Elia Gigante, Christian Hobeika, Brigitte Le Bail, Valérie Paradis, David Tougeron, Marie Lequoy, Mohamed Bouattour, Jean-Frederic Blanc, Nathalie Ganne-Carrié, Henri Tran, Clémence Hollande, Manon Allaire, Giuliana Amaddeo, Hélène Regnault, Paul Vigneron, Maxime Ronot, Laure Elkrief, Gontran Verset, Eric Trepo, Aziz Zaanan, Marianne Ziol, Massih Ningarhari, Julien Calderaro, Julien Edeline, Jean-Charles Nault
{"title":"酪氨酸激酶抑制剂和铂基化疗对不可切除或转移性肝胆管癌患者的全身治疗","authors":"Elia Gigante, Christian Hobeika, Brigitte Le Bail, Valérie Paradis, David Tougeron, Marie Lequoy, Mohamed Bouattour, Jean-Frederic Blanc, Nathalie Ganne-Carrié, Henri Tran, Clémence Hollande, Manon Allaire, Giuliana Amaddeo, Hélène Regnault, Paul Vigneron, Maxime Ronot, Laure Elkrief, Gontran Verset, Eric Trepo, Aziz Zaanan, Marianne Ziol, Massih Ningarhari, Julien Calderaro, Julien Edeline, Jean-Charles Nault","doi":"10.1159/000525488","DOIUrl":null,"url":null,"abstract":"<p><strong>Backgrounds and aims: </strong>Even if no systemic treatment is currently validated for unresectable hepatocellular-cholangiocarcinoma (cHCC-CCA), tyrosine kinase inhibitors (TKIs) and platinum-based chemotherapy are frequently used in clinical practice. Our study aims to describe the effectiveness of first-line systemic treatments in patients with cHCC-CCA.</p><p><strong>Patients and methods: </strong>Patients with histological diagnosis of unresectable or metastatic cHCC-CCA confirmed by a centralized review (WHO classification 2019) and who received systemic treatment from 2009 to 2020 were included retrospectively in 11 centers. The outcomes of patients with cHCC-CCA were compared with patients with hepatocellular carcinoma (HCC) treated by sorafenib (<i>n</i> = 117) and with intrahepatic cholangiocarcinoma (iCCA, <i>n</i> = 94) treated mainly by platinum-based chemotherapy using a frailty Cox model. The efficacy of TKIs and platinum-based chemotherapies in patients with cHCC-CCA was assessed using a doubly robust estimator.</p><p><strong>Results: </strong>A total of 83 patients with cHCC-CCA were included and were predominantly male (72%) with underlying cirrhosis (55%). 67% of patients had extrahepatic metastases and 31% macrovascular tumor invasion. cHCC-CCAs were more often developed on cirrhosis (55.4%) than iCCA (26.6%) but less frequently than HCC (80.2%) (<i>p</i> < 0.001). Both HCC (36.8% and cHCC-CCA (66.2%) had less frequent extrahepatic metastases than iCCA (81%) (<i>p</i> < 0.001). Unadjusted overall survival (OS) was better in iCCA (13 months) compared to cHCC-CCA (12 months) and HCC (11 months) (<i>p</i> = 0.130). In multivariable analysis, after adjustment by a Cox frailty model, patients with cHCC-CCA had the same survival as HCC and iCCA (HR = 0.67, 95% CI: 0.37-1.22, <i>p</i> = 0.189 and HR = 0.66, 95% CI: 0.43-1.02, <i>p</i> = 0.064, respectively). ALBI score (HR = 2.15; 95% CI: 1.23-3.76; <i>p</i> = 0.009), ascites (HR = 3.45, 95% CI: 1.31-9.03, <i>p</i> = 0.013), and tobacco use (HR = 2.29, 95% CI: 1.08-4.87, <i>p</i> = 0.032) were independently associated with OS in patients with cHCC-CCA. Among patients with cHCC-CCA, 25 patients treated with TKI were compared with 54 patients who received platinum-based chemotherapies. Patients treated with TKI had a median OS of 8.3 months compared to 11.9 months for patients treated with platinum-based chemotherapy (<i>p</i> = 0.86). After a robust doubly adjustment on tumor number and size, vascular invasion, ALBI, MELD, and cirrhosis, the type of treatment did not impact OS (HR = 0.92, 95% CI: 0.27-3.15, <i>p</i> = 0.88) or progression-free survival (HR = 1.24, 95% CI: 0.44-3.49, <i>p</i> = 0.67).</p><p><strong>Conclusions: </strong>First-line systemic treatments with TKIs or platinum-based chemotherapies have similar efficacy in patients with unresectable/metastatic cHCC-CCA. The ALBI score predicts OS.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"11 5","pages":"460-473"},"PeriodicalIF":11.6000,"publicationDate":"2022-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ac/9b/lic-0011-0460.PMC9485952.pdf","citationCount":"6","resultStr":"{\"title\":\"Systemic Treatments with Tyrosine Kinase Inhibitor and Platinum-Based Chemotherapy in Patients with Unresectable or Metastatic Hepatocholangiocarcinoma.