肝膽胰腺腫瘤綜合治療進(jìn)展

1、肝膽胰腺腫瘤綜合治療進(jìn)展,,2024/3/25,,,中國(guó)惡性腫瘤發(fā)病率,,,三大治療手段的作用地位,2024/3/25,中美主要癌癥5年相對(duì)生存率比較（%）,,肝癌屬于放射敏感腫瘤敏感性相當(dāng)于低分化鱗癌,,早期肝癌放療結(jié)果,不能手術(shù)肝癌放療結(jié)果,,肝癌伴門(mén)靜脈/下腔靜脈癌栓的放療,,1年生存率:外照射組34.8% 未接受外照射組11.4%,Int J Radiat Oncol Biol Phys 2005;61(2)432-443,肝

2、癌腹腔淋巴結(jié)轉(zhuǎn)移的放療,中位生存時(shí)間 外照射組:9.4月 未接受外照射組:3.3月(P<0.001),Int J Radiat Oncol Biol Phys 2005;63(4)1067-1076,,,Phase III SHARP Trial: OS,*O’Brien-Fleming threshold for statistical significance was P=0.0077. Llovet JM,

3、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,,SorafenibMedian: 46.3 weeks (10.7 mo)95% CI: 40.9-57.9,HR (95% CI): 0

4、.69 (0.55-0.88)P=0.00058*,PlaceboMedian: 34.4 weeks (7.9 mo)95% CI: 29.4-39.4,No. of Patients,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,肝癌放療的價(jià)值,大肝癌放療后中位生存期提高15個(gè)月（12-20個(gè)月）淋巴結(jié)轉(zhuǎn)移者中位生存期提高7個(gè)月（4-12個(gè)月）靜脈癌栓患者中位生存期提高6個(gè)月（4-9個(gè)月）骨骼轉(zhuǎn)

5、移能明顯有效止痛，增加生活質(zhì)量不能手術(shù)的肝內(nèi)膽管細(xì)胞癌中位生存期提高5個(gè)月（3-11個(gè)月）,,不能手術(shù)切除肝癌，選擇放療同步化療（證據(jù)2B）需要大樣本，前瞻性隨機(jī)對(duì)照研究期待更高級(jí)別證據(jù),intrahepatic CCA (iCCA),,perihilar CCA(pCCA),distal CCA (dCCA),NATALIYA RAZUMILAVA.Classification, Diagnosis, and Manageme

6、nt of Cholangiocarcinoma,Shahid A Khan,et al.Guidelines for the diagnosis and treatment ofcholangiocarcinoma: an update,Bismuthe-Corlette classification of biliary strictures.Guidelines Gut,Surgery,J. R. A. Skipworth.Re

7、view article: surgical, neo-adjuvant and adjuvantmanagement strategies in biliary tract cancer.Alimentary Pharmacology and Therapeutics,根治性手術(shù)切除是唯一治愈膽管癌的方法診斷時(shí)僅有13%-55%的患者能手術(shù)切除,studies of surgery alone reporting data on

8、survival,Prognosis,R0 or R1 statusvascular invasion lymph node involvement (occurring in 50% at presentation) is associated with OSTNM stage and multiplicity of lesion,Patterns of Recurrence Resection of Biliary Tra

9、ct Cancer,Se Jin Jung.Patterns of Initial Disease Recurrenceafter Resection of Biliary Tract Cancer.Oncology 2012;83:83–90,135 ps210 sites,Pattern of recurrence according to primary tumor origin; patients (n) with recu

10、rrence,,,unresectable extrahepatic and hilar cholangiocarcinoma or at high risk for disease recurrence after resection,Multidisciplinary Management,Adjuvant radiotherapyAdjuvant chemotherapyAdjuvant chemoradiation ther

11、apyNeoadjuvant chemoradiation therapyMetastatic disease:palliative radiochemtherapyTargeted therapy,META-POSTOPERATION35 TRAILS,survival of the selected studies of ART,,adjuvant RT have a significant lower risk of

12、dying compared to patients treated with surgery alone,,P = .23,,,,,,Twenty studies involving 6,712 patients were analyzed,Efficacy outcomes for overallpopulation,Efficacy outcomes for node positivedisease,Efficacy ou

13、tcomes for marginpositive disease,Neo-adjuvant therapy,Aims to down-stage disease,rendering it suitable for surgical resection and reducing the implantability of malignant cells during surgery. Both radio- and chemoth

14、erapy 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 locall

15、y advanced pancreaticobiliary cancerThe reported time to progression underlines the potential activity of this regimen. gemcitabine 1000mg/m2The dose of 60mg/m2 of oxaliplatin can be considered as the recommended dos

16、e.,The CORGI-U study,Conclusions,XELOX-RT (30 mg/m2 oxaliplatin/675 mg/m2 capecitabine in combination with 50.4 Gy/28 fractions) was well tolerated and effective for locally advanced pancreatic and biliary tract cancer,

