Covariate analysis of minimal mean hepatic tolerance dose 6 weeks after BT (per protocol, n = 22).

<p>*Two-way ANOVA for categorical factors, ANCOVA for metric covariables.</p><p>Covariate analysis of minimal mean hepatic tolerance dose 6 weeks after BT (per protocol, n = 22).</p

Patient characteristics (per protocol analysis).

<p>Continuous data: mean ± standard deviation, frequencies: counts or percent.</p><p>*Group comparison, continuous data compared by Mann-Whitney U test, frequency data compared by Pearson’s chi square test.</p><p>Patient characteristics (per protocol analysis).</p

Minimal mean hepatic tolerance dose (Gy) and evidence of detectable focal radiation-induced liver injury (fRILI) after BT, group comparison.

<p>Per protocol analysis (n = 22); Intention-to-treat analysis (n = 26) in square brackets.</p><p>Minimal mean hepatic tolerance dose (Gy) and evidence of detectable focal radiation-induced liver injury (fRILI) after BT, group comparison.</p

Laboratory parameters at baseline and follow-up (per protocol analysis).

<p>*Between group comparison, Mann-Whitney U test;</p><p>**Comparison versus baseline (in brackets p-value of control group), Wilcoxon test.</p><p>Laboratory parameters at baseline and follow-up (per protocol analysis).</p

T1w-axial THRIVE 20 min after application of Gd-EOB-DTPA (A, C–E and G, H) and BT planning CT with dosimetry (B and F).

<p>A–D, control group. A: pre-treatment MRI displaying a metastasis scheduled for BT treatment (black arrow). B: Planning-CT after introduction of the brachytherapy catheters (black arrows). Clinical target volume (CTV) represented by bold red circle and dosimetry by coloured lines (red: 20 Gy-, blue: 12 Gy-isodose). C: MRI at 6 weeks showing substantial reduction in Gd-EOB-DTPA uptake by liver parenchyma adjacent to treated metastases (i.e. focal radiation-induced liver injury, fRILI). Note: The area of fRILI matches the geometry of the dosimetry (B). Determined threshold dose: 9.75 Gy. D: MRI at 3 months showing shrinkage of the fRILI. Determined threshold dose: 11.9 Gy. E–H, treatment group. E: pre-treatment MRI displaying two metastases (black arrow); two more treated lesions are not displayed in the plane. F: Planning-CT (annotations: see B). G: MRI at 6 weeks showing no fRILI. H: MRI at 3 months after radiotherapy (and 1 month after finishing study treatment) showing a substantial region of fRILI. Determined threshold dose: 15.8 Gy.</p

CONSORT-diagram.

<p>*Exclusion criterion age was initially disregarded by error in this patient (aged 82). **Exclusion criterion prior radiotherapy was initially disregarded by error in this patient (prior radiotherapy was performed 2 years earlier with location in the contralateral liver lobe).</p

Summary of published studies on drug treatments for the prevention of VOD/RILD.

<p>*Group comparison; LMWH: Low molecular weight heparin; BMT: Bone marrow transplantation; Max: Maximum; NS: Not significant; VOD: Veno-occlusive disease; RCT: Randomized controlled trial; UDCA: ursodeoxycholic acid (ursodiol); aPTT: activated Partial Thromboplastin Time.</p><p>Summary of published studies on drug treatments for the prevention of VOD/RILD.</p