{"id":16348,"date":"2020-12-18T09:22:30","date_gmt":"2020-12-18T08:22:30","guid":{"rendered":"https:\/\/genomik-tuebingen.de\/?p=16348"},"modified":"2025-03-10T08:35:15","modified_gmt":"2025-03-10T07:35:15","slug":"clinical-and-genetic-tumor-characteristics-of-responding-and-non-responding-patients-to-pd-1-inhibition-in-hepatocellular-carcinoma","status":"publish","type":"post","link":"https:\/\/cegat.com\/de\/clinical-and-genetic-tumor-characteristics-of-responding-and-non-responding-patients-to-pd-1-inhibition-in-hepatocellular-carcinoma\/","title":{"rendered":"Clinical and Genetic Tumor Characteristics of Responding and Non-Responding Patients to PD-1 Inhibition in Hepatocellular Carcinoma."},"content":{"rendered":"<p><div class=\"fusion-fullwidth fullwidth-box fusion-builder-row-1 fusion-flex-container has-pattern-background has-mask-background nonhundred-percent-fullwidth non-hundred-percent-height-scrolling\" style=\"--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-flex-wrap:wrap;\" ><div class=\"fusion-builder-row fusion-row fusion-flex-align-items-flex-start fusion-flex-content-wrap\" style=\"max-width:1248px;margin-left: calc(-4% \/ 2 );margin-right: calc(-4% \/ 2 );\"><div class=\"fusion-layout-column fusion_builder_column fusion-builder-column-0 fusion_builder_column_1_1 1_1 fusion-flex-column\" style=\"--awb-bg-size:cover;--awb-width-large:100%;--awb-margin-top-large:0px;--awb-spacing-right-large:1.92%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:1.92%;--awb-width-medium:100%;--awb-order-medium:0;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-order-small:0;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;\"><div class=\"fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column\"><div class=\"fusion-text fusion-text-1\" style=\"--awb-font-size:24px;\"><p style=\"text-align: justify;\">Stephan Spahn <sup>1<\/sup>, Daniel Roessler <sup>2<\/sup>, Radu Pompilia <sup>3 4<\/sup>, Gisela Gabernet <sup>5<\/sup>, Beryl Primrose Gladstone <sup>1<\/sup>, Marius Horger <sup>6<\/sup>, Saskia Biskup <sup>7<\/sup>, Magdalena Feldhahn <sup>7<\/sup> , Sven Nahnsen <sup>5<\/sup>, Franz J Hilke <sup>8 9<\/sup>, Bernhard Scheiner <sup>10<\/sup>, Jean-Fran\u00e7ois Dufour <sup>3 4<\/sup>, Enrico N De Toni <sup>2<\/sup>, Matthias Pinter <sup>10<\/sup>, Nisar P Malek <sup>1 11<\/sup>, Michael Bitzer <sup>1 11<\/sup><\/p>\n<\/div><\/div><\/div><\/div><\/div><div class=\"fusion-fullwidth fullwidth-box fusion-builder-row-2 fusion-flex-container has-pattern-background has-mask-background nonhundred-percent-fullwidth non-hundred-percent-height-scrolling\" style=\"--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-padding-top:60px;--awb-padding-bottom:60px;--awb-flex-wrap:wrap;\" ><div class=\"fusion-builder-row fusion-row fusion-flex-align-items-flex-start fusion-flex-content-wrap\" style=\"max-width:1248px;margin-left: calc(-4% \/ 2 );margin-right: calc(-4% \/ 2 );\"><div class=\"fusion-layout-column fusion_builder_column fusion-builder-column-1 fusion_builder_column_1_1 1_1 fusion-flex-column\" style=\"--awb-bg-size:cover;--awb-width-large:100%;--awb-margin-top-large:0px;--awb-spacing-right-large:1.92%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:1.92%;--awb-width-medium:100%;--awb-order-medium:0;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-order-small:0;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;\"><div class=\"fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column\"><div class=\"fusion-title title fusion-title-1 fusion-sep-none fusion-title-text fusion-title-size-two\" style=\"--awb-text-color:var(--awb-custom_color_1);--awb-margin-top-small:10px;--awb-margin-right-small:0px;--awb-margin-bottom-small:10px;--awb-margin-left-small:0px;\"><h2 