乳腺癌放射治疗指南之演变及解读

乳腺癌放射治疗指南之演变及解读乳腺癌放射治疗指南之演变及解读 陈佳艺陈佳艺 交通大学医学院附属瑞金交通大学医学院附属瑞金医院医院 2016-11-26 1 20112016 NCCN指南指南变迁：保乳术后变迁：保乳术后 成熟部分：成熟部分： 全乳放疗全乳放疗+ +瘤床加量瘤床加量 可能减免术后放疗的老年患者可能减免术后放疗的老年患者 变迁部分变迁部分 全乳大分割全乳大分割 未明确部分未明确部分 部分乳腺短程照射部分乳腺短程照射 包含区域淋巴结照射的大分割治疗包含区域淋巴结照射的大分割治疗 2 3 保乳治疗的前瞻性保乳治疗的前瞻性III期研究期研究 TrialNo. 年限年限/ FU years T max切缘切缘N+% 局部复发局部复发% 保乳保乳乳房切除乳房切除p 米兰米兰期期7011973-80 /202cm-25.88.82.30.01 IGR1791972-80 /152cm-32.4914NS NSABP-B0612191976-84 /204cm-371410NS NCI2371979-87 /185cm+40.52200.001 EORTC9021980-86 /155cm+4320120.01 DBCG9051983-89 /205cm-354.66.5NS # # 对照组除米兰对照组除米兰期为根治术外均为改良根治术，研究组除米兰期为根治术外均为改良根治术，研究组除米兰期为象限切除外均为肿块切除术期为象限切除外均为肿块切除术 4 EBCTCG2005 单纯保乳手术单纯保乳手术 VS 术后全乳放疗术后全乳放疗 4 : 1 5 瘤床加量对局部控制的意义瘤床加量对局部控制的意义 作者作者病例数病例数全乳剂量全乳剂量BOOST 局部复发率局部复发率(%)随访随访(年年) Bartelink 2657 50Gy/25Fx /10.2 10 2661 16Gy/8Fx6.2 Romestaing 503 50Gy/20Fx /4.5 3.3 521 10Gy/4Fx3.6 Polgar 103 50Gy/25Fx /15.5 5.3 104 16Gy/8Fx6.7 Bartelink H, et al. J Clin Oncol. 2007. 25(22): 3259-65. Romestaing Pet al. J Clin Oncol. 1997. 15(3): 963-8. Polgar Cet al. Strahlenther Onkol. 2002. 178(11): 615-23 保乳术后全乳照射和瘤床加量保乳术后全乳照射和瘤床加量 6 保保乳术后全乳照射和瘤床加量乳术后全乳照射和瘤床加量 7 老年患者老年患者BCTRT Trial Inclusion criteria F-U Y Baseline therapy Local control RT Local control No RT Canadian 50Y, HR+, T1-2, cN0 5TAM0.6% 7.7% CALGB70Y, HR+, T1-2, cN0 5TAM1%4% 10.52%9% PRIME II65Y, HR+, T3cm, PN0, grade I-II 5Any endocrine therapy 1.3%4.1% 8 谁可以减免放疗？谁可以减免放疗？ 9 Breast irradiation may be omitted in patients 70 y of age with estrogen-receptor positive, clinically node- negative, T1 tumors who receive adjuvant endocrine therapy - CALGB的入组条件的入组条件 10 全乳大分割基石研究：全乳大分割基石研究：Canadian Trial 每周照射次数由每周照射次数由5次减少为次减少为 3次次 2.66Gy16F vs 2Gy25F 没有瘤床没有瘤床boost 美容效果没有明显差异美容效果没有明显差异 T1-2，N0 N ENGL J MED 362;6:513-520,2010 7.5% 7.4% Including non- invasive R UK START A 研究设计研究设计 2236，pT1-3a pN0-1 M0 BCT（1055） or mastectomy 50Gy/25F/5W, 74941.6Gy/13F/5W,75039Gy/13F/5W, 737 2Gy3.2Gy3Gy3.3Gy from RMH 疗程均为疗程均为5周，分次剂量和总剂量逐渐减少周，分次剂量和总剂量逐渐减少 局部控制和乳房外形分别的局部控制和乳房外形分别的/值值 局部控制局部控制 /=4.8Gy 乳房外形乳房外形 /=3.1Gy 2215，pT1-3a pN0-1 M0 BCT（2038） or mastectomy 50Gy/25F/5W, 1105 UK START B 研究设计研究设计 40Gy/15F/3W, 1100 2Gy 2.67Gy 16F from Canadian trial 2.67 Gy15F 总剂量减少总剂量减少2.67Gy，疗程为，疗程为3周周 START B 局部控制结果局部控制结果 14 START B 中位随访中位随访9.9年年 5.5% vs 4.3% 大分割指南推荐方案演变大分割指南推荐方案演变 15 全乳全乳45-50Gy, 1.8-2.0Gy/次次 42.5Gy, 2.66Gy/次，次，16次次 全乳全乳45-50Gy, 1.8-2.0Gy/次次 40-42.5Gy, 2.66Gy/次，次，15-16次次 Shorter course is preferred 16 部分乳腺短程照射部分乳腺短程照射 Accelerated Partial Breast Irradiation, APBI 即在低危患者中采用单纯照射肿瘤床及即在低危患者中采用单纯照射肿瘤床及 周围一定范围的正常乳腺组织来替代传周围一定范围的正常乳腺组织来替代传 统的全乳照射方法，从而在不影响局部统的全乳照射方法，从而在不影响局部 控制率的前提下达到显着降低正常组织控制率的前提下达到显着降低正常组织 损伤并大幅缩短疗程的方法损伤并大幅缩短疗程的方法(5-6.5周下周下 降至降至1周左右周左右) Semin Radiat Oncol. 