Alliance for clinical trials in Oncology (Alliance) trial A022101/NRG-GI009: a pragmatic randomized phase III trial evaluating total ablative therapy for patients with limited metastatic colorectal cancer: evaluating radiation, ablation, and surgery (ERASur).

BACKGROUND: For patients with liver-confined metastatic colorectal cancer (mCRC), local therapy of isolated metastases has been associated with long-term progression-free and overall survival (OS). However, for patients with more advanced mCRC, including those with extrahepatic disease, the efficacy of local therapy is less clear although increasingly being used in clinical practice. Prospective studies to clarify the role of metastatic-directed therapies in patients with mCRC are needed. METHODS: The Evaluating Radiation, Ablation, and Surgery (ERASur) A022101/NRG-GI009 trial is a randomized, National Cancer Institute-sponsored phase III study evaluating if the addition of metastatic-directed therapy to standard of care systemic therapy improves OS in patients with newly diagnosed limited mCRC. Eligible patients require a pathologic diagnosis of CRC, have BRAF wild-type and microsatellite stable disease, and have 4 or fewer sites of metastatic disease identified on baseline imaging. Liver-only metastatic disease is not permitted. All metastatic lesions must be amenable to total ablative therapy (TAT), which includes surgical resection, microwave ablation, and/or stereotactic ablative body radiotherapy (SABR) with SABR required for at least one lesion. Patients without overt disease progression after 16-26 weeks of first-line systemic therapy will be randomized 1:1 to continuation of systemic therapy with or without TAT. The trial activated through the Cancer Trials Support Unit on January 10, 2023. The primary endpoint is OS. Secondary endpoints include event-free survival, adverse events profile, and time to local recurrence with exploratory biomarker analyses. This study requires a total of 346 evaluable patients to provide 80% power with a one-sided alpha of 0.05 to detect an improvement in OS from a median of 26 months in the control arm to 37 months in the experimental arm with a hazard ratio of 0.7. The trial uses a group sequential design with two interim analyses for futility. DISCUSSION: The ERASur trial employs a pragmatic interventional design to test the efficacy and safety of adding multimodality TAT to standard of care systemic therapy in patients with limited mCRC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05673148, registered December 21, 2022.

Combination and Optimal Sequencing of Systemic and Locoregional Therapies in Hepatocellular Carcinoma: Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel.

Hepatocellular carcinoma, historically, has had a poor prognosis with very few systemic options. Furthermore, most patients at diagnosis are not surgical candidates. Therefore, locoregional therapy (LRT) has been widely used, with strong data supporting its use. Over the last 15 years, there has been progress in the available systemic agents. This has led to the updated Barcelona Clinic Liver Cancer (BCLC) algorithm's inclusion of these new systemic agents, with advocacy of earlier usage in those who progress on LRT or have tumor characteristics that make them less likely to benefit from LRT. However, neither the adjunct of LRT nor the specific sequencing of combination therapies is addressed directly. This Research Consensus Panel sought to highlight research priorities pertaining to the combination and optimal sequencing of LRT and systemic therapy, assessing the greatest needs across BCLC stages.

Comparison of Fibered versus Nonfibered Coils for Venous Embolization in an Ovine Model.

PURPOSE: To compare nylon fibered (F) with nonfibered (NF) coils for embolization in an ovine venous model. MATERIALS AND METHODS: Four- to 8-mm-diameter, 0.035-inch F and NF coils were deployed in 24 veins in 6 sheep. The number of coils, total length of the coils, and length of implanted coil pack required to achieve complete stasis were recorded, as were vessel diameter, radiation dose, ease of packing, damage to embolized vessel, and time to stasis. Venography at 1 and 3 months was used to assess the migration and durability of vessel occlusion. Veins were harvested at 3 months. RESULTS: F and NF coils were deployed in 24 veins, and stasis was achieved, without immediate coil migration or vessel damage. The mean numbers of F and NF coils per vein were 5 and 8.75, respectively (P = .007). The vessel diameter between the groups was not statistically different. The total coil length (F, 70 cm vs NF, 122.5 cm; P = .0007), coil pack length (F, 29.3 mm vs NF, 39.4 mm; P = .003), time to stasis (F, 5.3 minutes vs NF, 9.0 minutes; P = .008), and radiation dose (F, 25.3 mGy vs NF, 34.9 mGy; P = .037) were significantly different between the groups. Challenges with the animal model prevented conclusive long-term results. Migration occurred with 8 of 11 (72%) coil packs in the femoral veins and 0 of 13 (0%) coil packs in the internal iliac and deep femoral veins. Venography demonstrated that of 16 remaining coil packs, 11 were occluded at 1 month and 10 remained occluded at 3 months. CONCLUSIONS: Fibers allow for significantly fewer coils to achieve immediate venous occlusion.

