Eye90 Beads Provide Safe and Effective Direct Visualization in Radioembolization

Imageable Radioembolization Microspheres for Treatment of Unresectable Hepatocellular Carcinoma: Interim Results from a First-in-Human Trial

Clinical question 

Can radiopaque yttrium-90 microspheres safely and effectively treat unresectable hepatocellular carcinoma while providing real-time visibility of treatment?

Take away point 

Eye90, a radiopaque Y90 microsphere, enables real-time evaluation and treatment adjustment during radioembolization, potentially improving tumor targeting and serving as a tumor response biomarker. Initial study showed 50% complete response at 3 months with no severe adverse events.

Reference 

Abraham, R.J., Arepally, A., Liu, D., Lewandowski, R., Kappadath, S.C., Verma, A., Dobrowski, D. and Holden, A., 2024. Imageable Radioembolization Microspheres for Treatment of Unresectable Hepatocellular Carcinoma: Interim Results from a First-in-Human Trial. Journal of Vascular and Interventional Radiology, 35(10), pp.1464-1473.

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Study design 

Prospective, observational, descriptive study

Funding Source 

ABK Biomedical

Setting 

Auckland City Hospital, Auckland, New Zealand

Figure

A 53-year-old man with chronic hepatitis B. Axial contrast-enhanced computed tomography (CT) (arterial phase) demonstrated a 4.3-cm Segment 8 hepatocellular carcinoma (white arrow) adjacent to previous transarterial chemo- embolization scar (white arrowhead). CT image demonstrating radiopaque Eye90 microsphere distribution in hepatocellular carcinoma (arrow) and surrounding treated liver volume.

Summary

Current 90Y microspheres have limitations. Glass microspheres lack flexibility in quantity and activity customization, often necessitating multiple vials and kits for larger volumes. Resin 90Y provides quantity and activity customization, but at the cost of increased burden on nuclear medicine labs and operator risk. Both microspheres also have limitations in visibility, requiring post-treatment SPECT/ PET for assessing 90Y distribution, tumor targeting, and dosimetry.

Addressing these challenges, Eye90 Microspheres introduces radiopaque properties for direct CT visualization with a customizable dose with radioactivity between 0.4-9.6 GBq at 3 preset mass ranges: (a) small (100–200 mg), (b)medium (201–400 mg), and (c) large (401–600 mg). Personalized dose vial quantity and activity is determined using a 3-compartment partition model that considers various patient-specific factors based on the technetium-99m macro- aggregated albumin SPECT/CT. This personalized approach reportedly eliminates the need for dose-draw or multiple vials.

Accompanying the Eye90 Microspheres is the Eye90 delivery device, which utilizes a dual-syringe system to achieve a controlled uniform delivery concentration of 60 mg/mL. The delivery device also allows the users to pause, assess microcatheter location with contrast media, examine microsphere distribution using CT modalities, and resume administration as needed.

This study reports 6-month safety, effectiveness, and imageability results for Eye90 in 6 subjects with unresectable HCC (median size of 3.1 cm, range: 1.2 – 4.3 cm). Subjects underwent planning procedure (90Y mapping) followed by selective treatment (≤2 segments) using partition dosimetry by SurePlan LiverY90 aiming to deliver at least 205 Gy and preferably > 250 Gy to the tumor. Post-therapy SPECT/CT, unenhanced lung CT, and 4-phase liver CT within 24 hours of treatment were obtained to correlate microsphere radiopacity with radioactivity. Follow-up were scheduled on days 21, 42, 90, and 180 after treatment.

Post-treatment SPECT/CT demonstrated mean and median dose of 283 Gy and 132 Gy to the tumor, respectively. Microsphere density within the tumor was calculated at 26,988 per mL. All subjects reported adverse events, but no treatment-related Grade ≥3 AEs occurred. At 90 days, 50% achieved complete response (CR) and 33.3% partial response (PR). At 180 days, 50% maintained CR and 16.7% PR. The other patient with PR, and the patient with stable disease at 90 days, underwent TACE and could not be evaluated. Qualitative analysis showed agreement between microsphere radiopacity on CT and radioactivity on SPECT/CT, with CT revealing heterogeneous dose distribution, and absence of radiopacity in the region of a particular tumor despite SPECT/CT activity noted throughout this region. This particular tumor did not respond to treatment.

