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Liver function considerations for post-selective internal radiation therapy resection (hepatocellular carcinoma and metastatic colorectal cancer) Bruno Sangro*

Besides isolated changes in liver function tests, a form of sinusoidal obstruction syndrome appearing 4–8 weeks after selective internal radiation therapy (SIRT; also known as radioembolization) as jaundice, mild ascites and a moderate increase in γ-glutamyl transpeptidase and alkaline phosphatase has been described in noncirrhotic patients as radioembolization-induced liver disease (REILD) [1] . A similar syndrome may appear within the same time frame in cirrhotic patients with hepatocellular carcinoma, although the spontaneous liver decompensation that occurs in cirrhotics is impossible to differentiate from REILD [2] . REILD seems to develop only in patients with cirrhosis or in noncirrhotic patients exposed to systemic chemotherapy prior to SIRT [1] . In the largest series published on this topic, the incidence rates of all-grade and severe REILD were 5.4 and 2.2%, respectively [3] . Factors that may impact on the occurrence of REILD include: the dose of radiation delivered and the volume of liver tissue involved [4] ; prior liver function and functional reserve (e.g., as measured by total bilirubin or potentially by indocyanine green retention rate at 15 min clearance [5,6]); and prior or concurrent use of other antineoplastic therapies [7] . In the surgical setting, there are a number of well-recognized clinical risk factors that are associated with a low functional liver reserve compared with remnant liver volume (so-called ‘small-for-size syndrome’), such as age, steatosis, steatohepatitis, hepatitis, fibrosis and cirrhosis, as well as intraoperative blood loss and ischemia, obstructive cholestasis and preoperative chemotherapy [8,9] . However, the concurrent use of SIRT in combination with either oxaliplatin with fluorouracil and folinic acid (FOLFOX) or irinotecan as first- and second-line therapies, respectively, has produced little liver toxicity in patients with liver metastasis from colorectal cancer [10,11] , so the impact on resectability relies mainly on the impact of subclinical radiation-induced liver damage on the liver functional reserve (similar to what occurs with oxaliplatin-containing regimes [12,13]). Besides a potential effect of liver-protecting agents, such as ursodeoxycholic acid, the prevention of liver damage mainly relies on treatment design and dosimetry [3] . However, the absence of a clear dose–response relationship between the activity prescribed and the appearance of REILD [14] argues against the use of purely dosimetric approaches to the activity calculation, in which the activity only depends on the estimated dose of radiation delivered to the tumor and nontumoral tissues and not on the volume, status and function of the targeted liver.

KEYWORDS 

• colorectal adenocarcinoma • HCC • hepatocellular carcinoma • liver metastases • radioembolizationinduced liver disease • REILD

Modified protocol for SIRT We have recently proposed a modified protocol for the activity calculation of yttrium-90 resin microspheres so that with whole-liver treatment, for example, a 10–20% reduction in the calculated activity was applied on a general basis, which could be further reduced (towards 0.8 GBq/l) for those patients with cirrhosis or those heavily exposed to prior chemotherapy who had a small tumor burden or a reduced liver volume [3] . For selective treatment, the partition model was used in two *Liver Unit, Clinica Universidad de Navarra & Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), Avda. Pio XII, 36. 31008-Pamplona, Spain; Tel.: +34 948 296 637; Fax: +34 948 296 500; [email protected]

10.2217/FON.14.225 © 2014 Future Medicine Ltd

Future Oncol. (2014) 10(15s), 57–59

part of

ISSN 1479-6694

57

Symposium Paper Sangro

Whole liver

Treatment

Selective

Spared liver volume

0–1 segments

≥2 segments

Activity calculation

BSA formula

Partition model

Liver volume

Liver function considerations for post-selective internal radiation therapy resection (hepatocellular carcinoma and metastatic colorectal cancer).

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