Intention-to-Treat Analysis of Liver Transplantation in Selected, Aggressively Treated HCC Patients Exceeding the Milan Criteria

Abstract

This prospective study analyzed the dropout probability and intention-to-treat survival rates of patients with hepatocellular carcinoma (HCC) selected and treated according to our policy before liver transplantation (LT), with particular attention to those exceeding the Milan criteria. Exclusion criteria for LT were macroscopic vascular invasion, metastases, and poorly differentiated disease at percutaneous biopsy. A specific multi-modal adjuvant algorithm was used to treat HCC before LT. A total of 100 HCC patients were listed for LT: 40 exceeded the Milan criteria in terms of nodule size and number (MILAN OUT) either at listing or in list, while 60 patients continued to meet the criteria (MI-LAN IN). The Milan criteria did not prove to be a significant predictor of dropout probability or survival rates using Cox's analysis. Cumulative dropout probability at 6 and 12 months was 0% and 4% for MILAN OUT, and 6% and 11% for MILAN IN. The intention-to-treat survival rates at 1 and 3 years were 95% and 85% in MI-LAN OUT, and 84% and 69% in MILAN IN. None of the 68 transplanted patients had recurrent HCC after a median 16-month follow-up (0-69 months). In conclusion, LT may be effective for selected, aggressively-treated HCC patients exceeding the Milan criteria.

A Novel Prognostic Nomogram Accurately Predicts Hepatocellular Carcinoma Recurrence after Liver Transplantation: Analysis of 865 Consecutive Liver Transplant Recipients

“…These observed survival differences were attributable to cancer recurrence, as the inability to downstage recipients beyond MC strongly predicted HCC recurrence in both univariate and multivariate analysis. Our findings are consistent with prior studies (37)(38)(39)(40)(41)(42)(43)(44). While it is difficult to definitively attribute the improved post-transplant outcomes to the tumor necrosis achieved by downstaging, we do feel that the ability to downstage tumors is a surrogate for a more favorable underlying tumor biology.…”

Milan criteria in liver transplantation for hepatocellular carcinoma: An evidence-based analysis of 15 years of experience

“…108 Data from large cohorts in Japan and the United States have confirmed that most patients with early-stage HCC within the MC do not experience significant progression of their cancer for approximately 1 year after they join the waiting list. 17,25,89,109,110 Nevertheless, the risk of dropout due to cancer progression in patients meeting the MC at the time of listing still exists and is as high as 30% if no treatment is pursued; however, bridging therapies during the waiting period (either ablation or locoregional approaches) are able to reduce the dropout rate into the range of 0% to 21%. 111,112 In general, the dropout risk increases as the waiting time progresses; in the case of HCC patients who are listed for more than 3 months, the dropout rate is greater than that observed for patients with nonmalignant diseases.…”

“…111,112 In general, the dropout risk increases as the waiting time progresses; in the case of HCC patients who are listed for more than 3 months, the dropout rate is greater than that observed for patients with nonmalignant diseases. 112 Although there is no proven posttransplant advantage in treating patients within the MC who are listed for transplantation, the available evidence (average NOS score ¼ 7) 17,22,23,35,80 indicates that listed patients within the MC who are treated while they are on the waiting list with ablation (preferred for single nodules < 3 cm) or transarterial chemoembolization (TACE; preferred for HCCs > 3 cm or with a multinodular pattern) have reduced dropout rates in comparison with historical untreated controls. 23 Although no RCTs have confirmed this, up to 65% of the HCC patients on the Organ Procurement and Transplantation Network waiting list currently receive locoregional treatments.…”

Current status of the organ replacement approach for malignancies and an overture for organ bioengineering and regenerative medicine

“…A wide variety of treatment modalities have been described, such as liver resection, 14,15 transarterial chemoembolization or chemoinfusion, [16][17][18][19][20] radiofrequency ablation, 14,15,20,21 ethanol injection, 14,15 and more recently, radioembolization with yttrium-90. 19,20 Each transplant center is using its own inclusion criteria, downstaging protocol, definition of successful downstaging, timing of LT, and immunosuppressive protocol.…”