单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,Tianjin Medical University Cancer Institute&Hospital,HuanhuXi Road,TiYuanBei,He Xi District,Tianjin 300060,PRC,局部晚期非小细胞肺癌精准放疗的进展与挑战,天津医科大学肿瘤医院,赵路军,2021 天津,2024/11/15,局部晚期非小细胞精准放疗的进展与挑战,同步放化疗是局部晚期非小细胞肺癌的首选治疗方案,老年局部晚期非小细胞肺癌的放化疗,放疗技术进步与局部晚期非小细胞肺癌疗效,局部晚期非小细胞肺癌放化疗的放疗剂量研究进展,精准医学背景下非小细胞肺癌剂量提升研究进展,NCCN,局部晚期,NSCLC,治疗指南,Eberhardt WEE,et al.Ann Oncol 2021,欧洲局部晚期非小细胞肺治疗指南,2024/11/15,局部晚期非小细胞肺癌的放化综合治疗Meta 分析法,法国meta分析,6个随机对照研究共1205例病人比较同步放化疗和序贯放化疗,同步放化疗提高了总生存率,3年生存率提高绝对值5.7%(from 18.1%to 23.8%),5年提高绝对值4.5%,同步放化疗降低了局部区域进展(HR,0.77;95%CI,0.62 to 0.95;P=.01),但没有降低远处转移率(HR,1.04;95%CI,0.86 to 1.25;P=.69),同步放化疗增加了3-4级急性食管炎的发生从4%增加到18%,相对风险:4.9(95%CI,3.1 to 7.8;P,70 years,40%of pts,can receive,concurrent RT-CT,老年局部晚期非小细胞肺癌的同步放化疗,Overall survival,Progression-free survival,Median OS:17.0 and 20.7 months,Unadjusted HR=1.23,95%CI=1.13-1.35,Multivariable HR=1.20,95%CI=1.10=1.32,Median PFS:8.7 and 9.1 months,老年局部晚期NSCLC的同步放化疗WCLC 2021,Abstract 4219:A Pooled Analysis Comparing the Outcomes of Elderly to Younger Patients on NCTN,Trials of Concurrent CCRT for Stage 3 NSCLC Presenter:Tom Stinchcombe,Abstract 4219:A Pooled Analysis Comparing the Outcomes of Elderly to Younger Patients on NCTN,Trials of Concurrent CCRT for Stage 3 NSCLC Presenter:Tom Stinchcombe,Grade 3 adverse events in elderly and younger patients,Adverse event category,Age 70 years,(n=832),Age 70 years,(n=2768),P-value a,All AEs grade 3,86%,84%,0.04,Hematologic AEs grade 3,65%,61%,0.04,Non-hematologic AEs Grade 3,68%,62%,0.01,Grade 5 AEs,9%,4%,0.01,Treatment-related deaths b,3%,2%,0.12,a Chi-square test for adverse events comparison,and Fisher,s exact test for treatment related deaths,b Data were available on 2,091 patients for this analysis,老年局部晚期NSCLC的同步放化疗WCLC 2021,Abstract 4219:A Pooled Analysis Comparing the Outcomes of Elderly to Younger Patients on NCTN,Trials of Concurrent CCRT for Stage 3 NSCLC Presenter:Tom Stinchcombe,老年局部晚期NSCLC的同步放化疗WCLC 2021,End of treatment reasons,End of treatment reason,Age 70 years,(n=818),Age 70 years,(n=2711),P-value,b,Treatment completed,47%(n=387),57%(1541),0.01,Adverse event,20%(n=162),13%(361),0.01,Disease