Abstract
BackgroundPatients with hepatocellular carcinoma waiting for liver transplantation are commonly treated with locoregional treatments, such as TACE and ablation, to prevent tumor progression and dropout and to improve long-term outcome after transplantation. We wanted to prospectively assess feasibility of systemic antitumor treatment with sorafenib as neoadjuvant treatment for hepatocellular carcinoma while waiting for liver transplantation, evaluating tolerability, toxicity and posttransplant morbidity. We also wanted to evaluate perfusion CT parameters to assess tumor properties and response early after start of sorafenib treatment in patients with early hepatocellular carcinoma.MethodsTwelve patients assigned for liver transplantation due to hepatocellular carcinoma, within the UCSF and who fulfilled other criteria, were included January 2012–August 2014. After baseline evaluation, sorafenib treatment was started. Treatment was evaluated by perfusion CT at 1, 4 and 12 weeks and thereafter every 8 weeks. Toxicity and quality of life was assessed at 1 and 4 weeks and every 4 weeks thereafter during treatment. Treatment was stopped when patients were prioritized on the transplantation waiting list or when intolerable side effects or tumor progress warranted other treatments. Posttransplant morbidity after 90 days was registered according to Clavien-Dindo.ResultsBaseline perfusion CT parameters in the tumors predicted the outcome according to RECIST/mRECIST at three months, but no change in CTp parameters was detected as a result of sorafenib. Sorafenib as neoadjuvant treatment was associated with intolerability and dose reductions. Therefore the prerequisites for evaluation of the sorafenib effect on both CT parameters and tumor response were impaired.ConclusionsThis study failed to show changes in CTp parameters during sorafenib treatment. Despite the curative treatment intention, tolerability of neoadjuvant sorafenib treatment before liver transplantation was inadequate in this study.Trial registrationEudraCT number: 2010–024306-36 (date 2011-04-07).
Highlights
Patients with hepatocellular carcinoma waiting for liver transplantation are commonly treated with locoregional treatments, such as transarterial chemoembolization (TACE) and ablation, to prevent tumor progression and dropout and to improve long-term outcome after transplantation
All hepatocellular carcinoma (HCC)-patients had a tumor burden within the University of California San Fransisco (UCSF) criteria and 11 were within the Milan criteria according to pretransplant radiology
Baseline perfusion in the tumors predicted the outcome according to Response Evaluation Criteria in Solid Tumors (RECIST)/Modified Response Evaluation Criteria in Solid Tumors (mRECIST) at three months
Summary
Patients with hepatocellular carcinoma waiting for liver transplantation are commonly treated with locoregional treatments, such as TACE and ablation, to prevent tumor progression and dropout and to improve long-term outcome after transplantation. We wanted to prospectively assess feasibility of systemic antitumor treatment with sorafenib as neoadjuvant treatment for hepatocellular carcinoma while waiting for liver transplantation, evaluating tolerability, toxicity and posttransplant morbidity. We wanted to evaluate perfusion CT parameters to assess tumor properties and response early after start of sorafenib treatment in patients with early hepatocellular carcinoma. Liver transplantation is the only radical treatment for hepatocellular carcinoma (HCC) that treats the underlying liver disease. Sorafenib-induced tumor perfusion changes probably occur very early after the start of sorafenib treatment [17,18,19] and could perhaps provide an early prognosis of tumor response
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