龙浩NSCLC外科治疗的难点探讨N.ppt

Click to edit Master title style,*,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Topic:,局部晚期,NSCLC,的外科治疗,关于局限性切除和纵隔淋巴清扫,NSCLC,的辅助与新辅助治疗,老年,NSCLC,的外科治疗,局部晚期,NSCLC,的外科治疗,定义,locally advanced NSCLC,侵犯心包 心脏 食管 大血管 隆突等重要结构,(T4),限于胸部而无临床或病理远处转移的,IIIA,期和,IIIB,期的,NSCLC,占,NSCLC,的,60%,70,全部肺癌的,50%,左右,周清华，孙燕，主编,.,肺癌新理论新技术进展,.,第,1,版，成都,:,四川大学出版社，,2003,外科治疗现状,国内 近,20,年,20,多个单位行报道扩大手术治疗上千例,手术及术后早期死亡率,0 11%,术后并发症发生率,15.2%29.4%,术后,5,年生存率,20.8%33.1%,国外 近,30,年,手术死亡率,0 12.5%,手术,30,日内死亡率,2.4%25%,术后并发症发生率,28%50%,术后,5,年生存率,13%38%,对有选择的局部晚期,NSCLC,病人扩大的手术切除结合多学科综合治疗 可提高生存率,!,肺切除合并上腔静脉切除重建术 治疗肺癌上腔静脉综合征,15 years single center experience with surgical resection of the superior vena cava for non-small cell lung cancer,.Yaron Shargall,Lung Cancer(2004)45,357363,上腔静脉切除和人造血管移植,局部晚期,SCLC,侵犯心脏,112,例侵及左心房中心型肺癌,扩大左心房切除术,术后,1,、,3,、,5,年生存率,78.3%,、,59.8%,、,32.2%,同种异体肺移植术,目前观点多局限于无远处转移的,弥漫性肺泡细胞癌,部分肺功能严重受损的局限期肺,NSCLC,自体,肺移植术,治疗,中山大学首例肺移植,（,2005.11.28,）,侵犯心脏大血管的,LANSCLC,的手术治疗,675,例侵犯心脏大血管的,LANSCLC,的外科治疗,全组手术并发症,15.2%,手术死亡率,0.6%,术后,1,、,3,、,5,、,10,年生存率,78.5%,、,60.3%,、,33.45%,、,23.7,%,周清华，等,.,肺切除合并心脏大血管切除重建术治疗局部晚期肺癌,.,中国肺癌杂志，,2001,，,4,（,6,）,403,局部晚期,NSCLC,与新辅助化疗,周清华等,:,724,例,III,期,NSCLC,新辅助化疗可以明显提高术后,5,年生存率,（,34.4%VS.24.2%,p0.01,）,局部晚期,NSCLC,与新辅助化疗,Management of Locally Advanced Non Small Cell Lung Cancer from a Surgical Perspective,Millie S.Roy Jessica S.Donington*,Current Treatment Options in Oncology(2007)8:114,手术,vs,放化疗,The Role of Surgery in N2 Non-Small Cell Lung CancerMalcolmMDeCamp,Jr.,Simon Ashiku,and Robert ThurerClin Cancer Res 2005;11(13 Suppl)July 1,2005,Can we optimize chemo-radiation and surgery in locally advanced stage III non-small cell lung cancer based on evidence from randomized clinical trials?A hypothesis-generating studyDirk De Ruysscher a,Radiotherapy and Oncology 93(2009)389395,手术,vs,放化疗,局部晚期,NSCLC,的治疗指引,手术治疗，可改善生存,外科疗效明显优于内科，有条件手术者，力争手术治疗,新辅助化疗,/,放化疗能降低分期，提高切除率、,5,年生存率,侵犯心脏、大血管,有选择地进行肺切除扩大心脏、大血管切除重建术。手术治疗能明显提高患者的,5,年生存率，改善预后。,相当一部分除局部病变较晚外，并无远处转移存在。,无条件的医疗机构和医师，不要盲目地施行此类手术,治疗应当“个体化”,Vandenbroucke E,De Ryck F,Surmont V,What is the role for surgery in patients with stage III non-small cell lung cancer?,Curr Opin Pulm Med.2009 Jul;15(4):295-302.,关于局限性切除,sublobar resection,Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer.Lung Cancer Study Group.,does not confer improved perioperative morbidity,mortality,or late postoperative lung function.,higher death rate and locoregional recurrence rate,lobectomy