Commentary 

Eye90 Microspheres represent another advancement in transarterial radioembolization, offering direct visualization of microsphere and tumor targeting on CT modalities. This capability could lead to more precise treatment execution, real-time therapy adjustments, and potentially serve as a biomarker for predicting tumor response and a foundation for more accurate dose-response relationships. The dual-syringe administration system allows for customized quantity and activity of microspheres, enhancing treatment personalization.

While the initial results are promising, the small sample size, short follow-up period, lower-than-planned tumor doses, and mediocre treatment response necessitate further research. The ongoing U.S. Pivotal IDE Route90 trial will provide more comprehensive data on a larger cohort. If these results hold up in larger studies, Eye90 Microspheres could redefine the standard of care in HCC treatment. The potential for improved precision, personalization, and real-time assessment makes this a technology to watch closely in the coming years.

Post author
Leila Haghani, MD 

Research Fellow 

University of Massachusetts Chan Medical School
@dr_Leila_IRad

Paclitaxel Containing Devices in Femoropopliteal Arterial Disease: The Trees and the Forest

An Up To Date Meta-Analysis on Paclitaxel Containing Devices in Femoropopliteal Arterial Disease, And A Commentary On The Entirety of the Data to Date.

Clinical question

Is paclitaxel safe when used in drug eluting stents and drug coated balloons for revascularization of the femoropopliteal artery?

Take away point

Paclitaxel containing devices are safe and effective devices, especially in their current usage and at their current generation. Previous versions of the devices may have conveyed some mortality risk, but it’s important to understand both the meta-analyses and the individual studies that comprise the data reporting, and how clinical practice is nuanced and so does the literature..

Reference

Katsanos, K. (2024). Paclitaxel meta-analyses in the lower limbs: Missing the trees for the forest. Journal of Vascular and Interventional Radiology.
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Briody, H., Kearns, C. A., & Lee, M. J. (2024). Mortality, safety and efficacy of paclitaxel-containing balloons and stents in the femoropopliteal artery: systematic review and meta-analysis of randomized controlled trials since 2018. Journal of Vascular and Interventional Radiology. 

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Study design

Meta-analysis, commentary/perspective

Setting

Meta-analysis was performed at Beaumont Hospital, Dublin Ireland and the Royal College of Surgeons in Ireland.
Commentary is from University Hospital Patras, School of Medicine, Rio, Greece.

Figure

Summary

In revascularization efforts for peripheral arterial disease, paclitaxel has proven to be an excellent anti-restenotic agent in the femoropopliteal artery when used in drug coated balloons and drug eluting stents in multiple randomized controlled trials. While effective, its safety profile was called into question in a 2018 meta-analysis. The meta-analysis, published by Katsanos et al, found statistically significant increases in all-cause death in patients with paclitaxel coated devices, and urged further investigations. In 2023, a patient level, industry funded meta-analysis concluded there was no excess mortality. Based on this study, the FDA published their official statement that there is no discernible excess of mortality.

The current meta-analysis was performed to provide an independent analysis of safety and effectiveness outcomes, including but not limited to mortality. The literature search was performed from 2018 (a choice made so this study would act as an update of the aforementioned Katsanos study) and included 19 randomized controlled trials for a total of 4,284 participants. When selecting studies, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was utilized (see figure). Effectiveness outcomes were primary patency which was analyzed using risk ratios via inverse variance, random-effects model. Safety outcomes were all cause mortality, target limb amputation, target lesion revascularization, clinically driven target lesion revascularization, and thrombosis. These were also analyzed using risk ratios via inverse variance, random effects model, as well as heterogeneity assessment via visual inspection of forest plots, chi squared test and I^2 statistic.

The results found no evidence for all-cause mortality in paclitaxel containing devices in the femoropopliteal region from 12 to 60 months, nor did they find any other safety concerns. The study redemonstrated the effectiveness of paclitaxel devices in maintaining primary patency with a pooled risk ratio of 1.55. Taken together, this meta-analysis concluded that paclitaxel containing devices work, and are safe to use. They compare this study directly to the Katsanos study due to its similar methodology and design, however they offer no suggestions as to the source of the different findings.

