于金明放射肿瘤新进展

,2013放疗新进展 Advances of RT in 2013,山东肿瘤医院 于金明,August 2, 2013; Xian,中国卫生年鉴2010年 Cancer 2005;104:1129 Radiother Oncol 2005;75,肿瘤流行病学与治疗手段贡献度,肿瘤是威胁国人生命疾病之最，且呈上升趋势美国近年连续报道发病率和死亡率呈负增长 65%肿瘤患者需行放疗；放疗治愈贡献度达40%,手术,49%,放疗,40%,化疗,11%,2009年中国疾病死亡率,不同治疗手段对癌症治愈贡献度,168,129,126,159,113,152,CA Cancer J Clin 2013报告,1. Jemal A, et al. CA Cancer J Clin 2011; 61(2):69-90. 2. Zheng R, et al. China Cancer 2012; 21(1):1-12.,国际: 中国肿瘤发病率与世界肿瘤发病率的比例,1975-2008美国部分肿瘤5年生存率提高值,肺癌生存率相比其他主要瘤种提高较慢,2013 ASCO Abstract 7501,临 床 研 究 设 计,主要终点：OS高剂量 vs. 标准剂量RT西妥昔单抗 vs. 无西妥昔单抗期望总生存期从对照组的17.1个月延长到研究组的24个月,Bradley JD, et al. 2013 ASCO Abstract 7501.,*化疗=卡铂/紫杉醇,主 要 入 组 条 件,新诊断不可切除IIIA/B期NSCLC无锁骨上或对侧肺门淋巴结肿大ZPS 0/1年龄18岁FEV11.2L/秒或50%的预测值正常肝肾骨髓功能签署书面知情同意,Bradley JD, et al. 2013 ASCO Abstract 7501.,基 线 特 征,Bradley JD, et al. 2013 ASCO Abstract 7501.,剂量学数据分布,Bradley JD, et al. 2013 ASCO Abstract 7501.,与治疗相关的不良事件,Bradley JD, et al. 2013 ASCO Abstract 7501.,放 射 性 食 管 炎,Bradley JD, et al. 2013 ASCO Abstract 7501.,OS：总生存时间,Bradley JD, et al. 2013 ASCO Abstract 7501.,PFS：无进展生存时间,Bradley JD, et al. 2013 ASCO Abstract 7501.,LF: 局部失败率,Bradley JD, et al. 2013 ASCO Abstract 7501.,DM: 远处失败率,Bradley JD, et al. 2013 ASCO Abstract 7501.,Conclusions: 结论,高剂量放疗组的死亡风险比标准剂量组高56%高剂量组的局部失败风险比标准剂量组高37%高剂量组的食管炎发生率更高(21% vs. 7%)高剂量组的局部失败率更高高剂量组总生存较差的原因不详但可能解释是因治疗中断延长了治疗时间增加了心脏剂量尚未报告的毒性以及以上诸因素的合并原因,Bradley JD, et al. 2013 ASCO Abstract 7501.,SAKK 16/00: 新辅助化疗联合或不联合术前放疗治疗IIIA/N2 NSCLC的随机III期研究,Pless M, et al. 2013 ASCO Abstract 7503,研 究 设 计,Pless M, et al. 2013 ASCO Abstract 7503,化疗,手术,化疗,手术,放疗,随机,A组：放疗,B组：无放疗,顺铂100mg/m2 d1 q3w3多西他赛85mg/m2 d1 q3w3,3周,3-4周,44Gy/22fr/3w,3-4周,*,*分期：PET-CT PD则退出研究,入 组 条 件,年龄为18-75岁PS 0-1病理学确认为: IIIA/N2期NSCLC纵隔镜检查EBUSPET-CT可切除的肿瘤以及可手术患者，心与肺功能正常肝、肾、骨髓功能正常没有未控制的感染、糖尿病、心脏疾病和相关的神经病变或消化道溃疡等,主 要 研 究 终 点,主要终点：EFS定义：自随机至复发或进展或二次肿瘤或死亡期望EFS从对照组12个月延长到研究组18个月次要终点：OS术后30天死亡率ORR失败模式完全切除率手术可行性,患 者 特 征,手 术 情 况,化疗- 血液学毒性,手 术 - 毒 性,EFS,OS,生 存 总 结,初 步 结 论,针对研究所探索问题的首个完成的随机研究新辅助化疗基础上联合放疗不改善 EFS、OS或局控率总生存期结果令人鼓舞中位OS为27个月在目前的状态下，除临床研究以外不推荐新辅助化疗新辅助放疗：期待LungART的研究(IFCT/EORTC)结果,有关新辅助放化疗,N2患者在NCCN成员机构中， 50%成员使用新辅助放化疗，50%使用新辅助化疗新辅助放化疗可以有更高的病理缓解率和更多纵膈淋巴结降级率现在没有在诱导化疗时增加放疗对比单独化疗可以改善预后证据,Phase III Trial of Concurrent Thoracic RT with Either the 1st Cycle or 3rd Cycle of Cisplatin & Etoposide ChT to Determine the Optimal Timing of Thoracic-RT for Limited SCLC (NCT01125995),Keunchil Park et al, Republic of Korea, ASCO2012,Background,The standard treatment of LD-SCLC is concurrent thoracic RT (TRT) with ChTHowever, the optimal timing of TRT has not yet been definedLimitations in early RT given with the 1st cycle of ChTPotential enlarged RT fields due to in initial planning for bulky tumorsComplexity of administering TRT results delayed overall treatment for LD-SCLCThis study aimed to investigate whether TRT commenced with the 3rd cycle of ChT is non-inferior to TRT commence with the 1st cycle of EP chemotherapy,Study Design,Consort DiagramEnrollment between July 2003 and June 2010Median follow-up: 59.4 mons (range: 14.997.5 