2016病例分享 ppt課件

1、病例分享,晚期胰腺癌病例分享 2016年8月27日,病例特點,廖XX，男，45歲。2015-09-01因“腹痛2月，確診胰腺癌肝轉移3周”第一次入我科。既往：無糖尿病及家族史,無煙酒史。查體：KPS評分70分，NRS 3分，S:1.6㎡，全身皮膚及鞏膜無黃染，淺表淋 巴結未捫及，雙肺呼吸音

2、清，未聞及明顯干濕啰音。心率78次/分，律齊， 無雜音，腹部未捫及包塊，中腹部輕壓痛，無反跳痛，肝區(qū)叩痛陽性。 雙下肢不腫。,,,2015-07-22全腹CT:胰腺尾部乏血供病變，考慮胰腺囊腫腺瘤。肝內多發(fā)低密度影，考慮囊腫或血管瘤可能，不排除腫瘤。2015-08-04行彩超下肝臟穿刺活檢術， 2015-08-08術后病檢：(肝穿刺）中-低分化腺癌。考慮膽道源性

3、或胃腸道癌轉移.免疫組化結果:CgA(-),CD56(-),Syn(-),CK7(+),CK19(+),CK20(-)，CDX- 2(-),TTF-1(-),Napsi(-),Villin（+）。,基線評價,,20150729-0803多次監(jiān)測血糖及血尿淀粉酶大致正常。CEA,CA19-9(-) 20150811：電子直、結腸鏡:盲腸、升結腸、橫結腸脾曲、 降

4、結腸、乙狀結腸、直腸粘連充血水腫，血管紋理紊亂。 診斷為：慢性結腸炎。 20150811（湘雅）：電子食管、胃鏡：慢性非萎縮性（淺表性)胃竇炎。 20150812 （湘雅）:胸部X線：雙肺野清晰，心膈影正常。,,,基線評價,20150722我院全腹部CT,,,全腹CT:胰腺尾部乏血供病變，考慮胰腺囊腫腺瘤，不排除腫瘤。（＞2cm）,,20150722我院全腹

5、部CT,全腹CT:肝內多發(fā)低密度影，考慮囊腫或血管瘤可能，不排除轉移瘤。,,,,,2015-08-08術后病檢：(肝穿刺）中-低分化腺癌，考慮膽道源性或胃腸道癌轉移.免疫組化結果： CgA(-),CD56(-),Syn(-),CK7(+),CK19(+),CK20(-)，CDX- 2(-), TTF-1(-),Napsi(-),Villin（+）。,,,,,,,,,胰腺癌 中低分化腺癌 cT2N0M1（肝） IV期

6、 ——(AJCC 2010版TNM分期),診斷,,,下一步治療？,治療,我院治療經(jīng)過,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,

7、,,,,,,,,,,,,,,,,,,,,,,,,,,共 151 家中心在 2009 年 5 月 8 日至 2012 年 4 月 17 日期間入組了 861 例患者,Von Hoff DD, Ervin T, Arena FP, et al. Randomized Phase III Study of Weekly nab-Paclitaxel plus Gemcitabine vs Gemcitabine Alone in Patien

8、ts with Metastatic Adenocarcinoma of the Pancreas (MPACT) [abstract LBA148]. Oral presentation at: The Gastrointestinal Cancers Symposium 2013; January 24-26; San Francisco, CA.,III 期研究 MPACT (CA046),MPACT:研究設計,IV期;未經(jīng)針對

9、轉移性疾病的治療;KPS≥70;可測量病灶;總膽紅素 ≤ ULN(N = 861),nab-P 125 mg/m2 qw 3/4weeks Gem 1000 mg/m2 qw 3/4weeks,Gem 1000 mg/m2 qw7/8weeks, qw3/4weeks,,,,1:1, 根據(jù) by KPS, 地區(qū), 肝轉移分層,KPS, Karnofs

10、ky performance status; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; RECIST, Response Criteria In Solid Tumors; ULN, upper limit of normal.,Von Hoff DD, Ervin T, Arena FP, et al. Ra

11、ndomized Phase III Study of Weekly nab-Paclitaxel plus Gemcitabine vs Gemcitabine Alone in Patients with Metastatic Adenocarcinoma of the Pancreas (MPACT) [abstract LBA148]. Oral presentation at: The Gastrointestinal Can

12、cers Symposium 2013; January 24-26; San Francisco, CA.,主要終點: OS次要終點:獨立評估的 PFS 和 ORR (RECIST)安全性和耐受性 CTCAE v3.0,,MPACT研究:Overall Survial,Gem +Nab-P: Median OS= 8.5months VSGem:Median OS=6.7months,Von

