低基线CXCL9预测阿特唑单抗加贝伐单抗治疗不可切除HCC的早期进展性疾病

IF 11.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Liver Cancer Pub Date : 2023-06-01 DOI:10.1159/000527759
Shunichi Hosoda, Goki Suda, Takuya Sho, Koji Ogawa, Megumi Kimura, Zijian Yang, Sonoe Yoshida, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Osamu Maehara, Shunsuke Ohnishi, Akihisa Nakamura, Ren Yamada, Masatsugu Ohara, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kenichi Morikawa, Ken Furuya, Masaru Baba, Yoshiya Yamamoto, Kazuharu Suzuki, Takaaki Izumi, Takashi Meguro, Katsumi Terashita, Jun Ito, Takuto Miyagishima, Naoya Sakamoto
{"title":"低基线CXCL9预测阿特唑单抗加贝伐单抗治疗不可切除HCC的早期进展性疾病","authors":"Shunichi Hosoda,&nbsp;Goki Suda,&nbsp;Takuya Sho,&nbsp;Koji Ogawa,&nbsp;Megumi Kimura,&nbsp;Zijian Yang,&nbsp;Sonoe Yoshida,&nbsp;Akinori Kubo,&nbsp;Yoshimasa Tokuchi,&nbsp;Takashi Kitagataya,&nbsp;Osamu Maehara,&nbsp;Shunsuke Ohnishi,&nbsp;Akihisa Nakamura,&nbsp;Ren Yamada,&nbsp;Masatsugu Ohara,&nbsp;Naoki Kawagishi,&nbsp;Mitsuteru Natsuizaka,&nbsp;Masato Nakai,&nbsp;Kenichi Morikawa,&nbsp;Ken Furuya,&nbsp;Masaru Baba,&nbsp;Yoshiya Yamamoto,&nbsp;Kazuharu Suzuki,&nbsp;Takaaki Izumi,&nbsp;Takashi Meguro,&nbsp;Katsumi Terashita,&nbsp;Jun Ito,&nbsp;Takuto Miyagishima,&nbsp;Naoya Sakamoto","doi":"10.1159/000527759","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Atezolizumab plus bevacizumab treatment is highly effective in patients with unresectable hepatocellular carcinoma (HCC). However, progressive disease (PD) occurs in approximately 20% of HCC patients treated with atezolizumab plus bevacizumab, resulting in a poor prognosis. Thus, the prediction and early detection of HCC is crucial.</p><p><strong>Methods: </strong>Patients with unresectable HCC treated with atezolizumab plus bevacizumab and had baseline preserved serum (<i>n</i> = 68) were screened and classified according to their PD, 6 weeks after treatment initiation (early PD; <i>n</i> = 13). Of these, 4 patients each with and without early PD were selected for cytokine array and genetic analyses. The identified factors were validated in the validated cohort (<i>n</i> = 60) and evaluated in patients treated with lenvatinib.</p><p><strong>Results: </strong>No significant differences were observed in the genetic alterations in circulating tumor DNA. Cytokine array data revealed that baseline MIG (CXCL9), ENA-78, and RANTES differed substantially between patients with and without early PD. Subsequent analysis in the validation cohort revealed that baseline CXCL9 was significantly lower in patients with early PD than that in patients without early PD, and the best cut-off value of serum CXCL9 to predict early PD was 333 pg/mL (sensitivity: 0.600, specificity: 0.923, AUC = 0.75). In patients with lower serum CXCL9 (<333 pg/mL), 35.3% (12/34) experienced early PD with atezolizumab plus bevacizumab, while progression-free survival (PFS) was significantly shorter relative to that in patients without (median PFS, 126 days vs. 227 days; HR: 2.41, 95% CI: 1.22-4.80, <i>p</i> = 0.0084). While patients with objective response to lenvatinib had significantly lower CXCL9 levels compared with those of patients without.</p><p><strong>Conclusion: </strong>Baseline low serum CXCL9 (<333 pg/mL) levels may predict early PD in patients with unresectable HCC treated with atezolizumab plus bevacizumab.