Patient and Tumor Predictors of Progression-Free Survival in Y90-Treated Neuroendocrine Cancer with Liver Metastases

Purpose: This study aimed to investigate the progression-free survival effect of Yttrium-90 (Y90) treatment in patients with neuroendocrine cancer (NECs) with hepatic metastases. Locoregional treatment is often the best option for these patients who are often ineligible for surgery due to multifocal disease.{1-2} Identifying key markers of progression-free survival can improve disease surveillance and treatment planning.

Materials and Methods: A single-center retrospective analysis was conducted on patients with NECs with hepatic metastases (n=16) who underwent Y90 radioembolization between July 2014 and April 2023. The outcome of interest is progression-free survival (PFS), calculated from treatment date to date of progression, death, or last follow-up. Prior to Y90 mapping studies, baseline values of creatinine, bilirubin, INR, sodium, albumin, dialysis status, MELD, MELD-Na, MELD 3.0 scores, previous liver intervention, number of lesions, largest lesion size, portal vein invasion, lung shunt percentage, and areas of treatment were collected. PFS was estimated using Kaplan-Meier curves, and its association with preliminary factors were evaluated using Cox proportional hazards models in univariate and multivariate analyses; proportional-hazards assumption was assessed with Schoenfeld residual tests.

Results: The median PFS is 257.5 days. In univariate Cox models, higher bilirubin was associated with shorter PFS (HR 2.07, 95% CI 1.20–3.57, p=0.009), while higher sodium was associated with longer PFS (HR 0.87, 95% CI 0.78–0.97, p=0.012). INR (HR 1.54, p=0.071) and Child-Pugh score (HR 1.38, p=0.076) showed near-significant trends; other variables were not significant. In the multivariate Cox model, bilirubin remained independently associated with shorter PFS (HR 1.91, 95% CI 1.01–3.60, p=0.046), whereas sex, Child-Pugh score, and prior liver interventions were not statistically significant. Kaplan-Meier curves stratified by largest lesion size also showed no significant difference ( >5 cm [n=19], median 599 days; 3–5 cm [n=11], median 111 days; < 3 cm [n=4], median 184.5 days; p=0.81).

Conclusion: Preliminary markers of liver function, especially bilirubin, may be an important factor in predicting survival in patients with NECs with hepatic metastases being treated with Y90. Sodium showed a possible protective pattern in simple models, but this did not persist with adjustment. Further studies including larger patient populations are needed to fully understand which factors may influence or may be independent from PFS in this population.