Safety and Efficacy of¹⁶⁶Ho Radioembolization in Hepatocellular Carcinoma: The HEPAR Primary Study

Abstract

Safety and efficacy of 166 Ho-radioembolization was first determined in the HEPAR and HEPAR II studies, however excluding patients with hepatocellular carcinoma (HCC). The aim of this prospective clinical early phase II study was to establish the toxicity profile of 166 Ho-radioembolization in patients with measurable, liver-dominant HCC, BCLC stage B-C, Child-Pugh (CP) score ≤B7, ECOG 0-1 without curative treatment options.The primary endpoint was rate of unacceptable toxicity defined as grade 3 hyperbilirubinemia (Common Terminology Cancer Adverse Events version 4.03) in combination with low albumin and/or ascites in the absence of disease progression or treatment-related serious adverse events (SAEs). Secondary endpoints included overall toxicity, response, survival, change in α-fetoprotein (AFP), and quality of life.Thirty-one patients with BCLC stage B (71%) or C (29%) HCC were included, mostly multifocal (87%) bilobar (55%) disease. Common grade 1-2 clinical toxicity included fatigue (71%), back pain (55%), ascites (32%), dyspnea (23%), nausea (23%), and abdominal pain (23%), with no >10% grade 3-5 toxicity. Grade 3 laboratory toxicity (>10%) included AST and GGT increase (16%), hyperglycemia (19%), and lymphopenia (29%). Treatment-related unacceptable toxicity occurred in 3/31 patients. At three months, 54% of target lesions showed complete or partial response according to mRECIST. Median overall survival was 14•9 months (95% confidence interval (CI) 10•4 months-24.9 months). No significant changes in quality of life or pain were observed. 166 Ho-radioembolization safety was confirmed in HCC with <10% unacceptable toxicity. Efficacy data support further evaluation.

Intraprocedural MRI-based dosimetry during transarterial radioembolization of liver tumours with holmium-166 microspheres (EMERITUS-1): a phase I trial towards adaptive, image-controlled treatment delivery

“…The highest found healthy liver mean absorbed dose in that study was 55 Gy, and therefore, it has been recommended as the current healthy liver dose threshold. Similar safety data for patients with cirrhotic livers is expected in the near future from secondary analyses of the HEPAR Primary study [23,24]. An additional advantage of intraprocedural dosimetry is that the physician can assess not only the mean tumour dose in near real time, but also the coverage of tumours with microspheres through the heterogeneity of the dose distribution.…”

Holmium-166 Radioembolization: Current Status and Future Prospective

“…[ 27 ]. To conclude, a phase II study assessing toxicity profile of 166 Ho in patients with hepatocellular carcinoma reported unacceptable toxicity in 10% of the treated patients, but no cases of radioembolization-induced liver disease [ 28 ]. Additionally, target liver lesions with complete or partial response were found to be 54% and 84% at three- and six-month follow-up, respectively.…”

Radioembolization, Principles and indications

“…The median overall survival was 14.9 months (95 % CI 10.4 months-not reached), and median AFP levels declined 67 % (nadir). This study showed that 166 Ho-microsphere RE is a promising treatment option for HCC patients with limited complication risks [88].…”