Optimal patient selection for yttrium-90 glass plus chemotherapy in the treatment of colorectal liver metastases: additional quality of life, efficacy, and safety analyses from the EPOCH study.

BACKGROUND: Evaluating transarterial radioembolization (TARE) in patients with metastatic colorectal carcinoma of the liver who have progressed on first-line chemotherapy (EPOCH) demonstrated superior outcomes using yttrium-90 glass microspheres plus chemotherapy (TARE/Chemo) vs chemotherapy (Chemo) to treat colorectal liver metastases. Additional exploratory analyses were undertaken to assess the impact of TARE/Chemo on efficacy, safety, time to subsequent therapy, time to deterioration in quality of life (QoL), and identify criteria for improved patient selection. METHODS: Time to deterioration in QoL was analyzed for the primary study population. Subsequently, a post hoc analysis was undertaken to identify subgroups for which time to deterioration in QoL was improved with TARE/Chemo vs Chemo. Progression-free survival (PFS), hepatic (h)PFS, time to subsequent therapy, and safety outcomes were compared between treatments. RESULTS: The primary population showed no significant difference in time to deterioration in QoL between treatment arms; however, significance was seen in 2 identified subgroups, namely: Subgroup A (N = 303) which excluded patients with both Eastern Cooperative Oncology Group (ECOG) 1 and baseline CEA ≥ 35 ng/mL from both treatment arms; subgroup B (N = 168) additionally excluded patients with KRAS (Kirsten rat sarcoma) mutation. In subgroup A, TARE/Chemo patients (N = 143) demonstrated superior outcomes vs Chemo (N = 160): PFS (9.4 vs. 7.6 months, hazard ratio (HR): 0.64; 1-sided P = .0020), hPFS (10.8 vs. 7.6 months, HR: 0.53; 1-sided P < .0001), time to deterioration in QoL (5.7 vs. 3.9 months, HR: 0.65; 1-sided P = .0063), and time to subsequent therapy (21.2 vs. 10.5 months, HR: 0.52; 1-sided P < .0001). Subgroup B patients showed similar but larger significant differences between treatment arms. Median PFS, hPFS, and time to deterioration in QoL were numerically greater for TARE/Chemo in both subgroups vs the primary population, with the greatest magnitude of difference in subgroup B. Both subgroups exhibited higher percentage of CEA responders and improved ORR with TARE/Chemo vs chemo alone. Safety (reported as event rate/100 patient-years) was higher with Chemo in all populations. Additional efficacy analyses in the primary population are also reported. CONCLUSIONS: Careful patient selection, including consideration of the prognostic factors ECOG, baseline CEA, and KRAS status, sets outcome expectations in patients with colorectal liver metastases suitable for TARE/Chemo as second-line treatment (Trial Registry Number: NCT01483027).

Genicular Artery Embolization for Treatment of Symptomatic Knee Osteoarthritis - Two Year Outcome Data.

PURPOSE: To report the 24-month outcomes and subgroup analysis evaluating the safety and effectiveness of the genicular artery embolization (GAE) for the treatment of symptomatic knee osteoarthritis (OA). MATERIALS AND METHODS: Forty participants with symptomatic moderate to severe knee OA from a single-center, single-arm prospective trial of GAE were included in this study. Abnormal genicular artery neovascularity was identified at the subject's focal knee pain with digital subtraction angiography and cone-beam computed tomography. Embolization was performed with 100-µm microspheres. The primary end point was treatment effectiveness as measured by sustained improvement in OA symptoms at 24 months, quantified using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Treatment success was defined as ≥50% decrease in WOMAC relative to baseline. Clinical outcomes were assessed with mean age of 66.0 ± 8.1 years and BMI of 30.1 ± 6.2 kg/m2. RESULTS: Two of the forty (5.0%) patients were lost to follow up. Overall, 18 of 38 (47.4%) patients demonstrated ≥50% reduction in WOMAC at 24 months. In the subset of patients with initial clinical success at 12 months, 18 of 25 (72.0%) reported sustained clinical success at 24 months. Seven of 25 (28.0%) had symptom recurrence between 12 and 24 months and were determined to be clinical failures. All treatment-related adverse events occurred within 12 months following GAE, without additional events after 12 months. CONCLUSION: GAE is effective in achieving sustained symptom relief related to moderate to severe knee OA for up to 24 months with an acceptable safety profile.

