邢力剛-早期非小細胞肺癌SBRT-201803培訓班ppt課件.ppt

1、邢力剛 山東省腫瘤醫(yī)院 2018.03 濟南,早期非小細胞肺癌立體定向放射治療臨床應(yīng)用,早期非小細胞肺癌立體定向放療技術(shù)培訓班（第一屆） 1st Training Course of SBRT for Early-stage NSCLC,LDCT：1.5% Control：0.3%,Stereotactic Body Radiation Therapy (SBRT)Stereotactic Ablative RadioTherapy (SABR),體位固定重復(fù)性高，避免治療間患者運動對治療精確性的影響 劑量分布高度適形，高劑量區(qū)覆蓋腫瘤，周圍正常組織劑量迅速下降以保護正常組織 個體化測定圖像采

2、集、治療計劃和施照時腫瘤的運動并進行針對性的計劃制定與實施 通過在線及離線圖像引導(dǎo)確保精確施照 最重要的是，在2周內(nèi)通過3-8次治療給予超高生物劑量的照射,不可手術(shù)早期NSCLC的SBRT,SABR for Inoperable NSCLC,J Thorac Oncol. 2015;10: 872882,SBRT vs Proton vs Heavy Ion RT,NSCLC-病理 T1，T2(5cm)N0，M0 因其他醫(yī)學問題不適合手術(shù) 未采用其他治療 不做距離支氣管樹2cm之內(nèi)的,2004.5-2006.10 59人參加，55人可評估 62%女性，中位年齡72歲 T1，44人，T2，11人

3、 中位隨訪4年（7.2y，最長）,RTOG 0236,療效與失敗模式,5年DFS和OS分別是26%和40% 5年原發(fā)灶復(fù)發(fā)率僅7% 區(qū)域復(fù)發(fā)率（肺門和縱膈）：3年13%，5年38% 遠處失敗、同一肺葉和區(qū)域淋巴結(jié)復(fù)發(fā)是主要的失敗模式 未觀察到嚴重的長期毒性,周圍型肺癌 SABR的劑量,Karolinska/Nordic: 45Gy/3f Kyoto U/JCOG: 48Gy/4f Indiana U/RTOG: 60Gy/3f RTOG0915: 48Gy/4f vs 34Gy/1f,Japanese Multi-center Study,Onishi et al. JTO 2007,BED

4、=100 Gy had better tumor control.,SBRT 劑量思考,腫瘤體積與SBRT劑量,期外周型NSCLC兩種SBRT方案療效比較的長期隨訪數(shù)據(jù)（RTOG0915，期研究）,Patient population: Biopsy-proven NSCLC, medically inoperable Peripheral lung tumors (as defined by RTOG 0236, i.e., 2cm from tracheo- bronchial tree) T5cm, N0M0 Objective: To select the better of the

5、2 SBRT regimens by comparing them at 1 year (yr.) post SBRT: protocol-specified adverse events; primary tumor control,Int J Radiat Oncol Biol Phys. 2015 Nov 15;93(4):757-64.,16,17,The true rate of not experiencing a psAE is 83%.,期外周型NSCLC 34Gy1次vs. 12Gy4次（RTOG0915，期研究）,N=39,N=45,結(jié)論： 34Gy組1年不良反應(yīng)發(fā)生率和局

6、部控制率滿足研究終點要求，建議III 試驗中采用。,18,期外周型NSCLC兩種SBRT方案療效比較的長期隨訪數(shù)據(jù)（RTOG0915，期研究）,19,期外周型NSCLC兩種SBRT方案療效比較的長期隨訪數(shù)據(jù)（RTOG0915，期研究）,Arm 1( 34Gy1次):39例；Arm 2(12Gy4次):45例。中位隨訪3.8年。,不良反應(yīng)： 3級及以上不良反應(yīng)發(fā)生率較之前結(jié)果沒有明顯變化。,20,周圍型/中心型肺癌（SBRT）,Central tumors tumors located 2 cm from the trachea, mainstem bronchus, main bronchi

7、or esophagus tumors located 6 mm from the heart tumors located in the mediastinum.,SABR Dose for Central lung tumor,How about the SBRT treatment of central lung tumors? How about the complications Timmerman, J Clin Oncol 2006 Local control: 67/70 (95% for 24 months) 11 fold increase in G3 complicati

8、ons with 3 Fx 20Gy (P .004),Decline pulmonary function tests pneumonias pleural effusions apnea skin reaction,Timmerman,et al. J Clin Oncol,2006; 24:4833-4839.,SABR Toxicity of central lung tumor MDACC,2005.2-2011.5 101Pts, T1-2N0M0(n=82); isolated lung-parenchyma recurrent lesions (n=19) 50Gy/4f; o

