局部晚期非小細(xì)胞肺癌精準(zhǔn)放療的進(jìn)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(xì)胞肺癌精準(zhǔn)放療的進(jìn)展與挑戰(zhàn)天津醫(yī)科大學(xué)腫瘤醫(yī)院趙路軍2016 天津Tianjin Medical University Can2022/9/24局部晚期非小細(xì)胞精準(zhǔn)放療的進(jìn)展與挑戰(zhàn)同步放化療是局部晚期非小細(xì)胞肺癌的首選治療方案老年局部晚期非小細(xì)胞肺癌

2、的放化療放療技術(shù)進(jìn)步與局部晚期非小細(xì)胞肺癌療效局部晚期非小細(xì)胞肺癌放化療的放療劑量研究進(jìn)展精準(zhǔn)醫(yī)學(xué)背景下非小細(xì)胞肺癌劑量提升研究進(jìn)展2022/9/24局部晚期非小細(xì)胞精準(zhǔn)放療的進(jìn)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(xì)胞肺治療指南Eberhardt WEE, et al. Ann Onc2022/9/24局部晚期非小細(xì)胞肺癌的放化綜合治療Meta 分析（法）法國(guó)meta分析，6個(gè)隨機(jī)對(duì)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(duì)值5.7% (from 18.1% to 23.8%)，5年提高絕對(duì)值4.5% 同步放化療降低了局部區(qū)域進(jìn)展(HR, 0.77; 95% CI, 0.62 to 0.95; P = .01)，但沒有降低遠(yuǎn)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(jí)急性食管炎的發(fā)生（從4%增加到18%），相對(duì)風(fēng)險(xiǎn)：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(xì)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(guó)國(guó)家癌癥數(shù)據(jù)庫(kù)Overall Survival For All Patients According to as TreatedPresented By Zhongxing Liao at 2016 ASCO Annual Meeting調(diào)強(qiáng)放療對(duì)比質(zhì)子治療隨機(jī)對(duì)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(gè)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(gè)體化Optimization w/o lung perfusion guidingOptimization with lung perfusion guiding根據(jù)肺耐受量個(gè)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(gè)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(gè)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(gè)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(gè)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(xué)數(shù)據(jù)：2004-2013, 85例前瞻性劑量爬坡實(shí)驗(yàn)病人， 排除SBRT，檢測(cè)84個(gè)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(gè)與劑量效應(yīng)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(jí)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(xué)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(cè)：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(xiàng)目EGFR+ALK+KRAS+野生型

16、P值OS55.8未達(dá)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(dú)立預(yù)后因素 (P = 0.03), EGFR+ 病人局部復(fù)發(fā)較低 (P = 0.03)復(fù)發(fā)后生存分析顯示 EGFR+/ALK+ 病人接受適當(dāng)靶向治療后生存期較長(zhǎng) (HR = 0.57; P = 0.02) Mak RH, et al. ASTRO 20169/24/2022ASTRO 2016, Harvard醫(yī)學(xué)不是所有的靶區(qū)都需要高劑量照射:非小細(xì)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(xì)胞肺癌同步加量放療的40例III期病人中位生存時(shí)間24個(gè)月2年生存率為47.9%，2年無局部進(jìn)展生存率為66.7%。3級(jí)以上治療相關(guān)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(xì)胞肺癌同步加量放療的研究40例III期病人中位生存時(shí)間24個(gè)月Kai Ji, LujPET-CT指導(dǎo)下的自適應(yīng)加量放療密西根大學(xué)，II期

18、單臂臨床研究，不可手術(shù)治療的I-III期NSCLC調(diào)強(qiáng)適形放療30次，放療劑量根據(jù)2級(jí)以上肺損傷風(fēng)險(xiǎn)以及療中PET-CT高代謝區(qū)個(gè)體化加量，最高總劑量86GyII/II期病人同步應(yīng)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(gè)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(jìn)展生存率為38% 中位生存期25個(gè)月，2年生存率52%Kong FM, et al. ASTRO 2016PET-CT指導(dǎo)下的自適應(yīng)加量放療密西根大學(xué)，II期單臂臨床RTOG1106研究：功能影像指導(dǎo)下的同步加量照射Feng-ming Kong， RTOG Protocol9/24/20