非小细胞肺癌的放射治疗ppt演示课件

非小细胞肺癌 -放射治疗 1 . Lung Cancer Screening From Presentation at: 2011 ASCO Annual Meeting StageIncidenceTreatment5-YrSurvival I15-20%Surgery or SBRT60-80% II5-10%SurgeryChemotherapy40-50% III30-35%Combined-Modality Tr15-40% IV35-40%ChemoRT5% 2. rSBRT vs. 手术 rSBRT靶区勾画 rSBRT毒副反应 I期NSCLC-放射治疗 3. SBRT-Inoperable stage I NSCLC SBRT是无法耐受手术的外周型I期NSCLC的首选治疗 JAMA. 2010;303:1070-6. Phase II trial of SBRT for medically inoperable stage I/II NSCLC-RTOG 0236 55 patients T 5 cm, N0, M0 20 Gy in 3 fractions over 1.5 to 2 weeks rResults 3-year primary tumor control rate: 97.6% Disease-free survival at 3 years: 48.3% Overall survival at 3 years: 55.8% Median overall survival: 48.1 months 4. 2012 5. 2012 6. 2012 7. 2012 8. 9. SBRT vs 3DCRT 10. SBRT-Operable stage I NSCLC Int J Radiat Oncol Biol Phys.2011;81:1352-8. rS B R T i s s a f e a n d p r o m i s i n g t r e a t m e n t f o r o p e r a b l e S t a g e I N S C L C rT h e s u r v i v a l r a t e f o r S B R T i s p o t e n t i a l l y c o m p a r a b l e t o t h a t f o r s u r g e r y R e t r o s p e c t i v e A n a l y s i s 11. SBRT VS.Surgery Trials Closed prematurely Slowly accruing 12. SBRT vs Surgery RTOG foundation study 3502 is kicking off soon 中方PI 于金明 ，山东省肿瘤防治研究院 美国PIFeng-Ming (Spring) Kong，美国密西根大学肿瘤中心 A Randomized Trial in Patients with Operable Stage I Non-Small Cell Lung Cancer:Radical Resection Vs Ablative Stereotacitic Radiotherapy(POSITLV) 13. I期NSCLC-中心型 中心型NSCLC（距离支气管树2cm 内）可能对临近气管、食管及大血 管造成损伤 RTOG 0813 I/II期研究剂量爬坡 (50Gy/5f）研究适合中心型NSCLC 的分割模式及最大耐受剂量 14. 靶区勾画-SBRT GTV在肺窗进行勾画，纵膈窗可区分邻近血管或胸壁结构 GTV不外扩，GTV=CTV GTV在水平面上外扩0.5cm，在头尾方向外扩1cm为PTV 4D CT设备的中心使用呼气或吸气图像或最大密度投影 (MIP)时可能会产生一个内靶区（IGTV） 无4D-CT，GTV勾画应建立在慢CT扫描的基础上 PTV= IGTV+摆位 误差(根据各肿瘤中心而定） 15. SBRT毒副反应 55 inoperable patients with T1-2N0M0 peripheral NSCLC RT： 20Gy3 （RTOG 0236） Logistic regression to investigate relationship between Pulmonary Function(PF) and pulmonary toxicity. Cox proportional hazards models to evaluated between PF test and OS 2012 Results 95% CI, 0.762- 0.959; p=.0077) ANITA （2008） 840 (294 ) 亚组分析显示PORT提高了N2患者的5-ys(34% vs 47% ) 卢铀等 （2010） 183 与术后辅助化疗相比，术后辅助化疗、放疗提 高了患者的生存期（p=0.007） 王绿化等 （2011） 221 术后放疗显著改善OS（P=0.046）和无病生存 （P=0.009） 23. 术后放疗Meta分析结果及缺陷 结论：术后放疗对生存率的降低与分期 相 关。I、期明显，期病例术后放 疗对生存率没有明显影响 缺陷： 3/9随机研究是未发表资料 每组样本量偏小 时间跨度大 分期不明确 入选标准差异大 放疗技术特点： 大多数接受Co60 线照射 部分患者采用单野照射 4/9个临床试验的单次剂量2Gy 4/9个研究的总剂量=60Gy24. 该Meta分析，入组了自1965年以来符合标准的手术联合化疗放 疗13项临床研究 9项临床试验采用先化疗后放疗模式 4项临床试验采用同步放化疗模式 序贯化、放疗和同步放化疗之间无显著性差异（P=0.28） A术后化疗、放疗顺序 25. 