Is TARE in patients with TACE-refractory HCC safe and effective?

Effect of Previous Transarterial Chemoembolization on Survival and Toxicity after Yttrium-90 Transarterial Radioembolization of Hepatocellular Carcinoma in the Radiation-Emitting SIR-Spheres in Nonresectable Liver Tumor Registry

Clinical Question

Does prior transarterial chemoembolization impact outcomes in patients undergoing transarterial Y90 radioembolization in the context of nonresectable liver tumor?

Take Away Point

Outcomes in patients undergoing transarterial SIR-Sphere Y90 radioembolization with and without prior transarterial chemoembolization were similar. This suggests that transarterial radioembolization is a safe and effective treatment option for patients with hepatocellular carcinoma who previously received transarterial chemoembolization treatment.

Reference

Effect of Previous Transarterial Chemoembolization on Survival and Toxicity after Yttrium-90 Transarterial Radioembolization of Hepatocellular Carcinoma in the Radiation-Emitting SIR-Spheres in Nonresectable Liver Tumor Registry, Hund et al. Journal of Vascular and Interventional Radiology, Volume 34, Issue 12, P2147-2154



Link to abstract

Study Design

Prospective, observational, cohort study

Funding Source

Sirtex Medical

Setting

36 medical centers in the United States



Figure 2

Overall survival (OS) for previous TACE (red line) and TACE-naïve (black line) participants, with a median OS of (95% confidence interval [CI]: 15.4–25.2) and 21.5 months (95% CI: 14.9–29.9), respectively. TACE = transarterial chemoembolization.

Summary

Transarterial chemoembolization is an established treatment for hepatocellular carcinoma, serving as both a bridge to transplantation and as a definitive therapy. For patients whose disease burden is refractory to transarterial chemoembolization, systemic therapy, ablation, and transarterial radioembolization with yttrium-90 may be offered. Two single-center studies have shown radioembolization to be successful after chemoembolization however both studies had a relatively small sample size. This study aimed to analyze the outcomes of radioembolization in a larger multicenter patient population, comparing those with and without prior transarterial chemoembolization.



This study included 262 participants from 36 medical centers throughout the United States, using data obtained from the Radiation-Emitting SIR-Spheres in Nonresectable liver tumor registry. The study cohort included patients with treatment-naïve hepatocellular carcinoma or those who underwent prior transarterial chemoembolization. Patients with previous procedures, ablation, external beam radiation, or systemic therapy were excluded. The chemoembolization and treatment-naive groups consisted of 93 and 169 participants, respectively. There was no significant difference in age, sex, Child-Pugh, or Barcelona Clinic Liver Cancer Stages between the two groups. Both groups had significant proportion of participants with Barcelona Clinic Liver Cancer stages of B and C. The only notable difference between the two groups was that the chemoembolization group had more multifocal disease, while the treatment naïve group had a larger index tumor diameter.



Participants underwent treatment with resin Y90 microspheres and the median delivered activity was similar for two groups. The primary outcome of this study was overall survival, measured in months from date of radioembolization treatment to the date of death, completion of the study, or last follow-up. Secondary outcomes included best tumor response by the modified Response Evaluation Criteria in Solid Tumors and treatment toxicities at 6 months after radioembolization. Objective response rate was defined as the sum of complete and partial responses, while disease control rate further included stable disease.



In this study, the median overall survival for patients in the chemoembolization (22.3 months) and treatment-naive (21.5 months) groups showed no significant difference. Stratifying by Child-Pugh classification or Barcelona Clinic Liver Cancer stages did not change the results. Objective response rate at 6 months showed no significant difference between the two groups, at 49% and 64%, respectively. Disease control rates were achieved in 73% for the chemoembolization group and 86% for the treatment-naive group. Cox Proportional Hazard analysis identified Barcelona Clinic Liver Cancer Stage A, index tumor ≤5 cm, and Child-Pugh Class A as the strongest predictors of overall survival. Solitary lesion and no previous chemoembolization did not predict overall survival. Grade 3 or greater hepatic toxicities were comparable.



