Liver Cancer:卡博替尼(Cabozantinib)对比安慰剂治疗晚期肝细胞癌患者的基于血清标志物的预后分析:3期临床研究CELESTIAL

2021-12-04 yd2015 MedSci原创

研究表明,与安慰剂相比,Cabozantinib在基线所有分析标志物的高和低水平均改善患者的OS和PFS。基线的低水平MET、HGF、GAS6、IL-8和ANG2和高水平的IGF-1认为是良好预后指标

肝细胞癌(HCC)是常见的恶性肿瘤。在3期临床研究CELESTIAL(NCT01908426)中证实,晚期肝细胞癌患者既往索拉非尼和系统全身治疗进展后,卡博替尼(Cabozantinib)较安慰剂改善患者的OS和PFS。 Cabozantinib和安慰剂组的中位OS分别为10.2个月和8.0个月( HR=0.76, 95%CI 0.63 0.92;p = 0.005),中位PFS分别为5.2个月和1.9个月(HR=0.44,95%CI 0.36 0.52;p<0.001)近期,研究者基于在基线时的血浆生物标志物水平和第4周治疗时的变化,对CELESTIAL研究的OS和PFS进行了探索性分析。研究中选择的生物标志物包括cabozantinib靶蛋白(MET, AXL, VEGFR2,和c-KIT)及其配体(HGF, GAS6, VEGF-A, PlGF和VEGF-C)和其他血浆蛋白(IL-8, EPO, ANG2,和IGF-1)。因为基于AFP水平的预后分析已经报道了,因此并没有包括在当前的研究分析中。研究成果发表在Liver Cancer杂志上。

截至201761日,707名患者被随机2:1接受cabozantinib或安慰剂治疗。其中cabozantinib470例,安慰剂有237例。基线时,cabozantinib组的447/470(95%)患者和安慰剂组的227/237(96%)患者可获得用于生物标志物分析的血浆样本。Cabozantinib399(85%)和安慰剂组215(91%)患者在基线和第4周均可获得血浆样本。

基线水平的13个生物标志物(MET, AXL, VEG- FR2, HGF, GAS6, VEGF-A, PlGF, IL-8, EPO, ANG2, IGF-1, VEGF-C和c-KIT)被分为高低水平用于检测对于OS的预后价值。在cabozantinib组中,高水平MET、HGF、IL-8和ANG2在单变量和多变量分析中均与较短的OS相关(p<0.05)。在安慰剂组,高MET、HGF、GAS6、IL-8和ANG2水平和低IGF-1水平在单变量和多变量分析中均与较短的OS相关。

使用4种不同的方法,cabozantinib组中唯一与PFS一致相关的生物标志物是ANG2,在该组中,高基线水平与较短的PFS相关。在未经调整和调整的二分类分析中,cabozantinib组的高HGF和安慰剂组的高MET与较短的PFS相关,但在连续分析中未观察到这些结果。

研究进一步分析cabozantinib对比安慰剂组中基线水平生物标志物高低水平比较的预后价值。研究表明,低AXL水平的OS相关 HR为0.65,高AXL水平的OS相关 HR为0.92;高IGF-1水平的PFS相关HR为0.41,低IGF-1水平的PFS相关HR为0.54。

从基线到第4周,检测9种生物标志物(MET、AXL、VEGFR2、HGF、GAS6、VEGF-A、PlGF、IL-8和EPO)的血浆水平变化。Cabozantinib组中下降最大的是VEGFR2 (0.60倍)和HGF (0.71倍),而升高最大的是PlGF (4.28倍)和VEGF-A (3.80倍)。单变量分析表明,增加VEGFR2与cabozantinib组较长的OS相关,但对临床协变量进行调整后则不相关。在安慰剂组中,MET、AXL、VEGFR2、HGF、GAS6和IL-8水平的升高在单变量和多变量分析中均与OS缩短相关。

Cabozantinib组与安慰剂组相比,血浆MET、AXL、VEGFR2、HGF、GAS6和IL-8水平的增加被认为是OS相对较差的潜在预测因素。

综上,研究表明,与安慰剂相比,Cabozantinib在基线所有分析标志物的高和低水平均改善患者的OS和PFS。基线的低水平MET、HGF、GAS6、IL-8和ANG2和高水平的IGF-1被认为是既往治疗的晚期HCC潜在的良好预后生物标志物。

