局部晚期非小細胞肺癌精準放療的進展與挑戰(zhàn)-bestofwclcfinal課件

1、Tianjin Medical University Cancer Institute & HospitalHuanhuXi Road, TiYuanBei, He Xi District, Tianjin 300060, PRCTel: +86-22-23340123 Fax: + 86-22-23341405 Web site: 局部晚期非小細胞肺癌精準放療的進展與挑戰(zhàn)天津醫(yī)科大學腫瘤醫(yī)院趙路軍2016 天津Tianjin Medical University Can2022/9/24局部晚期非小細胞精準放療的進展與挑戰(zhàn)同步放化療是局部晚期非小細胞肺癌的首選治療方案老年局部晚期非小細胞肺癌

2、的放化療放療技術進步與局部晚期非小細胞肺癌療效局部晚期非小細胞肺癌放化療的放療劑量研究進展精準醫(yī)學背景下非小細胞肺癌劑量提升研究進展2022/9/24局部晚期非小細胞精準放療的進展與挑戰(zhàn)同步放NCCN局部晚期NSCLC治療指南NCCN局部晚期NSCLC治療指南Eberhardt WEE, et al. Ann Oncol 2015歐洲局部晚期非小細胞肺治療指南Eberhardt WEE, et al. Ann Onc2022/9/24局部晚期非小細胞肺癌的放化綜合治療Meta 分析（法）法國meta分析，6個隨機對照研究共1205例病人比較同步放化療和序貫放化療同步放化療提高了總生存率 ，3年

3、生存率提高絕對值5.7% (from 18.1% to 23.8%)，5年提高絕對值4.5% 同步放化療降低了局部區(qū)域進展(HR, 0.77; 95% CI, 0.62 to 0.95; P = .01)，但沒有降低遠處轉(zhuǎn)移率(HR, 1.04; 95% CI, 0.86 to 1.25; P = .69)同步放化療增加了3-4級急性食管炎的發(fā)生（從4%增加到18%），相對風險：4.9 (95% CI, 3.1 to 7.8; P 70 years, 40% of pts can receive concurrent RT-CT老年局部晚期非小細胞肺癌的同步放化療De Ruysscher et

4、 al. Ann Oncol Overall survivalProgression-free survival Median OS: 17.0 and 20.7 monthsUnadjusted 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 Unadjusted HR=1.02, 95% CI=0.94-1.11Multivariable HR=1.01, 95% CI=0.92-1.10老年局部晚期NSCLC的同步放化療WCLC 2016Abs

5、tract 4219: A Pooled Analysis Comparing the Outcomes of Elderly to Younger Patients on NCTN Trials of Concurrent CCRT for Stage 3 NSCLC Presenter: Tom StinchcombeOverall survivalProgression-frAbstract 4219: A Pooled Analysis Comparing the Outcomes of Elderly to Younger Patients on NCTN Trials of Con

6、current CCRT for Stage 3 NSCLC Presenter: Tom StinchcombeGrade 3 adverse events in elderly and younger patientsAdverse event categoryAge 70 years(n=832)Age 70 years (n=2768)P-value aAll AEs grade 386%84%0.04Hematologic AEs grade 365%61%0.04Non-hematologic AEs Grade 368%62%0.01Grade 5 AEs9%4%0.01Trea

7、tment-related deaths b3%2%0.12a Chi-square test for adverse events comparison, and Fishers exact test for treatment related deathsb Data were available on 2,091 patients for this analysis老年局部晚期NSCLC的同步放化療WCLC 2016Abstract 4219: A Pooled Analysis Comparing the Outcomes of Elderly to Younger Patients

8、on NCTN Trials of Concurrent CCRT for Stage 3 NSCLC Presenter: Tom StinchcombeAbstract 4219: A Pooled Analys老年局部晚期NSCLC的同步放化療WCLC 2016End of treatment reasonsEnd of treatment reasonAge 70 years(n=818)Age 70 years(n=2711)P-value bTreatment completed47% (n=387)57% (1541) 0.01Adverse event20% (n=162)13

9、% (361)0.01Disease progression13% (n=104)16% (445)0.01Patient refused further treatment5.8% (n=47)3.9% (105)0.02Died during treatment7.8% (n=64)2.9% (79)0.01Treatment never started1.0% (n=8)1.4% (39)0.39Developed other disease0.9% (n=7)0.1% (n=2) 0.05P 0.05P 0.05P 0.05Brower JV, et al. ASTRO 2016 提高

10、III期NSCLC放射治療的劑量美國國家癌癥數(shù)據(jù)庫Overall Survival For All Patients According to as TreatedPresented By Zhongxing Liao at 2016 ASCO Annual Meeting調(diào)強放療對比質(zhì)子治療隨機對照研究OS結(jié)果（ASCO 2016）Overall Survival For All 山東省腫瘤醫(yī)院李寶生等，WCLC2016不可切除的a-b NSCLCIMRT聯(lián)合同步化療PET-CT定位，SPECT肺灌注顯像根據(jù)肺組織V20逐步提升劑量 (27%, 30%, 33%,35%, 37%; 8 pt