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":null,"pages":null},"PeriodicalIF":11.6000,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a3/a1/lic-0012-0156.PMC10267515.pdf","citationCount":"4","resultStr":"{\"title\":\"Low Baseline CXCL9 Predicts Early Progressive Disease in Unresectable HCC with Atezolizumab Plus Bevacizumab Treatment.\",\"authors\":\"Shunichi Hosoda,&nbsp;Goki Suda,&nbsp;Takuya Sho,&nbsp;Koji Ogawa,&nbsp;Megumi Kimura,&nbsp;Zijian Yang,&nbsp;Sonoe Yoshida,&nbsp;Akinori Kubo,&nbsp;Yoshimasa Tokuchi,&nbsp;Takashi Kitagataya,&nbsp;Osamu Maehara,&nbsp;Shunsuke Ohnishi,&nbsp;Akihisa Nakamura,&nbsp;Ren Yamada,&nbsp;Masatsugu Ohara,&nbsp;Naoki Kawagishi,&nbsp;Mitsuteru Natsuizaka,&nbsp;Masato Nakai,&nbsp;Kenichi Morikawa,&nbsp;Ken Furuya,&nbsp;Masaru Baba,&nbsp;Yoshiya Yamamoto,&nbsp;Kazuharu Suzuki,&nbsp;Takaaki Izumi,&nbsp;Takashi Meguro,&nbsp;Katsumi Terashita,&nbsp;Jun Ito,&nbsp;Takuto Miyagishima,&nbsp;Naoya Sakamoto\",\"doi\":\"10.1159/000527759\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Atezolizumab plus bevacizumab treatment is highly effective in patients with unresectable hepatocellular carcinoma (HCC). However, progressive disease (PD) occurs in approximately 20% of HCC patients treated with atezolizumab plus bevacizumab, resulting in a poor prognosis. Thus, the prediction and early detection of HCC is crucial.</p><p><strong>Methods: </strong>Patients with unresectable HCC treated with atezolizumab plus bevacizumab and had baseline preserved serum (<i>n</i> = 68) were screened and classified according to their PD, 6 weeks after treatment initiation (early PD; <i>n</i> = 13). Of these, 4 patients each with and without early PD were selected for cytokine array and genetic analyses. The identified factors were validated in the validated cohort (<i>n</i> = 60) and evaluated in patients treated with lenvatinib.</p><p><strong>Results: </strong>No significant differences were observed in the genetic alterations in circulating tumor DNA. Cytokine array data revealed that baseline MIG (CXCL9), ENA-78, and RANTES differed substantially between patients with and without early PD. Subsequent analysis in the validation cohort revealed that baseline CXCL9 was significantly lower in patients with early PD than that in patients without early PD, and the best cut-off value of serum CXCL9 to predict early PD was 333 pg/mL (sensitivity: 0.600, specificity: 0.923, AUC = 0.75). In patients with lower serum CXCL9 (<333 pg/mL), 35.3% (12/34) experienced early PD with atezolizumab plus bevacizumab, while progression-free survival (PFS) was significantly shorter relative to that in patients without (median PFS, 126 days vs. 227 days; HR: 2.41, 95% CI: 1.22-4.80, <i>p</i> = 0.0084). While patients with objective response to lenvatinib had significantly lower CXCL9 levels compared with those of patients without.</p><p><strong>Conclusion: </strong>Baseline low serum CXCL9 (<333 pg/mL) levels may predict early PD in patients with unresectable HCC treated with atezolizumab plus bevacizumab.</p>\",\"PeriodicalId\":18156,\"journal\":{\"name\":\"Liver Cancer\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":11.6000,\"publicationDate\":\"2023-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a3/a1/lic-0012-0156.PMC10267515.pdf\",\"citationCount\":\"4\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Liver Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1159/000527759\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Liver Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000527759","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 4

