Federico Aucejo, MD
Liver Cancer Program
The prognosis for patients with liver metastases developing from colorectal cancer (CRC) is dismal. Although the standard-of-care treatment for this condition is liver resection, only one-third of these patients are candidates for surgery. The 5-year survival rate for this small subset of patients hovers between 25% and 60%. The remaining patients are treated with systemic chemotherapy as the standard of care; however, the 5-year survival rate for systemic chemotherapy is only about 10%, with a median survival of about 24 months.
To improve patient outcomes, physicianresearchers in Cleveland Clinic’s Liver Cancer Program have developed a new transplantation protocol for treating liver metastases from CRC. The team implemented the protocol to treat a patient with unresectable liver metastases from CRC, marking the first time that liver transplant surgery was performed for this indication in the United States.
The patient, whose cousin served as the live liver donor, had unresectable metastases in the liver, as well as liver disease from long-term chemotherapy toxicity. Following the successful procedure, both patient and donor were discharged from the hospital within the expected time frame.
We hope that by demonstrating the benefit of this approach, we can prolong the life of a significant number of patients who are not candidates for liver resection.
Norwegian Pilot Study
Cleveland Clinic began developing its new surgical protocol based on the results of a 2011 pilot study of 21 patients at the University of Oslo in Norway. The results of the study showed that liver transplantation helped patients with CRC unresectable liver metastases achieve a 5-year survival rate of 60%.1
The investigators found that metastatic recurrence of disease was common, particularly pulmonary recurrence. However, a significant proportion of the recurrences were accessible for surgery, and at follow-up (after a median of 27 months; range 8-60), 33% of patients had no evidence of disease. Prognostic factors included hepatic tumor load before liver transplantation, time from primary surgery to liver transplantation, and progressive disease on chemotherapy.
Proving Long-Term Efficacy and Shifting to Cadaver Donors
Now that the new protocol has been successfully employed with a patient, the next phase in research development involves proving long-term efficacy and shifting to cadaver donors. Initially, live donors for the transplants were identified because of the uncertainty of long-term oncological outcomes.
This uncertainty stems from the close association between immunosuppression therapy and posttransplant tumor recurrence. The investigators’ rationale was that if the initial experience performing liver transplantation in patients with liver metastases from CRC using live donors was promising, accessing the cadaveric pool would become easier in the future.
From an oncological standpoint, the transplant team’s goal is to achieve a 5-year survival rate of at least 50%. If the researchers can prove that the new protocol results in that rate, they will be able to justify this indication for transplantation.
Chemotherapy Infusion Pump
Along with the new transplant protocol, the Liver Cancer Program incorporated a hepatic artery chemotherapy infusion pump protocol for patients with disease limited to the liver. So far, clinicians have performed 13 pump implantations in combination with liver surgery to treat metastases from CRC.
In addition to systemic chemotherapy, patients have a chemotherapy pump that is implanted into the abdominal wall. The pump is connected to a catheter that is inserted into one of the arteries that connects to the liver. By infusing chemotherapy directly into the liver, the pump treats liver metastases more efficiently by preventing tumor recurrence after surgery or by reducing the bulk of disease so that it can be subsequently removed using surgery.
The concept of using advanced surgical protocols (eg, liver resection complemented by both systemic and hepatic artery pump chemotherapy and liver transplantation) to treat liver metastases from CRC could result in transforming the condition from a fast-moving and fatal disease to a chronic condition with prolonged patient survival. The investigators speculate that by extending patient survival through aggressive surgical and locoregional therapies, novel and more effective systemic therapies will develop and increase survival.
Liquid Biopsy Technology
Assessment of free circulating tumor DNA and mutations in patients with liver malignancy is an initiative under way through the Liver Cancer Program. Time will be needed to determine the true advantage and applicability of this technology, but hopefully it will result in improved efficiency compared with current tumor biomarkers, allowing for the identification of a subset of patients who may benefit the most from these advanced surgical protocols.
Investigators anticipate that liver transplant and hepatic artery chemotherapy pump protocols will complement each other. Directing chemotherapy to the liver via an implantable pump will help limit disease to the liver over time. When chronic liver disease from long-term chemotherapy toxicity develops, salvage liver transplantation would be the next step to consider.
Hagness M, Foss A, Line PD, et al. Liver transplantation for nonresectable liver metastases from colorectal cancer. Ann Surg. 2013;257(5):800-806. doi: 10.1097/SLA.0b013e3182823957.