Vertebral Body Bone Ablation with and without a Saline-Infused System in a Porcine Model.

The purpose of this study was to evaluate the effect of bone radiofrequency (RF) ablation in the spine with and without controlled saline infusion. RF ablation with and without controlled saline infusion was performed in the vertebral bodies of 2 swine with real-time temperature and impedance recordings. Histology and magnetic resonance (MR) imaging results were reviewed to evaluate the ablation zone size, breach of spinal canal, and damage to the spinal cord and nerves. There was no difference in maximum and mean temperatures between controlled saline and noninfusion groups. The impedance and power output were not significantly different between the groups. MR imaging and histopathology demonstrated ablation zones confined within the vertebral bodies. Ablation zone size correlated on MR imaging and histopathology by groups. No ablation effect, breach of posterior cortex, spinal cord injury, or nerve or ganglion injury was observed at any level using MR imaging or histology. Controlled saline infusion does not appear to impact bone RF ablation and, specifically, does not increase the ablation zone size.

Optimal Medical Therapy Following Deep Venous Interventions: Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel.

The optimal medical management of patients following endovascular deep venous interventions remains ill-defined. As such, the Society of Interventional Radiology Foundation (SIRF) convened a multidisciplinary group of experts in a virtual Research Consensus Panel (RCP) to develop a prioritized research agenda regarding antithrombotic therapy following deep venous interventions. The panelists presented the gaps in knowledge followed by discussion and ranking of research priorities based on clinical relevance, overall impact, and technical feasibility. The following research topics were identified as high priority: 1) characterization of biological processes leading to in-stent stenosis/rethrombosis; 2) identification and validation of methods to assess venous flow dynamics and their effect on stent failure; 3) elucidation of the role of inflammation and anti-inflammatory therapies; and 4) clinical studies to compare antithrombotic strategies and improve venous outcome assessment. Collaborative, multicenter research is necessary to answer these questions and thereby enhance the care of patients with venous disease.

Yttrium-90 Radioembolization in the VX2 Rabbit Model: Radiation Safety and Factors Influencing Delivery Efficiency.

The purpose of this study was to define the optimal infusion parameters and operator radiation exposure for yttrium-90 (90Y) radioembolization in the VX2 rabbit model of liver cancer. Forty-one rabbits with VX2 were treated with glass microspheres with vial sizes of 1, 3, and 5 GBq. The mean administered activity was 51.5 MBq (95% CI, 39.1-63.9). Delivery efficiency improved with 1 GBq versus with 3 GBq (residual 11.0% vs 46.4%, respectively; P = .0013) and improved with 1 GBq versus with 5 GBq (residual 11.0% vs 33.8%, respectively; P = .0060). The mean operator extremity exposure was 41.7 µSv/infusion. The optimal minimum infusion volume and rate was 49 mL and 21 mL/min, respectively. Fecal elimination occurred with microsphere uptake in the gallbladder at 1 and 2 weeks. 90Y radioembolization can be safely and efficiently performed in the VX2 rabbit model. Methodological considerations as a "how-to" for the setup of a preclinical 90Y laboratory are included to support future translational research.

Research Priorities in Lymphatic Interventions: Recommendations from a Multidisciplinary Research Consensus Panel.