class=\"fusion-title-heading title-heading-left fusion-responsive-typography-calculated\" style=\"margin:0;text-transform:none;--fontSize:36;line-height:var(--awb-typography1-line-height);\">Abstract<\/h2><\/div><\/div><\/div><div class=\"fusion-layout-column fusion_builder_column fusion-builder-column-2 fusion_builder_column_1_1 1_1 fusion-flex-column\" style=\"--awb-bg-size:cover;--awb-width-large:100%;--awb-margin-top-large:0px;--awb-spacing-right-large:1.92%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:1.92%;--awb-width-medium:100%;--awb-order-medium:0;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-order-small:0;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;\"><div class=\"fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column\"><div class=\"fusion-text fusion-text-2\"><p style=\"text-align: justify;\">Immune checkpoint inhibitors (ICIs) belong to the therapeutic armamentarium in advanced hepatocellular carcinoma (HCC). However, only a minority of patients benefit from immunotherapy. Therefore, we aimed to identify indicators of therapy response. This multicenter analysis included 99 HCC patients. Progression-free (PFS) and overall survival (OS) were studied by Kaplan-Meier analyses for clinical parameters using weighted log-rank testing. Next-generation sequencing (NGS) was performed in a subset of 15 patients. The objective response (OR) rate was 19% median OS (mOS)16.7 months. Forty-one percent reached a PFS &gt; 6 months; these patients had a significantly longer mOS (32.0 vs. 8.5 months). Child-Pugh (CP) A and B patients showed a mOS of 22.1 and 12.1 months, respectively. Ten of thirty CP-B patients reached PFS &gt; 6 months, including 3 patients with an OR. Tumor mutational burden (TMB) could not predict responders. Of note, antibiotic treatment within 30 days around ICI initiation was associated with significantly shorter mOS (8.5 vs. 17.4 months). Taken together, this study shows favorable outcomes for OS with low AFP, OR, and PFS &gt; 6 months. No specific genetic pattern, including TMB, could identify responders. Antibiotics around treatment initiation were associated with worse outcome, suggesting an influence of the host microbiome on therapy success.<\/p>\n<p style=\"text-align: left;\"><strong>Keywords<\/strong>: biomarkers; hepatocellular carcinoma; immunotherapy; microbiome; tumor mutational burden.<\/p>\n<\/div><\/div><\/div><\/div><\/div><div class=\"fusion-fullwidth fullwidth-box fusion-builder-row-3 fusion-flex-container has-pattern-background has-mask-background nonhundred-percent-fullwidth non-hundred-percent-height-scrolling\" style=\"--link_hover_color: var(--awb-color6);--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-padding-top:60px;--awb-padding-bottom:60px;--awb-flex-wrap:wrap;\" ><div class=\"fusion-builder-row fusion-row fusion-flex-align-items-flex-start fusion-flex-content-wrap\" style=\"max-width:1248px;margin-left: calc(-4% \/ 2 );margin-right: calc(-4% \/ 2 );\"><div class=\"fusion-layout-column fusion_builder_column fusion-builder-column-3 fusion_builder_column_1_1 1_1 fusion-flex-column\" style=\"--awb-bg-size:cover;--awb-width-large:100%;--awb-margin-top-large:0px;--awb-spacing-right-large:1.92%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:1.92%;--awb-width-medium:100%;--awb-order-medium:0;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-order-small:0;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;\"><div class=\"fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column\"><div class=\"fusion-tabs fusion-tabs-1 classic vertical-tabs icon-position-left