still must be considered the surgical procedure of choice for patients with peripheral T1 N0 NSCLC.,Ginsberg RJ,Rubinstein LV,.,Ann Thorac Surg.,1995 Sep;60(3):615-22;,Lobectomy versus limited resection to treat non-small cell lung cancer in stage I a study of 78 cases,Loco-regional recurrence:,lobectomies 9(18%),wedge resections 4(14.3%),Mortality:,lobectomies 8(16%),wedge resections 4(14.3%).,survival rate:,lobectomies 62.38,wedge resections 63.92.,Arch Bronconeumol.2003 May;39(5):217-20,Outcomes of sublobar resection versus lobectomy for stage I non-small cell lung cancer:a 13-year analysis.,Lobectomy 577,sublobar resection for 207,Sublobar resection increased local recurrence,No difference in disease-free survival for IA slightly worse disease-free survival for IB.,Ann Thorac Surg.2006 Aug;82(2):408-15;,University of Pittsburgh Medical Center,Margin and local recurrence after sublobar resection of non-small cell lung cancer,81 patients;,41 margin/=1 cm.segmentectomy 19(47.5%).,Mean follow-up was 20 months,local recurrence:14.6%vs 7.5%(P=.04),Segmentectomy appears to be a better choice,Ann Surg Oncol.2007 Aug;14(8):,El-Sherif A,et al,University of Pittsburgh Medical Center,Effect of tumor size on prognosis in patients with non-small cell lung cancer:the role of segmentectomy as a type of lesser resection.,1272 consecutive patients,肿瘤大小,3cm,5Y,生存率,100%,83.5%,76.5%,57.9%,Lobectomy 92.4%87.4%81.3%,Segmentectomy,96.7%84.6%62.9%,wedge resection 0,Okada M,J Thorac Cardiovasc Surg.2005 Jan;129(1):87-93,.,Selection of sublobar resection for c-stage IA non-small cell lung cancer based on a combination of structural imaging by CT and functional imaging by FDG PET,.,Yoshioka M,Ann Thorac Cardiovasc Surg.2009 Apr;15(2):82-8.,1 cm,PET grade is 0 or 1,(segmentectomy with LN dissection);,PET grade is 2,(lobectomy with systemic LN dissection).,早期肺癌病理组织大切片的研究,-,苏晓东,戎铁华,腺癌和腺鳞癌肿瘤边缘直接侵润距离大于鳞癌,3.62 mm,vs,1.09 mm,病灶周围肺间质见癌细胞沿淋巴管，血管或结蒂组织侵润（,27.6%,）,病灶周围肺泡内见癌细胞,(86.7%),局限性切除,sublobar resection,老年,肺功能限制,合并其他心脑血管疾病,病灶位于外周,2cm?or 3cm?LN?,BAC,非弥漫性,Segmentectomy or extended segmentectomy,vs,wedge resection,margin 1 cm,关于纵隔淋巴清扫,N1N2,淋巴结切除：,清扫,vs,取样,目前,没有证据表明淋巴结清扫的生存情况优于淋巴结采样,但是分期提高了,VATS,淋巴结清扫可行,ACOSOG Z30,随机试验,关于,VATS,系统性淋巴清扫,右上或右中肺叶清扫,2,、,3,、,4,、,7,组,LN,右下肺叶清扫,2,、,3,、,4,、,7,、,9,组,LN左上肺叶清扫,5,、,6,、,7,组,LN,左下肺叶清扫,5,、,6,、,7,、,9,组,LN,非小细胞肺癌的辅助治疗,Chemotherapy effece p=0.004,Pignon,ASCO 2006,患者生存率,(%),DC,与,GC,辅助化疗手术完全切除的,NSCLS,患者,1,年和,2,年生存率相似,GC,P,值均无统计学差异,DC,GC,不同三代药物的比较,F.Barlesi,et al.ASCO 2009.Abstract 7532,顺铂方案或卡铂方案？