摘要

简介:Atezolizumab联合贝伐单抗治疗对不可切除的肝细胞癌(HCC)患者非常有效。然而,在阿特唑单抗加贝伐单抗治疗的HCC患者中,大约20%的患者会出现进行性疾病(PD),导致预后不良。因此,HCC的预测和早期发现是至关重要的。方法:用阿特唑单抗联合贝伐单抗治疗的不可切除HCC患者,基线保存血清(n = 68),在治疗开始后6周(早期PD;N = 13)。选取4例早期PD患者(不论有无早期PD)进行细胞因子测序和基因分析。在已验证的队列(n = 60)中验证了确定的因素,并在lenvatinib治疗的患者中进行了评估。结果:循环肿瘤DNA的遗传改变无显著性差异。细胞因子阵列数据显示,基线MIG (CXCL9)、ENA-78和RANTES在早期PD患者和非早期PD患者之间存在显著差异。验证队列的后续分析显示,早期PD患者的基线CXCL9明显低于无早期PD患者,血清CXCL9预测早期PD的最佳临界值为333 pg/mL(敏感性:0.600,特异性:0.923,AUC = 0.75)。血清CXCL9较低的患者(p = 0.0084)。而对lenvatinib有客观反应的患者与无客观反应的患者相比,CXCL9水平显著降低。结论:基线低血清CXCL9 (
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

摘要图片

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Low Baseline CXCL9 Predicts Early Progressive Disease in Unresectable HCC with Atezolizumab Plus Bevacizumab Treatment.

Introduction: Atezolizumab plus bevacizumab treatment is highly effective in patients with unresectable hepatocellular carcinoma (HCC). However, progressive disease (PD) occurs in approximately 20% of HCC patients treated with atezolizumab plus bevacizumab, resulting in a poor prognosis. Thus, the prediction and early detection of HCC is crucial.

Methods: Patients with unresectable HCC treated with atezolizumab plus bevacizumab and had baseline preserved serum (n = 68) were screened and classified according to their PD, 6 weeks after treatment initiation (early PD; n = 13). Of these, 4 patients each with and without early PD were selected for cytokine array and genetic analyses. The identified factors were validated in the validated cohort (n = 60) and evaluated in patients treated with lenvatinib.

Results: No significant differences were observed in the genetic alterations in circulating tumor DNA. Cytokine array data revealed that baseline MIG (CXCL9), ENA-78, and RANTES differed substantially between patients with and without early PD. Subsequent analysis in the validation cohort revealed that baseline CXCL9 was significantly lower in patients with early PD than that in patients without early PD, and the best cut-off value of serum CXCL9 to predict early PD was 333 pg/mL (sensitivity: 0.600, specificity: 0.923, AUC = 0.75). In patients with lower serum CXCL9 (<333 pg/mL), 35.3% (12/34) experienced early PD with atezolizumab plus bevacizumab, while progression-free survival (PFS) was significantly shorter relative to that in patients without (median PFS, 126 days vs. 227 days; HR: 2.41, 95% CI: 1.22-4.80, p = 0.0084). While patients with objective response to lenvatinib had significantly lower CXCL9 levels compared with those of patients without.

Conclusion: Baseline low serum CXCL9 (<333 pg/mL) levels may predict early PD in patients with unresectable HCC treated with atezolizumab plus bevacizumab.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Liver Cancer
Liver Cancer Medicine-Oncology
CiteScore
20.80
自引率
7.20%
发文量
53
审稿时长
16 weeks
期刊介绍: Liver Cancer is a journal that serves the international community of researchers and clinicians by providing a platform for research results related to the causes, mechanisms, and therapy of liver cancer. It focuses on molecular carcinogenesis, prevention, surveillance, diagnosis, and treatment, including molecular targeted therapy. The journal publishes clinical and translational research in the field of liver cancer in both humans and experimental models. It publishes original and review articles and has an Impact Factor of 13.8. The journal is indexed and abstracted in various platforms including PubMed, PubMed Central, Web of Science, Science Citation Index, Science Citation Index Expanded, Google Scholar, DOAJ, Chemical Abstracts Service, Scopus, Embase, Pathway Studio, and WorldCat.
期刊最新文献
Nivolumab plus Ipilimumab: A Novel First-Line Combination Immunotherapy for Unresectable Hepatocellular Carcinoma. Neratinib Alone or in Combination with Immune Checkpoint Inhibitors with or without mTOR Inhibitors in Patients with Fibrolamellar Carcinoma Erratum. Prognostic Efficacy of the Albumin-Bilirubin Score and Treatment Outcomes in Hepatocellular Carcinoma: A Large-Scale, Multi-Center Real-World Database Study LI-RADS category can be a post-surgical prognostic factor for intrahepatic cholangiocarcinoma in patients with liver cirrhosis or chronic hepatitis B
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1