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Neoadjuvant Cabozantinib and Nivolumab Converts Locally Advanced HCC into Resectable Disease with Enhanced Antitumor Immunity.
Ho, Won Jin; Zhu, Qingfeng; Durham, Jennifer; Popovic, Aleksandra; Xavier, Stephanie; Leatherman, James; Mohan, Aditya; Mo, Guanglan; Zhang, Shu; Gross, Nicole; Charmsaz, Soren; Lin, Dongxia; Quong, Derek; Wilt, Brad; Kamel, Ihab R; Weiss, Matthew; Philosophe, Benjamin; Burkhart, Richard; Burns, William R; Shubert, Chris; Ejaz, Aslam; He, Jin; Deshpande, Atul; Danilova, Ludmila; Stein-O'Brien, Genevieve; Sugar, Elizabeth A; Laheru, Daniel A; Anders, Robert A; Fertig, Elana J; Jaffee, Elizabeth M; Yarchoan, Mark.
Afiliação
  • Ho WJ; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Zhu Q; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Durham J; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Popovic A; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Xavier S; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Leatherman J; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Mohan A; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Mo G; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Zhang S; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Gross N; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Charmsaz S; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Lin D; Fluidigm Corporation, San Francisco, CA, USA.
  • Quong D; Fluidigm Corporation, San Francisco, CA, USA.
  • Wilt B; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Kamel IR; Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Weiss M; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Philosophe B; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Burkhart R; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Burns WR; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Shubert C; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Ejaz A; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • He J; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Deshpande A; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Danilova L; Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Stein-O'Brien G; Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Sugar EA; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Laheru DA; Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Anders RA; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Fertig EJ; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Jaffee EM; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Yarchoan M; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nat Cancer ; 2(9): 891-903, 2021 09.
Article em En | MEDLINE | ID: mdl-34796337
ABSTRACT
A potentially curative hepatic resection is the optimal treatment for hepatocellular carcinoma (HCC), but most patients are not candidates for resection and most resected HCCs eventually recur. Until recently, neoadjuvant systemic therapy for HCC has been limited by a lack of effective systemic agents. Here, in a single arm phase 1b study, we evaluated the feasibility of neoadjuvant cabozantinib and nivolumab in patients with HCC including patients outside of traditional resection criteria (NCT03299946). Of 15 patients enrolled, 12 (80%) underwent successful margin negative resection, and 5/12 (42%) patients had major pathologic responses. In-depth biospecimen profiling demonstrated an enrichment in T effector cells, as well as tertiary lymphoid structures, CD138+ plasma cells, and a distinct spatial arrangement of B cells in responders as compared to non-responders, indicating an orchestrated B-cell contribution to antitumor immunity in HCC.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Neoplasias Hepáticas Limite: Humans Idioma: En Revista: Nat Cancer Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Neoplasias Hepáticas Limite: Humans Idioma: En Revista: Nat Cancer Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos