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1、同步放化疗在NSCLC的进展,主要内容,放疗在早期NSCLC的进展同步放化疗与靶向药物治疗NSCLC的进展同步放化疗联合培美曲塞治疗NSCLC的研究进展同步放化疗在晚期NSCLC的进展,放疗在早期NSCLC的进展同步放化疗与靶向药物治疗NSCLC的进展同步放化疗联合培美曲塞治疗NSCLC的研究进展同步放化疗在晚期NSCLC的进展,Stereotactic ablative radiotherapy (SABR) in potentially operable Stage I non-small cell lung cancer patients,立体定向消融放疗治疗潜在可手术的I期非小细胞肺癌
2、患者Frank J. LagerwaardDept. of Radiation Oncology VUmc Cancer Center Amsterdam,I期NSCLC经SABR治疗后的局部控制情况,不选择手术的原因,SABR对潜在科手术病人的基线特征,those with prior high-dose (chemo-)radiotherapy or pneumonectomy (N=23)GOLD Class 3 (N=216)WHO performance score 3 (N=23)因共患心血管疾病排除手术的(N=94)并发其他肿瘤的(N=50)因主要共患病除外手术的, e.g. 新
3、发冠心病, 肾衰(N=68),SABR的治疗剂量选择,Performed at VUmc since April 2003T1 tumors ( 3 cm), 肿瘤未达纵膈和胸壁3 x 18 Gy 80%; 3 fx/week (BED 134 Gy)T1 tumors 达胸壁和纵膈, and T2 tumors5 x 11 Gy 80%; 3 fx/week (BED 116 Gy)Tumors 临近心包，臂丛神经或肺门8 x 7.5 Gy 80%; 3 fx/week (BED 105 Gy),SABR的主要 毒性,SABR治疗117例潜在可手术患者的结果,结论,应用SABR是可行的治疗后
4、30天死亡率为0%，对比该群患者术后死亡率为2.6%尽管多数老年病人共患病率很高，经SABR治疗后中位生存仍超过5年鼓励内镜分期Nakajima T, 2010; Harley D, 2010SABR数据支持随机入组,放疗在早期NSCLC的进展同步放化疗与靶向药物治疗NSCLC的进展同步放化疗联合培美曲塞治疗NSCLC的研究进展同步放化疗在晚期NSCLC的进展,LCCC 0511: Phase I/II Trial of Induction Carboplatin/Paclitaxel plus Bevacizumab followed by Concurrent Thoracic Confo
5、rmal Radiotherapy with Carboplatin/Paclitaxel, Bevacizumab and Erlotinib in Stage IIIA/B NSCLC,卡铂紫杉醇联合贝伐单抗行诱导治疗继之以同步胸部适型放疗联合卡铂紫杉醇，贝伐单抗和厄罗替尼治疗IIIA/B期NSCLC的I/II期临床研究MA Socinski on behalf of the co-authorsUniversity of North Carolina, Yale University, Wake Forest University and Northeast Medical Center
6、,实验设计,入组病人基线特征,Age (yrs), median (range) 61 (34-74)Sex (M:F) 23 (51%):18 (49%)Stage (IIIA:IIIB) 29 (64%):16 (36%)PS 0:1 26 (71%):13 (29%HistologyAdeno 27 (60%) Squamous 12 (27%)Lg Cell 4 (9%)NSCLC NOS 2 (4%)RaceCaucasian （高加索） 34 (78%)Black （黑人） 9 (20%)Asian 2 (4%)FEV1(), median (range) 2.4 (0.8-3.9
7、),发生率多于等于1个病人且大于等于3级的毒性统计,反应率RECIST(n=45),Induction RR 39% (95% CI, 24-55%)ORR 60% (95% CI, 44-75%) *Judged 2-6 months after completion of RT,LCCC 生存结果,首要终点是PFS 假设检验= PFS at 1 year = 50%排除值if PFS 70%,LCCC高剂量同步放化疗的相关临床实验,Socinski MA et al Cancer 92:1213-23, 2001, Marks L et al J Clin Oncol 22:4329-40
8、, 2004, Socinski MA et al J Clin Oncol 22:4341-50, 2004, Stinchcombe TE et al J Thorac Oncol 3:250-7, 2008, Socinski MA et al J Clin Oncol 26:2457-63, 2008, Socinski MA et al J Clin Oncol 27:389s, 2009,LCCC 0511-结论,诱导CbP + Bev 是可以耐受并有效的同步Erlotinib + Bev 继之以强烈的同步放化疗治疗非鳞癌的NSCLC 的前提是 .放疗参数要预期设定对食管炎行最佳支
9、持治疗首要毒性是食管炎(经常为迟发型)联合Erlotinib + Bevacizumab 不可行This approach was associated with late PH in squamous histology patientsPFS and OS 的结果相对于我们的历史经验不被看好基于实验中观察到得毒性加倍, 应用Bev 和chemoRT 不被推荐,MultimodAlity treatment with Radio-chemoTherapy and Erlotinib in advanced NSCLC (MARTE trial)进展期NSCLC放化疗联合厄罗替尼的多模式治疗（