Even though radioembolization is gaining popularity as a first-line treatment given the favorable overall survival compared to drug-eluting embolic chemoembolization, as seen in the TRACE and LEGACY trials, transarterial chemoembolization remains the first-line option in many centers given its high profile in multispecialty treatment recommendations. This study has provided more robust evidence for the practice of transitioning patients with chemoembolization refractory hepatocellular carcinoma to radioembolization as the latter can achieve similar rates of overall survival, imaging response, and safety profile in this patient population compared to patients who were treatment naïve.



The study acknowledged the inherent limitations associated with real-world data and registries. As well as differences in practice patterns at some of the institutions and a lack of centralized interpretation of image findings. The authors suggested future research focusing on initiating radioembolization for patients with prior chemoembolization treatments and comparing radioembolization with systemic therapies.

Commentary

The purpose of this study was to assess the impact of prior chemoembolization on outcomes in patients with hepatocellular carcinoma undergoing radioembolization. Given that this area has been previously studied but in small patient populations at single institutions, the current study provided the much-needed supporting evidence from a large multi-institutional patient cohort. The methods and execution of the study were adequate given the data was based on a prospective observational registry. However, as the authors have pointed out, some standardizing measures could have improved the study, such as having independent radiologist(s) re-evaluate the response on imaging. The study comprehensively discussed the statistical analysis methods, which were appropriate for the data collected. The results supported previous findings demonstrating that radioembolization is a safe and effective treatment after chemoembolization. Future research focusing on radioembolization in patients with prior chemoembolization should employ robust study parameters such as an randomized clinical trial for more conclusive evidence. The authors also described that Kudo et al. performed a retrospective matched-pair study that determined overall survival was longer in Lenvatinib (37.9 months) compared with transarterial chemoembolization (21.3 months). Future research comparing radioembolization with systemic therapy and examining the effects of combination therapy may further impact the hepatocellular carcinoma treatment algorithm. Overall, while the study provided evidence that radioembolization is a safe and effective option in patients with chemoembolization refractory hepatocellular, it also highlights research areas in need of comparative data and robust conclusions.

Post Author

Aric Patel, MS
OMS-IV
University of New England
College of Osteopathic Medicine

Biomarker analysis in GAE

Genicular Artery Embolization for Treatment of Knee Osteoarthritis: Interim Analysis of a Prospective Pilot Trial Including Effect on Serum Osteoarthritis-Associated Biomarkers

Clinical Question

Is genicular artery embolization (GAE) a safe and effective disease modifying treatment for symptomatic knee osteoarthritis (OA)?

Take Away Point

GAE achieved minimal clinical important difference (MCID) in 5 of the 6 patients who completed their 12-month follow-up with significant reduction in mean WOMAC pain score and plasma nerve growth factor (NGF).

Reference

Taslakian B, Swilling D, Attur M, et al. Genicular artery embolization for treatment of knee osteoarthritis: Interim analysis of a prospective pilot trial including effect on serum osteoarthritis-associated biomarkers. Journal of Vascular and Interventional Radiology. Published online August 23, 2023. Link to article

Study Design

Single arm, prospective, observational and ongoing study containing 16 patients, 6 of whom completed treatment course

Funding Source

No reported funding

Setting

Academic, New York University Langone Health, New York, NY

Figure

Summary

Knee osteoarthritis is one of the most common causes of disability. Despite current options prescribed to combat this condition, many patients are either resistant to existing conservative management or poor surgical candidates to more invasive options such as total knee arthroplasty.