mons ),222 patients were randomized,Initial (1st cycle) Arm (N = 113),Delayed (3rdcycle) Arm (N = 108),111 patients were analyzed,108 patients were analyzed,2 were excluded 1 progressed with pleural seeding before treatment 1 withdrew consent,1 were excluded because diagnosis changed to lymphoma,Cut-off date for survival analysis: August 20 1011,Objective Response Rate,Overall Survival,Progression-free Survival,Patterns of Failure,Treatment Toxicity,Cetuximab, paclitaxel, cisplatin & concurrent RT in Chinese pts with locally advanced esophageal squamous cell carcinoma: An open-label, multicenter, phase II Study,X Meng, J Yu et al, ASCO2013,西妥昔单抗 + 紫杉醇+ 顺铂+ 同步放疗 ( 400/250mg/m2 ) (45mg/m2) (20mg/m2) ( 59.4Gy ),颈段和胸中上段食管鳞癌患者 (stage II-III期),试验设计,主要评价指标 临床缓解率（CR + PR）次要评价指标 安全性、生存率、无进展生存期、K-ras状态,筛 选 标 准,入组标准II-III期食管鳞癌患者存在可测量病灶患者年龄 18 岁基线时ECOG评分为0或1 骨髓储备功能正常肝肾功能正常患者签署正式知情同意书,排除标准 已行放化疗或手术切除 食管多中心病变 怀孕期或哺乳期患者 无法控制的严重疾病 无法签署知情同意书 存在远处转移 过去5年患任何恶性肿瘤,参与单位和入组例数,Primary Endpoint Response Second Endpoint Toxicity Overall survival K-ras status,Concurrent chemoradiotherapy+ cetuximab,Study Design,Total 55 pts with Cervical/ Upper/ Mid ThoracicAnd unresectable ESCC II-III Stage (Phase II ),Overall Survival,Proportion,Overall Survival (months),2-year OS rate 80.00% (45 pts),Time to Disease Progression,Proportion,Overall Survival (months),2-year PFS rate 74.87% (45 patients),TREMPLIN study: after induction TPF Erbitux+RT Vs DDP+RT for HNSCC,71% could receive the full Erbitux protocol & 43% for full cisplatin protocol,Previously untreated SCC larynx/hypopharynxSuitable for total laryngectomy,Erbitux (weekly),RT (70 Gy)Cisplatin,R,PR,Total laryngectomy + postoperative RT,TPF(3 cycles, q3w)(n=153),RT (70 Gy),PR,56 pts,60 pts,116 (76%) pts,对头颈鳞癌放疗或放化疗联合Erbitux是否获益,研 究 终 点,主要终点(治疗结束后3个月):保候率:Cisplatin vs Erbitux: 95% vs 93%; p = 0.63次要终点(治疗结束后18个月):喉功能保留: Cisplatin vs Erbitux: 87% vs 82%; p = 0.68OS:Cisplatin vs Erbitux: 92% vs 89%; p = 0.44,long-term toxicity: Cet+RT vs CRT,After induction TPF, Erbitux + RT is more manageable and better tolerated than CRT,CRT vs RT+Cet: Which Is Better?,随机对照研究正在进行中回顾性研究:MSKCC (Koutchner, IJROBP 2010)125 pt with RT/CDDP, 49 pts with RT/cetuximab2Y LRFR: 5.7% vs. 39.9%; p0.00012Y FFS: 87% vs. 45%; p0.00012Y OS: 92.8% vs. 66.6%; p = 0.0003,RTOG 0522,Accelerated RT Cisplatin,Accelerated RTCisplatinErbitux,R,N=895,Targeted sample size: N=940Stage III and IV* SCC of:OropharynxHypopharynxLarynx,RT: 72 Gy/42 F/6 WCisplatin: 100 mg/m2, q3W x2C-225: 400 mg/m2 x1, followed by 250 mg/m2/w *Excluded T1N+, T2N1,Phase III trial,Ang KK, et al. J Clin Oncol 2011;29:15s (5500),RTOG 0522: 结果,RT/CT RT/CT/Cet 2Y DFS 63% 64% 2Y OS 83% 80% No benefits of adding cetuximab to RT/CT,Ang KK, et al. J Clin Oncol 2011;29:15s (5500),当今肿瘤治疗亟需个体化,肿瘤诊疗要杜绝此类原则性错误！,肿瘤和正常组织的异质性,影响个体化治疗差异的因素,ChT & RT Response,Radiosensitivity,Age,Gender,Performance Status,Staging,Pathology,BiologicCharacteristics,Gene Mutation,Gene Expression,Gene Rearrangement,肿瘤治疗模式的转化Advances of Cancer Tr Model,