原始出处;

Lorenza Rimassa,Robin Kate Kelley,Tim Meyer, et al. Outcomes Based on Plasma Biomarkers for the Phase 3 CELESTIAL Trial of Cabozantinib versus Placebo in Advanced Hepatocellular Carcinoma. Liver Cancer. DOI: 10.1159/000519867. Published online: December 3, 2021

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GetPortalCommentsPageByObjectIdResponse(id=1530331, encodeId=0c0c15303312e, content=<a href='/topic/show?id=733a395650' target=_blank style='color:#2F92EE;'>#cabozantinib#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3956, encryptionId=733a395650, topicName=cabozantinib)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a95b12086600, createdName=zhao4620, createdTime=Mon Dec 06 11:25:31 CST 2021, time=2021-12-06, status=1, ipAttribution=)]
    2022-09-04 维他命
  4. [GetPortalCommentsPageByObjectIdResponse(id=1704078, encodeId=6ee71e0407863, content=<a href='/topic/show?id=f407894051e' target=_blank style='color:#2F92EE;'>#血清标志物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89405, encryptionId=f407894051e, topicName=血清标志物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=de7930650164, createdName=jichang, createdTime=Sun Jun 26 21:25:31 CST 2022, time=2022-06-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2051729, encodeId=72172051e2914, content=<a href='/topic/show?id=95f8e042dd' target=_blank style='color:#2F92EE;'>#EST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7042, encryptionId=95f8e042dd, topicName=EST)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e9a6357, 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topicName=细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e457184, createdName=qingting, createdTime=Thu Jun 16 11:25:31 CST 2022, time=2022-06-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1911282, encodeId=aee21911282b1, content=<a href='/topic/show?id=18171289d6' target=_blank style='color:#2F92EE;'>#3期临床#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1289, encryptionId=18171289d6, topicName=3期临床)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d275294, createdName=andy2087, createdTime=Fri Dec 10 02:25:31 CST 2021, time=2021-12-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1863629, encodeId=54c61863629e5, content=<a href='/topic/show?id=c0b68135561' target=_blank style='color:#2F92EE;'>#肝细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81355, encryptionId=c0b68135561, topicName=肝细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Fri Sep 09 20:25:31 CST 2022, time=2022-09-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1841784, encodeId=25091841e845b, content=<a href='/topic/show?id=18bf61953d3' target=_blank style='color:#2F92EE;'>#标志物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=61953, encryptionId=18bf61953d3, topicName=标志物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6ab940, createdName=hukaixun, createdTime=Wed May 11 21:25:31 CST 2022, time=2022-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1304420, encodeId=90fb130442062, content=<a href='/topic/show?id=81724580886' target=_blank style='color:#2F92EE;'>#安慰剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=45808, encryptionId=81724580886, topicName=安慰剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4cce318, createdName=wleon8895, createdTime=Mon Dec 06 11:25:31 CST 2021, time=2021-12-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1368217, encodeId=140b136821eab, content=<a href='/topic/show?id=a92e59863f2' target=_blank style='color:#2F92EE;'>#晚期肝细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59863, encryptionId=a92e59863f2, topicName=晚期肝细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=hb2008ye, createdTime=Mon Dec 06 11:25:31 CST 2021, time=2021-12-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1530331, encodeId=0c0c15303312e, content=<a href='/topic/show?id=733a395650' target=_blank style='color:#2F92EE;'>#cabozantinib#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3956, encryptionId=733a395650, topicName=cabozantinib)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a95b12086600, createdName=zhao4620, createdTime=Mon Dec 06 11:25:31 CST 2021, time=2021-12-06, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1704078, encodeId=6ee71e0407863, content=<a href='/topic/show?id=f407894051e' target=_blank style='color:#2F92EE;'>#血清标志物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89405, encryptionId=f407894051e, topicName=血清标志物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=de7930650164, createdName=jichang, createdTime=Sun Jun 26 21:25:31 CST 2022, time=2022-06-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2051729, encodeId=72172051e2914, content=<a href='/topic/show?id=95f8e042dd' target=_blank style='color:#2F92EE;'>#EST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7042, encryptionId=95f8e042dd, topicName=EST)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e9a6357, createdName=xiangyuzhou971, createdTime=Thu Nov 03 