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

Purpose: To prospectively investigate dynamic N-ammonia PET-CT for evaluating early treatment response and predicting prognosis in advanced hepatocellular carcinoma (HCC) patients who have undergone antiangiogenic therapy.

Methods: Dynamic N-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 (mL/cm/min) and (min) were estimated in HCC lesions and non-neoplastic liver using cardiologic N-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 ( < 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 in HCC lesions than all nine patients with later or no-progression ( = 0.03). Patients still alive 12 months after treatment (n = 11) showed significantly lower post-therapy ( = 0.05), ( = 0.05), and ( = 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 N-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.