王绿化术前放疗与放化疗-蚌埠

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,食管癌的术前放疗与化放疗,中国医学科学院肿瘤医院,王绿化,作者,病例数,切除率,5年生存率,张 大为-1994,张 毓德-1986,邵 令方-1987,3603,3675,4160,86.0%,83.4%,93.7%,30.4%,25.2%,47.1%,单纯手术治疗,不同分期的手术治疗,分期,5年生存率,0-1,2,3,淋巴结(-),淋巴结(+),83.3-92.9%,46.3-53.5%,6.7-15.1%,39.3-47.5%,10-25%,食管癌术前放疗,术前放疗,-,一项具有代表性的随机临床研究,汪楣 等，中国医学科学院肿瘤医院 胸外科/放疗科,治疗流程,入组,418,放疗+手术:195,单纯手术:,223,放疗:8MV-X, 40Gy/20次/28天,放疗后2-4周施行手术,术前放疗,并发症,治疗方式,手术死亡率,胸腔内吻合口漏,切缘阳性率,R+S,2.2%,2.2,0,S,4.2%,3.7,2.1,食管癌术前放疗对生存的影响：SEER研究Survival Effect of Neoadjuvant Radiotherapy Before Esophagectomy for Patients With Esophageal Cancer: A Surveillance, Epidemiology, and End-Results Study Int. J. Radiation Oncology Biol. Phys., Vol. 73, No. 2, pp. 449455, 2021,入组标准,病例来源：SEER数据库，1998-2004 病理类型：鳞癌 或 腺癌,疾病分期：T2, T3, T4,所有病人均接受手术切除,接受或未接受外照射新辅助放疗,排除标准,接受过术后放疗，既往治疗情况不详，伴有 转移，手术术式不详，年龄不详或多原发,共1033例病人符合入组标准,单因素分析:癌症专项生存,中位时间(月),3年癌症专项生存率 (%),5年癌症专项生存率 (%),HR*,95% CI,p,术前放疗,35,49,41,0.69,0.580.82,0.0001,单纯手术,21,39,34,术前放疗,单纯手术,单因素分析：总生存,中位生存时间(月),3年生存率 (%),5年生存率 (%),HR*,95% CI,p,新辅助放疗,27,43,34,0.64,0.550.75,0.0001,单纯手术,18,30,23,新辅助放疗,单纯手术,总生存率的多因素分析,变量,多因素分析,CHR,95% CI,p,总生存,术前放疗 (是 vs. 否),0.67,0.570.79,0.0001,年龄 (65 vs. 65 ),0.81,0.690.94,0.0071,组织学类型 (腺 vs. 鳞),0.71,0.610.85,0.0001,性别 (女 vs. 男),0.64,0.520.78,0.0001,淋巴结状态 (阴性 vs. 阳性),0.50,0.430.59,10 vs. 10),0.77,0.660.91,0.0015,T 分期 (T2 vs. T3/T4),0.75,0.630.90,0.0023,结 论,术前放疗显著改善可手术切除食管癌的癌症专项生存和总生存,有必要进行前瞻性研究来证实新辅助放疗的价值，并确定新辅助化放疗的最正确药物及化放疗的联合方式,食管癌术前放化疗,Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in esophageal carcinoma: a meta-analysis,荟萃分析： 食管癌从新辅助化放疗或新辅助化疗中获益,Val Gebski,et al .Lancet Oncol 2007; 8: 22634,主要目标：,所有原因的死亡率 总生存率,次要目标,治疗干预对不同病理类型所有原因死亡率的影响鳞癌或腺癌,化放疗联合模式对所有原因死亡率的影响续贯或同步,新辅助化放疗 vs 单纯手术,总生存率,2年生存绝对获益13%,p=0002,新辅助化疗 vs 单纯手术,总生存率,2年生存绝对获益 7%,p=005,分层分析：不同病理类型死亡率,新辅助化疗 vs 单纯手术,分层分析：不同病理类型+联合治疗模式死亡率,新辅助化放疗 vs 单纯手术,结 论,术前化放疗显著提高食管癌生存率，术前单纯化疗提高食管腺癌生存,这项研究为食管癌新辅助治疗提供了循证根底.,Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis,研究内容：,术前放化疗 vs 单纯手术,术前化疗 vs 单纯手术,术前放化疗 vs 术前化疗,观察指标：,主要目标：所有原因的死亡率 总生存率,次要目标：治疗对不同病理类型死亡率的影响鳞癌或腺癌,Lancet Oncol 2021; 12: 68192,Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis,Lancet Oncol 2021; 12: 68192,研究概况：,24组随机分组研究：4188例患者。,术前放化疗vs 手术：12组，1854例。,术前化疗vs手术：9组，1981例,术前放化疗vs术前化疗：2组，194例,术前放化疗vs 手术 &术前化疗vs手术：,1组，分别78和81例。,术前放化疗+手术 vs 单纯手术：,总生存率,Lancet Oncol 2021; 12: 68192,HR=0.780.70-0.88，P0.0001,不同病理类型术前放化疗的影响：,总生存率,Lancet Oncol 2021; 12: 68192,HR=0.800.68-0.93，P=0.004,HR=0.750.59-0.95，P=0.02,术前放化疗与,围手术期死亡率,Lancet Oncol 2021; 12: 68192,围手术期死亡率与术前放化疗没有显著相关性,术前化疗+手术 vs 单纯手术：,总生存率,Lancet Oncol 2021; 12: 68192,HR=0.870.79-0.96，P=0.005,不同病理类型术前化疗的影响：,总生存率,Lancet Oncol 2021; 12: 68192,HR=0.920.81-1.04，P=0.18,HR=0.830.71-0.95，P=0.01,术前化疗与,围手术期死亡率,Lancet Oncol 2021; 12: 