18:25:31 CST 2022, time=2022-11-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1962651, encodeId=cdf6196265119, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Sun Sep 04 13:25:31 CST 2022, time=2022-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1979254, encodeId=4d3619e9254d0, content=<a href='/topic/show?id=3b90e79787f' target=_blank style='color:#2F92EE;'>#细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77978, encryptionId=3b90e79787f, topicName=细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e457184, createdName=qingting, createdTime=Thu Jun 16 11:25:31 CST 2022, time=2022-06-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1911282, encodeId=aee21911282b1, content=<a href='/topic/show?id=18171289d6' target=_blank style='color:#2F92EE;'>#3期临床#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1289, encryptionId=18171289d6, topicName=3期临床)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d275294, createdName=andy2087, createdTime=Fri Dec 10 02:25:31 CST 2021, time=2021-12-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1863629, encodeId=54c61863629e5, content=<a href='/topic/show?id=c0b68135561' target=_blank style='color:#2F92EE;'>#肝细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81355, encryptionId=c0b68135561, topicName=肝细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Fri Sep 09 20:25:31 CST 2022, time=2022-09-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1841784, encodeId=25091841e845b, content=<a href='/topic/show?id=18bf61953d3' target=_blank style='color:#2F92EE;'>#标志物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=61953, encryptionId=18bf61953d3, topicName=标志物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6ab940, createdName=hukaixun, createdTime=Wed May 11 21:25:31 CST 2022, time=2022-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1304420, encodeId=90fb130442062, content=<a href='/topic/show?id=81724580886' target=_blank style='color:#2F92EE;'>#安慰剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=45808, encryptionId=81724580886, topicName=安慰剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4cce318, createdName=wleon8895, createdTime=Mon Dec 06 11:25:31 CST 2021, time=2021-12-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1368217, encodeId=140b136821eab, content=<a href='/topic/show?id=a92e59863f2' target=_blank style='color:#2F92EE;'>#晚期肝细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59863, encryptionId=a92e59863f2, topicName=晚期肝细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=hb2008ye, createdTime=Mon Dec 06 11:25:31 CST 2021, time=2021-12-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1530331, encodeId=0c0c15303312e, content=<a href='/topic/show?id=733a395650' target=_blank style='color:#2F92EE;'>#cabozantinib#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3956, encryptionId=733a395650, topicName=cabozantinib)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a95b12086600, createdName=zhao4620, createdTime=Mon Dec 06 11:25:31 CST 2021, time=2021-12-06, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1704078, encodeId=6ee71e0407863, content=<a href='/topic/show?id=f407894051e' target=_blank style='color:#2F92EE;'>#血清标志物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89405, encryptionId=f407894051e, topicName=血清标志物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=de7930650164, createdName=jichang, createdTime=Sun Jun 26 21:25:31 CST 2022, time=2022-06-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2051729, encodeId=72172051e2914, content=<a href='/topic/show?id=95f8e042dd' target=_blank style='color:#2F92EE;'>#EST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7042, encryptionId=95f8e042dd, topicName=EST)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e9a6357, createdName=xiangyuzhou971, createdTime=Thu Nov 03 18:25:31 CST 2022, time=2022-11-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1962651, encodeId=cdf6196265119, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Sun Sep 04 13:25:31 CST 2022, time=2022-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1979254, encodeId=4d3619e9254d0, content=<a href='/topic/show?id=3b90e79787f' target=_blank style='color:#2F92EE;'>#细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77978, encryptionId=3b90e79787f, topicName=细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e457184, createdName=qingting, createdTime=Thu Jun 16 11:25:31 CST 2022, time=2022-06-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1911282, encodeId=aee21911282b1, content=<a href='/topic/show?id=18171289d6' target=_blank style='color:#2F92EE;'>#3期临床#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1289, encryptionId=18171289d6, topicName=3期临床)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d275294, createdName=andy2087, createdTime=Fri Dec 10 02:25:31 CST 2021, time=2021-12-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1863629, encodeId=54c61863629e5, content=<a