Society of Interventional Radiology Research Reporting Standards for Genicular Artery Embolization.

Genicular artery embolization (GAE) is an emerging, minimally invasive therapy to address the global burden of knee osteoarthritis (OA) and the unmet needs for medically refractory disease. Although total knee arthroplasty has been a standard intervention for severe cases, GAE is developing into a promising alternative, particularly for patients ineligible for or unwilling to undergo surgery. GAE targets the inflammatory cascade underlying OA pathophysiology by arresting neoangiogenesis and preventing pathological neoinnervation, offering potential pain relief. Although early studies have established safety and short-term effectiveness, ensuing studies are needed to validate long-term safety, durability, and comparative effectiveness and to optimize patient selection, embolic agent selection, and administration techniques. Standardized reporting guidelines are therefore essential to enhance transparency and reproducibility across clinical trials, facilitating data aggregation and comparison. This Society of Interventional Radiology (SIR)-endorsed reporting standards consensus document provides a framework to harmonize future research efforts and to improve the interpretation of outcomes.

Clinical, dosimetric, and reporting considerations for Y-90 glass microspheres in hepatocellular carcinoma: updated 2022 recommendations from an international multidisciplinary working group.

PURPOSE: In light of recently published clinical reports and trials, the TheraSphere Global Dosimetry Steering Committee (DSC) reconvened to review new data and to update previously published clinical and dosimetric recommendations for the treatment of hepatocellular carcinoma (HCC). METHODS: The TheraSphere Global DSC is comprised of health care providers across multiple disciplines involved in the treatment of HCC with yttrium-90 (Y-90) glass microsphere-based transarterial radioembolization (TARE). Literature published between January 2019 and September 2021 was reviewed, discussed, and adjudicated by the Delphi method. Recommendations included in this updated document incorporate both the results of the literature review and the expert opinion and experience of members of the committee. RESULTS: Committee discussion and consensus led to the expansion of recommendations to apply to five common clinical scenarios in patients with HCC to support more individualized efficacious treatment with Y-90 glass microspheres. Existing clinical scenarios were updated to reflect recent developments in dosimetry approaches and broader treatment paradigms evolving for patients presenting with HCC. CONCLUSION: Updated consensus recommendations are provided to guide clinical and dosimetric approaches for the use of Y-90 glass microsphere TARE in HCC, accounting for disease presentation, tumor biology, and treatment intent.

Added Value of Cone-Beam CT to Identify Arterial Supply during Genicular Artery Embolization for Knee Osteoarthritis.

PURPOSE: To evaluate if the addition of cone-beam computed tomography (CT) to digital subtraction angiography (DSA) improves the identification of the genicular arteries during genicular artery embolization (GAE) for knee pain secondary to osteoarthritis (OA). MATERIALS AND METHODS: This single-center study retrospectively analyzed 222 patients who underwent GAE for painful knee OA between May 2018 and April 2022. Intraprocedural cone-beam CT and DSA images were reviewed independently by 2 sets of interventional radiologists. DSA was performed for all patients. Technically adequate cone-beam CT was available for 205 patients (92.3%). The presence of the genicular arteries identified by cone-beam CT and DSA was compared using Φ coefficients. Embolization targets identified by both cone-beam CT and DSA were evaluated against those identified by DSA alone. RESULTS: Genicular arteries with the highest concordance between cone-beam CT and DSA were the inferior lateral (196 vs 198; Φ = 0.3530; P < .0001), superior lateral (197 vs 200; Φ = 0.3060; P < .0001), and superior medial genicular (186 vs 161; Φ = 0.2836; P < .0001) arteries. Cone-beam CT demonstrated higher rates of detection of the inferior medial (195 vs 178; Φ = 0.04573; P = .5150) and median genicular arteries (200 vs 192; Φ = 0.04573; P = .5150). Meanwhile, genicular arteries less frequently identified by cone-beam CT were the descending genicular (197 vs 200; Φ = -0.03186; P = .6502), superior patellar (175 vs 184; Φ = 0.1332; P = .0569), and recurrent anterior tibial (156 vs 186; Φ = 0.01809; P = .7969) arteries. Cone-beam CT in combination with DSA identified 13.4% (372 vs 328) more targets compared to DSA alone. CONCLUSIONS: Based on the results of the current study, cone-beam CT serves as a valuable adjunct for visualizing the genicular arteries during GAE, and together with DSA, it identifies more potential embolization targets.

