Randomized Embolization Trial for NeuroEndocrine Tumors (RETNET)

Sunday, March 30, 2025

3:54 PM – 4:03 PM CT

Location: Music City Center, 201 AB

Presenting Author(s)

Michael C. Soulen, MD

Professor
Abramson Cancer Center, University of Pennsylvania, United States

Author/Co-author(s)

EW

E. Paul Wileyto, PhD

Professor
Abramson Cancer Center, United States
CD

Chris Dey, MD

Interventional Radiologist
University of Toronto/Sunnybrook HSC, Canada
Ghassan El-Haddad, MD

Senior Member Interventional Radiology, Medical Director Radionuclide Therapy Program
Moffitt Cancer Center and Research Institute, United States
RG

Ricardo Garcia-Monaco, MD, PhD

Professor
Hospital Italiano, Argentina
NF

Nicholas Fidelman, MD

Professor
University Of California San Francisco, United States
Khashayar Farsad, MD, PhD (he/him/his)

Professor
Oregon Health and Science University, United States
Nishita Kothary, MD

Professor of Radiology
Stanford University School of Medicine, United States
Sarah B. White, MD, FSIR, MS

Faculty
Froedtert & Medical College of Wisconsin, United States
Francesco De Cobelli, MD (he/him/his)

Full Professor
University Vita-Salute San Raffaele Milan, Italy
KB

Karen T. Brown, MD

Chief, Interventional Radiology
University of Utah, United States
Robert Lewandowski, MD

Professor of Radiology, Medicine and Surgery
Northwestern University, Dept. of Radiology, IR section, United States
EZ

Etay Ziv, MD PhD

Associate Attending
Memorial Sloan Kettering Cancer Center, United States

Purpose: : Transarterial bland and chemoembolization (TAE, TACE) are used to treat liver-dominant neuroendocrine tumor (NET) metastases and are part of international guidelines without recommendation of a preferred technique. This international multicenter trial randomized patients to TAE, cTACE or DEB-TACE and evaluated efficacy, toxicities, and HRQoL

Materials and Methods:

Patients with NET liver metastases of any histologic origin and grade that were progressive or symptomatic on somatostatin analog therapy or had >25% liver tumor burden were block randomized to bland embolization, cTACE, or DEB with doxorubicin. Prior biliary intervention was an exclusion. Trial design was pragmatic with treatment according to each institutions’ standard of care. Clinical, laboratory and imaging assessment was performed 1 month after liver-directed therapy, then every 3 months for 2 years. Toxicity was assessed by CTCAE and complications scored according to the SIR Classification. Blinded DSMB review was done at 10 and 30 patients per arm, then annually, with a 20% SAE rate as the stopping rule. Primary outcome was hepatic progression free survival (HPFS) by BICR. The study was powered for a hypothesized hazard ratio of 1.9 to detect a clinically meaningful difference.

Results:

The DEB-TACE arm was closed at the first safety review with an SAE rate of 40%. Between 2017-2022, 151 patients were randomized to TAE (n= 78) or cTACE (n=73) at 13 centers in North and South America and Europe. Primary sites of disease were midgut 54%, pancreas 36%, lung 4%, other/unknown 6%. Tumor grades 1/2/3/unknown were 36%, 56%, 3%, and 4%. 28% had prior liver resection or ablation. 76% had been on a somatostatin analog for an average of 3 years. Indications for embolization included symptom control in 44%, tumor progression in 74%, high baseline tumor burden in 50%, and downstaging in 6%. Baseline demographic and clinical parameters did not significantly differ between arms.

SIR Class D-E complications occurred in 34 (44%) in the TAE arm and 21 (29%) in the cTACE arm. CTCAE G3-4 toxicities occurred in 26 (36%) in the TAE arm and 42 (54%) in the TACE arm.

Changes in Carcinoid Symptom Severity Score were similar between groups.

Median HPFS by BICR for TAE vs cTACE was 18 months vs. 13 months, HR 1.40 [95% CI 0.80-2.46], p = 0.234. Median overall PFS was 15.9 mo vs. 11.1 mo, HR 1.43 [95% CI 0.90-2.26], p = 0.133.

Conclusion:

DEB's have unacceptable toxicity in NETs. There is no significant difference in HPFS or PFS between TAE and cTACE. Serious adverse events requiring elevated level of care occur more frequently with TAE.