lauren分型對胃癌治療的價值和意義

1、1會計學(xué)lauren分型對胃癌治療的價值和意義分型對胃癌治療的價值和意義胃癌病理組織學(xué)分型2021-12-5腸型 具有明顯的腺管結(jié)構(gòu) 腫瘤細(xì)胞分泌黏液 細(xì)胞呈極性排列彌漫型 無腺管樣結(jié)構(gòu) 缺乏細(xì)胞連接 癌細(xì)胞散在并呈浸潤性生長 混合型 兼有腸型和彌漫型成分Emily S. Turner,Jerrold R. Turnerdepartment of pathology,the university of ChicagoMiao-zhen Q, et al. Journal of Translational Medicine. 2013,11:58. 自1973-2000年，美國流病性調(diào)研顯示腸型

2、胃癌不斷減少，彌漫型胃癌逐漸增多。Henson DE, et al. Arch Pathol Lab Med. 2004; 128(7): 765-770P女性相似好發(fā)部位胃竇胃體轉(zhuǎn)移部位淋巴結(jié)，肝臟淋巴結(jié)，內(nèi)臟生物學(xué)特征雌激素保護(hù)？神經(jīng)內(nèi)分泌分化？幽門桿菌感染血清學(xué)常見（8090%）常見（90%）胃癌總生存率的多因素分析因素特征風(fēng)險比95%CLP年齡59591.1110.899-1.3740.328性別女男1.0570.843-1.3240.631Lauren 分型腸型彌漫型0.7360.595-0.9100.005組織學(xué)分級好/適度差1.0250.899-1.1670.714大小5 cm5

3、 cm1.6051.307-1.9720.001部位遠(yuǎn)端近端0.8520.697-1.0420.120腫瘤深度(T) 2/3/411.8901.230-2.7460.001淋巴結(jié)分期(N)1/2/301.3681.048-1.8940.001淋巴管血管浸潤(-)(+)1.2090.831-1.7590.321胃切除術(shù)的類型不完全完全1.1350.859-1.4680.582Qiu MZ, et al. J Transl Med. 2013; 11:581.Liu et al. Anticancer Aqents Med Chem. 2013 Feb;13(2):227-34.2.Qiu et

4、al. J Transl Med. 2013;11:58.P0.0011261.7%41.1%52.7%44.1%Yung-Jue Bang, et al. Lancet 2010; 376: 68797沈琳等。中華腫瘤雜志，2013Bang YJ, et al. Lancet 2010; 376: 68797Her-2過表達(dá)的晚期彌漫型胃癌接受化療聯(lián)合曲妥珠單抗靶向治療較單純化療沒有顯著的生存獲益Y. Yamada, et al. Journal of Clinical Oncology, 2009 ASCO Annual Meeting Proceedings. 27(15S): 4535

5、Y. Yamada, et al. Journal of Clinical Oncology. 2011 ASCO Annual Meeting Abstracts. 29(15): 4021二氫嘧啶脫氫酶（DPD）Yamada等學(xué)者的研究顯示：彌漫型胃癌的DPD表達(dá)水平顯著高于腸型00.511.52.532DPD-value彌漫型n=82腸型n=86秩和檢驗 IP 5-FU S-1P0.001*P0.0001Patrick Schoffskia. Anti-Cancer Drugs 2004, 15:85106骨髓毒性神經(jīng)毒性手足綜合癥心臟毒性胃腸道毒性(腹瀉,口腔炎)抗腫瘤活性F-丙氨酸5

6、-FU腫瘤胃腸道骨髓FdUMPOPRTFdUMPFdUMPS-1:DPD-吉美嘧啶Gimeracil奧替拉西鉀Oteracil替加氟Tegafur體內(nèi)代謝-DPD高表達(dá)-彌漫型生存率1.00.90.80.70.60.50.40.30.20.10.0051015PFS (mo)5-FUS-1DPD低表達(dá)-腸型1.0生存率0.90.80.70.60.50.40.30.20.10.0051015PFS (mo)5-FUS-1ArmNmPFS (months)5-FU202.1S-1314.2HR 2.05 95% Cl (1.13-3.71)Log rank p-value=0.016ArmNmPF

7、S (months)5-FU293.1S-1334.2HR 1.01 95% Cl (0.60-1.70)Log rank p-value=0.963Y. Yamada, et al. Journal of Clinical Oncology, 2009 ASCO Annual Meeting Proceedings. 27(15S): 4535傳統(tǒng)5-FU在彌漫型胃癌效果不佳292292270270226226198198161161122122999969695151393929292424161610105 53 30 0298298258258218218182182137137110

8、11085856060434330302020151510105 54 42 20 0Months From RandomizationMonths From Randomization% Survival% SurvivalN at RiskN at RiskS-1:S-1:5-FU:5-FU: 0 0 10 10 20 20 30 30 40 40 50 50 60 60 70 70 80 80 90 90 100 1000 02 24 46 68 8101012121414161618182020222224242626282830303232S1聯(lián)合順鉑（SP）顯著改善彌漫型胃癌生存：