Osteoarthritis is a pathological condition hypothesized to be caused by a triad of inflammation, angiogenesis, and neural growth around the cartilage of the joint. The subsequent neural growth adjacent to the neovessels is thought to be the source of the pain. Arresting these new vessel formations secondary to secreted inflammatory cytokines should theoretically subside the pain and is the basis for the treatment strategy of geniculate artery embolization. Furthermore, embolization retarding the cytokine-induced vessel formation should theoretically correlate with decrease in prognostic biomarkers used to measure inflammation and matrix degradation, providing evidence for the disease-modifying role of genicular artery embolization in knee osteoarthritis.



The authors of this paper performed a prospective, single-arm clinical trial. Out of 27 patients, 16 were enrolled with the inclusion criteria being moderate to severe osteoarthritis associated with knee pain resistant to conservative therapy for greater than 3 months. After undergoing genicular artery embolization, patients were followed up at 1 month, 3 months, and 12 months to assess for change in symptoms. Blood samples were collected at baseline and each follow-up visit for biomarker analyses.



Amongst the six patients who completed the 12 month follow up, technical success rate was 100%. Five of them demonstrated clinical success defined as achieving minimal clinically important difference with improvement in pain, stiffness, and function at early follow-up. However, improvement in WOMAC scores at 12-month follow-up did not achieve statistical significance, possibly related to the nature of interim analysis and small cohort. A single sampled biomarker achieved statistically significant decrease: neural growth factor. This decrease in neural growth factor, correlating with pain reduction experienced in patients after genicular artery embolization, highlighted the clinical relevance of NGF and suggested the disease-modifying nature of the procedure. Of note, there was no significant reduction in NGF levels at the 3-month follow-up, demanding further analyses with larger cohort size and timepoint study to determine the relationship of inflammation reduction and reduction in NGF.



Despite the promising results this trial is showing, there are several limitations, the most important of which is the small sample size of six patients who completed the 12-month follow-up. The power of this study will inevitably improve through the ongoing trial of the remaining 10 patients, after which results can be further tabulated and finetuned. The second limitation is the lack of a control group to compare the progress with given the nature of the study. Finally, the third limitation is the possibility that the accumulated fluid in the synovium that was not procured in the study may contain different levels of biomarkers than the ones collected in the plasma and serum.

Commentary

Genicular artery embolization shows immense potential for its widespread use and versatility. Despite the allure of the benefits this procedure can bring to both the members of the healthcare force and the patients, more data is still needed before definitively concluding the efficacy compared to other more established available options. Clinical trials with basic science correlates are also needed to better understand the specific role of embolization in modifying local inflammation, angiogenesis, and neural growth in the context of osteoarthritis. Results from prospective clinical trials, such as the one presented by this article, may eventually alter the algorithmic approach to the treatment of knee osteoarthritis.

Post author

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

Parametric Analysis of Intraprocedural DSA in GAE

Quantifying Change in Perfusion after Genicular Artery Embolization with Parametric Analysis of Intraprocedural Digital Subtraction Angiograms

Clinical question

After Genicular Artery Embolization, will perfusion be decreased in hyperemic target vessels but preserved in parent vessels?

Take away point

Objective parametric measures showed patent parent vessel with unchanged flow after embolization of distal hyperemic target vessels, validating the pruning technique in genicular artery embolization and demonstrating utility in quantification of intraoperative perfusion.

Reference

Quantifying Change in Perfusion after Genicular Artery Embolization with Parametric Analysis of Intraprocedural Digital Subtraction Angiograms. Badar W M.D. et al. Journal of Vascular and Interventional Radiology, Volume 34, Issue 12, 2189-2195.

Click here for abstract

Study design

Single center, single arm, retrospective study with 12 patients

Funding Source

No reported funding.

Setting

Academic hospital, University of Chicago, Illinois, United States

Figures

Figure 1:(a) Pre–genicular artery embolization selective digital subtraction angiography run of the right superior medial genicular artery, with region of interest (ROI) 1 (red) corresponding to the parent vessel (PV) and ROI 2 (green) corresponding to the hyperemic target vessel (TV). (b) Post-GAE selective digital subtraction angiography run of the same vessel, with ROI 3 (red) corresponding to the PV and ROI 4 (green) corresponding to the “pruned” TV.