Yttrium-90 Radioembolization for the Treatment of Solitary, Unresectable HCC: The LEGACY Study.

BACKGROUND AND AIMS: Locoregional therapies, including yttrium-90 radioembolization, play an important role in the treatment of unresectable HCC. The aim of the LEGACY (Local radioEmbolization using Glass Microspheres for the Assessment of Tumor Control with Y-90) study was to evaluate objective response rate (ORR) and duration of response (DoR) in patients with solitary unresectable HCC treated with yttrium-90 glass microspheres. APPROACH AND RESULTS: LEGACY is a multicenter, single-arm, retrospective study conducted at three sites that included all eligible, consecutive patients with HCC treated with radioembolization between 2014 and 2017. Eligibility criteria included solitary HCC ≤ 8 cm, Child-Pugh A cirrhosis, and Eastern Cooperative Oncology Group performance status 0-1. Primary endpoints were ORR and DoR based on modified Response Evaluation Criteria in Solid Tumors in the treated area (localized), as evaluated by blinded, independent, central review. Radioembolization was performed with intent of ablative-level dosimetry in a selective fashion when possible. Overall survival was evaluated using Kaplan-Meier and multivariate Cox proportional hazards. Among the 162 patients included, 60.5% were Eastern Cooperative Oncology Group 0, and the median tumor size was 2.7 cm (range: 1-8) according to blinded, independent, central review. Radioembolization served as neoadjuvant therapy for transplantation or resection in 21.0% (34 of 162) and 6.8% (11 of 162) of patients, respectively, and as primary treatment for all others. Median follow-up time was 29.9 months by reverse Kaplan-Meier. ORR (best response) was 88.3% (CI: 82.4-92.4), with 62.2% (CI: 54.1-69.8) exhibiting a DoR ≥ 6 months. Three-year overall survival was 86.6% for all patients and 92.8% for those neoadjuvant patients with resected or transplanted liver. CONCLUSIONS: In this multicenter study of radioembolization, clinical meaningful response rates and prolonged DoR were observed in the treatment of unresectable, solitary HCC ≤ 8 cm.

Promoting Surgical Resection through Future Liver Remnant Hypertrophy.

An inadequate future liver remnant (FLR) can preclude curative-intent surgical resection for patients with primary or secondary hepatic malignancies. For patients with normal baseline liver function and without risk factors, an FLR of 20% is needed to maintain postsurgical hepatic function. However, the FLR requirement is higher for patients who are exposed to systemic chemotherapy (FLR, >30%) or have cirrhosis (FLR, >40%). Interventional radiologic and surgical methods to achieve FLR hypertrophy are evolving, including portal vein ligation, portal vein embolization, radiation lobectomy, hepatic venous deprivation, and associating liver partition and portal vein ligation for staged hepatectomy. Each technique offers particular advantages and disadvantages. Knowledge of these procedures can help clinicians to choose the suitable technique for each patient. The authors review the techniques used to develop FLR hypertrophy, focusing on technical considerations, outcomes, and the advantages and disadvantages of each approach. Online supplemental material is available for this article. ©RSNA, 2022.

Correlation of Y90-absorbed radiation dose to pathological necrosis in hepatocellular carcinoma: confirmatory multicenter analysis in 45 explants.

