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. 2021 Apr 21;13(9):1992.
doi: 10.3390/cancers13091992.

Impact of Pharmaceutical Prophylaxis on Radiation-Induced Liver Disease Following Radioembolization

Max Seidensticker  1 , Matthias Philipp Fabritius  1 , Jannik Beller  2 , Ricarda Seidensticker  1 , Andrei Todica  3 , Harun Ilhan  3 , Maciej Pech  2 , Constanze Heinze  2 , Maciej Powerski  2 , Robert Damm  2 , Alexander Weiss  2 , Johannes Rueckel  1 , Jazan Omari  2 , Holger Amthauer  4 , Jens Ricke  1
Affiliations

Impact of Pharmaceutical Prophylaxis on Radiation-Induced Liver Disease Following Radioembolization

Max Seidensticker et al. Cancers (Basel). .

Abstract

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 (17.8-86.8) vs. 40.2 Gy (12.5-83.5), p = 0.017). All grade RILD events (mild: bilirubin ≥ 21 µmol/L (but <30 μmol/L); severe: (bilirubin ≥ 30 µmol/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 > 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.

Keywords: RILD; prophylaxis; radiation induced liver disease; radioembolization.

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Conflict of interest statement

The authors report the following conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Max Seidensticker declares consulting for Bayer, advisory arrangements with Bayer, Sirtex and Siemens, receiving research grants from Bayer and Sirtex, and receiving travel grants from Sirtex, BTG, Bayer, Cook, Boston Scientific and Siemens; Ricarda Seidensticker declares receiving research grants and travel grants from Sirtex; Harun Ilhan declares advisory arrangements with Bayer, and research grants from Novartis; Maciej Pech declares consulting, served on a speaker‘s bureau, and receiving travel grants from Sirtex; Holger Amthauer declares research grants, travel grants, and lecture fees from Sirtex Medical Europe; Jens Ricke declares consulting, advisory arrangements, and research grants and travel grants from Sirtex Medical, and consulting, advisory arrangements and receiving travel grants from BTG. Matthias P. Fabritius, Jannik Beller, Andrei Todica, Constanze Heinze, Maciej Powerski, Robert Damm, Alexander Weiss, Johannes Rueckel and Jazan Omari have no conflicts of interest to declare. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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