\",\"authors\":\"Elia Gigante, Christian Hobeika, Brigitte Le Bail, Valérie Paradis, David Tougeron, Marie Lequoy, Mohamed Bouattour, Jean-Frederic Blanc, Nathalie Ganne-Carrié, Henri Tran, Clémence Hollande, Manon Allaire, Giuliana Amaddeo, Hélène Regnault, Paul Vigneron, Maxime Ronot, Laure Elkrief, Gontran Verset, Eric Trepo, Aziz Zaanan, Marianne Ziol, Massih Ningarhari, Julien Calderaro, Julien Edeline, Jean-Charles Nault\",\"doi\":\"10.1159/000525488\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Backgrounds and aims: </strong>Even if no systemic treatment is currently validated for unresectable hepatocellular-cholangiocarcinoma (cHCC-CCA), tyrosine kinase inhibitors (TKIs) and platinum-based chemotherapy are frequently used in clinical practice. Our study aims to describe the effectiveness of first-line systemic treatments in patients with cHCC-CCA.</p><p><strong>Patients and methods: </strong>Patients with histological diagnosis of unresectable or metastatic cHCC-CCA confirmed by a centralized review (WHO classification 2019) and who received systemic treatment from 2009 to 2020 were included retrospectively in 11 centers. The outcomes of patients with cHCC-CCA were compared with patients with hepatocellular carcinoma (HCC) treated by sorafenib (<i>n</i> = 117) and with intrahepatic cholangiocarcinoma (iCCA, <i>n</i> = 94) treated mainly by platinum-based chemotherapy using a frailty Cox model. The efficacy of TKIs and platinum-based chemotherapies in patients with cHCC-CCA was assessed using a doubly robust estimator.</p><p><strong>Results: </strong>A total of 83 patients with cHCC-CCA were included and were predominantly male (72%) with underlying cirrhosis (55%). 67% of patients had extrahepatic metastases and 31% macrovascular tumor invasion. cHCC-CCAs were more often developed on cirrhosis (55.4%) than iCCA (26.6%) but less frequently than HCC (80.2%) (<i>p</i> < 0.001). Both HCC (36.8% and cHCC-CCA (66.2%) had less frequent extrahepatic metastases than iCCA (81%) (<i>p</i> < 0.001). Unadjusted overall survival (OS) was better in iCCA (13 months) compared to cHCC-CCA (12 months) and HCC (11 months) (<i>p</i> = 0.130). In multivariable analysis, after adjustment by a Cox frailty model, patients with cHCC-CCA had the same survival as HCC and iCCA (HR = 0.67, 95% CI: 0.37-1.22, <i>p</i> = 0.189 and HR = 0.66, 95% CI: 0.43-1.02, <i>p</i> = 0.064, respectively). ALBI score (HR = 2.15; 95% CI: 1.23-3.76; <i>p</i> = 0.009), ascites (HR = 3.45, 95% CI: 1.31-9.03, <i>p</i> = 0.013), and tobacco use (HR = 2.29, 95% CI: 1.08-4.87, <i>p</i> = 0.032) were independently associated with OS in patients with cHCC-CCA. Among patients with cHCC-CCA, 25 patients treated with TKI were compared with 54 patients who received platinum-based chemotherapies. Patients treated with TKI had a median OS of 8.3 months compared to 11.9 months for patients treated with platinum-based chemotherapy (<i>p</i> = 0.86). After a robust doubly adjustment on tumor number and size, vascular invasion, ALBI, MELD, and cirrhosis, the type of treatment did not impact OS (HR = 0.92, 95% CI: 0.27-3.15, <i>p</i> = 0.88) or progression-free survival (HR = 1.24, 95% CI: 0.44-3.49, <i>p</i> = 0.67).</p><p><strong>Conclusions: </strong>First-line systemic treatments with TKIs or platinum-based chemotherapies have similar efficacy in patients with unresectable/metastatic cHCC-CCA. The ALBI score predicts OS.</p>\",\"PeriodicalId\":18156,\"journal\":{\"name\":\"Liver Cancer\",\"volume\":\"11 5\",\"pages\":\"460-473\"},\"PeriodicalIF\":11.6000,\"publicationDate\":\"2022-06-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ac/9b/lic-0011-0460.PMC9485952.pdf\",\"citationCount\":\"6\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Liver Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1159/000525488\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/9/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Liver Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000525488","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/9/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Systemic Treatments with Tyrosine Kinase Inhibitor and Platinum-Based Chemotherapy in Patients with Unresectable or Metastatic Hepatocholangiocarcinoma.