In response to the multiple meta-analyses looking at the use of paclitaxel containing devices in the femoropopliteal arteries with no evidence of increased all-cause mortality, Dr. Konstantinos Katsonas provided a companion commentary. In the piece, he presents 27 studies from 2008-2021 which show an increase in all-cause mortality in the paclitaxel containing device arm, arguing that the recent studies demonstrate dilution of the mortality signal, but do not eradicate it completely. He presents a meta-regression of long-term risk ratio of all cause death against publication year and shows that the observed mortality risk decreases with publication year, which would seem to suggest earlier generation devices or clinical practices may be the cause for the mortality signal. He further subgroups the studies by paclitaxel dosage and shows that the relative mortality risks may be different among the different devices with variable paclitaxel dosing. He concludes that the reader must not miss the trees for the forest, meaning that the individual studies may have points of interest that become diluted in meta-analysis.

Commentary

The academic discussion around paclitaxel can make it difficult for providers to know if these devices are safe or not. This most recent meta-analysis is an excellent consolidation of the most recent literature on paclitaxel containing devices in femoropopliteal artery treatment. The results add to the body of evidence that these paclitaxel devices are safe and effective tools in peripheral arterial disease, especially at their current generations. Providers can use these devices and expect good outcomes for their patients without an increased mortality risk.

That being said, Dr. Katsonas does raise interesting questions. The 2018 Katsonas et al meta-analysis did show a significant increase in all-cause mortality. In his commentary, this effect appeared again when looking at all studies from 2008-2021. While there were shortcomings in the Katsonas paper, the fact remains that a mortality signal was present and hasn’t been fully accounted for. The fact that it seems to disappear when looking at studies from only 2018 onward could be indicative of the root cause. Moreover, the more recent studies did not subgroup based on device or paclitaxel dosing. The data he presents on the decrease of all-cause mortality risk over the years, as well as the trend of lower risk ratios with lower paclitaxel dosing, are suggestive that the mortality signal may be device-, device-generation, and/or paclitaxel dosage-dependent. Of course, this is only speculation based on available data, but could make excellent areas of inquiry should the question of safety in paclitaxel containing devices remain.

Dr. Katsonas’ final point is to not miss the “trees” (individual studies) for the “forest” (meta-analysis), as individual studies can yield insights that may be diluted in meta-analyses. However, he doesn’t really support this in his commentary, as most of his points are made by using grouping statistics based on multiple studies. Regardless, it is an important point to keep in mind when reading meta-analyses. Procedural practice and published literature are nuanced, and evidence-based medicine should be supported by both high-level meta-analyses as well as individual studies that befit the patient population and institutional experience.

Post Author
Sean Rogers, MD
Interventional Radiology Fellow, PGY-6
University of Massachusetts Chan Medical School

Radiofrequency Lung Ablation in ILD

Radiofrequency Ablation in Patients with Interstitial Lung Disease and Lung Neoplasm: A Retrospective Multicenter Study

Clinical Question

Is percutaneous radiofrequency ablation safe and effective against lung neoplasms in patients with interstitial lung diseases?

Take Away Point

Radiofrequency ablation is a feasible technique in combating lung neoplasms in patients with interstitial lung diseases but there are risks of post-procedural acute exacerbations which has a relatively high mortality rate of 45%.

Reference

Yamamoto A, Hiraki T, Ikeda O, et al. Radiofrequency ablation in patients with interstitial lung disease and lung neoplasm: A retrospective multicenter study. Journal of Vascular and Interventional Radiology. 2024;35(9):1305-1312. doi:10.1016/j.jvir.2024.06.010

Click here for abstract

Study Design

Retrospective, observation, cohort study

Funding Source

No reported funding

Setting

Academic, Osaka Metropolitan University, et al, Japan

Figure

Summary

Interstitial lung diseases are generally irreversible with poor prognosis. There is no optimal therapeutic approach for concomitant lung neoplasms, which has a frequency of 10-20%. Radiofrequency ablation is a safe and effective treatment strategy for inoperable primary and metastatic lung lesions. The authors of this paper decided to investigate the safety and efficacy of radiofrequency ablation in combating lung tumors in patients with interstitial lung diseases due to lack of pertinent data.