13、Hoff DD, Ervin T, Arena FP, et al. Randomized Phase III Study of Weekly nab-Paclitaxel plus Gemcitabine vs Gemcitabine Alone in Patients with Metastatic Adenocarcinoma of the Pancreas (MPACT) [abstract LBA148]. Oral pres

14、entation at: The Gastrointestinal Cancers Symposium 2013; January 24-26; San Francisco, CA.,,MPACT研究:Progression-free Survival,Gem +Nab-P: Median PFS= 5.5months VSGem:Median PFS= 3.7months,Von Hoff DD, E

15、rvin T, Arena FP, et al. Randomized Phase III Study of Weekly nab-Paclitaxel plus Gemcitabine vs Gemcitabine Alone in Patients with Metastatic Adenocarcinoma of the Pancreas (MPACT) [abstract LBA148]. Oral presentation a

16、t: The Gastrointestinal Cancers Symposium 2013; January 24-26; San Francisco, CA.,MPACT研究提示,白蛋白紫杉醇+吉西他濱組OS及PFS均優(yōu)于吉西他濱組。白蛋白紫杉醇+吉西他濱是轉移性胰腺癌的一項新標準治療，并可能成為更多新療法的基礎。,Von Hoff DD, Ervin T, Arena FP, et al. Randomized Phase I

17、II Study of Weekly nab-Paclitaxel plus Gemcitabine vs Gemcitabine Alone in Patients with Metastatic Adenocarcinoma of the Pancreas (MPACT) [abstract LBA148]. Oral presentation at: The Gastrointestinal Cancers Symposium 2

18、013; January 24-26; San Francisco, CA.,白蛋白紫杉醇聯(lián)合吉西他濱用于中國晚期胰腺癌患者的 I/II 期研究,Prodige –ACCORD 11 研究：,轉移性胰癌(N=342)一線治療;18-75歲;PS評分0-1;可測量病灶;總膽紅素＜1.5UNL;,FOLFIRINOX:奧沙利鉑：85mg/m2 d1CF：400mg/m2 d1伊立替康：180mg d15-FU：400m

19、g/m2 推注5-FU：2400mg/m2 維持46小時一個周期=14天(n=171),Gemcitabine 1000 mg/m2 qw7/8weeks, qw3/4weeks (n=171),,,,隨機分組,N Engl J Med. 2011 ，364(19):1817-1825, T Conroy, et al,主要終點OS次要終點:ORR，毒副反應，PFS，QoL,Prodige –ACCORD 11 研

20、究：,FOLFIRINOX: Median OS=11.1months VSGem:Median OS=6.8 months（p＜0.001）,N Engl J Med. 2011 ，364(19):1817-1825, T Conroy, et al.ASCO 2010 – T. Conroy, et al. Abstract # 4010,Prodige –ACCORD 11 研究：,N En

21、gl J Med. 2011 ，364(19):1817-1825, T Conroy, et al.,ACCORD 11 不良反應：,N Engl J Med. 2011 ，364(19):1817-1825, T Conroy, et al.,,,ACCORD 11研究結論:,FOLFIRINOX方案毒性更大，但仍屬可控；明顯改善了 PFS (6.4m, 降低53%疾病進展風險）；顯著延長OS(11.1m，HR 0.57, p

22、<0.0001)，延緩生活質量降低；FOLFIRINOX方案可作為PS 0-1，總膽紅素<1.5ULN轉移性胰腺癌的標準 一線治療方案。,N Engl J Med. 2011 ，364(19):1817-1825, T Conroy, et al.,GEST研究：,不可切除的晚期胰腺癌(N = 834),Gem 1000 mg/m2 d1, 8, 154周重復（n=277）,Gem + S-1 (n

23、=277) GEM: 1000 mg/m2 d1, 8 S-1: 60, 80, 100 mg*/body d1-14 3周重復,,,,優(yōu)效性比較： GEM + S-1 vs GEM非劣效性比較：S-1 vs Gem主要終點： OS次要終點：PFS, ORR, 不良反應、生活質量,S-1 80, 100, 120 mg*/body d1-28

24、 6周重復（n=280）,*根據(jù)體表面積（BSA）, BSA =1.5,,Ueno H, et al. JCO 2013, on line,GEST研究：,Ueno H, et al. JCO 2013, on line,GEST研究：,,Ueno H, et al. JCO 2013, on line,GEST研究提示：,S-1單藥治療的OS不劣于Gem單藥首個證實總生存非劣效性的III期研究S-1的緩解率較高 ( 21% )

25、GS聯(lián)合化療顯著提高RR、PFS，但是OS沒有延長GS化療可能帶來更好的生活質量,Ueno H, et al. JCO 2013, on line,,,吉西他濱聯(lián)合靶向治療：,Philip PA, et al. J Clin Oncol 2010; 28:3605-3610. 2.Kindler HL, et al. J Clin Oncol 2010; 28:3617-3622