href='/topic/show?id=c0b68135561' target=_blank style='color:#2F92EE;'>#肝细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81355, encryptionId=c0b68135561, topicName=肝细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Fri Sep 09 20:25:31 CST 2022, time=2022-09-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1841784, encodeId=25091841e845b, content=<a href='/topic/show?id=18bf61953d3' target=_blank style='color:#2F92EE;'>#标志物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=61953, encryptionId=18bf61953d3, topicName=标志物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6ab940, createdName=hukaixun, createdTime=Wed May 11 21:25:31 CST 2022, time=2022-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1304420, encodeId=90fb130442062, content=<a href='/topic/show?id=81724580886' target=_blank style='color:#2F92EE;'>#安慰剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=45808, encryptionId=81724580886, topicName=安慰剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4cce318, createdName=wleon8895, createdTime=Mon Dec 06 11:25:31 CST 2021, time=2021-12-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1368217, encodeId=140b136821eab, content=<a href='/topic/show?id=a92e59863f2' target=_blank style='color:#2F92EE;'>#晚期肝细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59863, encryptionId=a92e59863f2, topicName=晚期肝细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=hb2008ye, createdTime=Mon Dec 06 11:25:31 CST 2021, time=2021-12-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1530331, encodeId=0c0c15303312e, content=<a href='/topic/show?id=733a395650' target=_blank style='color:#2F92EE;'>#cabozantinib#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3956, encryptionId=733a395650, topicName=cabozantinib)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a95b12086600, createdName=zhao4620, createdTime=Mon Dec 06 11:25:31 CST 2021, time=2021-12-06, status=1, ipAttribution=)]
    2022-09-09 xjy02
  7. [GetPortalCommentsPageByObjectIdResponse(id=1704078, encodeId=6ee71e0407863, content=<a href='/topic/show?id=f407894051e' target=_blank style='color:#2F92EE;'>#血清标志物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89405, encryptionId=f407894051e, topicName=血清标志物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=de7930650164, createdName=jichang, createdTime=Sun Jun 26 21:25:31 CST 2022, time=2022-06-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2051729, encodeId=72172051e2914, content=<a href='/topic/show?id=95f8e042dd' target=_blank style='color:#2F92EE;'>#EST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7042, encryptionId=95f8e042dd, topicName=EST)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e9a6357, 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topicName=细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e457184, createdName=qingting, createdTime=Thu Jun 16 11:25:31 CST 2022, time=2022-06-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1911282, encodeId=aee21911282b1, content=<a href='/topic/show?id=18171289d6' target=_blank style='color:#2F92EE;'>#3期临床#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1289, encryptionId=18171289d6, topicName=3期临床)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d275294, createdName=andy2087, createdTime=Fri Dec 10 02:25:31 CST 2021, time=2021-12-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1863629, encodeId=54c61863629e5, content=<a href='/topic/show?id=c0b68135561' target=_blank style='color:#2F92EE;'>#肝细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, 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GetPortalCommentsPageByObjectIdResponse(id=1530331, encodeId=0c0c15303312e, content=<a href='/topic/show?id=733a395650' target=_blank style='color:#2F92EE;'>#cabozantinib#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3956, encryptionId=733a395650, topicName=cabozantinib)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a95b12086600, createdName=zhao4620, createdTime=Mon Dec 06 11:25:31 CST 2021, time=2021-12-06, status=1, ipAttribution=)]
  8. [GetPortalCommentsPageByObjectIdResponse(id=1704078, encodeId=6ee71e0407863, content=<a href='/topic/show?id=f407894051e' target=_blank style='color:#2F92EE;'>#血清标志物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89405, encryptionId=f407894051e, topicName=血清标志物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=de7930650164, createdName=jichang, createdTime=Sun Jun 26 21:25:31 CST 2022, time=2022-06-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2051729, encodeId=72172051e2914, content=<a href='/topic/show?id=95f8e042dd' target=_blank style='color:#2F92EE;'>#EST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7042, encryptionId=95f8e042dd, topicName=EST)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e9a6357, 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  9. 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  10. 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