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- Sternby Eilard, Malin, 1974, et al.
(author)
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A prospective clinical trial on sorafenib treatment of hepatocellular carcinoma before liver transplantation
- 2019
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In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 19
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Journal article (peer-reviewed)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 12weeks and thereafter every 8weeks. Toxicity and quality of life was assessed at 1 and 4weeks and every 4weeks 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 90days 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).
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| 2. |
- Sternby Eilard, Malin, 1974
(author)
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Prognostic factors and tumor treatments in hepatocellular cancer
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Background: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Prognosis is related to tumor burden, liver function, and performance status as well as treatment factors. Accurate prognostication is a requisite for optimal treatment decisions. Aims: The general aim was to explore specific prognostic factors in different settings of HCC, and to evaluate outcome after treatment with curative intent in patients eligible for multiple treatments. Methods: This thesis is based on four clinical studies in patients with HCC. Study I is a prospective observational study, investigating if patient-reported quality of life (QoL) can predict survival and increase the prognostic accuracy of established staging models. Study II is a review of medical records in a national cohort of patients with liver transplantation from 1996-2014, investigating if AFP levels increase the prognostic accuracy of current selection criteria. Study III is a prospective feasibility study, evaluating neo-adjuvant systemic treatment with sorafenib before liver transplantation. In the fourth study, data from a national registry 2008-2016, was used to assess risk factors and compare outcome in patients eligible for multiple treatments. Overall and recurrence-free survival rates were estimated using Kaplan-Meier and comparisons using log rank tests. Risk factor assessment was performed using Cox Regression analyses. Results and Conclusions: QoL data was prognostic for survival. Adding QoL data improved the prognostic accuracy of established scoring systems. Pre-transplant AFP was a prognostic factor for survival after liver transplantation for HCC. AFP combined with traditional criteria improved the accuracy of patient selection. Sorafenib treatment before liver transplantation was associated with low tolerability and inadequate tumor control. Survival differences after liver transplantation, resection, or ablation were limited in subgroups with well-preserved liver function and limited tumor burden. Liver function variables predicted survival and should be carefully considered in treatment decisions.
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