Backgrounds and aims: Even if no systemic treatment is currently validated for unresectable hepatocellular-cholangiocarcinoma (cHCC-CCA), tyrosine kinase inhibitors (TKIs) and platinum-based chemotherapy are frequently used in clinical practice. Our study aims to describe the effectiveness of first-line systemic treatments in patients with cHCC-CCA.
Patients and methods: Patients with histological diagnosis of unresectable or metastatic cHCC-CCA confirmed by a centralized review (WHO classification 2019) and who received systemic treatment from 2009 to 2020 were included retrospectively in 11 centers. The outcomes of patients with cHCC-CCA were compared with patients with hepatocellular carcinoma (HCC) treated by sorafenib (n = 117) and with intrahepatic cholangiocarcinoma (iCCA, n = 94) treated mainly by platinum-based chemotherapy using a frailty Cox model. The efficacy of TKIs and platinum-based chemotherapies in patients with cHCC-CCA was assessed using a doubly robust estimator.
Results: A total of 83 patients with cHCC-CCA were included and were predominantly male (72%) with underlying cirrhosis (55%). 67% of patients had extrahepatic metastases and 31% macrovascular tumor invasion. cHCC-CCAs were more often developed on cirrhosis (55.4%) than iCCA (26.6%) but less frequently than HCC (80.2%) (p < 0.001). Both HCC (36.8% and cHCC-CCA (66.2%) had less frequent extrahepatic metastases than iCCA (81%) (p < 0.001). Unadjusted overall survival (OS) was better in iCCA (13 months) compared to cHCC-CCA (12 months) and HCC (11 months) (p = 0.130). In multivariable analysis, after adjustment by a Cox frailty model, patients with cHCC-CCA had the same survival as HCC and iCCA (HR = 0.67, 95% CI: 0.37-1.22, p = 0.189 and HR = 0.66, 95% CI: 0.43-1.02, p = 0.064, respectively). ALBI score (HR = 2.15; 95% CI: 1.23-3.76; p = 0.009), ascites (HR = 3.45, 95% CI: 1.31-9.03, p = 0.013), and tobacco use (HR = 2.29, 95% CI: 1.08-4.87, p = 0.032) were independently associated with OS in patients with cHCC-CCA. Among patients with cHCC-CCA, 25 patients treated with TKI were compared with 54 patients who received platinum-based chemotherapies. Patients treated with TKI had a median OS of 8.3 months compared to 11.9 months for patients treated with platinum-based chemotherapy (p = 0.86). After a robust doubly adjustment on tumor number and size, vascular invasion, ALBI, MELD, and cirrhosis, the type of treatment did not impact OS (HR = 0.92, 95% CI: 0.27-3.15, p = 0.88) or progression-free survival (HR = 1.24, 95% CI: 0.44-3.49, p = 0.67).
Conclusions: First-line systemic treatments with TKIs or platinum-based chemotherapies have similar efficacy in patients with unresectable/metastatic cHCC-CCA. The ALBI score predicts OS.
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.
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