Phase II Study of Chemoembolization With Drug-Eluting Beads in Patients With Hepatic Neuroendocrine Metastases: High Incidence of Biliary Injury

Abstract

Purpose To evaluate safety in an interim analysis of transarterial chemoembolization (TACE) with doxorubicin-eluting beads (DEB) in 13 patients with hepatic metastases from neuroendocrine tumors (NETs) as part of a phase II trial. Methods Institutional Review Board approval and informed consent were obtained. Thirteen patients completed preliminary safety analysis. Their mean age was 65 years, Eastern Cooperative Oncology Group status was 0/1, tumor burden range was 4–75 %, and mean targeted tumor size was 5.9 cm. Up to four DEB-TACE sessions (100–300 μm beads loaded with ≤100 mg doxorubicin) within 6 months were allowed. Tumor response was assessed by magnetic resonance imaging 1 month after treatment using contrast-enhancement [European Association for the Study of the Liver (EASL) and size Response Evaluation Criteria in Solid Tumors (RECIST)] criteria. Safety was assessed by National Cancer Institute Common Terminology Criteria. Results DEB-TACE was successfully performed in all 13 patients. At 1 month follow-up, there was a mean 12 % decrease in tumor size (p <0.0003) and a 56 % decrease in tumor enhancement (p <0.0001). By EASL criteria, the targeted lesion objective response rate was 78 %. Grade 3 to 4 toxicities were fatigue (23 %), increased alanine amino transferase (15 %), hyperglycemia (15 %), and abdominal pain (8 %). Seven patients developed bilomas (54 %); all of these patients had multiple small (<4 cm) lesions. Subsequently, four underwent percutaneous drainage, three for abscess formation and one for symptoms related to mass effect. Conclusions Although biloma and liver abscess are known risks after TACE, the high incidence in our study population was unexpected and forced interruption of the trial. Although this occurred in a small group of patients, we have changed our technique and patient selection as a result of these findings, thus allowing resumption of the trial.

Comparison of Response Evaluation in Patients with Gastroenteropancreatic and Thoracic Neuroendocrine Tumors After Treatment with [177Lu-DOTA0,Tyr3]Octreotate

“…The EASL criteria have been applied to patients with NETs with liver metastases treated with hepatic arterial chemoembolization with doxorubicin-eluting beads (18,19) or with 90 Y radioembolization (20). The Choi criteria have been applied to a patient with a pancreatic NET treated with sunitinib and Octreotide LAR.…”

GEP-NETS UPDATE: Interventional radiology: role in the treatment of liver metastases from GEP-NETs

“…In this patient cohort, the occurrence of liver/biliary injury in non-tumoral territories was strongly and independently associated with DEB-TACE (odds ratio (OR)Z6.63; P!0.001), and more serious complications such as bilomas and parenchymal infarcts were as well both significantly associated with DEB-TACE vs Lipiodol-TACE (ORZ9.78; PZ0.002) (48). Baghat et al (49) reported interim analysis of DEB-TACE in 13 patients with NET hepatic metastases as part of a phase II trial. Despite an encouraging objective response rate of 78%, seven patients developed bilomas (54%), and four patients underwent percutaneous drainage (three for abscess formation and one for symptoms related to mass effect).…”

“…In the absence of such randomized clinical trials favoring DEB-TACE, it is advisable to use Lipiodol-TACE especially when the total liver is treated, due to safety concerns discussed earlier (48,49,72) RE carries the advantage of minimal side effects in the early post-treatment period, but irradiation delivered to the healthy liver makes the treatment less repeatable than TACE because of the risk of RILD. In the setting of a slowly progressive disease that remains localized to the liver for a long period of time, a repeatable technique is of clinical importance.…”

Intrahepatic biloma following transcatheter arterial chemoembolization for hepatocellular carcinoma: Incidence, imaging features and management

“…In the cirrhotic liver, hypertrophy of the peribiliary capillary plexus may function as a portoarterial shunt and compensate for the occluded arterial flow; therefore, the hypertrophied peribiliary capillary plexus in the cirrhotic liver is able to prevent the ischemic injury of bile ducts during TACE (13,16,17). On the other hand, the high incidence of bile duct injury in patients with metastatic tumors and normal liver morphology also indicates the protective role of the hypertrophied peribiliary plexus around the bile ducts (9,18). The low incidence (1.04%) in this study may be explained as the majority of patients had HCC originating from the cirrhotic liver with hepatitis B virus infection.…”

“…The other risk factors for intrahepatic biloma may include portal vein thrombosis, biliary obstruction and inflammation, the total number of TACE procedures undergone, and the total volume of iodized oil, anticancer drugs, microspheres, gelfoam and drug-eluting beads administered and undergoing segmental or subsegmental TACE (13,(18)(19)(20)(21). However, in the present study, with the exception of portal vein invasion in half of the patients, there was no obvious trend of repeat TACE procedures, embolic materials and anticancer drugs.…”