2013 NCCN ：化疗、放疗顺序尚无定论，但可优先选择先化 疗后放疗模式 关于a完全切除术后辅助化疗、放疗顺序有待随机临床试验 证明 A术后化疗、放疗顺序 26. A术后放疗靶区 目前术后放疗靶区勾画各肿瘤中心存在分歧 荷兰研究分析了来自不同肿瘤中心的17位胸部肿瘤 放疗专家勾画A（N2）NSCLC术后靶区: 不同医生之间术后放疗靶区勾画存在着较大差异 前瞻性临床试验的研究方案统一确定的靶区勾画能降低 这种差异 Int J Radiat Oncol Biol Phys, 2010, 76:1106-1113. 27. A术后放疗靶区 不同肿瘤中心放疗靶区 University of Michigan Cancer Center 支气管残端+同侧肺门+隆突下+阳性区 域淋巴结 同侧上下一站纵隔区域淋巴结 MD Anderson Cancer Center 支气管残端+阳性区域淋巴结同侧肺 门、隆突下 （根据肿瘤位置和淋巴结清扫程度） 中科院肿瘤医院 支气管残端+同侧肺门、同侧纵隔区域 淋巴结、隆突下 山东省肿瘤医院 支气管残端+阳性区域淋巴结+同侧肺 门+隆突下 Handbook of Evidence Based Radiation Oncology Second Edition 28. r同步化疗方案 r同步放疗剂量 r放疗靶区勾画 r靶向联合放疗 B期NSCLC-放射治疗 29. 同步化疗方案 同步放化疗为首选标准治疗 同步放化疗优于序贯放化疗和单纯放疗 同步化疗方案：2013NCCN增加了培美曲塞联合顺铂或卡铂 方案 同步化疗方案之间目前无孰优孰劣 顺铂为主的同步化疗方案优于卡铂（王绿化等，III期临床试验 -NCT01494558待发表） 30. 同步放疗剂量 Carbo/Taxol Weekly Radiation to 60Gy Carbo/Taxol 2-3 wk cycles Stage III NSCLC N=512 pts Carbo/Taxol Weekly +Weekly Erbitux Radiation to 60Gy Carbo/Taxol 2-3 wk cycles +Weekly Erbitux Carbo/Taxol Weekly Radiation to 74Gy Carbo/Taxol 2-3 wk cycles Carbo/Taxol Weekly +Weekly Erbitux Radiation to 74Gy Carbo/Taxol 2-3 wk cycles +Weekly Erbitux Jeffery Bradley et al. 2011 ASTRO Annual Meeting Overall survival 根治性放化疗通常推荐的放疗剂量仍是60Gy 放疗靶区勾画-IFI STD F IF Stage III NSCLC: ChT/RT; 200 Pts Randomized Parameter2Yr LF1Yr OS2Yr OS3Yr OS ENI4959.725.619.2 IFRT4167.238.727.3 P=0.048 Am J Cli Oncol 2007;30:239-244 放疗靶区勾画-IFI NSCLC累及野照射较预防照射提高了疗效并降低了放射损伤 2年生存率由常规放疗的25.6%提高到39.4% 放射性肺损伤由常规放疗的29%降低到17% 预防照射 累及野照射 美国国家癌症治疗协作网最新修订 的肿瘤治疗指南采用了我们的 研究：将肺癌放疗靶区的定义由预 防性淋巴结照射改为累及野照射 美国RTOG-0617临床试验 的参照 The Phase II Trial Of Erlotinib-RT After Chemo-RT For Patients With Stage III Non-Small Cell Lung Cancer Has Shown A Favorable Response NCI Trial Identifier: NCI-2012-01761 Ritsuko Komaki, M.D. FACR, FASTRO The University of Texas MD Anderson Cancer Center, Houston, TX 靶向联合放疗-Erlotinib 2012 Week1Week2Week3Week4Week5Week6Week7 Days123456 7 123456712345671234567123456 7 123456 7 123456 7 RT12345123451234512345123451234512345 Paclitaxel1111111 Carboplati n 1111111 Erlotinib 23456 7 234567 234567 234567 23456 7 23456 7 23456 7 XRT: 63Gy/35FX/7 weeks; 1.8 Gy/daily5 ; Paclitaxel: 45mg/m2,Carboplatin: AUC =2 ConsolidationChemotherapy (Every 3 weeks; Two cycles Paclitaxel:200mg/m2 Carboplatin: AUC=6 Concurrent ChemoRT + Tarceva(150mg PO) 48 Stage III NSCLC 2012 Results Tumor Responses by RECIST 3.0 CRPRSD or PD Not Available* All 46 cases14/46(30%)23/46(50%)8/46(18%)1/46(2%) EGFR mutation (EGRR-M) 3/4(75%)0(0%)0(0%)1/4(25%) EGFR wild type11/36(30%)19/36(53%)6/36(17%)0(0%) No data0(0%)4/5(80%)1/5(20%)0(0%) *One