Liver transplantation is more widely used in hepatocellular carcinoma (HCC) cases than it is in cholangiocarcinoma (CCA), but both cancers present similar problems and opportunities in terms of earlier diagnosis, more effective treatment options, neoadjuvant therapy and organ allocation, according to this year’s Thomas E. Starzl Transplant State-of-the-Art Lecturer on Sunday.
“We have already made some progress in HCC allocation policies,” said Julie Heimbach, MD, FAASLD, Professor of Surgery and Chair of Transplantation Surgery at the Mayo Clinic in Rochester. “HCC is one of the most common indications for liver transplantation in the United States.”
Dr. Heimbach discussed the challenges and opportunities in liver transplantation for hepatobiliary malignancies during the annual lecture honoring Dr. Starzl.
The Milan criteria established liver transplantation as an effective therapy for HCC in the 1990s, although clinical practice was hampered by liver allocation policy. It wasn’t until the implementation of the MELD system in 2002 that HCC patients began receiving livers in significant numbers.
The continuing challenge, Dr. Heimbach said, is that current screening with alpha-fetoprotein and ultrasound does not identify all patients at a curable stage. Improved screening could improve early detection and treatment.
The heterogeneous nature of HCC is also a challenge. The simpler the clonality of a cancer, the more likely treatment is to be successful.
“HCC has the clonality of a hedge,” Dr. Heimbach said. “The most effective treatments may entail multiple agents that attach different targets.”
There are at least as many opportunities in HCC as there are challenges. The implementation of a six-month delay in activating the HCC exception score in 2015 resulted in similar liver transplant rates in patients with or without HCC.
Another potential benefit is the adoption of the National Liver Review Board (NLRB) scheduled for 2019. The NLRB will have a separate board to consider HCC cases that do not meet standard criteria. The new policy includes a fixed MELD score for HCC patients based on the median MELD score in the area of organ distribution in order to expand geographic access to organs.
Early data suggest that cell-free DNA assays based on plasma methylated DNA appear to be able to detect HCC at an early stage, improving the potential for detection while the cancer is still treatable.
Novel machine learning techniques using convolutional neural networks are already able to distinguish between cancer and nonmalignant masses. The next step is to learn to characterize tumor biology for prognosis and treatment, a step that has already been taken in glioblastoma.
There is also hope for reducing demand for livers. HCV patients treated with direct acting antivirals with sustained viral response are at reduced risk of HCC and less likely to need liver transplantation.
Systemic therapies are already in use for patients with advanced HCC and may have a role in downstaging or treating recurrent HCC, Dr. Heimbach noted. And while checkpoint inhibitors have been approved for a subset of HCC patients, it is not clear what role they may play in downsizing or treating recurrent disease.
Surgical resection remains the primary treatment for CCA regardless of location, but prognosis is grim for most patients. Improved imaging could help, especially in peri-hilar CCA. MRI is superior to CT, Dr. Heimbach noted, while ultrasound is helpful to detect nodal disease. She added that early data show high accuracy from a cell-free DNA test.
CCA resection is anatomically challenging, Dr. Heimbach said. Neoadjuvant radiation and chemotherapy, external beam radiation and brachytherapy all offer promise for treatment or downsizing prior to liver transplantation.