肺癌同步放化疗进展.ppt

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

2、非小细胞肺癌患者 Frank J. Lagerwaard Dept. 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

3、除外手术的, e.g. 新发冠心病, 肾衰(N=68),SABR的治疗剂量选择,Performed at VUmc since April 2003 T1 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 tumors 5 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

4、结果,结论,应用SABR是可行的 治疗后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, 2010 SABR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

5、 Concurrent Thoracic Conformal 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-authors University of North Carolina, Yale University, Wake Forest University

6、and Northeast Medical Center,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% Histology Adeno 27 (60%) Squamous 12 (27%) Lg Cell 4 (9%) NSCLC NOS 2 (4%) Race Caucasian （高加索） 34 (78%) Black （黑人） 9 (20%) Asian 2

7、(4%) FEV1(), median (range) 2.4 (0.8-3.9),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, 2

8、001, Marks L et al J Clin Oncol 22:4329-40, 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

9、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 patients PFS 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 ad

10、vanced NSCLC (MARTE trial)进展期NSCLC放化疗联合厄罗替尼的多模式治疗（MARTE实验）,Sara Ramella Radiation 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/day Chemotherapy: Gemcitabine (GEM) 300 mg/m2/week (E-GEM group) Pemetrexed

11、(PEM) 500mg/m2 every 3 weeks (E-PEM group),病人基线特征和治疗相关毒性,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 m PFS 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

12、效的 临床生物学标志物保障了放射治疗的效应,Determination of standard dose cetuximab 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

13、期临床研究 Anne-Marie C. Dingemans Gerben Bootsma Angela van Baardwijk 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

14、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

15、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 (CT

16、x/RTx) PE/45 Gy (1.5 Gy bid) plus surgery (S) = TRIMODALITY phase-II 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

17、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 vs 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

18、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，肺疾病，再发肺癌和再发肿瘤是香港风险 (5yrs),SOCCAR trial results:,Comparing toxicity and efficacy of hypofractionated concurrent,chemoradiation to published regimens,Cancer Research UK advisory boards: Eli Lilly McMenamin,R: speakers honoraria: Pfi

19、zer; advisory boards: Bayer, GSK; support for meetings: GSK, Ibt, Ferring, Boeringer,Snee, M:,nil,Cancer Research UK & UCL Cancer Trials Centre Trial funding and Disclosure,3,CONCURRENT ARM 55Gy/20f/4weeks cisplatinum 80mg/m2 weeks 1,4 vinorelbine 15mgs/m2 weekly 4 weeks cisplatinum 80mg/m2 day 1 vi

20、norelbine 25mg/m2 d 1, d 8 2 cycles,SEQUENTIAL ARM cisplatinum 80mg/m2 day 1 vinorelbine 25mg/m2 day 1, 8 4 cycles 4 weeks 55Gy/20f/4weeks,SOCCAR,Trial Design 病理学确诊 NSCLC stage III , PS 0-1, CT mediastinoscopy, PET-CT unsuitable for surgery,SOCCAR,NSCLC Stage III PS 0 - 1,CON,SEQ,n median 1 year 2 y

21、ear 3 year 5 year Local PD,67 27.4 m 73.1% 54% 38% 33.6% 10%,59 18.6 m 83.1% 42% 27% NR 22%,Con Seq Months,Cancer Research UK & UCL Cancer Trials Centre Concurrent 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 c

22、arbo/etop,0,8,Belderbos 2006 Fournel 2005 Curran 2003 Huber 2006 Furuse 1999 Zatloukal 2004 Belani 2005 Vokes 2004,66 100 201 99 156 51 92 182,39 39 37 36 34.6 34 31 29,66/24 66/33 60/30 60/30 56/28split 60/30 63/34 66/33,daily cis cis/etop cis/vbl wkly taxol cis/vind cis/vin carbo/tax carbo/tax,1.5

23、 10 3 0 0.6 0 2 ?,17 32 25 13 3 18 28 31,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 NSCLC, 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 cisplatin versus vinorel

24、bine and cisplatin with concurrent thoracic radiotherapy for locally advanced unresectable stage III,non-small-cell lung cancer,NJLCG 0601,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,RANDOMIZATION Stratified factor,Age Gender Histology Stage,59 /6064/6569/7075 Male/Female Adeno./Sq./Large/Others IIIA/IIIB,ENROLLMENT,(n=70),UP arm (n=36) (35 patients were evaluable) UFT : 400mg/m2, day 1-14, 29-42