Long-term outcomes following 90Y Radioembolization of neuroendocrine liver metastases: evaluation of the radiation-emitting SIR-spheres in non-resectable liver tumor (RESiN) registry

Thomas Y Wong, Kevin S Zhang, Ripal T Gandhi, Zachary S Collins, Ryan O'Hara, Eric A Wang, Kirubahara Vaheesan, Lea Matsuoka, Daniel Y Sze, Andrew S Kennedy, Daniel B Brown, Thomas Y Wong, Kevin S Zhang, Ripal T Gandhi, Zachary S Collins, Ryan O'Hara, Eric A Wang, Kirubahara Vaheesan, Lea Matsuoka, Daniel Y Sze, Andrew S Kennedy, Daniel B Brown

Abstract

Background: The goal of this study was to evaluate efficacy and safety of 90Y radioembolization for neuroendocrine liver metastases (NELM) in a multicenter registry.

Methods: One hundred-seventy patients with NELM were enrolled in the registry (NCT02685631). Prior treatments included hepatic resection (n = 23, 14%), arterial therapy (n = 62, 36%), octreotide (n = 119, 83%), cytotoxic chemotherapy (n = 58, 41%), biologic therapy (n = 49, 33%) and immunotherapy (n = 10, 6%). Seventy-seven (45%) patients had extrahepatic disease. Seventy-eight (48%), 61 (37%), and 25 (15%) patients were Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or ≥ 2. Tumor grade was known in 81 (48%) patients: 57 (70%) were well-, 12 (15%) moderate-, and 12 (15%) poorly-differentiated. Kaplan-Meier analysis and log rank tests were performed to compare overall and progression-free survival (OS/PFS) by tumor location and grade. Toxicities were reported using Common Terminology Criteria for Adverse Events v.5. Cox Proportional Hazards were calculated for pancreatic primary, performance status, extrahepatic disease at treatment, unilobar treatment, baseline ascites, and > 25% tumor burden.

Results: One, 2, and 3-year OS rates were 75, 62 and 46%, respectively. Median OS was 33 months [(95% CI: 25-not reached (NR)]. The longest median OS was in patients with pancreatic (42 months, 95% CI: 33-NR) and hindgut 41 months, 95% CI: 12-NR) primaries. The shortest OS was in foregut primaries (26 months; 95% CI: 23-NR; X2 = 7, p = 0.1). Median OS of well-differentiated tumors was 36 months (95% CI: 10-NR), compared to 44 (95% CI: 7-NR) and 25 (95% CI: 3-NR) months for moderate and poorly differentiated tumors. Median progression-free survival (PFS) was 25 months with 1, 2, and 3-year PFS rates of 70, 54, and 35%, respectively. Thirteen patients (7.6%) developed grade 3 hepatic toxicity, most commonly new ascites (n = 8, 5%) at a median of 5.5 months. Performance status of ≥2 (HR 2.7, p = 0.01) and baseline ascites (HR 2.8, P = 0.049) predicted shorter OS.

Discussion: In a population with a high incidence of extrahepatic disease, 90Y was effective and safe in treatment of NELM, with median OS of 41 months for well differentiated tumors. Grade 3 or greater hepatic toxicity was developed in 7.6% of patients.

Trial registration: NCT02685631 .

Keywords: Liver cancer; Metastases; Neuroendocrine tumor.

Conflict of interest statement

Ripal T. Gandhi has a research grant from Sirtex Medical, has consulted with Sirtex Medical and Trisalus Life Sciences and has been a speaker for Sirtex Medical.

Zach S. Collins has a research grant from Sirtex Medical, has consulted for Sirtex Medical and has been a speaker for Sirtex Medical.

Eric A. Wang has consulted for Sirtex Medical.

Kirubahara Vaheesan has research grants from Sirtex Medical, Siemens Medical, Merit Medical and Guerbet Medical.

Daniel Y. Sze has a research grant with Sirtex Medical and has consulted for Sirtex Medical.

Andrew S. Kennedy has received institutional grants from Sirtex Medical, Bard Medical and ABK Medical.

Daniel B. Brown has research grants with Sirtex Medical and Guerbet, has consulted with Sirtex Medical, Astra-Zeneca, BTC and Bard Medical, and has been a speaker for Cook Medical.

The other authors have no conflicts to report.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
A-D Overall survival (A) for the entire cohort (B) by primary NET location (C) for Pancreatic primary (PNET) compared to all other primary tumors and (D) by tumor grade
Fig. 2
Fig. 2
A-D Progression-Free Survival (A) for the entire cohort (B) by primary location (C) for pancreatic primary tumors (PNET) vs all other types combined and (D) by tumor grade

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