Figure 2: (a) Time–intensity curves for the parent vessel before genicular artery embolization (GAE) (red) and after GAE (blue). (b) Time–intensity curves for the target vessel before GAE (red) and after GAE (blue). The deep spikes in the post curves represented artifact from patient movement at the end of the digital subtraction angiography acquisition when the regions of interest were shifted momentarily to empty or subtracted areas where there was no contrast density.

Summary

Geniculate Artery Embolization has shown promising results for the treatment of medically refractory knee osteoarthritis. Instead of attempting near-complete stasis, genicular artery embolization aims to achieve “pruning” where distal hyperemic vessels are embolized, but parent vessel flow is preserved. Parametric analysis of digital subtraction angiography is an established post processing method to quantitatively evaluate tissue perfusion changes and determine angiographic endpoints. But it has never been applied in the context of genicular artery embolization, specifically to validate the pruning method and to correlate with clinical success.

The authors performed this study in a single academic center with 12 patients who were diagnosed with mild to moderate osteoarthritis, age > 40, and pain refractory to 6 months of conservative management that included physical therapy and/or non-steroidal anti-inflammatory medication.

The genicular artery embolization procedure was performed through ipsilateral femoral access with a DSA run to identify the genicular arteries of interest, evaluate hyperemic vasculature, and ensure the resolution of hyperemia after administration of the embolic agent. genicular artery embolization was performed with 200-µm microspheres with a 1:3 dilution in contrast medium, in 0.1ml aliquoted to near stasis. Each patient received a call 1-day post-procedure and follow up visits at 1 week and 1, 3, 6, and 12 months.

For each vessel treated, regions of interest were marked within the lumen of the parent vessels and hyperemic vessels on digital subtraction angiography images. Perfusion parameters were computed for each region of interest before and after the embolization. These included area under the curve, peak intensity, and time to arrival, a measure of total blood volume, of highest blood concentration, and of blood velocity, respectively. 36 total vessels were identified with 2 vessels excluded due to motion artifacts.

Paired student t-tests were used to compare the area under the curve, peak intensity, and time to arrival. In the hyperemic vessels, there were significantly lower area under the curve and peak intensity, as well as significantly longer time to arrival on the post-embolization images compared to the pre-embolization images. There was no significant difference in area under the curve, peak intensity, or time to arrival in the parent vessels. These results provided quantitative support for the “pruning method” for genicular artery embolization. Skin changes were the most common adverse events and all instances resolved within 3 weeks. Each incidence occurred with an embolic volume greater than 3.0 ml. A Pearson correlation coefficient test showed no correlation between the volume of embolic agent administered and the parent vessel diameter. Unpaired student T-tests were used to show that higher volumes of embolic administered were associated with increased non-target embolization but no further reduction in hyperemia. Hence, overtreating vessels provides no additional benefit but increases the risk of non-target embolization. Baseline clinical symptoms were assessed with the Western-Ontario and McMaster Universities Arthritis index, showing significant reductions in total and pain scores at 1 and 3 months postoperatively.

Commentary

The authors in this study provided quantitative evidence of the pruning method often described in genicular artery embolization. These findings have implications in minimizing non-target embolization while ensuring treatment efficacy. The results also support the utility of intraprocedural quantitative perfusion parametric imaging to provide objective measures of embolization endpoints. While these results are encouraging, the study acknowledges that future studies with a larger sample size, knee immobilization techniques to reduce motion artifact, and use of different types of embolic agents would be helpful. Future research in other areas of interventional radiology may learn from this study and experiment the use of intraprocedural parametric imaging for objective procedural endpoint measures.

Post Author

Anthony M. Camargo, BA
MD candidate, Class of 2025
University of Massachusetts Chan Medical School
@anthonymcamargo