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

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 (NCT 02685631). 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 NCT 02685631.

American Radium Society Appropriate Use Criteria for the use of liver‐directed therapies for nonsurgical management of liver metastases: Systematic review and guidelines

“…Multiple studies have reported safety and outcomes for TARE treatment of LM. 79,80,[99][100][101][102][103][104] Three large multi-institutional randomized phase 3 trials (SIRFLOX, FOXFIRE, and FOXFIRE-Global) demonstrated that 90 Y TARE in addition to FOLFOX-based chemotherapy does not improve OS or PFS when compared with chemotherapy alone as first-line treatment for unresectable CRC LM. 105,106 A subgroup analysis of the SIRFLOX and FOXFIRE-Global trials demonstrated a 4.9-month increase in median OS in patients with HALLEMEIER ET AL.…”

Radioembolisation of liver metastases

“…Recent prospective registry data and pooled data from published retrospective studies show SIRT can be safely used as an alternative or salvage therapy for NELM, including patients who have undergone surgical resection, multiple prior systemic and arterial therapies, and for relief of symptoms of carcinoid syndrome, with median survival 28-33 months. 2,41,59 Median OS was 33 months in both the CIRT and RESiN registries. In the RESiN registry, well-differentiated tumours had a median OS of 41 months, compared to 13 and 25 months for moderate-and poorly differentiated tumours, respectively.…”

The Evolving Role of Radioembolization in the Treatment of Neuroendocrine Liver Metastases

“…However, the majority of the patients the study of Braat et al had more extensive extrahepatic disease (66%). To date, only Braat et al reported clinical outcomes, indicating the reduction in or resolution of hormone-related complaints in 44% and 34% of patients, respectively [ 9 , 20 , 21 ].…”