Jens Ricke1, Regina Schinner2, Max Seidensticker2, Antonio Gasbarrini3, Otto M van Delden4, Holger Amthauer5, Bora Peynircioglu6, Irene Bargellini7, Roberto Iezzi8, Enrico N De Toni9, Peter Malfertheiner10, Maciej Pech11, Bruno Sangro12. 1. Department of Radiology, Ludwig Maximilan University Munich, München, Germany. Electronic address: jens.ricke@med.uni-muenchen.de. 2. Department of Radiology, Ludwig Maximilan University Munich, München, Germany. 3. Fondazione Policlinico Universitario A. Gemelli IRCCS, Medicina interna e gastroenterologia, Roma, Italy. 4. Department of Radiology and Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 5. Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. 6. Department of Radiology, Hacettepe University, Ankara, Turkey. 7. Department of Vascular and Interventional Radiology, University Hospital of Pisa, Pisa, Italy. 8. Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC di Radiologia, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Roma, Italy. 9. Department of Medicine II, University Hospital, LMU Munich, Munich, Germany. 10. Department of Radiology and Department of Medicine II, University Hospital, LMU Munich, Munich, Germany. 11. Departments of Radiology and Nuclear Medicine, University of Magdeburg, Magdeburg, Germany. 12. Liver Unit and HPB Oncology Area, Clinica Universidad de Navarra-IDISNA and CIBEREHD, Pamplona, Spain.
Abstract
BACKGROUND & AIMS: SORAMIC is a previously published randomised controlled trial assessing survival in patients with advanced hepatocellular carcinoma who received sorafenib with or without selective internal radiation therapy (SIRT). Based on the per-protocol (PP) population, we assessed whether the outcome of patients receiving SIRT+sorafenib vs. sorafenib alone was affected by adverse effects of SIRT on liver function. METHODS: The PP population consisted of 109 (SIRT+sorafenib) vs. 173 patients (sorafenib alone). Comparisons were made between subgroups who achieved a significant survival benefit or trend towards improved survival with SIRT and the inverse group without a survival benefit: <65 years-old vs. ≥65 years-old, Child-Pugh 5 vs. 6, no transarterial chemoembolisation (TACE) vs. prior TACE, no cirrhosis vs. cirrhosis, non-alcohol- vs. alcohol-related aetiology. The albumin-bilirubin (ALBI) score was used to monitor liver function over time during follow-up. RESULTS: ALBI scores increased in all patient groups during follow-up. In the PP population, ALBI score increases were higher in the SIRT+sorafenib than the sorafenib arm (p = 0.0021 month 4, p <0.0001 from month 6). SIRT+sorafenib conferred a survival benefit compared to sorafenib alone in patients aged <65 years-old, those without cirrhosis, those with Child-Pugh 5, and those who had not received TACE. A higher increase in ALBI score was observed in the inverse subgroups in whom survival was not improved by adding SIRT (age ≥65 years-old, p <0.05; cirrhosis, p = 0.07; Child-Pugh 6, p <0.05; prior TACE, p = 0.08). CONCLUSION: SIRT frequently has a negative, often subclinical, effect on liver function in patients with hepatocellular carcinoma, which may impair prognosis after treatment. Careful patient selection for SIRT as well as prevention of clinical and subclinical liver damage by selective treatments, high tumour uptake ratio, and medical prophylaxis could translate into better efficacy. CLINICAL TRIAL NUMBER: EudraCT 2009-012576-27, NCT01126645 LAY SUMMARY: This study of treatments in patients with hepatocellular carcinoma found that selective internal radiation therapy (SIRT) has an adverse effect on liver function that may affect patient outcomes. Patients should be carefully selected before they undergo SIRT and the treatment technique should be optimised for maximum protection of non-target liver parenchyma.
BACKGROUND & AIMS: SORAMIC is a previously published randomised controlled trial assessing survival in patients with advanced hepatocellular carcinoma who received sorafenib with or without selective internal radiation therapy (SIRT). Based on the per-protocol (PP) population, we assessed whether the outcome of patients receiving SIRT+sorafenib vs. sorafenib alone was affected by adverse effects of SIRT on liver function. METHODS: The PP population consisted of 109 (SIRT+sorafenib) vs. 173 patients (sorafenib alone). Comparisons were made between subgroups who achieved a significant survival benefit or trend towards improved survival with SIRT and the inverse group without a survival benefit: <65 years-old vs. ≥65 years-old, Child-Pugh 5 vs. 6, no transarterial chemoembolisation (TACE) vs. prior TACE, no cirrhosis vs. cirrhosis, non-alcohol- vs. alcohol-related aetiology. The albumin-bilirubin (ALBI) score was used to monitor liver function over time during follow-up. RESULTS: ALBI scores increased in all patient groups during follow-up. In the PP population, ALBI score increases were higher in the SIRT+sorafenib than the sorafenib arm (p = 0.0021 month 4, p <0.0001 from month 6). SIRT+sorafenib conferred a survival benefit compared to sorafenib alone in patients aged <65 years-old, those without cirrhosis, those with Child-Pugh 5, and those who had not received TACE. A higher increase in ALBI score was observed in the inverse subgroups in whom survival was not improved by adding SIRT (age ≥65 years-old, p <0.05; cirrhosis, p = 0.07; Child-Pugh 6, p <0.05; prior TACE, p = 0.08). CONCLUSION: SIRT frequently has a negative, often subclinical, effect on liver function in patients with hepatocellular carcinoma, which may impair prognosis after treatment. Careful patient selection for SIRT as well as prevention of clinical and subclinical liver damage by selective treatments, high tumour uptake ratio, and medical prophylaxis could translate into better efficacy. CLINICAL TRIAL NUMBER: EudraCT 2009-012576-27, NCT01126645 LAY SUMMARY: This study of treatments in patients with hepatocellular carcinoma found that selective internal radiation therapy (SIRT) has an adverse effect on liver function that may affect patient outcomes. Patients should be carefully selected before they undergo SIRT and the treatment technique should be optimised for maximum protection of non-target liver parenchyma.
Authors: Osman Öcal; Kerstin Schütte; Christoph J Zech; Christian Loewe; Otto van Delden; Vincent Vandecaveye; Chris Verslype; Bernhard Gebauer; Christian Sengel; Irene Bargellini; Roberto Iezzi; Alexander Philipp; Thomas Berg; Heinz J Klümpen; Julia Benckert; Maciej Pech; Antonio Gasbarrini; Holger Amthauer; Peter Bartenstein; Bruno Sangro; Peter Malfertheiner; Jens Ricke; Max Seidensticker Journal: Eur J Nucl Med Mol Imaging Date: 2022-08-02 Impact factor: 10.057
Authors: Catherine Leyh; Ursula Ehmer; Daniel Roessler; Alexander B Philipp; Florian P Reiter; Petia Jeliazkova; Leonie S Jochheim; Matthias Jeschke; Janina Hammig; Johannes M Ludwig; Jens M Theysohn; Andreas Geier; Christian M Lange Journal: Cancers (Basel) Date: 2022-04-13 Impact factor: 6.575