title: Colorectal Cancer Liver Metastasis: Evolving Paradigms and Future Directions.
abstract: In patients with colorectal cancer (CRC) that metastasizes to the liver, there are several key goals for improving outcomes including early detection, effective prognostic indicators of treatment response, and accurate identification of patients at high risk for recurrence. Although new therapeutic regimens developed over the past decade have increased survival, there is substantial room for improvement in selecting targeted treatment regimens for the patients who will derive the most benefit. Recently, there have been exciting developments in identifying high-risk patient cohorts, refinements in the understanding of systemic vs localized drug delivery to metastatic niches, liquid biomarker development, and dramatic advances in tumor immune therapy, all of which promise new and innovative approaches to tackling the problem of detecting and treating the metastatic spread of CRC to the liver. Our multidisciplinary group held a state-of-the-science symposium this past year to review advances in this rapidly evolving field. Herein, we present a discussion around the issues facing treatment of patients with CRC liver metastases, including the relationship of discrete gene signatures with prognosis. We also discuss the latest advances to maximize regional and systemic therapies aimed at decreasing intrahepatic recurrence, review recent insights into the tumor microenvironment, and summarize advances in noninvasive multimodal biomarkers for early detection of primary and recurrent disease. As we continue to advance clinically and technologically in the field of colorectal tumor biology, our goal should be continued refinement of predictive and prognostic studies to decrease recurrence after curative resection and minimize treatment toxicity to patients through a tailored multidisciplinary approach to cancer care.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Oregon Heath and Science University, Portland, Oregon.
authors.forename: Luai R
authors.initials: LR
authors.lastname: Zarour
authors.affiliation: Department of Cell Developmental and Cancer Biology, Oregon Heath and Science University, Portland, Oregon; The Knight Cancer Institute, Oregon Heath and Science University, Portland, Oregon.
authors.forename: Sudarshan
authors.initials: S
authors.lastname: Anand
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Oregon Heath and Science University, Portland, Oregon; The Knight Cancer Institute, Oregon Heath and Science University, Portland, Oregon.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Billingsley
authors.affiliation: The Knight Cancer Institute, Oregon Heath and Science University, Portland, Oregon; Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon.
authors.forename: William H
authors.initials: WH
authors.lastname: Bisson
authors.affiliation: Department of Gastrointestinal Medical Oncology, Solid Tumor Division, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cercek
authors.affiliation: Stanford Institute for Stem Cell and Regenerative Medicine, Stanford University, Stanford, California; Division of Oncology, Department of Medicine, Stanford University, Stanford, California.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Clarke
authors.affiliation: Department of Cell Developmental and Cancer Biology, Oregon Heath and Science University, Portland, Oregon; The Knight Cancer Institute, Oregon Heath and Science University, Portland, Oregon.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Coussens
authors.affiliation: Department of Cell Developmental and Cancer Biology, Oregon Heath and Science University, Portland, Oregon.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Gast
authors.affiliation: Division of Colorectal Surgery, Department of Surgery, Oregon Heath and Science University, Portland, Oregon.
authors.forename: Cristina B
authors.initials: CB
authors.lastname: Geltzeiler
authors.affiliation: The Knight Cancer Institute, Oregon Heath and Science University, Portland, Oregon; School of Nursing, Oregon Heath and Science University, Portland, Oregon.
authors.forename: Lissi
authors.initials: L
authors.lastname: Hansen
authors.affiliation: Division of Colorectal Surgery, Department of Surgery, Oregon Heath and Science University, Portland, Oregon.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Kelley
authors.affiliation: The Knight Cancer Institute, Oregon Heath and Science University, Portland, Oregon; Division of Hematology and Medical Oncology, Department of Medicine, Oregon Heath and Science University, Portland, Oregon.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Lopez
authors.affiliation: Department of Radiation Medicine, Oregon Heath and Science University, Portland, Oregon.
authors.forename: Shushan R
authors.initials: SR
authors.lastname: Rana
authors.affiliation: Department of Cell Developmental and Cancer Biology, Oregon Heath and Science University, Portland, Oregon.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ruhl
authors.affiliation: The Knight Cancer Institute, Oregon Heath and Science University, Portland, Oregon; Division of Colorectal Surgery, Department of Surgery, Oregon Heath and Science University, Portland, Oregon.
authors.forename: V Liana
authors.initials: VL
authors.lastname: Tsikitis
authors.affiliation: The Knight Cancer Institute, Oregon Heath and Science University, Portland, Oregon; Division of Hematology and Medical Oncology, Department of Medicine, Oregon Heath and Science University, Portland, Oregon.
authors.forename: Gina M
authors.initials: GM
authors.lastname: Vaccaro
authors.affiliation: Department of Cell Developmental and Cancer Biology, Oregon Heath and Science University, Portland, Oregon; The Knight Cancer Institute, Oregon Heath and Science University, Portland, Oregon.
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Wong
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Oregon Heath and Science University, Portland, Oregon; The Knight Cancer Institute, Oregon Heath and Science University, Portland, Oregon.
authors.forename: Skye C
authors.initials: SC
authors.lastname: Mayo
keywords: 5-FU, fluorouracil; Biomarkers; CDX2, caudal-type homeobox transcription factor 2; CEA, carcinoembryonic antigen; CK, cytokeratin; CRC, colorectal cancer; CRLM, colorectal cancer liver metastasis; CTC, circulating tumor cells; Colorectal Cancer Liver Metastasis; DFS, disease-free survival; EGFR, epidermal growth factor receptor; EpCAM, epithelial cell adhesion molecule; HAI, hepatic arterial infusion; Hepatic Arterial Infusion; High-Risk Colorectal Cancer; IL, interleukin; LV, leucovorin; MSI, microsatellite instability; OS, overall survival; PD, programmed death; Recurrence; TH, T-helper; cfDNA, cell-free DNA; dMMR, deficient mismatch repair; miRNA, microRNA