PURPOSE: To study the correlation between absorbed perfused liver dose using Y90 radioembolization and degree of hepatocellular carcinoma (HCC) necrosis in liver explants in a multicenter cohort analysis METHODS: A retrospective analysis of 45 HCC patients treated between 2014 and 2017 is presented. Inclusion criteria were treatment-naïve solitary HCC ≤ 8 cm and Child-Pugh A liver status using the radiation segmentectomy approach. All patients underwent liver resection or transplantation (LT). Liver explants were examined per institutional routine protocols to assess histopathological viability of HCC. Tumor pathological necrosis was classified into complete (100% necrosis), extensive (> 50% and ≤ 99%) necrosis, and partial (< 50%) necrosis. Absorbed perfused liver doses were estimated using MIRD calculations. Associations between dose and degree of necrosis were studied. RESULTS: Thirty-four (76%) patients underwent LT, and 11 (24%) patients underwent hepatic resection. Median radiation dose was 240 (IQR: 136-387) Gy. Thirty (67%) patients had complete pathologic necrosis (CPN) at explant, while 10 (22%) and 5 (11%) had extensive and partial necrosis, respectively. There were significant differences among perfused liver doses that exhibited partial, extensive, and complete necrosis (p = 0.001). Twenty-four out of twenty-eight (86%) patients who had dose > 190 Gy achieved CPN, while 11/17 (65%) who had < 190 Gy did not (Fisher's exact test; p = 0.001). Using binary logistic regression, only absorbed radiation dose was significantly associated with CPN (p = 0.01), while tumor size was not (p = 0.35). All patients receiving > 400 Gy exhibited CPN. CONCLUSION: Radiation segmentectomy for early HCC with ablative dosing > 400 Gy results in CPN. This represents the new standard target dose for radiation segmentectomy.

Yttrium-90 radiation segmentectomy for hepatic metastases: A multi-institutional study of safety and efficacy.

BACKGROUND AND OBJECTIVES: This study assessed the outcomes of Yttrium-90 (90 Y) radiation segmentectomy for hepatic metastases unamenable to resection or ablation. MATERIALS AND METHODS: Over 6 years, 36 patients with 53 tumors underwent segmental radioembolization. Patients were not candidates for surgical resection or thermal ablation. Malignancies included metastases from colorectal cancer (31%), neuroendocrine tumors (28%), sarcoma (19%), and others (22%). Eighty-one percent of patients had undergone prior treatment with systemic chemotherapy. Ongoing systemic chemotherapy was continued. Toxicity, tumor response, tumor progression, and survival were assessed. RESULTS: The median tumor size was 3.6 cm (range 1.2-6.1 cm). Adverse event rates were low, with no hepatic-related Common Terminology Criteria for Adverse Events Grade 3 or 4 toxicity. Target tumor Response Evaluation Criteria in Solid Tumors disease control rate was 92% (28% partial response, 64% stable disease). For patients with enhancing tumors (n = 14), modified Response Evaluation Criteria in Solid Tumors target tumor objective response rate was 100%. During a median follow-up of 12 months, target tumor progression occurred in 28% of treated tumors. Overall survival was 96% and 83% at 6 and 12 months, respectively. CONCLUSIONS: 90 Y radiation segmentectomy for hepatic metastases demonstrates high rates of tumor control and minimal toxicity. Radiation segmentectomy should be considered for patients with metastatic hepatic malignancy who are not candidates for surgical resection.

Society of Interventional Radiology Quality Improvement Standards on Percutaneous Ablation of Non-Small Cell Lung Cancer and Metastatic Disease to the Lungs.

PURPOSE: To provide guidance on quality improvement thresholds for outcomes and complications of image-guided thermal ablation for the treatment of early stage non-small cell lung cancer, recurrent lung cancer, and metastatic disease. MATERIALS AND METHODS: A multidisciplinary writing group conducted a comprehensive literature search to identify studies on the topic of interest. Data were extracted from relevant studies and thresholds were derived from a calculation of 2 standard deviations from the weighted mean of each outcome. A modified Delphi technique was used to achieve consensus agreement on the thresholds. RESULTS: Data from 29 studies, including systematic reviews and meta-analyses, retrospective cohort studies, and single-arm trials were extracted for calculation of the thresholds. The expert writing group agreed on thresholds for local control, overall survival and adverse events associated with image-guided thermal ablation. CONCLUSION: SIR recommends utilizing the indicator thresholds to review and assess the efficacy of ongoing quality improvement programs. When performance falls above or below specific thresholds, consideration of a review of policies and procedures to assess for potential causes, and to implement changes in practices, may be warranted.