9、r 70Gy/10f Median Follow-up 30.3m(40.5m for survivor),NO Grade 4 Toxcity,ASTRO 2014,中心型肺癌SBRT劑量,Indiana U/RTOG: 60Gy/3f （毒性過高） MDACC: 50Gy/4f RTOG0813: 50-60Gy/5f VUMC “Risk adapted”: 60Gy/3f,5f, or 8f,早期非小細胞肺癌SBRT的劑量,早期非小細胞肺癌SBRT的劑量不應(yīng)低于BED 100Gy 小于3厘米腫瘤，中高劑量的（BED 100-150Gy）應(yīng)該足夠 大于3厘米腫瘤，具體劑量有待進一步確定

10、中央型腫瘤要充分考慮正常組織損傷,可手術(shù)早期NSCLC的SBRT探索,SBRT for Operable Stage I NSCLC,J Thorac Oncol. 2015;10: 872882,SBRT Versus Surgery Matched Studies,2-year OS,2-year LC,2-year CSS,Zheng (Kong), Int J Radiat Oncol Biol Phys. 2014;90(3):603-11,Stereotactic Body Radiation Therapy Versus Surgery for Early Lung Cancer

11、 Among US Veterans,4,069 patients (veterans) with biopsy-proven clinical stage I non-small cell lung cancer diagnosed between 2006 and 2015 449 SBRT, 2,986 lobectomy, 634 sublobar resection Higher cancer-specific mortality for SBRT compared with lobectomy (subdistribution hazard ratio 1.45, 95% conf

12、idence interval: 1.09 to 1.94, p = 0.01) no survival difference between SBRT and sublobar resection (subdistribution hazard ratio 1.25, 95% confidence interval: 0.93 to 1.68, p = 0.15),Ann Thorac Surg. 2017,SBRT in Early Stage NSCLCRandomized Trials,2013 CLOSED Due to Poor Recruitment,2011 CLOSED Du

13、e to Poor Recruitment,2013 CLOSED Due to Poor Recruitment,爭議與展望,2項入組失敗的pooled analysis 隨訪時間短（SABR組40.2月/手術(shù)組35.4月） 均未達到中位總生存 手術(shù)組不良反應(yīng)高 SABR組8例（26%）無病理診斷，手術(shù)組6例（22%）術(shù)前無病理（1例手術(shù)良性）,Ongoing trails,RTOG 3502 VALOR SABRTooth,RTOG Foundation 3502POSTILV: A Randomized Trial in Patients with Operable Stage I No

14、n-Small Cell Lung Cancer: Radical Resection Vs Ablative Stereotactic Radiotherapy,Study Team Radiation oncologist PIs: J Yu (L Xing); FM Kong Surgeon Co-Chairs: Y Wu/J He/W Mao/G Chen; A Chang/M Orringer/T DAmico Radiation Co-Chairs: L Wang/X Fu; Z Liao/J Chang Physicist PIs: J Dai/Y Yin; F Yin/Y Xi

15、ao/J Yue ,First 5 selected participating Sites,Schema of RTOG Foundation Study 3502Phase II Randomized Study,Primary Endpoint: 2 year local regional tumor control, freedom from local-regional recurrence after RODS and freedom from progression of local primary tumor and disease occurrence at nodal re

16、gions after SBRT.,早期非小細胞肺癌SBRT復(fù)發(fā)后的挽救性治療,37,Salvaging Local-Regional Recurrence after Stereotactic Ablative Radiotherapy (SABR) for Early-Stage NSCLC,Presented By Eric Brooks at 2017 ASCO Annual Meeting,38,Methods,Presented By Eric Brooks at 2017 ASCO Annual Meeting,39,Slide 18,Presented By Eric Broo

17、ks at 2017 ASCO Annual Meeting,40,Slide 29,Presented By Eric Brooks at 2017 ASCO Annual Meeting,41,Benefit of Salvage Treatment,Presented By Eric Brooks at 2017 ASCO Annual Meeting,42,Effect of Salvage on Survival,Presented By Eric Brooks at 2017 ASCO Annual Meeting,43,Slide 48,Presented By Eric Bro

18、oks at 2017 ASCO Annual Meeting,44,Slide 56,Presented By Eric Brooks at 2017 ASCO Annual Meeting,45,Conclusions,Presented By Eric Brooks at 2017 ASCO Annual Meeting,46,SBRT的質(zhì)量保證與控制,SBRT的特點,對醫(yī)師、物理師、技師提出更苛刻的要求 模擬定位、體位固定-可重復(fù)性 呼吸運動-有效管理、控制 靶區(qū)勾畫-精確細致 計劃制定-控制劑量限值 計劃執(zhí)行-精確謹慎,QA detectors optimized for low-dose imaging,Conventional