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1、肝胆胰腺肿瘤综合治疗进展,2018/9/11,中国恶性肿瘤发病率,三大治疗手段的作用地位,2018/9/11,中美主要癌症5年相对生存率比较（%）,肝癌属于放射敏感肿瘤 敏感性相当于低分化鳞癌,早期肝癌放疗结果,不能手术肝癌放疗结果,肝癌伴门静脉/下腔静脉癌栓的放疗,1年生存率:外照射组34.8% 未接受外照射组11.4%,Int J Radiat Oncol Biol Phys 2005;61(2)432-443,肝癌腹腔淋巴结转移的放疗,中位生存时间 外照射组:9.4月未接受外照射组:3.3月(P0.001),Int J Radiat Oncol Biol Phys 2005;63(4)1
2、067-1076,Phase III SHARP Trial: OS,*OBrien-Fleming threshold for statistical significance was P=0.0077.Llovet JM, et al. J Clin Oncol. 2007;25(suppl 18):LBA1. Updated from oral presentation.,Survival Probability,Weeks,0,80,8,16,24,32,40,48,56,64,72,Sorafenib Median: 46.3 weeks (10.7 mo) 95% CI: 40.9
3、-57.9,HR (95% CI): 0.69 (0.55-0.88) P=0.00058*,Placebo Median: 34.4 weeks (7.9 mo) 95% CI: 29.4-39.4,No. of Patients,肝癌放疗的价值,大肝癌放疗后中位生存期提高15个月（12-20个月） 淋巴结转移者中位生存期提高7个月（4-12个月） 静脉癌栓患者中位生存期提高6个月（4-9个月） 骨骼转移能明显有效止痛，增加生活质量 不能手术的肝内胆管细胞癌中位生存期提高5个月（3-11个月）,不能手术切除肝癌，选择放疗同步化疗（证据2B） 需要大样本，前瞻性随机对照研究 期待更高级别证据,
4、intrahepatic CCA (iCCA),perihilar CCA (pCCA),distal CCA (dCCA),NATALIYA RAZUMILAVA.Classification, Diagnosis, and Management of Cholangiocarcinoma,Shahid A Khan,et al.Guidelines for the diagnosis and treatment of cholangiocarcinoma: an update,Bismuthe-Corlette classification of biliary strictures.Gu
5、idelines Gut,Surgery,J. R. A. Skipworth.Review article: surgical, neo-adjuvant and adjuvant management strategies in biliary tract cancer.Alimentary Pharmacology and Therapeutics,根治性手术切除是唯一治愈胆管癌的方法 诊断时仅有13%-55%的患者能手术切除,studies of surgery alone reporting data on survival,Prognosis,R0 or R1 status vas
6、cular invasion lymph node involvement (occurring in 50% at presentation) is associated with OS TNM stage and multiplicity of lesion,Patterns of Recurrence Resection of Biliary Tract Cancer,Se Jin Jung.Patterns of Initial Disease Recurrence after Resection of Biliary Tract Cancer.Oncology 2012;83:839
7、0,135 ps 210 sites,Pattern of recurrence according to primary tumor origin; patients (n) with recurrence,unresectable extrahepatic and hilar cholangiocarcinoma or at high risk for disease recurrence after resection,Multidisciplinary Management,Adjuvant radiotherapy Adjuvant chemotherapy Adjuvant che
8、moradiation therapy Neoadjuvant chemoradiation therapy Metastatic disease:palliative radiochemtherapy Targeted therapy,META-POSTOPERATION 35 TRAILS,survival of the selected studies of ART,adjuvant RT have a significant lower risk of dying compared to patients treated with surgery alone,P = .23,Twent
9、y studies involving 6,712 patients were analyzed,Efficacy outcomes for overall population,Efficacy outcomes for node positive disease,Efficacy outcomes for marginpositive disease,Neo-adjuvant therapy,Aims to down-stage disease,rendering it suitable for surgical resection and reducing the implantabil
10、ity of malignant cells during surgery. Both radio- and chemotherapy can be more effective in the neo-adjuvant setting is to combine both modalities to achieve a synergistic effect.,Conclusions,RT in combination with gemcitabine and oxaliplatin is feasible in patients with locally advanced pancreatic
11、obiliary cancerThe reported time to progression underlines the potential activity of thisregimen. gemcitabine 1000mg/m2 The dose of 60mg/m2 of oxaliplatin can be considered as the recommended dose.,The CORGI-U study,Conclusions,XELOX-RT (30 mg/m2 oxaliplatin/675 mg/m2 capecitabine in combination wit
12、h 50.4 Gy/28 fractions) was well tolerated and effective for locally advanced pancreatic and biliary tract cancer,Overall survival and Progression-free survival,ABC-02 randomly phase 2 study ClinicalTrials.gov number, NCT00262769,Conclusion,cisplatin plus gemcitabine was associated with a significan
13、t survival advantage without the addition of substantial toxicity. Cisplatin plus gemcitabine is an appropriate option for the treatment of patients with advanced biliary cancer,Targeted therapy,Phase II and Phase III clinical trials investigating targeted agents in BTC,结 论,根治性手术切除是治愈胆管癌的主要手段； 局部晚期病
14、变新辅助放化疗能明显降期，增加R0切除率，显示生存优势，有望成为标准治疗方法； 术后辅助化疗和辅助放化疗未能明显增加局部控制率，延长PFS和OS；亚组表明，对R1切除和淋巴结转移能增加局控率、延长PFS和OS； R1,R2手术切除，或淋巴结转移者术后同步放化疗是标准治疗。,不能手术切除的局部晚期病变同步放化疗是标准治疗，50Gy/25-28f，每周同步XILOX或GP方案； 转移性胆管癌姑息化疗较BSC延长OS和PFS；GP较单药gemcitabine延长PFS3个月，是标准一线方案； 初步研究表明西妥昔单抗联合GP能获得较好的控制率，但需多中心，随机III期临床试验进一步证实。,2015年4
15、7000例50% 临床局限期，30%局部晚期，10%为局部可切除,10%边界可切除;50%为全身晚期,局限无远地转移可手术切除 5年生存率 15%-20% 中位生存期 12-20个月 局部进展无远地转移 中位生存期 6-10个月 已远地转移 中位生存期 3-6个月,手术治疗结果,American Joint Committee on Cancer 2010,中国2340例胰腺癌手术病例分析结果,手术根治切除率约20 胰头癌中位生存期17.1个月，5年生存率8.5%胰体尾癌中位生存期7.2个月， 5年生存率0,2004 CACA,新辅助放化疗的目的 达到好的局部控制率，降期，减少手术中的局部种植 降低局部复发率，增加R0切除率，增加OS,可切除胰腺癌的辅助和新辅助治疗 临床研究,结果,中位生存期12.4m（9-16） 可以切除病例22.0m（12-32），不能切除的病例9.7m（8-41） 可切除病例1年生存率61%，2年生存率44%。,提高剂量可提高疗效,作者 例数 剂量 有效率（%） 1年（%） 2年（%）,于金明 13 5-7Gy(70-90%) 100 92.3 7040-48Gy/5-8次,蔡 晶 18 4-7Gy（90%） 72.2 55.6 27.832-44Gy /5-9次,周桂霞 23 20-40Gy 81.2 264-7Gy /21-42Gy,