2005. 15(2): 69-75 17 GEC-ESTROASTRO 1.Age 50yr 60yr 2. Tumor size 3cm 2cm 3. T stagepT12T1 4. Margins 2mm 2mm 5. GradeAnyAny 6. LVSINot allowedNot allowed 7. ER statusNot allowedPositive 9. MultifocalityUnifocalC. unif with total size 2.0 cm 10. HistologyIDC, mucinous, tubular medullary colloid IDC or other favorable 11. Pure DCISNot allowedNot allowed 12. EICNot allowedNot allowed 13. Asso LCISAllowedAllowed 14. N stageAnypN0 (i-, i+) 15. Nodal TxpN0 SLNB /ALNDSLNB or ALND 16.NACTNot allowedNot allowed 绝经前早期乳腺癌亚临床病灶特点绝经前早期乳腺癌亚临床病灶特点 APBI, 不同技术比较不同技术比较 技术技术剂量梯度剂量梯度体积剂量体积剂量评估评估处方剂量点处方剂量点 外照射外照射*可行可行靶区体积内靶区体积内 多排插植近距离治多排插植近距离治 疗疗 *可行可行在插植平面内或之在插植平面内或之 间间 水囊导管近距离治水囊导管近距离治 疗疗 *可行可行水囊表面下水囊表面下1cm 术中电子线术中电子线*不可行不可行90%等剂量曲线等剂量曲线 术中低能术中低能X线线*不可行不可行瘤床表面瘤床表面 19 保乳术后放射治疗指南稳定部分保乳术后放射治疗指南稳定部分 1.全乳放疗及瘤床加量始终是指南全乳放疗及瘤床加量始终是指南I类推荐类推荐 2. 单纯全乳可以接受单纯全乳可以接受45-50Gy的的5周方案或周方案或2.6615或或16次的次的 大分割方案大分割方案 3. 区域淋巴结照射没有大分割的推荐区域淋巴结照射没有大分割的推荐 4. 部分乳腺短程照射没有重大更新，在部分乳腺短程照射没有重大更新，在RTOG 0413结果之结果之 前，仍然推荐前，仍然推荐2009年出台的年出台的ASTRO“低危”标准“低危”标准 20 20112016 NCCN指南变迁指南变迁：区域淋巴：区域淋巴 结照射结照射 PMRT总体结果总体结果 在局部（乳房在局部（乳房/胸壁）照射基础上单独评价区域淋巴胸壁）照射基础上单独评价区域淋巴 结照射的研究结照射的研究 在局部照射基础上单独评价内乳淋巴结照射的研究在局部照射基础上单独评价内乳淋巴结照射的研究 21 腋淋巴结腋淋巴结4+患者的术后放疗患者的术后放疗 22EBCTCG 2014 Trials of RT after mastectomy and ALND RT: significant benefit 腋淋巴结腋淋巴结1 1- -3+3+患者的术后放疗患者的术后放疗 Trials of RT after mastectomy and ALND RT: significant benefit 1.5B : 1C4A : 1C 乳房乳房/ /胸壁基础上区域淋巴结照射的研究胸壁基础上区域淋巴结照射的研究 French TrialEORTC22922/10925MA.20 入组年限入组年限1991-19971996-20042000-2007 样本量样本量133440041832 主要入组标准主要入组标准N+或内侧或内侧/中央区中央区N+或内侧或内侧/中央区中央区N+或高危或高危N0 N0 比例比例40%44.4%9.7% 中位年龄中位年龄575454 手术类型手术类型乳房切除乳房切除76.1%保乳保乳保乳保乳 化疗化疗%618591 ER/PR-71625 HR不详比例不详比例%40%16%不详不详 乳房乳房/胸壁剂量胸壁剂量入组中心决定入组中心决定50Gy/25F50Gy/25F 锁骨上淋巴结锁骨上淋巴结研究组和对照组研究组和对照组 45Gy/25F 研究组研究组50Gy/25F研究组研究组45Gy/25F 内乳淋巴结内乳淋巴结研究组研究组45Gy/25F研究组研究组50Gy/25F研究组研究组45Gy/25F 25 MA 20 高危定义：高危定义：T5cm，或，或T2cm，同时，同时10枚腋窝淋巴结取样，且枚腋窝淋巴结取样，且ER-，G3或淋巴脉管受侵或淋巴脉管受侵 入组标准比较入组标准比较 MA.20（1832例）例）EORTC（4004例）例） 入组条件入组条件LN+或高危或高危LN-LN+或或中央中央/内侧内侧肿块肿块 T1-T299%95.8% N0/N110%/85%44.4%/43.1% HR阳性阳性75%77.5% 