{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T08:33:13Z","timestamp":1777710793907,"version":"3.51.4"},"reference-count":44,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T00:00:00Z","timestamp":1618963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Radioembolization (RE) with yttrium-90 (90Y) resin microspheres yields heterogeneous response rates in with primary or secondary liver cancer. Radiation-induced liver disease (RILD) is a potentially life-threatening complication with higher prevalence in cirrhotics or patients exposed to previous chemotherapies. Advances in RILD prevention may help increasing tolerable radiation doses to improve patient outcomes. This study aimed to evaluate the impact of post-therapeutic RILD-prophylaxis in a cohort of intensely pretreated liver metastatic breast cancer patients; Methods: Ninety-three patients with liver metastases of breast cancer received RE between 2007 and 2016. All Patients received RILD prophylaxis for 8 weeks post-RE. From January 2014, RILD prophylaxis was changed from ursodeoxycholic acid (UDCA) and prednisolone (standard prophylaxis [SP]; n = 59) to pentoxifylline (PTX), UDCA and low-dose low molecular weight heparin (LMWH) (modified prophylaxis (MP); n = 34). The primary endpoint was toxicity including symptoms of RILD; Results: Dose exposure of normal liver parenchyma was higher in the modified vs. standard prophylaxis group (47.2 Gy (17.8\u201386.8) vs. 40.2 Gy (12.5\u201383.5), p = 0.017). All grade RILD events (mild: bilirubin \u2265 21 \u00b5mol\/L (but &lt;30 \u03bcmol\/L); severe: (bilirubin \u2265 30 \u00b5mol\/L and ascites)) were observed more frequently in the SP group than in the MP group, albeit without significance (7\/59 vs. 1\/34; p = 0.140). Severe RILD occurred in the SP group only (n = 2; p &gt; 0.1). ALBI grade increased in 16.7% patients in the MP and in 27.1% patients in the SP group, respectively (group difference not significant); Conclusions: At established dose levels, mild or severe RILD events proved rare in our cohort. RILD prophylaxis with PTX, UDCA and LMWH appears to have an independent positive impact on OS in patients with metastatic breast cancer and may reduce the frequency and severity of RILD. Results of this study as well as pathophysiological considerations warrant further investigations of RILD prophylaxis presumably targeting combinations of anticoagulation (MP) and antiinflammation (SP) to increase dose prescriptions in radioembolization.<\/jats:p>","DOI":"10.3390\/cancers13091992","type":"journal-article","created":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T12:47:07Z","timestamp":1619009227000},"page":"1992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Impact of Pharmaceutical Prophylaxis on Radiation-Induced Liver Disease Following Radioembolization"],"prefix":"10.3390","volume":"13","author":[{"given":"Max","family":"Seidensticker","sequence":"first","affiliation":[{"name":"Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3471-4701","authenticated-orcid":false,"given":"Matthias Philipp","family":"Fabritius","sequence":"additional","affiliation":[{"name":"Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jannik","family":"Beller","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Radiologie und Nuklearmedizin, Otto-von-Guericke Universit\u00e4tsklinikum, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricarda","family":"Seidensticker","sequence":"additional","affiliation":[{"name":"Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1504-6565","authenticated-orcid":false,"given":"Andrei","family":"Todica","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harun","family":"Ilhan","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7140-6775","authenticated-orcid":false,"given":"Maciej","family":"Pech","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Radiologie und Nuklearmedizin, Otto-von-Guericke Universit\u00e4tsklinikum, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Constanze","family":"Heinze","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Radiologie und Nuklearmedizin, Otto-von-Guericke Universit\u00e4tsklinikum, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maciej","family":"Powerski","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Radiologie und Nuklearmedizin, Otto-von-Guericke Universit\u00e4tsklinikum, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Damm","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Radiologie und Nuklearmedizin, Otto-von-Guericke Universit\u00e4tsklinikum, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Weiss","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Radiologie und Nuklearmedizin, Otto-von-Guericke Universit\u00e4tsklinikum, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6695-2958","authenticated-orcid":false,"given":"Johannes","family":"Rueckel","sequence":"additional","affiliation":[{"name":"Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jazan","family":"Omari","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Radiologie und Nuklearmedizin, Otto-von-Guericke Universit\u00e4tsklinikum, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4414-0657","authenticated-orcid":false,"given":"Holger","family":"Amthauer","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Ricke","sequence":"additional","affiliation":[{"name":"Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1159\/000348325","article-title":"Treatment for Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis: The Emerging Role for Radioembolization Using Yttrium-90","volume":"84","author":"Lau","year":"2013","journal-title":"Oncology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.2967\/jnumed.113.119545","article-title":"Radioembolization for Treatment of Salvage Patients with Colorectal Cancer Liver Metastases: A Systematic Review","volume":"54","author":"Rosenbaum","year":"2013","journal-title":"J. Nucl. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1053\/j.gastro.2010.10.049","article-title":"Radioembolization Results in Longer Time-to-Progression and Reduced Toxicity Compared With Chemoembolization in Patients With Hepatocellular Carcinoma","volume":"140","author":"Salem","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1016\/j.jhep.2019.08.006","article-title":"Impact of combined selective internal radiation therapy and sorafenib on survival in advanced hepatocellular carcinoma","volume":"71","author":"Ricke","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1002\/hep.29691","article-title":"Institutional decision to adopt Y90 as primary treatment for hepatocellular carcinoma informed by a 1000-patient 15-year experience","volume":"68","author":"Salem","year":"2018","journal-title":"Hepatology"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Garin, E., Palard, X., and Rolland, Y. (2020). Personalised Dosimetry in Radioembolisation for HCC: Impact on Clinical Outcome and on Trial Design. Cancers, 12.","DOI":"10.3390\/cancers12061557"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1148\/radiol.2020191606","article-title":"Relationship of Tumor Radiation\u2013absorbed Dose to Survival and Response in Hepatocellular Carcinoma Treated with Transarterial Radioembolization with 90Y in the SARAH Study","volume":"296","author":"Hermann","year":"2020","journal-title":"Radiology"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Alsultan, A.A., van Roekel, C., Barentsz, M.W., Smits, M.L.J., Kunnen, B., Koopman, M., Bruijnen, R.C., de Keizer, B., and Lam, M.G. (2021). Dose-response and dose-toxicity relationships for yttrium-90 glass radioembolization in patients with colorectal cancer liver metastases. J. Nucl. Med., 10.","DOI":"10.2967\/jnumed.120.255745"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1097\/MNM.0000000000001345","article-title":"Yttrium-90 dosimetry and implications on tumour response and survival after radioembolisation of chemo-refractory hepatic metastases from breast cancer","volume":"42","author":"Cheng","year":"2021","journal-title":"Nucl. Med. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"109539","DOI":"10.1016\/j.ejrad.2021.109539","article-title":"Relationship of radiation dose to efficacy of radioembolization of liver metastasis from breast cancer","volume":"136","author":"Ridouani","year":"2021","journal-title":"Eur. J. Radiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.semradonc.2019.08.005","article-title":"Transarterial Radioembolization for Hepatocellular Carcinoma and Hepatic Metastases: Clinical Aspects and Dosimetry Models","volume":"30","author":"Mikell","year":"2020","journal-title":"Semin. Radiat. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1002\/cncr.23339","article-title":"Liver disease induced by radioembolization of liver tumors","volume":"112","author":"Sangro","year":"2008","journal-title":"Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1097\/MEG.0000000000000772","article-title":"Radioembolization-induced liver disease","volume":"29","author":"Braat","year":"2017","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_14","first-page":"584","article-title":"Pathogenesis of veno-occlusive liver disease after radiation","volume":"104","author":"Fajardo","year":"1980","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1016\/0360-3016(94)00418-K","article-title":"Hepatic toxicity resulting from cancer treatment","volume":"31","author":"Lawrence","year":"1995","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_16","first-page":"597","article-title":"The human liver after radiation injury. A form of veno-occlusive disease","volume":"48","author":"Reed","year":"1966","journal-title":"Am. J. Pathol."},{"key":"ref_17","first-page":"549","article-title":"Hepatic veno-occlusive disease after bone marrow transplantation. Immunohistochemical identification of the material within occluded central venules","volume":"127","author":"Shulman","year":"1987","journal-title":"Am. J. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1002\/hep.26191","article-title":"Prognostic factors and prevention of radioembolization-induced liver disease","volume":"57","author":"Chopitea","year":"2013","journal-title":"Hepatology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1002\/hep.29207","article-title":"Prevention and treatment of complications of selective internal radiation therapy: Expert guidance and systematic review","volume":"66","author":"Sangro","year":"2017","journal-title":"Hepatology"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Seidensticker, M., Seidensticker, R., Damm, R., Mohnike, K., Pech, M., Sangro, B., Hass, P., Wust, P., Kropf, S., and Gademann, G. (2014). Prospective Randomized Trial of Enoxaparin, Pentoxifylline and Ursodeoxycholic Acid for Prevention of Radiation-Induced Liver Toxicity. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112731"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/S0002-9343(00)00318-1","article-title":"Ursodeoxycholic acid therapy in hepatobiliary disease","volume":"108","author":"Kowdley","year":"2000","journal-title":"Am. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0016-5085(98)70377-4","article-title":"Role of cytokines in ethanol-induced cytotoxicity in vitro in Hep G2 cells","volume":"115","author":"Neuman","year":"1998","journal-title":"Gastroenterology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s00270-014-0872-7","article-title":"Radiation-Induced Liver Damage: Correlation of Histopathology with Hepatobiliary Magnetic Resonance Imaging, a Feasibility Study","volume":"38","author":"Seidensticker","year":"2014","journal-title":"Cardiovasc. Interv. Radiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1016\/j.ijrobp.2008.10.005","article-title":"Treatment Parameters and Outcome in 680 Treatments of Internal Radiation With Resin 90Y-Microspheres for Unresectable Hepatic Tumors","volume":"74","author":"Kennedy","year":"2009","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1007\/s00259-014-2799-2","article-title":"Twelve-year