26、.3 Vervenne W et al; J Clin Oncol 2009,27(13):2231-2237.4 4.A. Goncalves, et al. 2011 ASCO abstr 4028,,,特羅凱：在胰腺癌治療中唯一證實生存獲益， 但獲益極小的靶向藥物。,靶向治療：,Locally advanced/metastatic pancreatic can

27、cerNCIC CTG PA.3,局部晚期或者有遠處轉移的胰腺癌患者，既往未接受化療(N = 569),Gemcitabine 1000 mg/m2 聯(lián)合Erlotinib 100/150 mg(n = 285),Gemcitabine 1000 mg/m2 聯(lián)合安慰劑(n = 284),,,Moore MJ, et al. J Clin Oncol. 2007;25:1960-1966.,,* Adjusted for PS,

28、 pain and disease extent at randomization,,HR = 0.81*95% CI (0.67, 0.97)P = 0.025,Gemcitabine + ErlotinibMedian = 6. 24months1 Year Survival =23 %,Gemcitabine + PlaceboMedian = 5.91months1 Year Survival = 17%,,Loca

29、lly advanced/metastatic pancreatic cancerNCIC CTG PA.3 – Overall Survival,Moore MJ, et al. J Clin Oncol. 2007;25:1960-1966,Locally advanced/metastatic pancreatic cancerNCIC CTG PA.3 – ORR,CBR,Moore MJ, et al. J Clin On

30、col. 2007;25:1960-1966.,* Adjusted for PS, pain and disease extent at randomization,Locally advanced/metastatic pancreatic cancerNCIC CTG PA.3 – PFS,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,P,e,r,c,e,n,t,a,g,e,0,20,40,60,80,100,

31、,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,Time (Months),0,5,10,15,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,

32、,,,,,,,,,,,,,,,,,,,,,,,,,,,,HR = 0.76*95% CI (0.63, 0.91)P = 0.003,Gemcitabine + ErlotinibMedian = 3.75 monthsN=285,Gemcitabine + PlaceboMedian = 3.55 monthsN=284,Moore MJ, et al. J Clin Oncol. 2007;25:1960-1966.,N

33、CIC-CTG PA.3 Study提示：,胰腺癌中第一次證實TKI與化療藥物聯(lián)用可帶來臨床獲益。抑制EGFR通路治療有效。,臨床研究小結：,,,,,,免疫治療,免疫治療,治療方案：,于我院2015-08-12至2016-02-17先后行8周期化療；方案:吉西他濱1.6g D1，8 + 白蛋白紫杉醇 200mg D1,8 Q3W.期間每2周期化療后行療效評價;,,,WHO與RECIST療效評價標

34、準,,,20150812、0906 2周期化療后→PR20150927、1018 4周期化療后→PR20151110、1203 6周期化療后→PR20160108、0217 8周期化療后→PR,化療時間,2周期化療后療效評價--PR,,,,,治療前肝M最長徑27.34*26.93mm 20150926 最長徑22.42*20.35mm,,,4周期化療后療效評價--PR,,,,,治療前肝

35、M最長徑27.34*26.93mm 20151109 最長徑15.85*14.60mm,,,,6周期化療后療效評價--PR,,,治療前肝M最長徑27.34*26.93mm 20160105 最長徑10.50*9.71mm,,,8周期化療后療效評價--PR,,,,,治療前肝M最長徑27.34*26.93mm 20160328 最長徑9.72*8.97mm,,,,,治療經(jīng)過：,患者規(guī)律行8周

36、期白蛋白紫杉醇聯(lián)合吉西他濱化療，6周期化療后出現(xiàn)神經(jīng)毒性(CTC II-III級)；調整為吉西他濱單藥維持化療2周期（20160402及0505): 吉西他濱1.6g D1，8 Q3W.2周期化療后行療效評價,,,2周期GEM化療后療效評價--PD,,,,,20160328 肝M最長徑9.72*8.97mm 20160604最長徑18.05*14.16mm,,,,,,,,,再次調整為吉西他濱1.6g

37、 D1，8 +白蛋白紫杉醇 200mg D1,8 ,Q3W 化療2周期（20160613及0714）。,治療經(jīng)過：,再次行2周期聯(lián)合化療后療效評價--PD,20160604最長徑18.05*14.16mm 20160826最大徑23.50*22.97mm,,,總結：,20150808 確診胰腺癌肝轉移 20150812-20160217 8周

38、期吉西他濱+白蛋白紫杉醇→PR 20160402-0505 2周期吉西他濱單藥維持化療→ PD20160613-0714 2周期吉西他濱+白蛋白紫杉醇化療→PD20150808-20160604 患者PFS達10m；20150808-至今 OS＞12.05m,,,,,討論,1.晚期胰腺癌一線化療PR后改為單藥化療是否恰當？2.