保乳手术保乳手术100%76.1% 区域淋巴结照射范围区域淋巴结照射范围SC+IMN+ALNSC+IMN 化疗化疗91%54.8% NEJM: 2015, NEJM: 2015, 3 373 (4) : 31773 (4) : 317- -327327 Study Design：EORTC22922/10925 Phase 3 trial N = 4004 Stage I-III Centrally or medially; or externally with LN(+) BCS or Mastectomy + ALND/SLND R A N D O M I Z E Non-RNI (N = 2002) Whole Breast or chest wall irradiation: 50Gy/25 Fx RNI (N = 2002) Whole Breast or CW irr-a diation: 50Gy/25Fx Regional nodes: 50Gy/ 2 5Fx Primary end points was overall survival Secondary end points included DFS, Distant DFS and toxicity, Breast Cancer Mortality EORTC 22922/10925 28 EORTC 22922/10925 29 无远处转移复发率无远处转移复发率 总生存率总生存率 ER tumors: 10-year DFS in the control and RNI arms ：(71% and 82%, P0.05); 10-year OS：74% and 81% NEJM: 2015, NEJM: 2015, 3 373 (4) : 30773 (4) : 307- -316316 Study Design- MA 20 cT4，cN2-N3 were ineligible High risk was defined as T5cm; T2cm，nodes analyzed10 and one of these: ER-, Grade III, LVI+ II (nodes analyzed10, 4 involved nodes), Phase 3 trial N = 1832 Invasive breast cance r LN (+) or High risk* L N(-) BCS+ALND/SLND Chemotherapy and/or endocrine therapy R A N D O M I Z E WBI (N = 916) Whole Breast: 50Gy/25Fx Tumor Bed Boost (selective): 10-16Gy/5-8Fx WBI+RNI (N = 916) Whole Breast: 50Gy/25Fx Tumor Bed Boost (selective): 10-16Gy/5-8Fx Regional nodes Primary end points was overall survival Secondary end points included DFS, isolated LRRFS, distant DFS and toxicity MA 20 31 MA 20 32 无远处转移复发率无远处转移复发率 总生存率总生存率 Following Following BSC,BSC, RTRT should includeshould include, If If pN+pN+ Breast only5 Breast and regional nodes but not IMN50 Breast and regional nodes including IMNBreast and regional nodes including IMN30 30* * Abstain16 PMRTPMRT should includeshould include : Chest wall only11.4 Chest wall and regional nodes but not IMN40.9 Chest wall and regional nodes including IMNChest wall and regional nodes including IMN15.915.9* * Abstain31.8 2015 St. Gallen Consensus High risk factors of IMN metastasis 1,679 Chinese patients were underwent ERM: 1956-2003 High risk factors including: (1) patients with 4 or more positive ALNs. (2) patients with medial tumor and positive ALNs. (3) patients with T3 tumor and younger than 35 y. (4) patients with T2 tumor and positive ALNs. (5) patients with T2 tumor and medial tumor The incidences of IMNS metastasis for those patients w ere more than 20%. Irradiation of IMN? Dose