9、FLAGSSP=S-1 + 順鉑FP=5FU+ 順鉑p=0.0413中位OS(月)HR95%CISP9.00.830.70-0.99FP7.1Jaffer A. Ajani, et al. J Clin Oncol. 2010 Mar 20;28(9):1547-53. 16主要終點:OS次要終點:PFS,TTF,RR,安全性病例數(shù):500例彌漫型轉(zhuǎn)移性胃癌、無化療史S-1+CDDPS-1 : 25mg/m2 bid for 21 days, q4wks CDDP : 75 mg/m2 iv on day 1 (最多6cycles)FU+CDDP5-FU : 800 mg/m2 24 hr c

10、iv day1-5, q3wksCDDP : 80 mg/m2 iv on day 1 (最多8cycles)RS-1+L-OHP(SOX)n=340S-1:40mg/m2bid，治療14天L-OHP:100mg/m2iv，第1天，每隔3周S-1+CDDP(SP)n=340S-1:40mg/m2bid，治療21天CDDP:60mg/m2iv,第8天，每隔5周無法切除/復(fù)發(fā)胃癌初治病例隨機(jī)分組結(jié)論：主要終點PFS獲得非劣效性統(tǒng)計結(jié)果。SOX方案無需靜脈水化和住院，臨床使用更方便。SOX方案可以考慮替代SP方案，作為晚期胃癌化療的一線方案?！驹囼炘O(shè)計】【試驗結(jié)果】【緩解率】SOX（n=318）SP

11、（n=324）類別亞組n性別男性477女性165年齡65305653377044370199PS0452118327疾病狀態(tài)不可切除533輔助(+)54輔助(-)55病理類型腸型289彌漫型353主要病灶無146有496轉(zhuǎn)移部位肝253腹膜125腹部淋巴結(jié)568腹水271轉(zhuǎn)移數(shù)目120322773162合計642HR95%CI0.9540.779-1.1690.9040.640-1.2781.0580.821-1.3640.8680.682-1.1051.0160.824-1.2530.8250.601-1.1330.8830.714-1.0931.1730.858-1.6051.4140.1

12、96-10.1921.0350.857-1.2490.4580.243-0.8981.0280.526-2.0061.0750.830-1.3920.8390.661-1.0640.7160.486-1.0561.0450.860-1.2711.0070.769-1.3200.8580.580-1.2680.9210.766-1.1080.9220.710-1.1981.0480.756-1.4540.9300.715-1.2110.8220.588-1.1491.0040.840-1.199K Higuchi, et al. ASCO-GI 2013.SOX更好SP更好SPS-1：80-12

13、0mg/dd1-14順鉑：75mg/m2d1-3iv每3周為一個周期SOXS-1：80-120mg/dd1-14奧沙利鉑：130mg/m2d1iv每3周為一個周期經(jīng)組織學(xué)證實的不能手術(shù)的晚期或復(fù)發(fā)性彌漫型胃腺癌18歲75歲有客觀可測量腫瘤病灶ECOG全身狀態(tài)評分為02RXu Ruihua，et al.NCT018244591.Yamaguchi K, et al.Gastric cancer 2002;5(2):90-52.Emi Y.et al. Surg Today. 2008;38(11):1013-20.%單藥紫杉醇的反應(yīng)率彌漫型紫杉醇+替吉奧（PS）S-1：80-120mg/d d1

14、-14紫杉醇：135mg/m2 d1 iv每3周為一個周期奧沙利鉑+替吉奧（SOX）S-1：80-120mg/d d1-14奧沙利鉑：130mg/m2 d1 iv每3周為一個周期初治進(jìn)展期彌漫型胃癌18歲ECOG全身狀態(tài)評分為02RBifeng，et al.1.Hiroyukl N, et al. Gastric Cancer. 2011;14:72-80.2.Narikazu B, et al. Lancet Oncol 2009;10:1063-1069.GC0301/TOP-002研究1JCOG9912研究2Emily S. Turner,Jerrold R. Turnerdepartm

15、ent of pathology,the university of ChicagoGastroenterology 2013;145:554565Nature, 23 July 2014胃癌病理組織學(xué)分型胃癌總生存率的多因素分析因素特征風(fēng)險比95%CLP年齡59591.1110.899-1.3740.328性別女男1.0570.843-1.3240.631Lauren 分型腸型彌漫型0.7360.595-0.9100.005組織學(xué)分級好/適度差1.0250.899-1.1670.714大小5 cm5 cm1.6051.307-1.9720.001部位遠(yuǎn)端近端0.8520.697-1.0420

16、.120腫瘤深度(T) 2/3/411.8901.230-2.7460.001淋巴結(jié)分期(N)1/2/301.3681.048-1.8940.001淋巴管血管浸潤(-)(+)1.2090.831-1.7590.321胃切除術(shù)的類型不完全完全1.1350.859-1.4680.582Qiu MZ, et al. J Transl Med. 2013; 11:58DPD高表達(dá)-彌漫型生存率1.00.90.80.70.60.50.40.30.20.10.0051015PFS (mo)5-FUS-1DPD低表達(dá)-腸型1.0生存率0.90.80.70.60.50.40.30.20.10.0051015PFS (mo)5-FUS-1ArmNmPFS (months)5-FU202.1S-1314.2HR 2.05 95% Cl (1.13-3.71)Log rank p-value=0.016ArmNmPFS (months)5-FU293.1S-1334.2HR 1.01 95% Cl (0.60-1.70)Log rank p-value=0.963Y. Yamada, et al. Journal of Clinical Oncology, 2009 ASCO Annual Meeting Proceedings. 27(15S): 4535