68192,围手术期死亡率与术前化疗没有显著相关性,术前放化疗 vs 术前化疗：,总生存率,Lancet Oncol 2021; 12: 68192,HR=0.880.76-1.01，P=0.07,Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis,Lancet Oncol 2021; 12: 68192,结论：,术前放化疗或术前化疗显著改善总生存,术前放化疗显著改善鳞癌或腺癌总生存,术前化疗显著改善腺癌总生存,术前放化疗相对于术前化疗有提高生存率的趋势,Meta-analysis of neoadjuvant treatment modalities and definitive non-surgical therapy for oesophageal squamous cell cancer,研究内容：,术前放化疗vs单纯手术,术前化疗vs单纯手术,根治性放化疗vs放化疗+手术或单纯手术,观察指标：,1-,2-, 3- and 5-y 生存率, R0切除率，治疗并发症，手术死亡率和肿瘤复发率,Br J Surg. 2021 Jun;98(6):768-83,术前放化疗+手术 vs 单纯手术,9组随机分组研究1992-2021：1099例患者,鳞癌：6组；鳞癌/腺癌：3组,中位年龄：60.8岁；男性：87%,化疗：PDD5-Fu/VLB/BLM,化放疗与手术间隔：2-8周,总切除率：80-98%；pCR：11-43%,Br J Surg. 2021 Jun;98(6):768-83,术前放化疗 vs 单纯手术：,总生存率,HR=081 (070 to 095， P = 0008,Br J Surg. 2021 Jun;98(6):768-83,术前放化疗 vs 单纯手术：,R0切除率,术前放化疗组：55-100%；单纯手术组：37-100%,HR=1151.00-1.32, P = 0043,Br J Surg. 2021 Jun;98(6):768-83,术前放化疗 vs 单纯手术：,术后并发症,术前放化疗组：5-80%；单纯手术组：3-92%,HR=094,0.82-1.07, P = 0363,Br J Surg. 2021 Jun;98(6):768-83,术前放化疗 vs 单纯手术：,手术死亡率,术前放化疗组：8%；单纯手术组：5%,HR=1.46,0.91-2.33, P = 0116,Br J Surg. 2021 Jun;98(6):768-83,术前化疗+手术 vs 单纯手术,8组随机分组研究：1707例患者,中位年龄：62.5岁；男性：79%,化疗：PDD5-Fu/VLB/BLM,2/3患者按方案完成化疗,化放疗与手术间隔：2-5周,总切除率：70-95%；pCR：3-50%,Br J Surg. 2021 Jun;98(6):768-83,术前化疗 vs 单纯手术：,总生存率,HR=093 (081 -1.08， P = 0368,Br J Surg. 2021 Jun;98(6):768-83,术前化疗 vs 单纯手术：,R0切除率,术前化疗组：44-87%；单纯手术组：35-74%,HR=1161.05-1.30, P = 0006,Br J Surg. 2021 Jun;98(6):768-83,术前化疗 vs 单纯手术：,术后并发症,术前化疗组：1-50%；单纯手术组：3-47%,HR=1.03,0.90-1019, P = 0638,Br J Surg. 2021 Jun;98(6):768-83,术前化疗 vs 单纯手术：,手术死亡率,HR=1.04,0.76-1.43, P = 0810,Br J Surg. 2021 Jun;98(6):768-83,根治放化疗 vs 放化疗+手术或单纯手术,3组随机分组研究：512例患者,中位年龄：59.1岁；男性：87%,Br J Surg. 2021 Jun;98(6):768-83,根治放化疗 vs 放化疗+手术或单纯手术,：,总生存率,3组研究均无差异,Br J Surg. 2021 Jun;98(6):768-83,根治放化疗 vs 放化疗+手术或单纯手术：,术后并发症,HR=0.78,0.47-1.30, P = 0332,Br J Surg. 2021 Jun;98(6):768-83,根治放化疗 vs 放化疗+手术或单纯手术,：,治疗相关死亡率,HR=7.60,1.76-32.88, P = 0007,Br J Surg. 2021 Jun;98(6):768-83,1,2,Meta-analysis of neoadjuvant treatment modalities and definitive non-surgical therapy for oesophageal squamous cell cancer,结论：,术前放化疗显著改善可手术食管癌患者生存。,术前放化疗或术前化疗显著提高R0切除率。,根治性放化疗的作用不优于术前放化疗+手术的治疗结果，但前者治疗相关死亡显著低于后者p=0.007),Br J Surg. 2021 Jun;98(6):768-83,Systematic review of the benefits and risks of neoadjuvant chemoradiation for oesophageal cancer,研究概况：,2000-2021,38组-期临床研究：3640例患者。,化疗：PDD+5Fu为主。,放疗：30-60Gy，1.8-2.0Gy/f为主,Br J Surg. 2021 Oct;97(10):1482-96,Systematic review of the benefits and risks of neoadjuvant chemoradiation for oesophageal cancer,研究结果：,化放疗毒性以粒细胞减少多见。,化放疗相关死亡率2.3%。,R0切除：88.4%；病理完全缓解：25.8%。,围手术期死亡率：5.2%。