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Clinical Trial
. 2022 Dec;63(12):1891-1898.
doi: 10.2967/jnumed.122.263823. Epub 2022 May 19.

Safety and Efficacy of 166Ho Radioembolization in Hepatocellular Carcinoma: The HEPAR Primary Study

Margot T M Reinders  1 , Karel J van Erpecum  2 , Maarten L J Smits  3 , Arthur J A T Braat  3 , Joep de Bruijne  2 , Rutger Bruijnen  3 , Dave Sprengers  4 , Robert A de Man  4 , Erik Vegt  5 , Jan N M IJzermans  6 , Adriaan Moelker  5 , Marnix G E H Lam  1
Affiliations
Clinical Trial

Safety and Efficacy of 166Ho Radioembolization in Hepatocellular Carcinoma: The HEPAR Primary Study

Margot T M Reinders et al. J Nucl Med. 2022 Dec.

Abstract

The safety and efficacy of 166Ho radioembolization was first determined in the HEPAR and HEPAR II studies, which, however, excluded patients with hepatocellular carcinoma (HCC). The aim of this prospective clinical early phase II study was to establish the toxicity profile of 166Ho radioembolization in patients with measurable, liver-dominant HCC; Barcelona clinic liver cancer stage B or C; a Child-Pugh score of no more than B7; and an Eastern Cooperative Oncology Group performance status of 0-1 without curative treatment options. Methods: The primary endpoint was a rate of unacceptable toxicity defined as grade 3 hyperbilirubinemia (Common Terminology Cancer Adverse Events, version 4.03) in combination with a low albumin or ascites level in the absence of disease progression or treatment-related serious adverse events. Secondary endpoints included overall toxicity, response, survival, change in α-fetoprotein, and quality of life. Thirty-one patients with Barcelona clinic liver cancer stage B (71%) or C (29%) HCC were included, mostly multifocal (87%) or bilobar (55%) disease. Results: Common grade 1 or 2 clinical toxicity included fatigue (71%), back pain (55%), ascites (32%), dyspnea (23%), nausea (23%), and abdominal pain (23%), with no more than 10% grade 3-5 toxicity. Grade 3 laboratory toxicity (>10%) included an aspartate transaminase and γ-glutamyltransferase increase (16%), hyperglycemia (19%), and lymphopenia (29%). Treatment-related unacceptable toxicity occurred in 3 of 31 patients. At 3 mo, 54% of target lesions showed a complete or partial response according to modified RECIST. Median overall survival was 14.9 mo (95% CI, 10.4-24.9 mo). No significant changes in quality of life or pain were observed. Conclusion: The safety of 166Ho radioembolization was confirmed in HCC, with less than 10% unacceptable toxicity. Efficacy data support further evaluation.

Keywords: hepatocellular carcinoma; holmium; locoregional treatment; oncology; radioembolization.

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Figures

None
Graphical abstract
FIGURE 1.
FIGURE 1.
Flow diagram showing initial number of patients and those excluded for any given reason.
FIGURE 2.
FIGURE 2.
Child–Pugh score development over time.
FIGURE 3.
FIGURE 3.
An 85-y-old patient with HCC, no underlying liver disease, and no previous treatment (ECOG performance status 1, Child–Pugh score A5, BCLC stage B) with large hypervascular tumor spanning segments 4–8 (A, axial contrast-enhanced MRI) that had multiple tumor-feeding vessels from right hepatic artery (B, digital subtraction angiography). He received 166Ho-microsphere scout procedure and SPECT (C), which showed good targeting of tumor. Scout procedure proved highly predictive for posttreatment 166Ho-microsphere distribution (D) and resulted in complete response of target liver lesions at 3 mo (E, axial contrast-enhanced MRI) and 6 mo (F, axial contrast-enhanced MRI).
FIGURE 4.
FIGURE 4.
Response assessment of target liver lesions at 3 and 6 mo after treatment with 166Ho-microsphere radioembolization according to mRECIST. Some patients did not undergo imaging at 3- or 6-mo follow-up because of death (n = 2 and 8, respectively) or withdrawn consent (n = 2 or 0, respectively). Some patients were not evaluable because of absence of arterial enhancement of tumor or low-quality imaging (e.g., artifacts or breathing motion) (n = 3 and 2, respectively).
FIGURE 5.
FIGURE 5.
Overall survival of HEPAR Primary patients.
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