Massive liver metastasis from colon adenocarcinoma causing cardiac tamponade

Treatment response

After 2 doses of chemotherapy and completion of radiotherapy, the edema and shortness of breath improved. A follow-up echocardiogram performed a month after completion of EBRT, 1 dose of FOLFOX, and 1 dose of FOLFOXIRI showed resolution of the cardiac compression (Figure 4).

A CT scan of the abdomen and pelvis obtained after 3 cycles of FOLFOXIRI showed marked decrease in the size of the right lobe hepatic mass from 17.6 x 12.1 cm to 12.0 x 8.0 cm. Given the survival benefit of VEGF inhibition in colon cancer, bevacizumab (5 mg/kg) was added to the FOLFOXIRI regimen with cycle 4. Unfortunately, after the 5^th cycle, a CT scan of the abdomen showed an increase in size of the hepatic lesions. At this time, FOLFOXIRI and bevacizumab were stopped, and given the tumor’s KRAS/NRAS wild type status, systemic therapy was changed to panitumumab (6 mg/kg). The patient initially tolerated treatment well, but after 9 cycles, the total bilirubin started to increase. CT abdomen at this point was consistent with progression of disease. The patient was not eligible for a clinical trial targeting BRAF mutation given the elevated bilirubin. Regorafanib (80 mg daily for 3 weeks on and 1 week off) was started. After the first cycle, the total bilirubin increased further and the regorafanib was dose reduced to 40 mg daily. Unfortunately, a repeat CT scan of the abdomen demonstrated progression of disease, and given that he developed a progressive transaminitis and hyperbilirubinemia, hospice care was recommended. The patient died shortly thereafter, about 15 months after his initial diagnosis.
 

Discussion

Massive liver metastasis in the setting of disseminated cancer is not an uncommon manifestation of advanced cancer that can have life-threatening consequences. In te present case, a bulky liver metastasis caused extrinsic compression of the right atrium, resulting in obvious clinical and echocardiogram-proven cardiac tamponade physiology. To our knowledge, this is the first reported case of the treatment of a bulky hepatic metastasis causing cardiac tamponade. In this patient’s case, both radiotherapy and chemotherapy were given safely in rapid sequence resulting in quick resolution of the patient’s symptoms and echocardiogram findings. The presence of a BRAF mutation conferred a poor prognosis and poor response to systemic chemotherapy. Nevertheless, the patient showed good response to a FOLFOXIRI regimen, chosen in this emergent situation given its significantly higher response rates compared with the standard FOLFIRI regimen, which was tolerated well with minimal adverse effects.

Findings from randomized controlled trials examining the role of palliative radiotherapy for metastatic liver disease have suggested that dose escalation above 30 Gy to the whole liver may lead to unacceptably high rates of radiation-induced liver disease, which typically leads to mortality.^4-8 Two prospective trials comparing twice daily with daily fractionation have shown no benefit to hyperfractionation, with possibly increased rates of acute toxicity in the setting of hepatocellular carcinoma.^9,10 There is emerging evidence that partial liver irradiation, in the appropriate setting in the form of boost after whole-liver RT or stereotactic body radiotherapy, may allow for further dose escalation while avoiding clinical hepatitis.¹¹ Although there is no clear consensus about optimal RT dose and fractionation, the aforementioned studies show that dose and fractionation schemes ranging between 21 Gy and 30 Gy in 1.5 Gy to 3 Gy daily fractions likely provide the best therapeutic ratio for whole-liver irradiation.

In conclusion, this case demonstrates the resolution of cardiac tamponade from a massive liver colorectal metastasis after chemoradiation and illustrates the potential utility of adding radiotherapy to chemotherapy in an urgent scenario where the former might not typically be considered.