 18.4 months in TT/Chemo-RT and 9.9 and 16.2 months in Chemo-RT (p=0.98 and P=0.37),2012,47,PPT,学习交流,ResultsEight trials(4 phase I,Conclusions,The use of TT combined to Chemo-RT seemed to increase significantly the rate of severe adverse events in NSCLC pts as compared to Chemo-RT,No significant difference was observed in survial endpoints,Heterogeneity was observed between different trials,2012,48,PPT,学习交流,ConclusionsThe use of TT combi,一项前瞻性、开放、随机对照、多中心期临床研究评估同期厄洛替尼联合放疗对比同期依托泊甙顺铂（,EP,）方案联合放疗用于伴有表皮生长因子受体,19,或,21,外显子活化突变的不可切除期非小细胞肺癌（,NSCLC,）的疗效及安全性,(,RECEL ML 28545,),A multicenter, randomized, open-label, phase II trial of Erlotinib versus Etoposide plus Cisplatin with concurrent radiotherapy in unresectable stage III non-small cell lung cancer (NSCLC) with activating mutation of epidermal growth factor receptor (EGFR) in exon 19 or 21,山东省肿瘤医院； 中国医学科学院肿瘤医院,复旦大学附属肿瘤医院； 天津肿瘤医院,河北省肿瘤医院； 浙江省肿瘤医院,北京肿瘤医院； 四川华西医院,中国人民解放军总医院； 杭州市第一人民医院等,49,PPT,学习交流,一项前瞻性、开放、随机对照、多中心期临床研究评估同期厄洛替,不可切除,IIIA/IIIB NSCLC,未行任何治疗,EGFR 19,或,21,外显子突变,(+),18,岁，,75,岁,ECOG PS 0,1,n,100,R,PD,同步放化疗（,8,周）,顺铂,50mg/m,2,d1,8,29,36,依托泊甙,50mg/m,2,d1-5,29-33,同期,RT 60-66Gy/30-33fr,同步治疗,(8,周,),厄洛替尼,150mg/day,同期,RT 60-66Gy/30-33fr,PD,厄洛替尼,150mg/day,最长,2,年,RECEL,研究方案,主要终点：,PFS,（,progression free survival rate,）,次要终点：,ORR (,objective response rate,);,LCR (,local control rate,),OS,(overall survival, OS);,安全性,(NCI CTCAE,4.02,版,);,采用,FACT-LC,及,LCSS,量表比较两组的生活质量,;,探索性分子标志物分析,分层因素：,分期：,IIIA vs. IIIB,组织病理学：腺癌,vs.,非腺癌,EGFR,突变类型：,19,号 外显子,vs. 21,号外显子,50,PPT,学习交流,不可切除IIIA/IIIB NSCLCRPD同步放化疗（8周,同步放化疗后巩固治疗作用,51,PPT,学习交流,同步放化疗后巩固治疗作用51PPT学习交流,GILT study: Oral vinorelbine (NVBo) and cisplatin (P) with concomitant radiotherapy (RT) followed by either consolidation (C) with NVBo plus P plus best supportive care (BSC) or BSC alone in stage (st) III non-small cell lung cancer (NSCLC): Final results of a phase (ph) III study,Huber,et al.Abstr 7001.2012 ASCO,52,PPT,学习交流,GILT study: Oral vinorelbine,TITLE,53,PPT,学习交流,TITLE53PPT学习交流,TITLE,54,PPT,学习交流,TITLE54PPT学习交流,TITLE,55,PPT,学习交流,TITLE55PPT学习交流,TITLE,56,PPT,学习交流,TITLE56PPT学习交流,Conclusions,Cisplatin doses were standard, oral NVBo is no standard of care for CCRT or systemic CTx in stage III disease,Concurrent chemoradiotherapy alone remains a valid standard for a large number of patients in stage III NSCLC disease,57,PPT,学习交流,Conclusions Cisplatin doses we,Is consolidation chemotherapy after concurrent chemoradiotherapy beneficial for locally advanced non-small cell lung cancer?,A pooled analysis of the literature,Yamamoto,et al.Abstr 7000.2012 ASCO,58,PPT,学习交流,Is consolidation chemothera,TITLE,59,PPT,学习交流,TITLE59PPT学习交流,TITLE,60,PPT,学习交流,TITLE60PPT学习交流,TITLE,61,PPT,学习交流,TITLE61PPT学习交流,Conclusions,This pooled ananlysis on publication basis failed to provide evidence that consolidation chemotherapy improves overall survival in pts with LA-NSCLC,Currently, Concurrent ChemoRT is still standard care in LA-NSCLC,62,PPT,学习交流,ConclusionsThis pooled ananlys,放疗技术,仰卧位，双手上举，采用体膜或真空负压带固定,4D-CT,或,PET-CT,定位,如果没有,4D-CT,，可在模拟定位机透视下测定病变上下,前后、左右方向上的移动度，作为,PTV,参考数据,建议增强,CT,扫描，范围包括锁骨上、肺及纵膈、上腹部到肾上腺水平,63,PPT,学习交流,放疗技术仰卧位，双手上举，采用体膜或真空负压带固定63PPT,靶区勾画原则,GTV,包括肺窗中所见肿瘤范围及纵膈窗中所见纵膈淋巴结范围,病变毛刺是否画在,GTV,里存在争议,毛刺应勾画在,CTV,内，毛刺与血管鉴别在于血管上下层可看出分叉走行,Stanford Universiy Billy W. Loo, 2011 ASTRO-eContouring,原发灶,CTV,为鳞癌外放,6mm,，腺癌外放,8mm;,除非确有外侵存在， CTV 不应,超出解剖屏障,(,李万隆，于金明等,),淋巴结,CTV,为,8mm;,除非确有外侵存在， CTV 不应,超出解剖屏障（孟雪，于金明等）,纵隔淋巴结勾画标准,-,参考,OLIVIER,et al Int J Rad Onco Bio Phy 2005,危及器官靶区勾画,-,参考,RTOG ATLAS,（,RTOG 1106,）,FDG PET,引导肺癌靶区勾画,-,参考,RTOG ATLAS,（,RTOG 1106,）,64,PPT,学习交流,靶区勾画原则GTV包括肺窗中所见肿瘤范围及纵膈窗中所见纵膈淋,Summary,65,PPT,学习交流,Summary65PPT学习交流,Function Imaging Guided Plan-optimization,99mTC-MAA,Perfusion,Fused image,Blue: Functional,Yellow: Non-function,Optimized Plan for function lung,Yin et al. Chin Med J (Engl) 2009;122:509-513,The introduction of radionuclide lung perfusion images into RT of lung cancer could significantly decrease RT dose of the functional lung,66,PPT,学习交流,Function Imaging Guided Plan-o,We Are on the Way,Individualized RT,To determine RT,dose & technique,individually,To determine treatment strategy individually,To contour target volume individually,Molecular pathology guided,Functional imaging guided,Anatomical imaging guided,Cooperation in multi-disciplines,67,PPT,学习交流,We Are on the WayIndividualiz,Thanks for Your Kind Attention,68,PPT,学习交流,Thanks for Your Kind Attention,