patient was not evaluable for tumor response due to no follow-up image p=0.07 2012 2012 Conclusions Chemoradiotherapy F/B erlotinib/RT well tolerated Excellent 2-year OS 67.7% and median survival time 34.1 months Grade 3 pneumonitis rate was 6.5% Erlotinib seemed to demonstrate a radiosensitization effect in combination with chemoradiotherapy EGFR mutated patients might need maintenance EGFR-TKI to reduce DM Need to validate with a larger number of patients or in a randomized prospective trial 2012 Phase II Study of Nimotuzumab in Combination With Concurrent Chemoradiation Therapy in Patients With Locally Advanced Non-small Cell Lung Cancer Kinki University Faculty Of medicine, Japan Shizuoka Cancer Center, Japan Hyogo Cancer Center, Japan The Cancer Institute Hospital, Japan 2012 靶向联合放疗- Nimotuzumab Materials/Methods Multicenter phase II study evaluated tolerability and efficacy of nimotuzumab in combination with concurrent CRT in pts with unresectable locally advanced NSCLC Pts receive concurrent RT(60Gy/30F) and 4 cycles of Chemo(NP) Nimotuzumab(200mg)was administrated once a week from cycle 1 to 4 2012 Results 39 pts were eligible from 7 institutions 34 Pts(87%) met criteria for treatment tolerability grade 3 skin rash, grade 3 radiation pneumonitis or grade 4 nonhematological toxicity were not observed The 2 Yr OS rate was 76%;The median PFS was 16.7 months In-field relapse rates were low for Sq(19%) and non-Sq(13%) 2012 Conclusions Addition of nimotuzumab to concurrent CRT was well tolerated with clinical benefit The low in field relapse rates may be attributed to radio-sensitizing effect of nimotuzumab The finds warrant further clinical evaluation in a phase III trial 2012 Meta-analysis of toxicities in Phase I or II trials studying the use of target therapy combined with radiation therapy in patients with locally advanced non-small cell lung cancer M.Santos , D.Lefeuvre, G.Le Teuff, et al. Institute Gustave Roussy, Paris, France. 靶向联合放疗-Meta analysis 2012 Materials/Methods Phase I, I/II and II trials published between 2000 and 2011 treated by targeted therapy(TT) with Chemo-RT Pooled incidence rates of all and specific AEs were estimated Pooled medians of PFS and OS were studied 2012 Results Eight trials(4 phase I, 4 phase II) including 242 pts testing 4 drugs(Bevacizumab, Cetuximab, Erlotinib and Gefitinib) The pooled incidence rates of AE in TT/Chemo-RT was statistically higher than that estimated in Chemo-RT group Median PFS and OS were 10.0 and 18.4 months in TT/Chemo-RT