Recognizing the increasing importance of lymphatic interventions, the Society of Interventional Radiology Foundation brought together a multidisciplinary group of key opinion leaders in lymphatic medicine to define the priorities in lymphatic research. On February 21, 2020, SIRF convened a multidisciplinary Research Consensus Panel (RCP) of experts in the lymphatic field. During the meeting, the panel and audience discussed potential future research priorities. The panelists ranked the discussed research priorities based on clinical relevance, overall impact, and technical feasibility. The following research topics were prioritized by RCP: lymphatic decompression in patients with congestive heart failure, detoxification of thoracic duct lymph in acute illness, development of newer agents for lymphatic imaging, characterization of organ-based lymph composition, and development of lymphatic interventions to treat ascites in liver cirrhosis. The RCP priorities underscored that the lymphatic system plays an important role not only in the intrinsic lymphatic diseases but in conditions that traditionally are not considered to be lymphatic such as congestive heart failure, liver cirrhosis, and critical illness. The advancement of the research in these areas will lead the field of lymphatic interventions to the next level.

Interventional Radiology Obesity Therapeutics: Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel.

The Society of Interventional Radiology Foundation commissioned a Research Consensus Panel to establish a research agenda on "Obesity Therapeutics" in interventional radiology (IR). The meeting convened a multidisciplinary group of physicians and scientists with expertise in obesity therapeutics. The meeting was intended to review current evidence on obesity therapies, familiarize attendees with the regulatory evaluation process, and identify research deficiencies in IR bariatric interventions, with the goal of prioritizing future high-quality research that would move the field forward. The panelists agreed that a weight loss of >8%-10% from baseline at 6-12 months is a desirable therapeutic endpoint for future IR weight loss therapies. The final consensus on the highest priority research was to design a blinded randomized controlled trial of IR weight loss interventions versus sham control arms, with patients receiving behavioral therapy.

Defining the Value of Interventional Radiology to Healthcare Stakeholders: Proceedings from a Society of Interventional Radiology Research Consensus Panel.

Interventional radiology (IR) has collectively struggled to articulate and prove its value to several external stakeholders. The goal of this research consensus panel was to provide a summary of the existing knowledge, identify current gaps in knowledge, identify the strengths and weaknesses in existing data, and prioritize research needs related to the value of IR. Panelists were asked to identify the critical relationships/alliances that should be fostered to advance the prioritized research and determine how the Society of Interventional Radiology and the Society of Interventional Radiology Foundation can further support these initiatives. Following presentations and discussions, it was determined that proving and quantifying how IR decreases the length of stay and prevents hospital admissions are the most salient, value-related research topics to pursue for the specialty.

Musculoskeletal Oncologic Interventions: Proceedings from the Society of Interventional Radiology and Society of Interventional Oncology Research Consensus Panel.

Musculoskeletal interventions are increasingly used with palliative and curative intent in the multidisciplinary treatment of oncology patients with bone and soft-tissue tumors. There is an unmet need for high-quality evidence to guide broader application and adoption of minimally invasive interventional technologies to treat these patients. Therefore, the Society of Interventional Radiology Foundation and the Society of Interventional Oncology collaborated to convene a research consensus panel to prioritize a research agenda addressing the gaps in the current evidence. This article summarizes the panel's proceedings and recommendations for future basic science and clinical investigation to chart the course for interventional oncology within the musculoskeletal system. Key questions that emerged addressed the effectiveness of ablation within specific patient populations, the effect of combination of ablation with radiotherapy and/or immunotherapy, and the potential of standardization of techniques, including modeling and monitoring, to improve the consistency and predictability of treatment outcomes.

Correlation and Agreement of Yttrium-90 Positron Emission Tomography/Computed Tomography with Ex Vivo Radioembolization Microsphere Deposition in the Rabbit VX2 Liver Tumor Model.