17、Overall survival and Progression-free survival,ABC-02 randomly phase 2 studyClinicalTrials.gov number, NCT00262769,Conclusion,,cisplatin plus gemcitabine was associatedwith a significant survival advantage without the

18、 addition of substantial toxicity.Cisplatin plus gemcitabine is an appropriate option for thetreatment of patientswith advanced biliary cancer,Targeted therapy,,Phase II and Phase III clinical trials investigating t

19、argeted agents in BTC,結(jié) 論,根治性手術(shù)切除是治愈膽管癌的主要手段；局部晚期病變新輔助放化療能明顯降期，增加R0切除率，顯示生存優(yōu)勢(shì)，有望成為標(biāo)準(zhǔn)治療方法；術(shù)后輔助化療和輔助放化療未能明顯增加局部控制率，延長(zhǎng)PFS和OS；亞組表明，對(duì)R1切除和淋巴結(jié)轉(zhuǎn)移能增加局控率、延長(zhǎng)PFS和OS；R1,R2手術(shù)切除，或淋巴結(jié)轉(zhuǎn)移者術(shù)后同步放化療是標(biāo)準(zhǔn)治療。,不能手術(shù)切除的局部晚期病變同步放化療是標(biāo)準(zhǔn)治療，50Gy/25-

20、28f，每周同步XILOX或GP方案；轉(zhuǎn)移性膽管癌姑息化療較BSC延長(zhǎng)OS和PFS；GP較單藥gemcitabine延長(zhǎng)PFS3個(gè)月，是標(biāo)準(zhǔn)一線方案；初步研究表明西妥昔單抗聯(lián)合GP能獲得較好的控制率，但需多中心，隨機(jī)III期臨床試驗(yàn)進(jìn)一步證實(shí)。,,2015年47000例50% 臨床局限期，30%局部晚期，10%為局 部可切除,10%邊界可切除;50%為全身晚期,,,,,局限無(wú)遠(yuǎn)地轉(zhuǎn)移可手術(shù)切除 5年生存率 15%-

21、20% 中位生存期 12-20個(gè)月 局部進(jìn)展無(wú)遠(yuǎn)地轉(zhuǎn)移 中位生存期 6-10個(gè)月 已遠(yuǎn)地轉(zhuǎn)移中位生存期 3-6個(gè)月,手術(shù)治療結(jié)果,American Joint Committee on Cancer 2010,中國(guó)2340例胰腺癌手術(shù)病例分析結(jié)果,手術(shù)根治切除率約20％ 胰頭癌中位生存期17.1個(gè)月，5年生存率8.5% 胰體尾癌中位生存期7.2個(gè)月， 5年生存率0％,2004 CACA,,,,,,,新輔助放化療的目

22、的達(dá)到好的局部控制率，降期，減少手術(shù)中的局部種植降低局部復(fù)發(fā)率，增加R0切除率，增加OS,,,,,,可切除胰腺癌的輔助和新輔助治療臨床研究,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,結(jié)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%。,,,,,,,,提高劑量可提高療效,,,作者　　例數(shù)　 劑量

23、　 有效率（%）　 1年（%） 2年（%）,于金明　 13　 5-7Gy(70-90%)　 100　　　　92.3　　　 70 40-48Gy/5-8次,蔡　晶　 18　 4-7Gy（90%）　 72.2　 55.6　　　 27.8　　　　　　 3

24、2-44Gy /5-9次,周桂霞　 23 20-40Gy　　　 81.2　　　 26 4-7Gy /21-42Gy,夏廷毅　 52　 3-5Gy（50%）　 87.5 76.9 46.7　　　　　

25、 40-51Gy/10-17次 56.5 23.1,,李金高　 32 1.8Gy/45Gy+化療　　　　　 31.3　　　 9.4,現(xiàn)代放療效果,,,,不能手術(shù)切除的局部晚期胰腺癌，同步放化療是標(biāo)準(zhǔn)治療,,胰腺癌根治手術(shù)后的化放療可能改善腫瘤的局部控 制，部分研究表明能提高生存率，但是沒(méi)有前瞻性 對(duì)照試驗(yàn)的證據(jù)。對(duì)

26、局部晚期沒(méi)有遠(yuǎn)處轉(zhuǎn)移胰腺癌，化放同步治療是 一種可考慮的治療選擇。姑息止痛療效明顯。胰腺癌術(shù)后局部復(fù)發(fā)同步放化療是最好選擇。,Before 1 month after,9 month after,45 Gy55 Gy60 Gy,,15f,,胰腺癌根治手術(shù)后的化放療可能改善腫瘤的局部控 制，部分研究表明能提高生存率，但是沒(méi)有前瞻