The Insider summarizes important, recent and pertinent publications to the SIO community.
There was no difference in waitlist mortality or dropout in liver transplant candidates with hepatocellular carcinoma (HCC) who underwent transarterial chemoembolization (TACE) compared with radiofrequency (RF) ablation, according to data from the Scientific Registry of Transplant Recipients. The study included 11,824 patients with HCC who received RF ablation or TACE between 2004 and 2013. The patients were followed until December 31, 2019, or 5 years, and stratified by the Milan criteria. Waitlist mortality and dropout were compared with competing risk and Cox regression analyses using adjusted hazard ratios (asHRs, with RF ablation group as reference). For the 1,226 patients outside the Milan criteria, waitlist mortality and dropout for TACE recipients was 19.2% and 19.0% for RF ablation (asHR, 0.91). Waitlist mortality and dropout rates for patients inside the Milan criteria were 13.4% for TACE and 12.9% for RF ablation (asHR, 1.29). In a subgroup analysis within the Milan criteria, no differences were seen between TACE and RF ablation in patients with a single tumor of =3 cm (asHR, 0.92), with a single tumor of >3 cm (asHR, 1.03), or with >1 tumor (asHR, 1.03).
Journal of Vascular and Interventional Radiology (10/22) Vol. 33, No. 10, P. 1222 AR Kolarich; T Ishaque; J Ruck; et al.
New research backs the use of percutaneous ethanol injection (PEI), either by itself or combined with transarterial chemoembolization (TACE), for patients with hepatocellular carcinoma (HCC) when radiofrequency ablation (RFA) is not possible. The study, which was conducted from 2011-2020, included 129 consecutive cirrhotic patients with HCC who were awaiting orthotopic liver transplantation (OLT). The patients were divided into three locoregional therapy (LRT) groups: PEI (N=56), TACE (N=43), and PEI+TACE (N=30). Among the three groups, the waitlist dropout rate due to tumor progression — the primary outcome — was similar, with respective rates of 8.9%, 14%, and 16.7% (p=0.54). A total of 13 patients received OLT after successful downstaging: 3 in the PEI group, 5 in the TACE group, and 5 in the combination group. The 5-year post-transplant recurrence-free survival rate for the 96 patients undergoing OLT was 55.6% for the PEI group, 55.1% for the TACE group, and 71.4% for PEI+TACE (p=0.42). The rate of complete or near-complete pathological response was also similar for the three groups.
Langenbeck's Archives of Surgery (01/14/23) G Lazzarotto-da-Silva; TJM Grezzana-Filho; LA Scaffaro; et al.
Transarterial radioembolization (TARE) with Yttrium-90 (Y90) resin microspheres is safe and effective for patients with hepatocellular carcinoma (HCC), according to new research. Noting the difficulties of optimizing treatment application and patient selection, researchers used data on TARE for HCC in the prospective observational CIRT study, assessing the efficacy, safety, and prognostic factors of the treatment. A total of 422 patients with HCC (mean age 67 years, 80.8% male) were enrolled from 2015 through 2017, and they had follow-up visits every 3 months for up to 2 years after their first TARE. The median length of overall survival (OS) for the cohort was 16.5 months, while the median progression-free survival (PFS) was 6.1 months and the median hepatic PFS was 6.7 months. Multivariable analysis showed that partition model dosimetry led to better OS compared with standard body surface area calculations. ECOG-performance status >0, ascites, right-sided tumors, portal vein thrombosis, and ALBI grades 2-3 were also predictive of survival outcomes following TARE. Some 36.7% of patients experienced adverse events, and 9.7% had serious adverse events, grade 3 or higher. "This large prospective observational data set suggests that TARE with resin Y90 microspheres has a favorable toxicity profile and that patients with good liver function and no extrahepatic disease are ideal candidates for this therapy," the researchers conclude. "Furthermore, our data revealed that optimizing the application of the therapy by using the partition model instead of BSA models, can significantly improve survival outcomes."
JHEP Reports (02/01/23) Vol. 5, No. 2, P. 100633 F Kolligs; D Arnold; R Golfieri; et al.
A recent study assessed the efficacy of voxel-based dosimetry for predicting treatment response and adverse events (AEs) after resin-based Yttrium 90 (Y90) radioembolization in patients with hepatocellular carcinoma (HCC). The prospective single-arm clinical trial evaluated the efficacy of low/scout (555 MBq) activity of resin-based Y90 for treatment planning. Using a partition model, the goal was a tumor dose (TD) >200 Gy and non-tumoral liver dose (NTLD) <70 Gy for non-segmental therapies; a single compartment dose of 200 Gy was used for segmentectomies. For therapeutic Y90, prescribed Y90 activity minus scout activity was administered, and treatment response was evaluated at 3 and 6 months. Thirty patients with 33 tumors (19 segmental and 14 non-segmental) were