to HEART in Left-sided BC 左侧患者心脏剂量显著高于右侧患者左侧患者心脏剂量显著高于右侧患者 IMN-RTNo-IMN RT meanSDmeanSD Heart Dmean（cGy）1151231569205 LV Dmean（cGy）1110398811276 Cao Lu et al. Cancer / Radiothrapie, 2014 Cao Lu et al. the Oncologist, 2015 Cao Lu et al. Oncotarget, 2016 pNmic were ineligible 10% of patients with left-sided breast cancer did receive IMNI, who were more frequently had many lymph nodes involved or a medial/central tumor DBCG-IMN study Early Stage; Lymph node positive Right-sided (N=1492) Follow-up Left-sided (N=1597) WB/CW+RNI (With IMN) N=1437 WB/CW+RNI (Without IMN) N=1432 The study was a nationwide, prospective, population-based cohort study, 2003/1-2007/12 Primary end points was overall survival Secondary end points were breast cancer mortality and distant recurrence First recurrence Events IMNNon-IMN Local recurrence48 (3.2%)45 (2.8%) Regional recurrence 31 (2.1%)53 (3.3%) Distant recurrence390 (26.1%)423 (26.5%) opposite breast 39 (2.6%)29 (1.8%) Note: Similar numbers of patients died of ischemic heart disease in the two groups 1.2%差别差别 8-year OS (HR=0.82, p=0.005) 75.9% vs. 72.2% 8-year breast cancer mortality (HR=0.85, p=0.03） 20.9% vs. 23.4% 8-year distant recurrence (HR=0.89, p=0.07) 27.4% vs. 29.7% DFS Subgroups analysis IMNI was more effective in the subgroups of medial/central tumor and/or four or more positive nodes the 8-year OS was 72.2% vs. 64.8% in combined subgroup The adjusted HR for death was 0.76 (P = .001). The number of patients needed to treat to avoid one death at 8 years was 14 (95% CI, 9 to 30). 区域淋巴结照射推荐变迁（区域淋巴结照射推荐变迁（2011） 41 ALN + 4枚及以上：全乳和瘤床枚及以上：全乳和瘤床/胸壁胸壁RT：I类，锁骨上类，锁骨上/下：下：2A类，内乳：类，内乳：3类类 ALN + 13：全乳和瘤床：全乳和瘤床RT：1类，胸壁和锁骨上类，胸壁和锁骨上/下：下：2A类，内乳：类，内乳：3类类 区域淋巴结照射推荐变迁（区域淋巴结照射推荐变迁（2012-2015） 42 ALN+ 4枚及以上：全乳和瘤床枚及以上：全乳和瘤床/胸壁胸壁RT：I类，锁骨上类，锁骨上/下：下：2A类，内乳：类，内乳：2B类类 ALN + 13：全乳和瘤床：全乳和瘤床RT：1类，胸壁和锁骨上类，胸壁和锁骨上/下：下：2A类，内乳：类，内乳：2B类类 区域淋巴结照射推荐变迁（区域淋巴结照射推荐变迁（2016） 43 ALN + 4枚及以上：全乳和瘤床枚及以上：全乳和瘤床/胸壁胸壁RT：I类，锁骨上类，锁骨上/下及腋窝：下及腋窝：1类，内乳：类，内乳：1类类 ALN + 13：全乳和瘤床：全乳和瘤床RT：1类，胸壁和锁骨上类，胸壁和锁骨上/下及腋窝：下及腋窝：2A类，内乳：类，内乳：2A类类 ASCO PMRT guidelines: 2016 44 聚焦问题：聚焦问题： Is postmastectomy radiotherapy (PMRT) indicated in patients with T1-2 tumors with 13 + ALN who undergo axillary lymph node dissection (ALND)? Is PMRT indicated in patients with T1-2 tumors and a positive sentinel node biopsy (SNB) who do not undergo completion ALND? Is PMRT indicated in pat