Faculty Bibliography

BACKGROUND/UNASSIGNED:Histotripsy is a novel, non-invasive, non-ionising, non-thermal method of mechanical tumour disruption that received US FDA approval in October 2023 for the treatment of liver tumours. This study aims to summarise and evaluate the safety and outcomes data following histotripsy of primary and secondary liver tumours. METHODS/UNASSIGNED:statistic and Cochran's Q test. Publication bias was assessed using funnel plot visual inspection and Egger's regression test. Finally, the histotripsy technology was assessed using the IDEAL framework to inform the design of future trials. This work was registered with PROSPERO (CRD420261299804). FINDINGS/UNASSIGNED:= 6.6%). No significant publication bias was detected for mortality and safety outcomes; however, formal assessment of publication bias was limited by the small number of studies for these and all outcomes. All radiological control outcomes showed substantial heterogeneity across studies. INTERPRETATION/UNASSIGNED:Although there is notable heterogeneity across studies, pooled results indicate that histotripsy has high rates of technical feasibility and local control with a favourable side effect profile. Interpretation of these findings is limited by the small number of available studies, variability in outcome definitions and imaging assessment methods, and short follow-up durations. These results underscore the need for larger, prospectively designed studies with standardised reporting frameworks and longer follow-up to more precisely characterise the clinical, radiologic, and quantitative imaging outcomes following histotripsy. FUNDING/UNASSIGNED:None.

PURPOSE/OBJECTIVE:Histotripsy is a noninvasive, nonionizing, nonthermal method of treating liver tumors receiving US Food and Drug Administration (FDA) clearance in October 2023. This study aims to describe histotripsy as a method of achieving local tumor control (LTC) for primary and secondary liver tumors. METHODS:All patients receiving histotripsy since FDA clearance (December 2023-December 2024) at four institutions (two academic; two private) with >30 days of active follow-up were included. Patients were classified into palliative intent and complete treatment intent. LTC was assessed using contrast-enhanced imaging on the basis of modified response evaluation criteria in solid tumors (mRECIST) and standardized ablation criteria at postoperative days (POD) 30 and 90. RESULTS:= .146). CONCLUSION/CONCLUSIONS:Histotripsy achieved high rates of LTC at 30 and 90 days in this preliminary multicenter cohort. Longer-term follow-up is needed to confirm stable results.

PURPOSE/OBJECTIVE:Histotripsy is a non-invasive ultrasound-based tumor ablation modality. This study aims to describe the preliminary safety and short-term imaging findings related to histotripsy of liver metastases. MATERIALS AND METHODS/METHODS:All patients who underwent histotripsy for liver metastases from February 2024 to January 2025 at a single center were retrospectively reviewed. Demographic, clinical, imaging, procedural, and adverse event data were collected via chart review. Immediate post-treatment ablation zones were measured on CT and compared to pretreatment tumor size and treatment cavity size on follow-up imaging. Untreated tumors were assessed using revised RECIST criteria to evaluate for off-target effects. RESULTS:Histotripsy was performed on 56 metastatic liver tumors (most common: 32% colorectal, 18% breast) in 26 patients (54% female, age 59.1 ± 15.6y). All patients were discharged within 36 h. Immediate post-procedural ablation zones (36.6 + 13.1 mm) were larger compared to pretreatment tumors (30.5 + 18.5 mm) (p = 0.0013). One-month ablation zones (31.5 + 16.7 mm) were smaller compared to immediate post-procedural ablation zones (p = 0.00064). Two patients experienced off-target effects in non-treated liver tumors following histotripsy while off cytotoxic therapy. One patient experienced a Grade 3 complication of bacteremia requiring prolonged inpatient admission. No deaths occurred within 30 days. CONCLUSION/CONCLUSIONS:Histotripsy demonstrates a favorable safety profile for liver metastases. Observed off-target effects in untreated lesions suggest systemic immunomodulatory responses. Further investigation is warranted to elucidate patient-specific factors (e.g., tumor biology, concurrent therapies) that optimize systemic immune activation. Larger prospective studies with longitudinal immune profiling are needed to validate histotripsy's potential dual role as a locoregional therapy and immune primer in metastatic liver disease. LEVEL OF EVIDENCE/METHODS:Level 2b, retrospective cohort study.

Patients with pancreatic ductal adenocarcinoma (PDAC) frequently present with liver metastases, which severely limit treatment options and prognosis. In other cancers, treatment of liver disease can improve outcomes and similar approaches are being explored in PDAC. Clinical data for locoregional control of pancreatic cancer liver metastases (PCLM) are limited, and histotripsy offers a new noninvasive tool for disease control. This study evaluates the preliminary safety, efficacy, and imaging findings of histotripsy in patients with PCLM.