11、s/cohort ) 根據(jù)肺耐受量個體化提高同步放化療的放療劑量WCLC2016Baosheng Li, et al. WCLC 2016 山東省腫瘤醫(yī)院李寶生等，WCLC2016根據(jù)肺耐受量個體化Optimization w/o lung perfusion guidingOptimization with lung perfusion guiding根據(jù)肺耐受量個體化提高同步放化療的放療劑量WCLC2016Baosheng Li, et al. WCLC 2016Optimization w/o lung perfusio差異更明顯根據(jù)肺耐受量個體化提高同步放化療的放療劑量WCLC2016

12、Baosheng Li, et al. WCLC 2016差異更明顯根據(jù)肺耐受量個體化提高同步放化療的放療劑量WC G3 toxic events (SD: 66Gy vs. HD: 66Gy) 21.1% vs.33.3%, P=0.488 G3 pulmonary toxicity (SD vs. HD) 10.5% vs. 14.3%, P=1.00 根據(jù)肺耐受量個體化提高同步放化療的放療劑量WCLC2016Baosheng Li, et al. WCLC 2016 G3 toxic events (SD: 66Gy OS for stage IIIa/IIIb OS for SD/HD

13、 31m vs. 21 m P=0.02916m vs. 27m P=0.053根據(jù)肺耐受量個體化提高同步放化療的放療劑量WCLC2016Baosheng Li, et al. WCLC 2016 OS for stage miRNA與局部晚期NSCLC的高劑量放療ASTRO 2016，密西根大學數(shù)據(jù)：2004-2013, 85例前瞻性劑量爬坡實驗病人， 排除SBRT，檢測84個miRNA病人中位年齡66歲，III期病人占83%，中位等效劑量（gEUD）68.2 Gy采用Cox Elastic Net模型篩選出18個與劑量效應有交互影響的miRNA具有能夠從提高劑量獲益 的miRNA類型的病人

14、42例，高劑量組（ 68Gy)和低劑量組(A肺損傷發(fā)生率（%）P低危組Arg/Pro or Pro/ProGG10.60.024中危組Arg/ArgGG15.4Arg/Pro or Pro/ProGA/AA高危組Arg/ArgGA/AA29.4P53和ATM基因多態(tài)性與放射性肺炎Yang M, et aATM基因多態(tài)性與放射性肺損傷Xiong H, Int J Radiat Oncol Bio Phys 2013MDACC數(shù)據(jù)：362例NSCLC放化療病人3級以上RILT發(fā)生率(a) ATM rs189037 AG vs. AA and GG vs. AA(b) ATM rs228590 CT

15、+TT vs. CC(c) ATM rs1801516 AG+AA vs. GG(d) ATM rs189037 G and ATM rs228590 T combined allelesATM基因多態(tài)性與放射性肺損傷Xiong H, Int J 9/24/2022ASTRO 2016, Harvard醫(yī)學院回顧性分析數(shù)據(jù)：1998-2014年， 接受放射治療為主綜合治療的699局部晚期NSCLC250例行基因檢測：EGFR+：19%, ALK+：9%, KRAS+：32%, 野生型40%EGFR, KRAS和ALK基因型與局部晚期 NSCLC放射治療療效項目EGFR+ALK+KRAS+野生型

16、P值OS55.8未達到2833.20.02PFS15.313.713.014.50.473Y-LRFS773849460.083Y-DMFS424927250.25多因素分析ALK+是OS提高的獨立預后因素 (P = 0.03), EGFR+ 病人局部復發(fā)較低 (P = 0.03)復發(fā)后生存分析顯示 EGFR+/ALK+ 病人接受適當靶向治療后生存期較長 (HR = 0.57; P = 0.02) Mak RH, et al. ASTRO 20169/24/2022ASTRO 2016, Harvard醫(yī)學不是所有的靶區(qū)都需要高劑量照射:非小細胞肺癌同步加量放療的研究6000cGy6600cG

17、yKai Ji, Lujun Zhao, Weishuai Liu, et al. BJR 20149/24/2022不是所有的靶區(qū)都需要高劑量照射:非小細胞肺癌同步加量放療的40例III期病人中位生存時間24個月2年生存率為47.9%，2年無局部進展生存率為66.7%。3級以上治療相關性肺炎5例（9.6%）Kai Ji, Lujun Zhao, Weishuai Liu, et al. BJR 20149/24/2022不是所有的靶區(qū)都需要高劑量照射:非小細胞肺癌同步加量放療的研究40例III期病人中位生存時間24個月Kai Ji, LujPET-CT指導下的自適應加量放療密西根大學，II期

18、單臂臨床研究，不可手術治療的I-III期NSCLC調(diào)強適形放療30次，放療劑量根據(jù)2級以上肺損傷風險以及療中PET-CT高代謝區(qū)個體化加量，最高總劑量86GyII/II期病人同步應用卡鉑紫杉醇化療共42例病人入組，中位年齡63歲，男性67%，III期92%，中位物理劑量83Gy（范圍63Gy-86Gy）存活病人中位隨訪47個月，總的2年局部區(qū)域腫瘤控制率為62%，2年局部區(qū)域無進展生存率為38% 中位生存期25個月，2年生存率52%Kong FM, et al. ASTRO 2016PET-CT指導下的自適應加量放療密西根大學，II期單臂臨床RTOG1106研究：功能影像指導下的同步加量照射Feng-ming Kong， RTOG Protocol9/24/20