Multimodality Treatment for Early-Stage Hepatocellular Carcinoma: A Bridging Therapy for Liver Transplantation

Abstract

Purpose: To evaluate the efficiency of a multimodality approach consisting of transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) as bridging therapy for patients with hepatocellular carcinoma (HCC) awaiting orthotopic liver transplantation (OLT) and to evaluate the histopathological response in explant specimens. Materials and Methods: Between April 2001 and November 2011, 36 patients with 50 HCC nodules (1.4–5.0 cm, median 2.8 cm) on the waiting list for liver transplantation were treated by TACE and RFA. The drop-out rate during the follow-up period was recorded. The local efficacy was evaluated by histopathological examination of the explanted livers. Results: During a median follow-up time of 29 (4.0–95.3) months the cumulative drop-out rate for the patients on the waiting list was 0, 2.8, 5.5, 11.0, 13.9 and 16.7% at 3, 6, 12, 24, 36 and 48 months, respectively. 16 patients (with 26 HCC lesions) out of 36 (44.4%) were transplanted by the end of study with a median waiting list time of 13.7 (2.5–37.8) months. The histopathological examination of the explanted specimens revealed a complete necrosis in 20 of 26 HCCs (76.9%), whereas 6 (23.1%) nodules showed viable residual tumor tissue. All transplanted patients are alive at a median time of 29.9 months. Imaging correlation showed 100% specificity and 66.7% sensitivity for the depiction of residual or recurrent tumor. Conclusion: We conclude that TACE combined with RFA could provide an effective treatment to decrease the drop-out rate from the OLT waiting list for HCC patients. Furthermore, this combination therapy results in high rates of complete tumor necrosis as evaluated in the histopathological analysis of the explanted livers. Further randomized trials are needed to demonstrate if there is a benefit in comparison with a single-treatment approach.

Current management of hepatocellular carcinoma: An Eastern perspective

“…To avoid dropout, the rate of which approaches 20%, bridging therapies may be needed [121] . Most commonly applied therapies are RFA, TACE, and surgical resection, although data from Asian countries are rather sparse.…”

“…PEI appears to be less efficacious than RFA, but can be chosen if the lesions are close to adjacent organs, where RFA is dangerous to perform. If the tumor size is > 3 cm, TACE or TACE plus RFA may be favored as tumors become more vascularized and the effect of RFA may be diminished [121] . Surgical resection can precede liver transplantation, and salvage transplantation can be performed in the event of recurrence, without a decrease in overall post-transplant survival [123] .…”

Mexican consensus on the diagnosis and management of hepatocellular carcinoma

“…The MELD score does not reflect disease severity or the risk for death from tumor progression, and so the points are defined as follows: 61 • HCC > 2 cm: 22 MELD points at the time of enrollment (points are added every 3 months to the waiting list, with a 10% increase in risk for death) • HCC < 2 cm: no additional points are figured in Because HCC patients are expected to be on the waiting list for more than 6 months, locoregional therapies (RFA or transarterial chemoembolization) are a good «treatment bridge» option if liver function allows it (Child-Pugh A or B). 17,60,62 Stage can be lowered provided that the aim of tumor size reduction is met, staying within the Milan or UCSF criteria. 63---65 Liver transplantation can be regarded as «salvage therapy» in patients that underwent previous liver resection and then presented with recurrence.…”

Failure mode and effects analysis of linac‐based liver stereotactic body radiotherapy

“…Recent studies have demonstrated that stereotactic body radiation therapy (SBRT) is a safe and effective treatment technique for unresectable primary and metastatic liver tumors . Liver SBRT is also recognized as a potent bridging therapy to orthotopic liver transplantation, either alone or in combination with other locoregional therapies . Given the high complexity of liver SBRT workflow and the potential risks associated with the delivery of large doses per fraction, it is important to prospectively identify weaknesses and hazards that may occur, and implement safety improvement interventions.…”

“…2,3 Liver SBRT is also recognized as a potent bridging therapy to orthotopic liver transplantation, either alone or in combination with other locoregional therapies. 4,5 Given the high complexity of liver SBRT workflow and the potential risks associated with the delivery of large doses per fraction, it is important to prospectively identify weaknesses and hazards that may occur, and implement safety improvement interventions. Task Group 100 (TG 100) of American Association of Physicist in Medicine (AAPM) recommends the ongoing use of risk-based methodologies like failure mode and effects analysis (FMEA) to supplement traditional approaches to quality management programs.…”