PURPOSE: To demonstrate a stronger correlation and agreement of yttrium-90 (90Y) positron emission tomography (PET)/computed tomography (CT) measurements with explant liver tumor dosing compared with the standard model (SM) for radioembolization. MATERIALS AND METHODS: Hepatic VX2 tumors were implanted into New Zealand white rabbits, with growth confirmed by 7 T magnetic resonance imaging. Seventeen VX2 rabbits provided 33 analyzed tumors. Treatment volumes were calculated from manually drawn volumes of interest (VOI) with three-dimensional surface renderings. Radioembolization was performed with glass 90Y microspheres. PET/CT imaging was completed with scatter and attenuation correction. Three-dimensional ellipsoid VOI were drawn to encompass tumors on fused images. Tumors and livers were then explanted for inductively coupled plasma (ICP)-optical emission spectroscopy (OES) analysis of microsphere content. 90Y PET/CT and SM measurements were compared with reference standard ICP-OES measurements of tumor dosing with Pearson correlation and Bland-Altman analyses for agreement testing with and without adjustment for tumor necrosis. RESULTS: The median infused activity was 33.3 MBq (range, 5.9-152.9). Tumor dose was significantly correlated with 90Y PET/CT measurements (r = 0.903, P < .001) and SM estimates (r = 0.607, P < .001). Bland-Altman analyses showed that the SM tended to underestimate the tumor dosing by a mean of -8.5 Gy (CI, -26.3-9.3), and the degree of underestimation increased to a mean of -18.3 Gy (CI, -38.5-1.9) after the adjustment for tumor necrosis. CONCLUSIONS: 90Y PET/CT estimates were strongly correlated and had better agreement with reference measurements of tumor dosing than SM estimates.

Standing Waves on Computed Tomography Angiography in Multiple Vessels in a Young Trauma Patient.

ABSTRACT: Standing waves are a phenomenon of uncertain etiology seen on imaging. We present the first case demonstrating standing waves on computed tomography angiography in multiple vessels in a single patient with imaging evidence of resolution in some of the vessels. Our case further supports the literature that standing waves are a physiologic phenomenon, likely because of flow mechanics, rather than modality.

VenaTech Convertible Vena Cava Filter 6 Months after Conversion Follow-up.

PURPOSE: To report device-related adverse events 6 months after placement or conversion of the VenaTech convertible vena cava filter (VTCF). MATERIALS AND METHODS: A review of 6-month follow-up data of an investigational device exemption multicenter, prospective, single-arm study was performed. The VTCF was implanted in 149 patients. Conversion was attempted in 64.4% of those patients (n = 96) and successfully in 96.9% of the patients (n = 93). A total of 76 patients completed imaging evaluation at 6 months after filter conversion. Patients who required continued venous thromboembolism prophylaxis at 6 months did not undergo a conversion attempt and were designated as nonconverted filter subjects. A total of 28 nonconverted filter subjects completed imaging evaluation at 6 months after implantation. RESULTS: Evaluation of patients at 6 months after conversion demonstrated 1 of 76 (1.3%) inferior vena cava (IVC) perforations with a filter strut greater than 3 mm outside of the caval lumen. No cases of recurrent PE, clinically significant filter migration, filter fracture, or IVC thrombosis were reported in the converted subjects. In the nonconverted filter subjects, there was a 14.3% (4 of 28) complete or nearly complete rate of IVC thromboses. There were no cases of recurrent pulmonary embolism, penetration, fracture, or spontaneous conversion in the nonconverted filter subjects. There was a significant reduction in the rate of IVC thrombosis and migration in the converted cohort compared to that in the nonconverted cohort. CONCLUSIONS: At 6 months, the VTCF demonstrated low adverse event rates in the converted configuration, whereas a minority of patients with the nonconverted configuration demonstrated a high risk of IVC thrombosis.

Outcomes and Cost Comparison of Percutaneous Endovascular Aortic Repair versus Endovascular Aortic Repair With Open Femoral Exposure.

