This document discusses liver metastases and Y90 radioembolization. It notes potential adverse events like weight gain, ascites, and bilirubin increase in patients. Risk factors for radioembolization-induced liver disease (REILD) are discussed. Medications like dexamethasone and ondansetron are recommended for premedication. A study comparing sequential versus bilobar radioembolization found higher bilirubin levels and more grade 3/4 toxicity with bilobar treatment. Next steps discussed include a study on using heparin, ursodeoxycholic acid and pentoxiphylline to prevent liver toxicity following treatment. Recommended treatments for ascites post Y90 radioembol

1. Liver mets and Y90 radioembolisation
Tips and Tricks
1
Jens Ricke
Radiology and Nuclear medicine, University of Magdeburg

2. Potential Serious Adverse Events
CTCAE v3: Common Terminology Criteria for Adverse Events version 3.0
ENRY, Hepatology 2011

3. Pathophysiology of RILD

4. • Weight gain in 90 – 95 %
• Ascites in 50 – 85%
• Bilirubin ↑ in 98 % with
– Moderate increase: AST & ALT, intense: AP
– Right upper quadrant pain in 50-75%
• Biopsy, hepatic porto-venous pressure ↑
• Incidence 20% in total liver RE*
Clinical criteria of REILD
*Sangro 2008

5. Risk factors for REILD
Sangro 2008

6. Recommended Medication
Premedication:
20 mg dexamethasone iv (e.g., Fortecortin®)*
8 mg ondansetrone iv (e.g., Zofran®)
*Gil-Alzugaray, Sangro et al. Hepatology 2013

7. Sequential lobar vs. bilobar
radioembolisation
Primary endpoint
•Hepatotoxicity
Secondary endpoint
•Overall survival
REILD: prevention by split dose?
Seidensticker CVIR 2011

8. 12,0%
0,0%
35,0%
18,0%
0%
5%
10%
15%
20%
25%
30%
35%
40%
AnteilPatientenmitGrad3/4Toxizität
6 Wochen
3 Monate
bilobar sequential
(n=17) (n=17)
Liver toxicity: grade 3 or 4
p=0.4
Seidensticker CVIR 2011

9. 13,2
10,2
19,1
10,4
52,3
18,7
0
10
20
30
40
50
60
Bilirubin[µmol/l]
vor RE
6 Wochen
3 Monate
bilobar sequential
(n=17) (n=17)
Results: bilirubin
Bilirubin elev. 3months post RE: p=0.02
Seidensticker CVIR 2011

10. Next step: liver protection
•Current protocol: ELDORADO, NCI 2078864
•Preventive effect of low dose heparine, ursodesoxicolic
acid and pentoxyfiline after HDR single fraction
irradiation of liver metastases
•Sponsor: University of Magdeburg
•Endpoint: Uptake of Gd-EOB-DTPA at 6 and 12 weeks
in relation to dose exposure
Seidensticker, Ricke EASL 2014

11. Ursodeoxycholic acid
3 x 250 mg daily,
oral administration
Pentoxiphylline
3 x 400 mg daily
oral administration
Enoxaparin
1 x 40 mg daily
subcutaneous injection
Study medication
Rationale:
Improvement of biliary excretion
Improvement of blood flow in
sinusoids and ventral veins
Improvement of blood flow in
sinusoids and ventral veins

12. 6 weeks 3 months
after HDR brachytherapy
before
HDR brachytherapy
Control Group
No protective medication administered!
Images: Ricke

13. Medication Group
6 weeks 3 months
after HDR brachytherapy
Baseline
Medication given for 8 weeks after therapy!
Images: Ricke

14. • 56y old male, mCRC, total liver Tx
– Salvage post 3rd line, Tu-load 50%
• Weight gain of 6kg
• Massive Ascites
• Bilirubin 6md/dl
– AST, ALT ↑
– AP ↑ ↑ ↑
Y90-Radioembolisation hazards

16. Gianturco venous stent

19. Take home RILD
•Ascites 6 weeks post Y90 RE is not tumor progression!
•Recommended treatment:
– Symptomatic relief (e.g. paracenthesis, diuresis)
– Treat RILD directly:
• Ursodeoxycholic acid 3 x 250 mg daily
• Pentoxiphylline 3 x 400 mg daily
• Enoxaparin 40mg s.c.
– Cortisone maybe considered for long term outcome

20. www.dafmt.com