,晚期,NSCLC,的,meta,分析：生存,与含卡铂方案相比含顺铂方案总生存绝对提高了,5,Hazard ration=1.050(95%CI=1.005-1.218),P=0.514,Hotta,K.et al.J Clin Oncology;22:3852-3859,2004,泰索帝,/,顺铂 泰索帝,/,卡铂 长春瑞滨,/,顺铂,(n=408)(n=406)(n=404),中位周期数,5(1-13)6(1-10)4(1-9),完成,6,周期（,%,）,49.8 51.4 33.6,顺铂方案或卡铂方案？,不良反应,-,耐受性和依从性,Fossella FV.JCO 2003,TAX326,在,NSCLC,辅助化疗阳性的随机临床试验中,4,5,年的生存仅改善,4%14%,40.4%,77.2%,单纯手术患者存活,15%,55.5%,辅助化疗后仍出现复发和转移,应用生物标记或其它预后指标,实施个体化辅助化疗,!,如何提高辅助化疗的治疗效益？,非小细胞肺癌的新辅助治疗,新辅助化疗的优势,新辅助化疗的不足,新辅助化疗组,（,n=258,）,单纯手术组,（,n=261,）,依从性,75%,化疗期进展,2%,CR+PR,45%,2,年,PFS,53%,52%,5,年生存率,44%,45%,以铂类为基础的化疗,+,手术,VS.,单纯手术,MRC LU22-EORTC-NVALT,研究,新辅助化疗对,QOL,、手术方式、术后并发症、根治性切除率等,无不良影响,Lacet 2007,369:1929-37,吉西他滨,+,卡铂,+,手术,VS.,单纯手术,最后的新辅助化疗研究,2008 Ch.E.S.T.,最后的新辅助化疗研究,Ch.E.S.T.,最后的新辅助化疗研究,Ch.E.S.T.,术前还是术后化疗？,缺乏头对头研究证据,NATCH,研究由于每组仅为,200,例,较多学者认为说服力不强,Meta,分析,2009,32,个研究,21,个术前,/10,个术后化疗研究,OS,与,PFS,均无明显差异,70%,的患者完成新辅助化疗,45-60%,的患者完成辅助化疗,J Thorac Oncol,2009;4:1380-1388,老年,NSCLC,的外科治疗,“老年”的定义,随着生存时间的延长，老年肺癌的发生率逐年上升,1,新确诊,NSCLC,患者中，,65,岁：,50%,，,70,岁：,30%-40%,1,肺癌患者中相当比例为老年患者,2,“老年”的定义尚不统一，,通常临床研究中以,70,岁为界,1,Pallis AG,et al.Ann Oncol 2010;21:692-706.,Jaklitsch MT,et al.Lancet Oncol 2003;4:463-471.,老年肺癌的年龄与组织学类型,组织学类型的分布,(%),Taofeek K et al,JCO,2007;25:5570-5577.,老年,NSCLC,患者面临的问题,无论性别，老年患者的生存率不如年轻患者,Jaklitsch MT,et al.Lancet Oncol 2003;4:463-471.,男性生存率,(%),老年,NSCLC,患者面临的问题,老年患者参与临床研究的机会远少于年轻患者老年患者接受标准治疗的机会不如年轻患者,164,项,SWOG,研究,N=16396,Raymond Ng,et al.Clinical Lung Cancer 2005;7(3):168-174.,老年,NSCLC,患者的评估（一）,肿瘤的临床分期,N2,阳性结节患者，可行,EUS-FNAB/TBNA/VATS,脑部,CT,只适用于存在症状时,肺功能评估,术前,FEV,1,70%,的患者术后死亡率和长期生存率与年轻患者相似,心功能评估,存在增加围手术期心血管风险因素者应接受术前心功能评估,1C,年龄相关的心血管变化包括心输出量降低，最大心率降低等,如患者存在心肌梗塞风险，应增加心脏应激试验或超声心动图,Gonzalez-Aragoneses F,et al.Critical Reviews in Oncology/Hematology 2009;71:266-271.,EUS-FNAB=,内镜超声下细针穿刺活检；,TBNA=,经支气管针吸活检；,VATS=,电视辅助胸腔镜手术,老年,NSCLC,患者的评估（二）,存在的伴发疾病,术前排除,COPD/,糖尿病,/,脑卒中,/,营养不良等危险因素至关重要,麻醉风险评估,术前,APACHE,评分有助于预测选择性肝切除术后并发症和死亡,手术风险的评估,经证实综合性老年人心身评估,(CGA),能预测死亡率和发病率,老年癌症术前总体评估,(PACE),PACE,作为一项,20,分钟的访谈应在手术干预中作为常规应用,Gonzalez-Aragoneses F,et al.Critical Reviews in Oncology/Hematology 2009;71:266-271.,APACHE II=,急性生理和慢性健康评分标准,I,期,NSCLC,不同年龄段患者的手术切除率,Chambers A,et al.Interactive CardioVascular and Thoracic Surgery 2010 in press.,手术切除率,(%),P0.001,老年,NSCLC,的手术治疗一览,Pallis AG,et al.Ann Oncol 