experience of radioembolization for colorectal hepatic metastases in 214 patients: Survival by era and chemotherapy","volume":"41","author":"Lewandowski","year":"2014","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/j.jvir.2011.06.006","article-title":"Toxicities after Radioembolization with Yttrium-90 SIR-Spheres: Incidence and Contributing Risk Factors at a Single Center","volume":"22","author":"Piana","year":"2011","journal-title":"J. Vasc. Interv. Radiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/0360-3016(93)90428-X","article-title":"Accelerated hyperfractionated hepatic irradiation in the management of patients with liver metastases: Results of the rtog dose escalating protocol","volume":"27","author":"Russell","year":"1993","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1007\/s00330-012-2556-5","article-title":"Radioembolisation with 90Y-labelled resin microspheres in the treatment of liver metastasis from breast cancer","volume":"23","author":"Cianni","year":"2012","journal-title":"Eur. Radiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/S1470-2045(09)70029-4","article-title":"Hepatic complications of breast cancer","volume":"10","author":"Diamond","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1016\/j.jvir.2014.07.007","article-title":"Yttrium-90 Radioembolization Stops Progression of Targeted Breast Cancer Liver Metastases after Failed Chemotherapy","volume":"25","author":"Gordon","year":"2014","journal-title":"J. Vasc. Interv. Radiol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Seidensticker, M., Garlipp, B., Scholz, S., Mohnike, K., Popp, F., Steffen, I., Seidensticker, R., St\u00fcbs, P., Pech, M., and Powerski, M. (2015). Locally ablative treatment of breast cancer liver metastases: Identification of factors influencing survival (the Mammary Cancer Microtherapy and Interventional Approaches (MAMMA MIA) study). BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1499-z"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/sj.bjc.6601038","article-title":"Prognostic factors for patients with hepatic metastases from breast cancer","volume":"89","author":"Wyld","year":"2003","journal-title":"Br. J. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1200\/JCO.1987.5.5.773","article-title":"Clinical course of breast cancer patients with liver metastases","volume":"5","author":"Zinser","year":"1987","journal-title":"J. Clin. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1007\/s00270-011-0295-7","article-title":"Hepatic Toxicity After Radioembolization of the Liver Using 90Y-Microspheres: Sequential Lobar Versus Whole Liver Approach","volume":"35","author":"Seidensticker","year":"2012","journal-title":"Cardiovasc. Interv. Radiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"975","DOI":"10.7326\/0003-4819-128-12_Part_1-199806150-00002","article-title":"Ursodiol Prophylaxis against Hepatic Complications of Allogeneic Bone Marrow Transplantation","volume":"128","author":"Essell","year":"1998","journal-title":"Ann. Intern. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/(SICI)1096-8652(200005)64:1<32::AID-AJH6>3.0.CO;2-N","article-title":"The Japanese multicenter open randomized trial of ursodeoxycholic acid prophylaxis for hepatic veno-occlusive disease after stem cell transplantation","volume":"64","author":"Ohashi","year":"2000","journal-title":"Am. J. Hematol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1200\/JCO.2017.76.0892","article-title":"SIRveNIB: Selective Internal Radiation Therapy Versus Sorafenib in Asia-Pacific Patients With Hepatocellular Carcinoma","volume":"36","author":"Chow","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1016\/S1470-2045(17)30683-6","article-title":"Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): An open-label randomised controlled phase 3 trial","volume":"18","author":"Vilgrain","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1038\/s41409-019-0474-8","article-title":"Systematic review of defibrotide studies in the treatment of veno-occlusive disease\/sinusoidal obstruction syndrome (VOD\/SOS)","volume":"54","author":"Richardson","year":"2019","journal-title":"Bone Marrow Transplant."},{"key":"ref_40","unstructured":"Sanofi-Aventis Canada (2011). Product Monograph TRENTAL\u00ae (Pentoxifylline), Sanofi-Aventis Canada. ATC Code: C04AD03."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1007\/s00270-011-0217-8","article-title":"Changes in Normal Liver and Spleen Volume after Radioembolization with 90Y-Resin Microspheres in Metastatic Breast Cancer Patients: Findings and Clinical Significance","volume":"34","author":"Paprottka","year":"2011","journal-title":"Cardiovasc. Interv. Radiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/0360-3016(91)90171-Y","article-title":"Tolerance of normal tissue to therapeutic irradiation","volume":"21","author":"Emami","year":"1991","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s00270-018-2127-5","article-title":"Radioablation by Image-Guided (HDR) Brachytherapy and Transarterial Chemoembolization in Hepatocellular Carcinoma: A Randomized Phase II Trial","volume":"42","author":"Mohnike","year":"2019","journal-title":"Cardiovasc. Interv. Radiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.ijrobp.2004.11.022","article-title":"In vivo assessment of the tolerance dose of small liver volumes after single-fraction HDR irradiation","volume":"62","author":"Ricke","year":"2005","journal-title":"Int. J. Radiat. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/9\/1992\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:50:35Z","timestamp":1760161835000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/9\/1992"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,21]]},"references-count":44,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["cancers13091992"],"URL":"https:\/\/doi.org\/10.3390\/cancers13091992","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,21]]}}}