progression,13%(n=104),16%(445),0.01,Patient refused further treatment,5.8%(n=47),3.9%(105),0.02,Died during treatment,7.8%(n=64),2.9%(79),0.01,Treatment never started,1.0%(n=8),1.4%(39),0.39,Developed other disease,0.9%(n=7),0.1%(n=2),0.05,P 0.05,P 0.05,P,66Gy),21.1%vs.33.3%,P=0.488,G3 pulmonary toxicity(SD vs.HD),10.5%vs.14.3%,P=1.00,根据肺耐受量个体化提高同步放化疗的放疗剂量WCLC2021,Baosheng Li,et al.WCLC 2021,OS for stage IIIa/IIIb OS for SD/HD,31m vs.21 m P=0.029,16m vs.27m P=0.053,根据肺耐受量个体化提高同步放化疗的放疗剂量WCLC2021,Baosheng Li,et al.WCLC 2021,miRNA,与局部晚期,NSCLC,的高剂量放疗,ASTRO 2021,密西根大学数据:,2004-2021,85例前瞻性剂量爬坡实验病人,排除SBRT,检测84个miRNA,病人中位年龄66岁,III期病人占83%,中位等效剂量gEUD68.2 Gy,采用Cox Elastic Net模型筛选出18个与剂量效应有交互影响的miRNA,具有能够从提高剂量获益 的miRNA类型的病人42例,高剂量组 68Gy)和低剂量组(A,肺损伤发生率(,%,),P,低危组,Arg/Pro or Pro/Pro,GG,10.6,0.024,中危组,Arg/Arg,GG,15.4,Arg/Pro or Pro/Pro,GA/AA,高危组,Arg/Arg,GA/AA,29.4,ATM,基因多态性与放射性肺损伤,Xiong H,Int J Radiat Oncol Bio Phys 2021,MDACC,数据:,362,例,NSCLC,放化疗病人,3,级以上,RILT,发生率,(a)ATM rs189037 AG vs.AA and GG vs.AA,(b)ATM rs228590 CT+TT vs.CC,(c)ATM rs1801516 AG+AA vs.GG,(d)ATM rs189037 G and ATM rs228590 T combined alleles,11/15/2024,ASTRO 2021,Harvard医学院回忆性分析数据:,1998-2021年,接受放射治疗为主综合治疗的699局部晚期NSCLC,250例行基因检测:EGFR+:19%,ALK+:9%,KRAS+:32%,野生型40%,EGFR,KRAS和ALK基因型与局部晚期,NSCLC,放射治疗疗效,项目,EGFR+,ALK+,KRAS+,野生型,P,值,OS,55.8,未达到,28,33.2,0.02,PFS,15.3,13.7,13.0,14.5,0.47,3Y-LRFS,77,38,49,46,0.08,3Y-DMFS,42,49,27,25,0.25,多因素分析,ALK+,是,OS,提高的独立预后因素,(,P,=,0.03,),EGFR+,病人局部复发较低,(P,=,0.03),复发后生存分析显示,EGFR+/ALK+,病人接受适当靶向治疗后生存期较长,(HR,=,0.57;P,=,0.02),Mak RH,et al.ASTRO 2021,不是所有的靶区都需要高剂量照射,:,非小细胞肺癌同步加量放疗的研究,6000cGy,6600cGy,Kai Ji,Lujun Zhao,Weishuai Liu,et al.BJR 2021,11/15/2024,40例III期病人中位生存时间24个月,2年生存率为47.9%,2年无局部进展生存率为66.7%。,3级以上治疗相关性肺炎5例9.6%,Kai Ji,Lujun Zhao,Weishuai Liu,et al.BJR 2021,11/15/2024,不是所有的靶区都需要高剂量照射,:,非小细胞肺癌同步加量放疗的研究,PET-CT,指导下的自适应加量放疗,密西根大学,II期单臂临床研究,不可手术治疗的I-III期NSCLC,调强适形放疗30次,放疗剂量根据2级以上肺损伤风险以及疗中PET-CT高代谢区个体化加量,最高总剂量86Gy,II/II期病人同步应用卡铂紫杉醇化疗,共42例病人入组,中位年龄63岁,男性67%,III期92%,中位物理剂量83Gy范围63Gy-86Gy,存活病人中位随访47个月,总的2年局部区域肿瘤控制率为62%,2年局部区域无进展生存率为38%,中位生存期25个月,2年生存率52%,Kong FM,et al.ASTRO 2021,RTOG1106,研究:功能影像指导下的同步加量照射,Feng-ming Kong,RTOG Protoc