10、MARTE实验）,Sara RamellaRadiation Oncology Campus Bio-Medico University, Rome (Italy),材料和方法,之前经过化疗目前正在行放化疗的病人包括局限野放疗(IF RT) 中值升高至59.4 Gy, 标准分割(1.8Gy/day)Erlotinib (E) 150 mg/dayChemotherapy: Gemcitabine (GEM) 300 mg/m2/week (E-GEM group)Pemetrexed (PEM) 500mg/m2 every 3 weeks (E-PEM group),病人基线特征和治疗相关毒
11、性,病人基线特征和毒性统计数据,有效性,随访范围6-45 months整体人群:中位生存23.3 mPFS 4.7 m,27.9 vs 19.3 months; p=0.021,7.5 vs 3.7 months; p=0.05,27.9 vs 18.2 months; p=0.004,23.1 vs 22 months; p=0.791,非鳞癌总生存,鳞癌总生存,结论,临床前期数据证实厄罗替尼的靶向治疗有放射增敏作用之前经过多次化疗的病人行厄罗替尼联合同步放化疗治疗是可行的有效的临床生物学标志物保障了放射治疗的效应,Determination of standard dose cetuxim
12、ab together with concurrent individualised, isotoxic accelerated radiotherapy and cisplatin-vinorelbine for patients with stage III non-small cell lung cancer: A phase I study(NCT00522886),测定标放疗准计量的西妥昔单抗联合同步个体化，同毒性加速放疗联合顺铂长春瑞宾治疗III期非小细胞肺癌的I期临床研究Anne-Marie C. Dingemans Gerben Bootsma Angela van Baard
13、wijk Bart Reijmen Rinus Wanders Monique Hochstenbag Arne van Belle Ruud Houben Philippe Lambin Dirk de Ruysscher,治疗流程表,*Vinorelbine: step 1 10 mg/m2d 1-8, 8 mg/m2 d22-29 step 2 20 mg/m2d 1-8, 8 mg/m2 d22-29 step3 20 mg/m2d 1-8, 15 mg/m2 d 22-29,毒性,治疗3个月后经FDG-PET测定代谢反应 (N=22) CR:8 PR:11 PD:3结论 同步放化疗联
14、合顺铂，长春瑞宾及西妥昔单抗时可行的 长春瑞宾不能选择最大剂量 毒性在预期内 3月后治疗结果令人鼓舞,放疗在早期NSCLC的进展同步放化疗与靶向药物治疗NSCLC的进展同步放化疗联合培美曲塞治疗NSCLC的研究进展同步放化疗在晚期NSCLC的进展,力比泰卡铂同步3D适形放疗后以力比泰卡铂巩固化疗治疗中国局部晚期NSCLC患者,Ma S, et al. ASCO 2009 abstract e18502.,摘要e18502：研究设计,摘要e18502：研究结果 缓解情况,摘要e18502：研究结果 不良反应,放疗在早期NSCLC的进展同步放化疗与靶向药物治疗NSCLC的进展同步放化疗联合培美曲塞
15、治疗NSCLC的研究进展同步放化疗在晚期NSCLC的进展,15-year (very) long-term survival (VLTS) and competing risks (CR) analysis of induction (IND) chemotherapy (CTx) with three cycles cisplatin(P)/etoposide(E) followed by concurrent (cc) chemoradiation (CTx/RTx) PE/45 Gy (1.5 Gy bid) plus surgery (S) = TRIMODALITY phase-II
16、 West German Cancer Centre (WGCC) trial (JCO 98).R.Hepp1, T.C.Gauler2, C. Poettgen1, S. Korfee2, S. Bildat2, G. Stamatis3, S. Seeber4, H. Wilke4, V. Budach5, M. Stuschke1, W. E. E. Eberhardt2,西德癌症中心TRIMODALITY II期临床试验：三周期EP诱导化疗继以同步放化疗联合手术治疗的一项15年长期生存和竞争风险分析,试验设计,OS (stage), OS (R0) and OS (R0: pCR v
17、s no pCR),Fig. 2. OS (stage),Fig. 3. OS (R0),Fig. 4. OS (R0: pCR),LTS/VLTS 在选择性亚群的CR分析,Tab.1. VLTS in selected subgroups,Fig.5. Competing Risk-analysis,结论,LTS/VLTSontheWGCC-trialJCO98定义为第一个选择性可切除IIIA期NSCLC患者的随机对照多中心临床试验探索性分析显示前期治疗对15年长期结果无影响基于选择性的R0-可切除的IIIA和IIIB期患者继以诱导治疗手长期随访结果优60个月的竞争性风险分析提示(心血管，肺
18、疾病，再发肺癌和再发肿瘤是香港风险 (5yrs),SOCCAR trial results:,Comparing toxicity and efficacy ofhypofractionated concurrent,chemoradiation to published regimens,Cancer Research UK & UCL Cancer Trials Centre,N ORourke, J Maguire, R McMenamin, C Peedell, M Snee,Funding: CRUKSponsor: University CollegeLondonTrial adm
19、inistration: UCLcancer trials centreSupported by British,Thoracic Oncology Group,ORourke, N: support for meetingRocheMaguire, J: research support andspeakers honoraria:Pierre Fabre, Astra Zeneca;advisory boards: Eli LillyMcMenamin,R: speakers honoraria:Pfizer; advisory boards: Bayer, GSK;support for
