Low Baseline CXCL9 Predicts Early Progressive Disease in Unresectable HCC with Atezolizumab Plus Bevacizumab Treatment.

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

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引用次数: 4

Abstract

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.

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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

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 (

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来源期刊

Liver Cancer Medicine-Oncology

CiteScore

20.80

自引率

7.20%

发文量

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.