BACKGROUND: The objective of this study was to assess cost differences between patients who underwent percutaneous endovascular aortic repair (PEVAR) and open surgical femoral exposure in elective endovascular aortic repair (EVAR) of abdominal aortic aneurysms. MATERIALS AND METHODS: An IRB-approved single center retrospective analysis of patients who underwent elective EVAR for abdominal aortic aneurysms from 2009 to 2016 was performed. One hundred patients were selected with 50 patients who underwent PEVAR and 50 patients who underwent open surgical femoral exposure. Patient demographics, procedural variables, and hospital outcomes were collected and compared. Primary outcomes assessed used in cost calculations included operating time (OR time), hospital length of stay (LOS), and intensive care unit stay (ICU LOS). Extrapolated cost differences were based on known, published cost multipliers for the primary outcomes observed. RESULTS: Patients undergoing PEVAR had significant reduction in mean OR time (113.9 min versus 144.9 min, P < 0.001), mean ICU LOS (19.7 h versus 28.9 h, P = 0.094), and overall LOS (28.3 h versus 33.1 h, P = 0.020). There was no statistically significant difference in access related complications, although there was a trend toward less complication rates with PEVAR (0% versus 5%, P = 0.056). Calculated cost of procedures based on mean ICU LOS, hospital LOS, and OR time, showed significant reduction in mean hospital costs with PEVAR ($16,628.5 versus $21,705.8, P < 0.001). Multiple linear regression analysis demonstrated an overall 23% cost reduction with PEVAR. CONCLUSIONS: Prior reports comparing PEVAR versus EVAR with open femoral exposures have shown improvement in overall patient time to ambulation and other hospital metrics such as LOS with PEVAR. There is, however, a paucity of overall cost comparison data regarding PEVAR. In this study, adoption of PEVAR was seen to significantly reduce OR times (19%) and overall hospital LOS (50%). The outcomes observed ultimately translated into significant reduction in hospital costs.

Research Priorities in Pelvic Venous Disorders in Women: Recommendations from a Multidisciplinary Research Consensus Panel.

Pelvic venous disorders (PeVDs) in women can present with chronic pelvic pain, lower-extremity and vulvar varicosities, lower-extremity swelling and pain, and left-flank pain and hematuria. Multiple evidence gaps exist related to PeVDs with the consequence that nonvascular specialists rarely consider the diagnosis. Recognizing this, the Society of Interventional Radiology Foundation funded a Research Consensus Panel to prioritize a research agenda to address these gaps. This paper presents the proceedings and recommendations from that Panel.

Influence of Academic Productivity on Gender Disparity in Academic Interventional Radiology.

OBJECTIVE. This study aimed to determine the effect of academic productivity measured using surrogate metrics, including h-index, publication number, and citation number, on the advancement of academic interventional radiology (IR) staff. MATERIALS AND METHODS. Publicly available data on faculty members in IR departments across academic institutions in Canada and the United States were collected. Gender, academic ranking, leadership position (if any), publication number, citation number, years of active research, and h-index were collected for each faculty member, and these data were used to create a prediction equation. RESULTS. Four hundred twenty IR faculty members met the inclusion criteria for this study. Overall, women were the minority, representing 10% of all IR faculty. Women in academic IR attained academic ranks at a rate comparable to that of men, with 59% of women attaining the rank of assistant professor and 32% attaining associate professor, compared with 59% of men at the assistant professor and 25% at the associate professor level. A trend toward lower female representation was present at the full professor level (women, 8%; men, 15%) but this difference did not reach statistical significance. Leadership position by gender as a percentage of their overall representation in the field was also similar between women and men (first-in-command women, 15%; first-in-command men, 15%; second-in-command women, 2%; second-in-command men, 2%). No significant difference was found between women and men in terms of academic achievement metrics, including publication number, citation number, h-index, and years of active research. CONCLUSION. Women in academic IR achieve similar publication metrics as men and attain promotion to higher academic rank and leadership positions equal to their overall representation in the field. However, women remain the minority among academic IR faculty across North America.

Real time evaluation of tissue optical properties during thermal ablation of ex vivo liver tissues.