BACKGROUND:Advanced-stage non-small cell lung cancer treatment has evolved with the introduction of molecularly targeted therapy, immunotherapy and combination frontline therapies. Despite these advancements, most patients experience treatment failure, resulting in poor prognosis characterized by low median progression-free survival (PFS) and overall survival (OS). Second-line chemotherapy has demonstrated minimally improved survival compared to best supportive care. Exploring new mechanisms to enhance treatment response in this patient population is critical. OBJECTIVE:This retrospective study aims to assess if there is survival benefit in a cohort of patients with stage IV lung cancer who have failed previous systemic therapy treated with pulsed electrical fields (PEF) therapy compared to a propensity-matched cohort. METHODS:A retrospective review of patients treated with PEF at three academic institutions from January 1, 2023, to July 1, 2024, yielded 41 patients with progressive stage IV non-small cell lung cancer. Tumor response was evaluated by RECIST 1.1 criteria. A propensity matched cohort of 50 patients with advanced NSCLC undergoing systemic therapy was identified. Statistical analyses, including Kaplan-Meier survival estimates and Hazard ratios, were conducted. RESULTS:The PEF-treated cohort exhibited a 1-year PFS of 63.2 % and OS of 74.3 %. In contrast, the matched cohort demonstrated a 1-year PFS of 11.8 % and OS of 33 %. The hazard ratio for PFS in the PEF group was 3.66 (p < 0.0001) and for OS was 3.5 (p = 0.0007), indicating a significant survival advantage for patients receiving PEF. CONCLUSION/CONCLUSIONS:This study suggests that PEF therapy may be associated with significantly improved PFS and OS in patients with progressive stage IV non-small cell lung cancer compared to the matched cohort. Prospective controlled studies are required to confirm these preliminary findings, to better understand the mechanism of action of PEF, and to identify which patient populations would best benefit from this therapy.

PURPOSE/OBJECTIVE:To assess the safety and feasibility of Pulsed Electrical Fields (PEF) ablation in various organs and patient populations. MATERIALS AND METHODS/METHODS:This multi-center, retrospective study collected data from five academic medical centers on patients undergoing percutaneous PEF ablation, with a minimum of 30 days follow-up. Parameters assessed included demographics, treatment specifics, immediate adverse events, and survival rates. Procedures used CT or ultrasound guidance with a 19-gauge insulated needle and PEF probe. RESULTS:This study included 155 patients with a mean age of 60.7 years, predominantly with lung cancer (77/155). Most patients 85 % (131/155) had stage IV disease. The mean hospital stay post PEF was 0.3 days, with most discharged the same day. In lung procedures adverse events of pneumothorax occurred in 21.5 % of lung procedures, with 11.3 % requiring chest tube placements. No adverse events were observed in liver procedures. The 1-year overall survival rate for the entire cohort was 74.6 %, with patients with colorectal cancer having the highest survival rate of 89.7 %, and patient with sarcomas lowest at 18.0 %. CONCLUSION/CONCLUSIONS:Percutaneous PEF is feasible to be performed across a variety of organs. Although difficult to compare with other modalities, this data suggests that PEF ablation is relatively safe. However, further prospective studies with larger sample sizes and comprehensive imaging are needed to confirm these findings and establish efficacy.

BACKGROUND:Histotripsy is a novel, noninvasive, nonionizing, and nonthermal approach that uses focused ultrasound waves to treat liver tumors. This technology received a de novo Food and Drug Administration grant in late 2023. This study aimed to provide the first report on post-trial real-world clinical safety data. METHODS:Safety outcomes within 30 days of histotripsy were collected after obtaining Food and Drug Administration clearance (December 22, 2023 to July 26, 2024). All centers that performed histotripsy were invited to participate in this study. Complications requiring treatment were graded using the Clavien-Dindo classification and Comprehensive Complication Index (CCI). RESULTS:A total of 295 patients underwent histotripsy for 510 tumors at 18 centers. The treated liver tumor types included colorectal metastases (n = 140), neuroendocrine tumors (n = 46), hepatocellular carcinomas (n = 31), pancreatic tumors (n = 30), and breast metastases (n = 26). The most common numbers of tumors treated per procedure were 1 (n = 170), 2 (n = 69), and 3 (n = 37). All 8 liver segments were treated for tumors. Safety data were available for 230 patients from 9 centers. Of note, 12 of 230 patients (5.2%) experienced complications of any grade. Most patients (9 [75%]) had minor cases (Clavien-Dindo grade ≤ II). The median and mean CCIs were 0.00 (IQR, 0.00-0.00) and 0.00 (95% CI, 0.00-0.75). All 3 major complications (Clavien-Dindo grade > II [1.3%]) were death due to disease progression. All 3 patients underwent histotripsy with palliative intent for known advanced intra- and extrahepatic diseases. CONCLUSION/CONCLUSIONS:To the best of our knowledge, this is the first study to report on the real-world therapeutic use of histotripsy for liver tumors. Histotripsy was well tolerated, with few overall complications and rare serious complications, indicating a safety profile that compares favorably with that of other liver-directed and surgical therapies for the treatment of liver tumors. Long-term follow-up data, including oncologic outcomes, were collected.

