Published June 17, 2022
Incomplete response to liver-directed therapies lead to negative outcomes in transplant patients
Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, occurs most frequently in people who have cirrhosis caused by chronic hepatitis B or hepatitis C viral infections, chronic alcohol consumption or non-alcoholic fatty liver disease. It is the fourth leading cause of cancer-related death in the world.
Liver transplantation is the only option for curing non-removable, early-stage HCC with underlying cirrhosis. As patients await transplant, liver-directed therapies (LDT) are used to damage cancer cells enough that the tumor stops growing and shrinks, reducing symptoms and keeping the cancer in enough control that the patient meets eligibility criteria for transplantation.
Patients with poor responses to LDT have lower rates of survival in the year after being added to the transplant list and an increased risk of cancer recurrence post-transplant. However, even among patients who achieve complete radiographic response to LDT, 25 to 43% require additional treatment and more than 80% of treated tumors remain viable on the removed liver. Failure to respond to LDT and the presence of viable tumors increase the risk of post-transplant recurrence with negative outcomes.
An Ochsner Health research team, which included: Kelley Núñez, PhD, Research Scientist; Paul Thevenot, PhD, Lead Researcher for the Transplant Translational Research Program; Tyler Sandow, MD; Interventional Radiologist; Meredith Lakey, MD, Anatomic and Clinical Pathologist; Daniel Fort, PhD, Biomedical Research Informatics Manager; and Ari Cohen, MD, Medical Director of Multi-Organ Transplant Institute and Section Head of Transplant Surgery; investigated viable HCC in LDT-treated bridged-to-transplant patients to understand how treatment may affect tumor signaling pathways.
HCC tissue was obtained from 17 patients diagnosed with HCC before and after they underwent LDT and transplant at Ochsner Health through an Institutional Research Board-approved, observational study. The researchers performed multiplex transcriptomic gene analysis with messenger RNA (mRNA) extracted from viable tumors, using the NanoString nCounter® Tumor Signaling 360 panel. This panel contained 780 genes from 48 pathways involved in tumor biology within the cellular microenvironment as well as innate and adaptive immune responses which lead to tumor control.
The team found that incomplete response to LDT may drive expression patterns that inhibit an effective anti-tumor response through immune exclusion and induce spread throughout the liver. Findings of the study were published in the June 2022 issue of Frontiers in Oncology.