mobile-mode-carousel\" style=\"--awb-title-border-radius-top-left:0px;--awb-title-border-radius-top-right:0px;--awb-title-border-radius-bottom-right:0px;--awb-title-border-radius-bottom-left:0px;--awb-title-padding-top:10px;--awb-title-padding-right:50px;--awb-title-padding-bottom:10px;--awb-title-padding-left:50px;--awb-alignment:start;--awb-inactive-color:var(--awb-custom_color_1);--awb-title-text-color:var(--awb-color5);--awb-title-active-text-color:var(--awb-custom_color_1);--awb-background-color:var(--awb-color5);--awb-border-color:rgba(0,0,0,0.06);--awb-active-border-color:var(--awb-color6);\"><div class=\"nav\"><ul class=\"nav-tabs\" role=\"tablist\" aria-orientation=\"vertical\"><li class=\"active\" role=\"presentation\"><a class=\"tab-link\" data-toggle=\"tab\" role=\"tab\" aria-controls=\"tab-7058a26f9220b44c081\" aria-selected=\"true\" tabindex=\"0\" id=\"fusion-tab-7058a26f9220b44c081\" href=\"#tab-7058a26f9220b44c081\"><h3 class=\"fusion-tab-heading\">Referenzen<\/h3><\/a><\/li><li  role=\"presentation\"><a class=\"tab-link\" data-toggle=\"tab\" role=\"tab\" aria-controls=\"tab-a6cf3d868ddab4fd659\" aria-selected=\"false\" tabindex=\"-1\" id=\"fusion-tab-a6cf3d868ddab4fd659\" href=\"#tab-a6cf3d868ddab4fd659\"><h3 class=\"fusion-tab-heading\">Autorinnen\/Autoren<\/h3><\/a><\/li><\/ul><\/div><div class=\"tab-content\"><div class=\"tab-pane fade fusion-clearfix in active\" role=\"tabpanel\" tabindex=\"0\" aria-labelledby=\"fusion-tab-7058a26f9220b44c081\" id=\"tab-7058a26f9220b44c081\"><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33353145\/\" target=\"_blank\" rel=\"noopener\">Ver\u00f6ffentlichung auf NCBI anschauen<\/a><\/p>\n<p><a href=\"\/de\/diagnostik\/tumorerkrankungen\/\" target=\"_blank\" rel=\"noopener\"><span class=\"avia_iconbox_title\">Zu unserer Tumor-Diagnostik<\/span><\/a><\/div><div class=\"tab-pane fade fusion-clearfix\" role=\"tabpanel\" tabindex=\"0\" aria-labelledby=\"fusion-tab-a6cf3d868ddab4fd659\" id=\"tab-a6cf3d868ddab4fd659\">\n<ol>\n<li>Department Internal Medicine I, Eberhard-Karls University, 72076 Tuebingen, Germany.<\/li>\n<li>Department of Medicine II, University Hospital Ludwig-Maximilians-University (LMU), 81377 Munich, Germany.<\/li>\n<li>Hepatology-Department of Biomedical Research, University of Bern, 3010 Bern, Switzerland.<\/li>\n<li>University Clinic for Visceral Surgery and Medicine, Inselspital, University of Bern, 3010 Bern, Switzerland.<\/li>\n<li>Quantitative Biology Center (QBiC), Eberhard-Karls University, 72076 Tuebingen, Germany.<\/li>\n<li>Department of Diagnostic and Interventional Radiology, Eberhard-Karls University, 72076 Tuebingen, Germany.<\/li>\n<li>CeGaT GmbH and Praxis f\u00fcr Humangenetik, 72076 Tuebingen, Germany.<\/li>\n<li>Institute of Medical Genetics and Applied Genomics, Eberhard-Karls University, 72076 Tuebingen, Germany.<\/li>\n<li>Department of Dermatology, Venerology and Allergology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany.<\/li>\n<li>Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria.<\/li>\n<li>Center for Personalized Medicine, Eberhard-Karls University, 72076 Tuebingen, Germany.<\/li>\n<\/ol>\n<\/div><\/div><\/div><\/div><\/div><\/div><\/div><\/p>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":18,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[53],"tags":[258],"class_list":["post-16348","post","type-post","status-publish","format-standard","hentry","category-veroeffentlichungen","tag-tumorerkrankungen"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.1.1 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Clinical and Genetic Tumor Characteristics of Responding and Non-Responding Patients to PD-1 Inhibition in Hepatocellular 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