,5年OS：16-59%,pCR患者5年OS：34-62%,Br J Surg. 2021 Oct;97(10):1482-96,小结,有较多的临床证据支持可手术食管癌的术前放化疗或术前化疗,对食管鳞癌和腺癌病例，术前放化疗有较为充分的研究结果能够提高生存率,术前化疗仅能提供食管腺癌的生存率,Preoperative Chemoradiotherapy for Esophageal or Junctional Cancer,van Hagen P .N Engl J Med 2021;366(22):2074-84,Introduction,Esophageal cancer,new case 480,000 per year,deaths case 400,000 per year,surgery R1 25%,5y-OS 40%,Neoadjuvant chemoradiotherapy,Mainly eligibility criteria,SCC AC,Large-cell undifferentiated,Thoracic esophagus or EGJ,T1N1M0 (UICC 2002),T2-3N0-1M0,Design,(2004.03 -2021.12),368,underwent randomization,2 withdrew consent,CR: CBP,AUV,2mg/L min ; TAX 50mg/ weekly,5 circle. 41.4Gy/1.8Gy/23f,Statistical analysis,Overall survival (OS),Intention-to-treat,The KaplanMeier method,Log-rank test,Cox models,SPSS 17.0,Results,Characteristic,CR+S,(N=178),S alone,(N=188),Tumor typeno.(%),Adenocarcinoma,134(75),141(75),Squamous-cell carcinoma,41(23),43(23),Other,3(2),4(2),Tumor locationno.(%),esophagus,133(75),135(72),Esopgagogastric junction,39(22),49(26）,Missing data,6(3),4(2),Clinical N stage-no.(%),N0,59(33),58(31),N1,116(65),120(64),Clinical T stage-no.(%),cT1,1(1),1(1),cT2,26(15),35(19),cT3,150(84),147(78),cT4,0,1(1),Could not be determined,1(1),4(2),Table 1.,Results,Toxic effects,Event of grade 3during chemoradiotherapy- no. of patients(%),CR+S,(N=178),S alone,(N=186),Anorexia,9(5),Constipation,1(1),Diarrhea,2(1),Esophageal perforation,1(1),Esophagitis,2(1),Fatigue,5(3),Nausea,2(1),Vomiting,1(1),Leukopenia,11(6),Neutropenia,4(2),Thrombocytopenia,1(1),Table 2. adverse event during neoadjuvant chemoradiotherapy,Results,surgery complication,CR+S,(N=178),S alone,(N=186),Postoperative events-no. of patients/total no.(%),Pulmonary complications,78/168(46),82/186(44),Cardiac complications,36/168(21),31/186(17),Chylothorax,17/168(10),11/186(6),Mediastinitis,5/168(3),12/186(6),Anastomotic leakage,36/161(22),48/161(30),Death,In hospital,6/168(,4,),8/186(,4,),After 30 days,4/168(2),5/186(3),Table 3. adverse event after surgery,Results,pathological assessment,CR+S,S alone,P value,R0 resection-no.%,148 (92),111 (69),0.001,N+ -no.%,50 (31),120 (75),0.001,pCR 47(29%) AC 28(23%),P=0.008,SCC 18(49%),Results,CR+S,(m),S alone,(m),P value,mDFS,-,24.2,0.001,mOS,49.4,24.0,0.003,Results OS,1-Year,3-Year,5-Year,CR+S,82%,58%,47%,S alone,70%,44%,34%,Figure 1,13%,Results,Figure 1,Discussion,Postoperative complication rates,High!,meticulous record,Discussion,EGJ(CR+S),treatment,R0 resection,3Y-OS,5Y-OS,Present,22%,CRT,CP weekly 5w 41.4Gy,92% VS 69%,58%VS 44%,P=0.003,47%VS 34%,POET,100%,C+R,DF 2.5circle 12w,30Gy,69.5%VS72%,28%VS27%,P=0.07,-,Conclusion,preoperative chemoradiotherapy is safe and leads to a significant increase in OS among patients with AC or SCC of the esophagus or esophagogastric junction.,(5 courses of carboplatin and paclitaxel, with 41.4 Gy of concurrent radiotherapy),Methods,Treatment,CBP,AUV,2mg/L min ; TAX 50mg/,41.4Gy /1.8Gy/23f,surgery,4-6w,CR+S group,在中国，食管癌综合治疗的临床研究面临着机遇和挑战！,谢谢,