and 9.9 and 16.2 months in Chemo-RT (p=0.98 and P=0.37) 2012 Conclusions The use of TT combined to Chemo-RT seemed to increase significantly the rate of severe adverse events in NSCLC pts as compared to Chemo-RT No significant difference was observed in survial endpoints Heterogeneity was observed between different trials 2012 一项前瞻性、开放、随机对照、多中心期临床研究评估同期 厄洛替尼联合放疗对比同期依托泊甙顺铂（EP）方案联合放疗 用于伴有表皮生长因子受体19或21外显子活化突变的不可切除 期非小细胞肺癌（NSCLC）的疗效及安全性 (RECEL ML 28545) A multicenter, randomized, open-label, phase II trial of Erlotinib versus Etoposide plus Cisplatin with concurrent radiotherapy in unresectable stage III non-small cell lung cancer (NSCLC) with activating mutation of epidermal growth factor receptor (EGFR) in exon 19 or 21 山东省肿瘤医院； 中国医学科学院肿瘤医院 复旦大学附属肿瘤医院； 天津肿瘤医院 河北省肿瘤医院； 浙江省肿瘤医院 北京肿瘤医院； 四川华西医院 中国人民解放军总医院； 杭州市第一人民医院等 l不可切除IIIA/IIIB NSCLC l未行任何治疗 lEGFR 19或21外显子突变 (+) l18岁， 75岁 lECOG PS 01 n100 R PD 同步放化疗（8周） 顺铂 50mg/m2 d1,8,29,36 依托泊甙 50mg/m2 d1-5,29-33 同期RT 60-66Gy/30-33fr 同步治疗(8周) 厄洛替尼 150mg/day 同期 RT 60-66Gy/30-33fr PD 厄洛替尼 150mg/day 最长2年 RECEL研究方案 主要终点： PFS（progression free survival rate） 次要终点： ORR (objective response rate); LCR (local control rate) OS (overall survival, OS); 安全性(NCI CTCAE 4.02版); 采用FACT-LC及LCSS量表比较两组的生活质量; 探索性分子标志物分析 分层因素： 分期：IIIA vs. IIIB 组织病理学：腺癌 vs. 非腺癌 EGFR突变类型：19号 外显子vs. 21号外显子 同步放化疗后 巩固治疗作用 GILT study: Oral vinorelbine (NVBo) and cisplatin (P) with concomitant radiotherapy (RT) followed by either consolidation (C) with NVBo plus P plus best supportive care (BSC) or BSC alone in stage (st) III non-small cell lung cancer (NSCLC): Final results of a phase (ph) III study Huber,et al.Abstr 7001.2012 ASCO TITLE TITLE TITLE TITLE Conclusions Cisplatin doses were standard, oral NVBo is no standard of care for CCRT or systemic CTx in stage III disease Concurrent chemoradiotherapy alone remains a valid standard for a large number of patients in stage III NSCLC disease Is consolidation chemotherapy after concurrent chemoradiotherapy beneficial for locally advanced non-small cell lung cancer? A pooled analysis of the literature Yamamoto,et al.Abstr 7000.2012 ASCO TITLE TITLE TITLE Conclusions This pooled ananlysis on publication basis failed to provide evidence that consolidation chemotherapy improves overall survival in pts with LA-NSCLC Currently, Concurrent ChemoRT is still standard care in LA-NSCLC 放疗技术 仰卧位，双手上举，采用体膜或真空负压带固定 4D-CT或PET-CT定位 如果没有4D-CT，可在模拟定位机透视下测定病变上下 前后、左右方向上的移动度，作为PTV参考数据 建议增强CT扫描，范围包括锁骨上、肺及纵膈、上腹部到 肾上腺水平 靶区勾画原则 GTV包括肺窗中所见肿瘤范围及纵膈窗中所见纵膈淋巴结范围 病变毛刺是否画在GTV里存在