20、 meetings: GSK, Ibt,Ferring, Boeringer,Snee, M:,nil,Cancer Research UK & UCL Cancer Trials CentreTrial funding and Disclosure,3,CONCURRENT ARM55Gy/20f/4weekscisplatinum 80mg/m2 weeks 1,4vinorelbine 15mgs/m2 weekly4 weekscisplatinum 80mg/m2 day 1vinorelbine 25mg/m2 d 1, d 82 cycles,SEQUENTIAL ARMcisp
21、latinum 80mg/m2 day 1vinorelbine 25mg/m2 day 1, 84 cycles4 weeks55Gy/20f/4weeks,SOCCAR,Trial Design病理学确诊NSCLC stage III , PS 0-1,CT mediastinoscopy, PET-CTunsuitable for surgery,SOCCAR,NSCLC Stage III PS 0 - 1,CON,SEQ,nmedian1 year2 year3 year5 yearLocal PD,6727.4 m73.1%54%38%33.6%10%,5918.6 m83.1%4
22、2%27%NR22%,ConSeqMonths,Cancer Research UK & UCL Cancer Trials CentreConcurrent Schedules Compared,Trial,no.,%2ys,RT,CT,%TRM,G3/4oes,patients,Gy/f,SOCCAR 2010,70,54,55/20,cis/vin,4,17%,Jeremic 1996,65,43,69.6/58/6w carbo/etop,0,8,Belderbos 2006Fournel 2005Curran 2003Huber 2006Furuse 1999Zatloukal 20
23、04Belani 2005Vokes 2004,66100201991565192182,3939373634.6343129,66/2466/3360/3060/3056/28split60/3063/3466/33,daily ciscis/etopcis/vblwkly taxolcis/vindcis/vincarbo/taxcarbo/tax,1.510300.602?,173225133182831,Conclusions,Cancer Research UK & UCL Cancer Trials Centre, 55Gy/20f/26-28d 同步顺铂联合长春瑞宾治疗III N
24、SCLC, PS 0-1高度有效, 2 year survival 同步放化疗组 50%, 相比于16 RCTs, 1733 患者经同步CTRT治疗后的总生存最高且耐受性良好,Randomized phase II trial of uracil/tegafur (UFT) and cisplatinversus vinorelbine and cisplatin with concurrent thoracicradiotherapy for locally advanced unresectable stage III,non-small-cell lung cancer,NJLCG 06
25、01,试验目标,尿嘧啶替加氟(UFT)联合顺铂(UP arm)对比长春瑞宾联合顺铂辅以同步胸部放疗,治疗进展期不可切除的stage III NSCLC 的有效性和安全性., 首要终点,整体有效率(ORR), 次要终点,Progression free survival (PFS)Overall survival (OS)Toxicity profile,RANDOMIZATIONStratified factor,AgeGenderHistologyStage,59 /6064/6569/7075Male/FemaleAdeno./Sq./Large/OthersIIIA/IIIB,ENROL
26、LMENT,(n=70),UP arm (n=36)(35 patients were evaluable)UFT : 400mg/m2, day 1-14, 29-42CDDP : 80mg/m2, day 8, 36RT : 2Gy x 5days/week, day 1-40, 60Gy,试验设计,NP arm (n=34)(31 patients were evaluable)VNR : 20mg/m2, day 1, 8, 29, 36CDDP : 80mg/m2, day 1, 29RT : 2Gy x 5days/week, day 1-40, 60Gy, 组织学或细胞学确诊为N
27、SCLC 不可切除的 stage IIIA or IIIB disease, 无胸部放疗，胸部外科手术和化疗史, ECOG 评分0 or 1 年龄介于20 and 75 years,Patients Recruitment : Between February 2006 and May 2009,反应和生存数据毒性数据(Grade3),* Two patients died of radiation pneumonitis.,中位随访时间: 20.2 monthsNCI-CTC ver. 3.0,Summery,ORRs 为80% and 71% 在UP 组 和NP 组.中位随访时间是20.2 months, median PFS 和中位生存在UP组是8.8months和26.9months，在NP组为6.8months和21.8months2-年生存率两组分别是UP 51.0% ，NP 46.9%Grade 3/4 血液学毒性两组分别是UP 20% 和 NP58%发热性嗜中性粒细胞减少仅见于NP组两组肺炎发生率都是6% ，但在NP 组2例病人死于放射性肺炎,Conclusion,联合同步放疗，UP组更显优势，可作为局晚期NSCLC的候选方案进一步评估UP 联合 c-TRT 的有效性有待于在将来的以顺铂为基础的第三代化疗联合c-TRT 的 III期临床研究中证实,谢 谢,
