Response to transarterial chemoembolization as a biological selection criterion for liver transplantation in hepatocellular carcinoma

Abstract

Criteria to select patients with hepatocellular carcinoma (HCC) for liver transplantation (LT) are based on tumor size and number of nodules rather than on tumor biology. The present study was undertaken to assess the role of transarterial chemoembolization (TACE) in selecting patients with tumors suitable for LT. Ninety-six consecutive patients with HCC were treated by repeatedly performed TACE, 62 of them exceeding the Milan criteria. Patients meeting the Milan criteria were immediately listed, and patients beyond the listing criteria were listed upon downstaging of the tumor following successful TACE. Fifty patients were finally transplanted. Of these 50 patients, 34 exceeded the Milan criteria. In these 96 patients, overall 5-year survival was 51.9%. However, it was 80.9% for patients undergoing LT and 0% for patients without transplantation (P Ͻ 0.0001). Tumor recurrence was primarily influenced by the control of the disease through continued TACE during the waiting time. Freedom from recurrence after 5 years was 94.5% in patients (n ϭ 39) with progression-free TACE during the waiting time. Tumor recurrence was significantly higher in patients (n ϭ 11) who after initial response to TACE progressed again before LT (freedom from recurrence 35.4%; P ϭ 0.0017). Progression-free course of TACE during the waiting time (P ϭ 0.006; risk ratio, 8.95), and a limited number of tumor nodules as assessed in the surgical specimen (P ϭ 0.025; risk ratio, 0.116) proved to be significant predictors for freedom from recurrence in the multivariate analysis. Milan criteria were without impact on recurrence. Our data suggest that sustained response to TACE is a better selection criterion for LT than the initial assessment of tumor size or number.

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

“…111 The paucity of data and the lack of evidence do not allow any firm conclusions about the improvement of posttransplant survival for patients within the MC who receive pretransplant treatments, although some positive effects can be inferred from preliminary experiences with TACE. 117,118 …”

Does a patient qualify for liver transplantation after the down-staging of hepatocellular carcinoma?

“…[3][4][5][6][7][8][9][10][11][12] This outcome measure starts from the time at which a patient with HCC is subjected to down-staging treatments before LT listing and takes into consideration tumor progression beyond acceptable limits (ie, changes in the tumor size or number, vascular invasion, or extrahepatic tumor dissemination) that leads to delisting or dropout from the LT waiting list. Dropout from the waiting list depends not only on the tumor biology but also on the time on the wait-list for deceased donor LT in a particular transplant center or region.…”

“…Most of the published reports have used the Milan criteria as the endpoint of down-staging. [3][4][5][6][7][8] The Response Evaluation Criteria in Solid Tumors (RECIST) [9][10][11] and other criteria 12,13 have also been used to define the response to tumor down-staging, especially when eligibility for LT is not restricted to patients meeting the Milan criteria. Because we are defining the response to down-staging according to measurements of only the viable tumor after locoregional therapy, the RECIST approach does not fit well into this scheme: it defines treatment responses according to the measurement of the entire tumor (including both the ablated or necrotic portion and the viable tumor).…”

“…Two subsequent studies have suggested that a response to locoregional therapy with transarterial chemoembolization (TACE) for HCC meeting or exceeding the Milan criteria could serve as a prognostic marker for improved posttransplant outcomes and for the selection of LT candidates. 10,11 A number of more recent studies have formally evaluated the intention-to-treat outcomes of HCC down-staging to the Milan criteria for LT eligibility [2][3][4][5][6][7][8] (Table 1). The endpoints of these studies include posttransplant survival, HCC recurrence, and dropout from the waiting list due to tumor progression or other causes.…”

Reply: Selection criteria for liver transplantation in patients with hepatocellular carcinoma: Beyond tumor size and number?

“…1,2 Indeed, transarterial catheter embolization (TACE) before LT is not new. It has been performed by several transplantation centers.…”