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A multidisciplinary approach is recommended for all patients, with a combination of systemic therapy and one or more liver-directed local treatments determined based on the goals of therapy. For unresectable CRLM (uCRLM), hepatic artery infusion pump therapy, stereotactic body radiation therapy (SBRT), image-guided ablation, and transarterial chemo- or radioembolization are local-regional options to consider. More recently, emerging evidence supports the use of liver transplantation in selected patients with uCRLM. 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