# 13N-Ammonia PET-CT for Evaluating Response to Antiangiogenic Therapy and Prognosis in Patients with Advanced Hepatocellular Carcinoma: A Pilot Study

## TL;DR

This study explores using 13N-ammonia PET-CT scans to predict treatment outcomes in advanced liver cancer patients receiving antiangiogenic therapy.

## Contribution

The study introduces dynamic 13N-ammonia PET-CT as a potential tool for predicting early progression and survival in hepatocellular carcinoma patients.

## Key findings

- Lower baseline K1mean in HCC lesions was linked to earlier disease progression.
- Post-therapy K1 values in non-neoplastic liver correlated with longer survival.
- PET-CT could not distinguish responders from non-responders after 8–10 weeks of treatment.

## Abstract

The aim of this prospective study was to investigate the role of kinetic parameters derived from dynamic 13N-ammonia PET-CT for evaluating early treatment response and predicting prognosis in patients with advanced hepatocellular carcinoma (HCC) treated with antiangiogenic therapy. Patients with earlier radiological progression showed lower baseline K1mean in HCC lesions. Patients with longer overall survival showed significantly lower post-therapy K1mean, K1max, and K1peak values in non-neoplastic liver parenchyma. However, kinetic parameters could not distinguish between responders and non-responders after 8–10 weeks of treatment. This study suggests a potential role of 13N-ammonia PET-CT in selecting advanced HCC patients that will benefit from antiangiogenic therapy.

Purpose: To prospectively investigate dynamic 13N-ammonia PET-CT for evaluating early treatment response and predicting prognosis in advanced hepatocellular carcinoma (HCC) patients who have undergone antiangiogenic therapy. Methods: Dynamic 13N-ammonia PET-CT was performed in 23 advanced HCC patients before antiangiogenic therapy (baseline) and in 18/23 patients after 8-10 weeks of treatment (post-therapy). At kinetic PET-CT analysis, mean, maximum, and peak values of K1 (mL/cm3/min) and k2 (min−1) were estimated in HCC lesions and non-neoplastic liver using cardiologic 13N-ammonia PET-CT in 15 patients without any liver diseases as normal controls. Outcome endpoints were treatment response after 8–10 weeks assessed by contrast-enhanced CT, progression-free survival (PFS), and overall survival (OS). Results: At both baseline and post-therapy PET-CT, all kinetic PET parameters were significantly higher (p < 0.05) in HCC lesions than in non-neoplastic and healthy liver of HCC patients and controls. According to mRECIST criteria, 13/18 patients (72.2%) were responders (1 CR, 1 PR, and 11 SD), and 5/18 patients (27.8%) were non-responders (PD), with no significant differences in baseline and post-therapy PET parameters between the two groups. At follow-up (median: 14.2 months), 15/18 patients (83.3%) experienced radiological progression, and 14/18 (77.8%) died (7/14 within 12 months from treatment). The nine earlier-progression patients (within 6 months from treatment) showed significantly lower baseline K1mean in HCC lesions than all nine patients with later or no-progression (p = 0.03). Patients still alive 12 months after treatment (n = 11) showed significantly lower post-therapy K1mean (p = 0.05), K1max (p = 0.05), and K1peak (p = 0.03) in non-neoplastic liver than patients with shorter OS (n = 7). Conclusions: In advanced HCC patients treated with antiangiogenic agents, kinetic parameters from baseline and post-therapy 13N-ammonia PET-CT may predict early disease progression and survival. PET-CT seems not able to discriminate responders and non-responders after 8-10 weeks of treatment, suggesting the need for future and larger studies after a longer treatment period.