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.

Trial registration: ClinicalTrials.gov NCT00730483.

Conflict of interest statement

Conflict of interest Nikhil Bhagat, Mingde Lin, and Jean-Francois Geschwind were partially funded by National Institutes of Health Grant No. R01 CA 160771-2. Jean-Francois Geschwind was partially funded by Biocompatibles UK Ltd.

Figures

Fig. 1

A 68 year-old man with 70 s postcontrast T1-weighted MRI through lower liver showing baseline image with tumor (A), biloma adjacent to tumor (B, black arrow on left), and resolved biloma after drainage, now with mostly necrotic tumor (C)

Fig. 2

A 69 year-old woman with 70 s postcontrast T1-weighted MRI through the mid-liver showing baseline image (A), biloma adjacent to tumor after second DEB-TACE (B, black arrow on left), and resolved biloma after drainage (C)

Fig. 3

A 66 year-old man with 70 s postcontrast T1-weighted MRI through the mid-liver showing baseline image (A). A biloma formed after the second DEB-TACE procedure, and the patient had a prolonged hospital course and developed multiple small abscesses adjacent to original biloma (B, arrow)