treated; one patient died before the first imaging. An objective response (OR) was seen in 81% (26) of the tumors, while 72% (23) had a complete response (CR). The mean TD that predicted an OR with 92% sensitivity and 83% specificity was 253 Gy, while the mean TD that predicted a CR with predicted a CR with 83% sensitivity and 89% specificity was 337 Gy. At 3 and 6 months post-Y90 treatment, a mean NTLD of 81 Gy and 87 Gy, respectively, predicted grade 3 AEs with 100% sensitivity and 100% specificity. Based on their findings, the researchers conclude "that in patients with HCC treated with 2- or 3-day pre-calibrated resin-based Y90 radioembolization, mean target tumor dose should be greater than 337 Gy to achieve complete imaging response. However, and specific to non-segmental treatment, mean non-tumoral liver dose should be planned to be less than 80 Gy in order to minimize serious treatment-related toxicity." European Journal of Nuclear Medicine and Molecular Imaging (01/23) N Kokabi; L Arndt-Webster; B Chen; et al.
A Phase I study investigated the safety and feasibility of performing transarterial radioembolization (TARE) with holmium-166 (166Ho) within an MRI scanner and the potential of intraprocedural MRI-based dosimetry. Because 166Ho microspheres can be quantified with MRI, they could be used for intraprocedural dosimetry, which could be used for an image-guided approach to TARE. In a hybrid operating room, six patients underwent 166Ho TARE. The microspheres were injected in four fractions, at 10%, 30%, 30%, and 30% of the planned activity, alternating with holmium-sensitive MRI acquisition to evaluate the distribution of the microspheres. MRI-based dose maps were then created from each intraprocedural image series using 166Ho TARE dosimetry software. In 82% (9/11) of the injection positions, it was possible to administer 166Ho microspheres within the MRI scanner. Additionally, tumor dosimetry was possible in 95% (18/19) of the treated tumors using intraprocedural holmium-sensitive MRI. No adverse events were associated with treatment in the MRI. In 22% (4/18) of tumors, there were signs of microsphere saturation toward the last fraction, while in 78% (14/18) the microsphere uptake patterns correlated linearly with the injected activity. "This study demonstrated the feasibility and safety of a first in-human application of TARE within a clinical MRI system," the researchers report. "Intraprocedural MRI-based dosimetry enabled dynamic insight in the microsphere distribution during TARE and illustrated different uptake patterns between tumours."
European Journal of Nuclear Medicine and Molecular Imaging (07/22) J Roosen; LELW Gotby; MJ Arntz; et al.
A retrospective study of patients with hepatocellular carcinoma treated with glass-based lobar Yttrium-90 radioembolization (Y90-RE) found that a non-tumor liver (NTL) dose of > 112 Gy is linked with severe treatment-related adverse events (AE) 3-6 months post-treatment. In all, 229 patients — 115 lobar and 114 segmental — were evaluated at 3 and 6 months with Common Terminology Criteria for Adverse Events v5, dose-volume histograms of treated area of liver, multivariate analysis, and chi-square analysis. The rate of any grade AE at 3 months was lower (46% segmental and 31% lobar), while the rate of severe AEs was higher for lobar compared with segmental, at 8% vs. 2%. The rate of severe AEs at 6 months continued to be higher among lobar patients compared with segmental patients, at 9% vs. 1%. No meaningful association was seen between NTL dose and severe treatment-related AEs at 3 and 6 months for patients in the segmental group. However, the researchers concluded that a mean NTL dose of 112 Gy was predictive of severe AEs in that time frame post-treatment for those treated with lobar Y90-RE.
CardioVascular and Interventional Radiology (11/30/22) LA Webster; A Villalobos; B Cheng; et al.
The Society of Interventional Oncology presents an opportunity to share key findings from interesting patient cases within the interventional oncology community. Access to these cases and engaging in the discussion surrounding their content is a benefit of SIO membership. New cases will be released in the SIO Insider.

February Case Spotlight - Cryoablation of Skeletal HCC Metastases
Publications Committee
AJ Gunn, MD
SIO Publications Chair

Elena Violari, MD
SIO Publications Vice Chair

Edward Kim, MD, FSIR
SIO Board Liaison
Christine E. Boone, MD, PhD
Ji Buethe, MD
Juan C. Camacho, MD
Xindi Chen, BS
Husameddin El Khudari, MD
Christos Georgiades, MD, PhD, FSIR, FCIRSE
Anish Ghodadra, MD
Andrew Kolarich, MD
Yilun Koethe, MD, RPVI
Giovanni Mauri, MD
Greg Pommier, BA
Junaid Raja, MD
Ishu Sivakumar, BS
Alex J. Solomon, MD
Chi Trinh, BA
Maria Tsitskari, MD
Chiara Zini, MD
This newsletter is brought to you by the Society of Interventional Oncology (SIO). SIO's mission is to advance interventional oncology by developing evidence supporting IO therapies, educating IO practitioners, and improving patient access to IO therapies.

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