BACKGROUND/UNASSIGNED:Mitomycin-C is an older drug which has a synergistic mechanism of action with irinotecan. This study evaluated the outcomes of selective intra-arterial mitomycin-C infusions in combination with bi-weekly systemic irinotecan for treatment of liver-dominant metastatic colorectal cancer (CRC) which progressed after hepatic arterial infusion (HAI) pump chemotherapy with floxuridine and at least two lines of systemic chemotherapy. METHODS/UNASSIGNED:An IRB-approved retrospective review of patients receiving at least two sessions of selective monthly mitomycin-C infusions in interventional radiology (IR) was performed. Anatomic and metabolic imaging was initially obtained at 4 weeks after the second infusion, and every 2-3 months thereafter. Response was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and European Organization for Research and Treatment of Cancer (EORTC) criteria. Patient, disease and procedural parameters were recorded. Progression-free survival (PFS), liver progression-free survival (LPFS) and overall survival (OS) were assessed with Kaplan Meier methodology. RESULTS/UNASSIGNED:mutations and 35/46 (76.1%) had extrahepatic disease at the time of the first infusion. On initial follow-up, liver disease control was observed in 38/46 using RECIST 1.1 (82.6%; partial response 13%, stable disease 69.6%) and 26/31 using EORTC criteria (83.9%; complete response 6.5%, partial response 48.4%, stable disease 29%). Median PFS, LPFS and OS were 4.1 [95% confidence interval (CI): 3.2-4.9], 5.5 (95% CI: 2.5-8.4) and 9.6 (95% CI: 8.2-11.1) months respectively. The infusions were discontinued in 26 (56.5%) patients due to disease progression. Eighteen patients (39.1%) discontinued the infusion protocol due to toxicities/complications, including hepatic/biliary toxicity (26.1%), hepatic arterial thrombosis (15.2%) and/or pulmonary toxicity (8.7%). CONCLUSIONS/UNASSIGNED:In this heavily pretreated population, addition of intra-arterial mitomycin-C was associated with initial liver disease control rates exceeding 80%. Toxicities were observed, particularly in patients with prolonged disease control who received ≥4 infusions.

PURPOSE:To evaluate the safety, primary patency, and clinical outcomes of hepatic artery stent graft (SG) placement for vascular injuries. MATERIALS AND METHODS:Patients treated with hepatic arterial SG placement for vascular injuries between September 2018 and September 2021 were reviewed. Data on demographic characteristics, indication, stent graft characteristics, antiplatelet/anticoagulant use, clinical success rate, complications, and type of follow-up imaging were collected. Follow-up images were reviewed by 2 independent reviewers to assess primary patency. A time-to-event analysis was performed. The median duration of stent graft patency was estimated using Kaplan-Meier curves. A Cox proportional hazard model was used to evaluate factors related to stent graft patency. RESULTS:Thirty-five patients were treated with hepatic arterial SG placement, 11 for postoperative bleeds and 24 for hepatic artery infusion pump catheter-related complications. Clinical success was achieved in 32 (91%) patients (95% CI, 77-98). The median primary patency was 87 days (95% CI, 73-293). Stent grafts of ≥6-mm diameter retained patency for a longer duration than that with stent grafts of smaller diameters (6 mm vs 5 mm; hazard ratio, 0.35; 95% CI, 0.14-0.88; P = .026; and 7+ mm vs 5 mm; hazard ratio, 0.27; 95% CI, 0.09-0.83; P = .023). Anticoagulation/antiplatelet regimen was not associated with increased stent graft patency duration (P > .05). Only minor complications were reported in 2 (5.7%) patients. CONCLUSIONS:Stent grafts can be used safely and effectively to treat injuries of the hepatic artery. Stent graft diameters of ≥6 mm seem to provide more durable patency.