The authors performed a multi-institutional retrospective observational study acquiring data of all the patients diagnosed with lung neoplasm and interstitial lung disease from April 2002 and October 2017 who underwent radiofrequency ablation, with their respective images reassessed by radiologic review. After central radiologic review excluded patients who did not have interstitial lung disease, 49 patients remained in the sample, 43 men and 6 women. Within the 49 patients, there were 64 tumors—34 of which were primary neoplasms and 30 of which were metastatic—with 66 treatment sessions.

Technical success was defined as completion of the radiofrequency procedure. Adverse events were based on the parameters set by the modified definitions of Society of Interventional Radiology, including unexpected increase in the level of care, prolonged hospital stay, or death. The following variables were also included in the study: local tumor progression, overall survival, and acute exacerbation of interstitial lung disease after ablation. Acute exacerbation diagnosis was based on radiologic or clinical diagnosis.

Technical success rate was 100%. While no adverse events occurred during the procedure, multiple events occurred after the procedure, the most frequent being pneumothorax in 53% (35/66 treatment sessions). The rest of the listed adverse events are summarized in Table 3 provided in this article. Acute exacerbations occurred in 8% of the study (5 patients). Among these 5 patients, 3 passed away despite initiation of steroid treatment (60%). The events of acute exacerbations did not differ significantly between patients with UIP (8%) and those without UIP (7%). Additionally, onset of acute exacerbation always occurred at least 8 days after radiofrequency ablation. Univariate analysis determined that pleural effusion and fever were statistically significant risk factors for development of acute exacerbations. Local tumor progression rate was 43% at one year. The overall survival rate at one, three, and five-years were 83%, 62%, and 36%, respectively.

While the results have demonstrated that radiofrequency ablation can be feasible for treating lung neoplasm in patients with interstitial lung disease, the results do not provide consensus recommendations. With regards to procedural safety, prior literature has demonstrated that ablation for lung neoplasms is safe, with mortality rate <1%, which is significantly lower than the mortality rate in patients with interstitial lung disease reported in this series, at 5% per session. The rate of 8% for acute exacerbation and an associated mortality rate of 45% may seem alarming at first. However, the rate of acute exacerbation after surgery was similar to that of ablation at 9.3%, with a similar mortality rate at 43.9%. Similarly, acute exacerbation can occur after thoracic radiotherapy and pharmacotherapy. After all, patients with idiopathic pulmonary fibrosis and non-idiopathic pulmonary fibrosis interstitial lung diseases develop acute exacerbations at a rate of 10-20%, and 3-5%, respectively annually during the natural course. The safety profile of radiofrequency ablation for lung neoplasm should be considered within this specific patient population and not taken out-of-context.

With regards to the local tumor progression rates, various factors may have contributed, both from the operator and from the lesion pathology. The operator may not have had sufficient margin, partly due to the intention to minimize adverse events. Additionally, patients with severe emphysema or UIP may present challenges to the accurate identification of the overall tumor burden, complicating the assessment of local tumor progression. Furthermore, fibrotic changes such as those seen in usual interstitial pneumonia may reduce the ablation’s electrical and thermal conductivity, limiting the tumoricidal effect of radiofrequency ablation.

This study had several limitations apart from its retrospective design. Firstly, interstitial lung disease diagnosis was not based on pathological findings. Secondly, central reading to evaluate interstitial lung disease was only applied to those that were already diagnosed as such, making the study prone to additional selection bias. Multivariate analysis to identify independent risk factors for acute exacerbations could improve the quality of the study. Sub-analyses, which may require a larger study, focusing on patients with primary neoplasms, and patients with metastatic lesions, separately, will provide further clinically relevant information and guidance.

Commentary

Despite several limitations, this article assessing radiofrequency ablation for the treatment of lung neoplasms in patients with concomitant pulmonary pathologies like interstitial lung disease is of significant clinical relevance. Risk factors that predispose patients to interstitial lung disease such as smoking are very prevalent, especially in certain countries like Japan. Referring and treatment physicians of patients with interstitial lung disease need information specific to the patient population. Clinical guidelines and treatment algorithms also require such information for development and refinement. In conclusion, radiofrequency ablation appears feasible in patients with interstitial lung disease with a risk of post-procedural acute exacerbation grossly similar to other treatment modalities.

Post author
Naeem Patel, DO
Radiology Resident, PGY4
Department of Radiology, Interventional Radiology Division
Hartford Hospital, Hartford, CT
@Naeemp7Patel