Liver Disease

Reference, year

Device

Lobar

FUP interval

No. patients

Cirrhosis

Child B

Grade > 3 Bilirubin^a

Ascites

Findings

(Dancey et al. 2000)

Glass

0 %

22 %*

2 potential REILD-related deaths

(Geschwind et al. 2004)

Glass

65 %

Any time

10 %

28 %*

7 %

1 treatment-related death

(Carr et al. 2004)

Glass

100 %

0–180

75 %

38 %*

12 %

1 definite and 2 probable treatment-related deaths

(Salem et al. 2005)

Glass

51 %

0–90

60 %^b

14 %

7 %

(Sangro et al. 2006)

Resin

46 %

0–90

71 %

0 %

12 %

2 treatment-related deaths

(Kulik et al. 2008)

Glass

0–180

100 %

33 %

40 %*

18 %

(Kulik et al. 2008)

Glass

0–180

0 %

–

4 %*

4 %

(Hilgard et al. 2010)

Glass

most

0–90

108

76 %

22 %

23 %

0 %

(Salem et al. 2010)

Glass

Any time

291

87 %

55 %^c

19 %

(Sangro et al. 2011)

Resin

55 %

0–90

325

78 %

17 %

5 %

(Mazzaferro et al. 2012)

Glass

94 %

0–90

100 %

17 %

13 %

8 %

23 % of patients developed liver decompensation^d

FUP interval days after radioembolization. TRD treatment-related death. nr not reported

^aCTC grade 3 (>3 x ULN increase) unless otherwise specified. *SWOG grade 3 (>200 % increase from baseline)

^bportal hypertension

^cincludes 3 % of patients with Child C

^dliver decompensation was defined as the occurrence of any of the following features during follow-up: clinically detectable ascites, bleeding from esophageal varices, hepatic encephalopathy, total bilirubin >3 mg/dL, or prothrombin time INR >2.2

Table 2

Liver-related adverse events among patients with liver metastases from colorectal carcinoma treated by radioembolization

Ref, year	Device	Lobar	FUP Interval	No. patients	Prior chemo	Concurrent chemo	Grade > 3 bilirubin^a	Ascites	Findings
(Sharma et al. 2007)	Resin	25 %	Any time	20	1st line	FOLFOX6	10 %	–
(Van Hazel et al. 2004)	Resin	–	Any time	11	1st line	5FU/LV (Mayo)	0 %**		No difference with 5FU/LV alone
(Gray et al. 2001)	Resin	–	Any time	35	1st line (86 %)	IA FUDR	3 %**		RCT nonsignificant difference with FUDR alone
(van Hazel et al. 2009)	Resin	nr	Any time	25	2nd line (68 %)	Irinotecan	4 %**	–
(Seidensticker et al. 2011)	Resin	14 %	Any time	29	Salvage	No	–	–	3 % REILD
(Hendlisz et al. 2010)	Resin	0 %	Any time	21	Salvage	Protracted Iv 5FU	–	–	RCT No liver-related toxicities
(Mulcahy et al. 2009)	Glass	17 %	Any time	72	Salvage	No	13 %
(Jakobs et al. 2008)	Resin	–	Any time	41	Salvage	No	–	–
(Kennedy et al. 2006)	Resin	27 %	Any time	208	Salvage	No	1.5 %	–	No VOD
(Lim et al. 2005)	Resin	–	Any time	30	Salvage	5FU^b	nr	nr	1 RILD

FUP interval days after radioembolization. nr not reported. FU fluorouracil. LV leucovorin. RCT randomized controlled trial. REILD radioembolization-induced liver disease. VOD veno-occlusive disease. RILD radiation-induced liver disease

^aCTC grade 3 (>3 xULN increase) unless otherwise specified. *UICC grade 3 (not defined)

^bas radiosensitizer

Table 3

Liver-related adverse events among patients with liver metastases from neuroendocrine tumors treated by radioembolization

Reference, year	Device	Lobar	FUP Interval	No. patients	Prior Treat	Concurrent chemo	Grade > 3 Bilrubin^a	Ascites	Findings
(Ezziddin et al. 2012)	Resin/Glass	22 %	0–180	23	PRRT	No	9 %	–
(King et al. 2008)	Resin	–	Any time	32	SSA 15 % Chemo	5FU	nr	–	1 jaundiced patient
(Kennedy et al. 2008)	Resin	59 %	0–90	148	nr	nr	nr	0.5 %

PRRT: Peptide Receptor Radionuclide Therapy. SSA: somatostatin analogs 5FU as radiosensitizer (x7 days). nr: not reported

^aCTC grade 3 (> 3 xULN increase)

Fig. 1

Potentially relevant factors in the development of liver toxicities after radioembolization of liver tumors

The incidence of REILD in other series cannot be established because they usually report separately those individual parameters such as increased bilirubin or ascites. And they do it along different periods of time, from 30 days to the entire follow-up period. Patients with liver tumors, particularly if they are cirrhotics, may develop hyperbilirubinemia or ascites as a consequence of tumor or cirrhosis progression. A causal relationship between RE and these findings may thus be confirmed only in controlled clinical trials in which adverse events are recorded prospectively and compared to those occurring in a control arm. However, it is very likely that the increased bilirubin levels reflect REILD in a significant fraction of these patients with early hyperbilirubinemia. This opinion is further supported by the fact that the early increase in bilirubin is not associated with other changes that may reflect abating liver function such as decreased albumin levels or prothrombin activity, even in cirrhotic patients (Sangro et al. 2011).

Only gold members can continue reading. Log In or Register to continue