A more accurate prediction for assessing the eligibility of candidates for liver transplantation who received neoadjuvant therapies was shown when mRECIST radiologic response was included within the Metroticket 2.0 framework, according to a study published in the Journal of Hepatology. 

One of the leading indications for liver transplantation is hepatocellular carcinoma (HCC), which is commonly the result of chronic infection with hepatitis C virus. A main limitation in performing liver transplantation on all patients with HCC is the need to minimize the postoperative recurrence of the tumor. Previous studies have shown that radiologic features and biological surrogates, including alpha-fetoprotein and response to pretransplant neoadjuvant therapies can provide important information on candidate selection, prioritization, and post-transplant survival. The Metroticket 2.0 criteria was developed in 2018 with the aim of predicting post-transplant HCC-specific survival by appropriately weighing the oncologic determinants of post-transplant mortality in the presence of other confounding causes of death.

However, Metroticket 2.0 fails to specify whether the final tumor burden was the consequence of a partial response to neoadjuvant therapies, or of a stable disease or progressive disease of an untreated tumor or after neoadjuvant therapies. Because neoadjuvant regional therapies are commonly used in HCC candidates and the response to these treatments can suggest the aggressiveness of disease from a biological point of view that deserves consideration.

Therefore, this study aimed to re-evaluate the relationship between tumor features and radiologic behavior before to liver transplantation observed in the Metroticket 2.0 by including the biological history of the transplanted tumors by showing that the Metroticket 2.0 model for prediction of “tumor-related death” occuring for hepatocellular carcinoma recurrence after liver transplantation has improved accuracy when mRECIST radiologic response is incorporated.


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Data from 859 patients who received neoadjuvant therapies were included from 2000 to 2015 with a median follow-up of 5 years. The last radiologic assessment before liver transplantation was reviewed according to mRECIST criteria. A competing-risk analysis was performed. The category-based Net Reclassification Improvement scale was used to explore the added value of including radiological response into the Metroticket 2.0. The primary outcome measure was patient survival where death was defined as HCC-related. All other causes of death were defined as “non-tumor related” and were considered as competing events.

Results suggested that including mRECIST criteria into the Metroticket 2.0 framework can refine outcome prediction. In total, 111 patients had post-transplant HCC recurrence and 208 patients died, of whom 81 were HCC-related. At the last radiologic assessment prior to liver transplantation using mRECIST criteria, 41.3% patients were diagnosed with complete response, 24.9% patients were diagnosed with partial response/stable disease, and 33.8% patients were diagnosed with progressive disease. Patients with a complete response had 5-year rates of HCC-related death of 3.1%, those with partial response/stable disease had 9.6%, and those with progressive disease had 13.4% (P <.001).

Determinants of HCC-related death for patients with partial response/stable disease and those progressive disease included log10 for alpha-fetoprotein (P <.001) and the sum of the number and diameters of the tumor(s) (P <.05)   When Metroticket 2.0 criteria included radiologic response, the results demonstrated a correct reclassification of 9.4% of patients who died from HCC-related death within 5 years from liver transplantation, but at the expenditure of 3.5% patients who did not have the event. However, the overall Net Reclassification Improvement was positive and of 5.8.

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Overall, the study authors concluded that, “Inclusion of mRECIST criteria with the Metroticket 2.0 framework can provide further clinical information when judging eligibility for candidates to [liver transplantation] who received neo-adjuvant therapies.”

Reference

Cucchetti A, Serenari M, Sposito C, et al. Including mRECIST in the Metroticket 2.0 criteria improves prediction of hepatocellular carcinoma-related death after liver transplant [published online March 19, 2020]. J Hepat. doi:10.1016/j.jhep.2020.03.01