Transarterial Chemoinfusion for Hepatocellular Carcinoma as Downstaging Therapy and a Bridge toward Liver Transplantation

Abstract

Favorable outcomes after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) are well described for patients who fall within defined tumor criteria. The effectiveness of tumor therapies to maintain tumor characteristics within these criteria or to downstage more advanced tumors to fall within these criteria is not well understood. The aim of this study was to examine the response to transcatheter arterial chemoinfusion (TACI) in HCC patients awaiting LT and its efficacy for downstaging or bridging to transplantation. We performed a retrospective study of 248 consecutive TACI cases in 122 HCC patients at a single U.S. medical center. Patients were divided into two groups: those who met the Milan criteria on initial HCC diagnosis (n = 95) and those with more advanced disease (n = 27). With TACI treatment, 87% of the Milan criteria group remained within the Milan criteria and 63% of patients with more advanced disease were successfully downstaged to fall within the Milan criteria. In conclusion, TACI appears to be an effective treatment as a bridge to LT for nearly 90% patients presenting within the Milan criteria and an effective downstaging modality for over half of those whose tumor burden was initially beyond the Milan criteria.

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.…”

“…Some of the studies were small (20 or fewer patients The radiographic assessment of the response was based on measurements of the entire tumor (including the treated or necrotic portions and not just the viable tumor). undergoing LT after down-staging [6][7][8] ) and had short follow-up. Two larger studies 3,4 prospectively applied a downstaging protocol that defined the upper tumor size and number limits for inclusion, and the Milan criteria were used as the endpoint for successful downstaging.…”

“…[6][7][8][9][10][11][12][13] Only a few reports have clearly stated the upper limits of the tumor burden before down-staging. [3][4][5] In the UCSF experience, 3,4 the upper limits for down-staging were a single tumor with a diameter up to 8 cm, 2 to 3 tumors with individual diameters up to 5 cm and with a total diameter up to 8 cm, or 4 to 5 tumors with individual diameters up to 3 cm and with a total diameter up to 8 cm.…”