2010;21:692-706.,第一作者,患者数,年龄,(,岁,),分期,5YS(%),发病率,(%),死亡率,(%),Ciriaco,76,70,I-IIIA,53,(54,月生存率,),19.7,1.3,Hanagiri,18,80,I-IIIA,42.6,50,0,Thomas,500,70,I-IIIA,34,NR,7,Pagni,385,70,NR,NR,34,4.2,Oliaro,258,70,I-IIIA,I,期：,73.6,II,期：,23,IIIA,期：,8.9,39.1,3.1,NR,：未报告；,ND,：淋巴结清除术；,ND0,：未进行淋巴结清除术,老年,NSCLC,的手术治疗一览,Pallis AG,et al.Ann Oncol 2010;21:692-706.,第一作者,患者数,年龄,(,岁,),分期,5YS(%),发病率,(%),死亡率,(%),Sawada,66,75,I-IV,(,术后病理分期,),NR,NR,4.1,Mery,2382,75,I-II,MST,28,月,NR,NR,Yazgan,30,70,NR,21.3,NR,NR,Muraoka,33,80,I-II,MST,ND,：,26,ND0,：,76,ND,：,45,ND0,：,23,0,0,Matsuoka,40,80,I-IIIA,56.9,20,0,NR,：未报告；,ND,：淋巴结清除术；,ND0,：未进行淋巴结清除术,老年,NSCLC,的手术治疗一览,Pallis AG,et al.Ann Oncol 2010;21:692-706.,第一作者,患者数,年龄,(,岁,),分期,5YS(%),发病率,(%),死亡率,(%),Aoki,35,80,I-IIIB,39.8,60,0,Brock,68,80,I-IV,(,术后,分期,),34,44,8.8,Port,61,80,I-IIIA,38,38,13,(,主要,并发症,),1.6,Scanagatta,145,75,I-IV,49.8,11,0.6,Aoki,35,80,I-IIIB,39.8,60,0,NR,：未报告；,ND,：淋巴结清除术；,ND0,：未进行淋巴结清除术,不同年龄段患者接受完全切除的预后,（一）手术死亡率,Chambers A,et al.Interactive CardioVascular and Thoracic Surgery 2010 in press.,手术死亡率,(%),P,0.2,一项为期,5,年的前瞻性研究,(N=6450),不同年龄段患者接受完全切除的预后,（二）并发症,一项为期,5,年的前瞻性研究,(N=6450),并发症,(%),P,0.98,Chambers A,et al.Interactive CardioVascular and Thoracic Surgery 2010 in press.,不同年龄段患者接受完全切除的预后,（,三）主要并发症,一项为期,5,年的前瞻性研究,(N=6450),主要并发症,(%),P,1.00,Chambers A,et al.Interactive CardioVascular and Thoracic Surgery 2010 in press.,不同年龄段患者接受完全切除的预后,（四）住院天数,一项为期,5,年的前瞻性研究,(N=6450),住院时间,(,天,),P,0.54,Chambers A,et al.Interactive CardioVascular and Thoracic Surgery 2010 in press.,不同年龄段患者接受肺叶切除术的预后,（五）生活质量,Chambers A,et al.Interactive CardioVascular and Thoracic Surgery 2010 in press.,功能评分,一项为期,1,年的前瞻性研究,(N=422),手术方式,Gonzalez-Aragoneses F,et al.Critical Reviews in Oncology/Hematology 2009;71:266-271.,患者,(%),75,岁以上,I,期患者不同切除方式的生存率,Gonzalez-Aragoneses F,et al.Critical Reviews in Oncology/Hematology 2009;71:266-271.,100,80,60,40,20,0,0,12,24,36,48,60,72,时间,(,月,),生存率,(%),局部切除,肺叶切除,5,年生存率,55%,54%,并发症,32%,38%,2010 EORTC,老年,NSCLC,治疗指南,Pallis AG,et al.Ann Oncol 201021:692-706.,2010 EORTC,老年,NSCLC,手术治疗推荐,Pallis AG,et al.Ann Oncol 2010;21:692-706.,2010 EORTC,老年,NSCLC,手术治疗推荐,老年患者不能因为其逐渐增大的年龄而放弃手术治疗机会,为老年患者制定是否手术治疗的方案时，应充分考虑肿瘤分期、患者预期生存、体力状态评分和并发症,尽管现有回顾性数据显示治疗效果相似，但目前尚不清楚肺叶切除术是否能作为“标准治疗”或是否能采用更为局限的方法,(,如楔形切除术,),由于死亡率较高，应尽可能避免全肺切除，如需选择全肺切除术，则应更谨慎,应强制性对术前患者的心脏和呼吸功能进行评估及选择，可显著提高治疗结果,Pallis AG,et al.Ann Oncol 2010;21:692-706.,2010 EORTC,老年,NSCLC,术后辅助化疗的推荐,Pallis AG,et al.Ann Oncol 2010;21:692-706.,尽管老年患者辅助化疗的总剂量低于年轻患者，但疗效与年轻患者相似，且并未显著增加毒性,2010 EORTC,老年,NSCLC,术后辅助放疗的推荐,Pallis AG,et al.Ann Oncol 2010;21:692-706.,由于缺乏辅助放疗在老年患者,中的数据，因此不推荐老年患者,接受辅助放疗,谢谢！,