Course of Treatment: In accordance with the 2016 European Society for Medical Oncology (ESMO) guidelines, a preoperative computed tomography (CT) scan (Figure 1A) and colonoscopy including biopsy of the hepatic metastasis were performed.^[2] The standard course of treatment, to operate first, was subsequently modified with first-line chemotherapy followed by surgical resection.^[2] A 12-cycle dose of FOLFOX plus bevacizumab (Bv) (5mg/kg) was administered, starting 11/2018 until 05/2019 (Figure 1B), before a right hemihepatectomy procedure in 07/2019 and a resection of liver segments IVa, II and III in 09/2019 (Figure 1C). Despite successful liver resections, the patient relapsed shortly after recovering from liver surgery in 12/2019 and before adjuvant chemotherapy could be started. The magnetic resonance imaging (MRI) and CT scans showed a hepatic relapse and new metastases of the lung and peritoneum. Immediately after disease progression was identified, the patient received second-line therapy FOLFIRI plus Bv, starting in 01/2020 until 07/2020, during which time the disease had stabilized. However, the disease progressed again in 08/2020, one month after the second-line treatment phase was completed.

**Figure 1.** CT scans showing: A) primary tumor at initial presentation; B) hepatic metastasis after first-line FOLFOX plus Bv.; and C) progression of hepatic metastasis after right hemihepatectomy and resections of liver segments IVa, II and III.

Due to the two previous unsuccessful attempts at stabilizing the disease with surgery and chemotherapy, third-line trifluridine/tipiracil (Lonsurf^®) was prescribed, starting in 08/2020 until 02/2021. The dose (35 mg/m²/dose administered orally, twice daily, from day 1 to day 5 and from day 8 to day 12 of each 28-day cycle) remained constant throughout the treatment phase, with the patient only experiencing minor neutropenia that was quickly resolved without dose modification. Unvaryingly, the disease status of the patient remained stable for 6 months from 08/20 until 02/21 (Figures 2 and 3). Unfortunately, despite initial promising results, the disease progressed in 02/2021. The patient is currently receiving fourth-line regorafenib (80mg).

**Figure 2.** CT scan showing: A) hepatic metastasis before trifluridine/tipiracil administration (08/20); B) stable disease of hepatic metastasis after 3 months of trifluridine/tipiracil treatment (11/20); and C) progressive disease of hepatic metastasis after 6 months of trifluridine/tipiracil treatment (02/21).

**Figure 3.** CT scan showing: A) pulmonary metastasis before trifluridine/tipiracil administration (08/20); B) stable disease of pulmonary metastasis after 3 months of trifluridine/tipiracil treatment (11/20); and C) progressive disease of pulmonary metastasis after 6 months of trifluridine/tipiracil treatment (02/21).

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