Complete ablation of liver tumors is vital for minimizing the risk of local tumor recurrence. Accurately identifying the hallmarks of tissue necrosis during thermal ablative therapies may significantly increase the efficacy of ablation, while minimizing unnecessary damage to the surrounding normal tissues or critical structures. Light propagation in biological tissues is sensitive to the tissue microstructure and chromophore concentrations. In our previous studies, we found that the wavelength (λ) averaged liver tissue absorption coefficient (µa) and reduced scattering coefficient (µs') change significantly upon heating which may be used for assessment of tissue damage during thermal ablation of solid tumors. Here, we seek to demonstrate the use of an integrated fiber-optic probe for continuous monitoring of the local tissue temperature (T), µa(λ) and µs'(λ) during thermal ablation of ex vivo porcine livers. The wavelength-averaged (435-630 nm) tissue absorption and scattering (µa and µs' ) increased rapidly at 45 °C and plateaued at 67 °C. The mean µa and µs' for liver tissue at 37 °C (n = 10) were 8.5 ± 3.7 and 2.8 ± 1.1 cm-1, respectively. The relative changes in µa and µs' at 37, 55, and 65 °C were significantly different (p < .02) from each other. A relationship between the relative changes in µa and µs' and the degree of tissue damage estimated using the temperature-based Arrhenius model for porcine liver tissues was established and studied.

90Y Radioembolization for Hepatic Malignancy in Patients with Previous Biliary Intervention: Multicenter Analysis of Hepatobiliary Infections.

Purpose To determine the frequency of hepatobiliary infections after transarterial radioembolization (TARE) with yttrium 90 (90Y) in patients with liver malignancy and a history of biliary intervention. Materials and Methods For this retrospective study, records of all consecutive patients with liver malignancy and history of biliary intervention treated with TARE at 14 centers between 2005 and 2015 were reviewed. Data regarding liver function, 90Y dosimetry, antibiotic prophylaxis, and bowel preparation prophylaxis were collected. Primary outcome was development of hepatobiliary infection. Results One hundred twenty-six patients (84 men, 42 women; mean age, 68.8 years) with primary (n = 39) or metastatic (n = 87) liver malignancy and history of biliary intervention underwent 180 procedures with glass (92 procedures) or resin (88 procedures) microspheres. Hepatobiliary infections (liver abscesses in nine patients, cholangitis in five patients) developed in 10 of the 126 patients (7.9%) after 11 of the 180 procedures (6.1%; nine of those procedures were performed with glass microspheres). All patients required hospitalization (median stay, 12 days; range, 2-113 days). Ten patients required percutaneous abscess drainage, three patients underwent endoscopic stent placement and stone removal, and one patient needed insertion of percutaneous biliary drains. Infections resolved in five patients, four patients died (two from infection and two from cancer progression while infection was being treated), and one patient continued to receive suppressive antibiotics. Use of glass microspheres (P = .02), previous liver resection or ablation (P = .02), and younger age (P = .003) were independently predictive of higher infection risk. Conclusion Infectious complications such as liver abscess and cholangitis are uncommon but serious complications of transarterial radioembolization with 90Y in patients with liver malignancy and a history of biliary intervention.

Early Immunologic Response of Irreversible Electroporation versus Cryoablation in a Rodent Model of Pancreatic Cancer.

PURPOSE: To investigate the differences in immune responses between cryoablation and irreversible electroporation (IRE) in a preclinical mouse model. MATERIAL AND METHODS: A mouse pancreatic cancer cell line (PANC-2) was implanted in the bilateral flanks of mice, and tumor-bearing mice were divided into 6 groups. One of the tumors was ablated either with contact cryoablation using an argon-cooled cryoablation probe for 1 minute at 5% power or by IRE for a total of 64 100-µs-duration, 1250-V/cm2 pulses with 100-ms spacing. The contralateral tumors in the same animal served as controls. At immediate, 6, 12, and 24 hours after ablation, the tumors were processed for immunostaining with F480 (macrophages), CD3 (T cells), and CD-56 (natural killer cells) antibodies. RESULTS: CD3 staining demonstrated significantly more T cells in the IRE group than in the cryoablation group at 6 hours (45 vs 16; P = .027), 12 hours (67 vs 33; P = .020), and 24 hours (161 vs 94; p = .003), with almost a 2-fold increase at every time point. Although the mean number of natural killer cells in the treated tumors was higher, no significant differences were observed between the 2 groups at any of the time points. A significant difference was observed in F480 positivity between the cryoablation group and the IRE group at 12 hours (210 vs 356; P = .0004) and 24 hours (220 vs 328; P = .04), respectively. CONCLUSIONS: In a mouse model of pancreatic cancer, IRE evokes a more robust infiltration of macrophages and T cells than cryoablation within 24 hours.