Faculty Bibliography

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.

BACKGROUND:Real-time split-dose PET can identify the targeted colorectal liver metastasis (CLM) and eliminate the need for repeated contrast administration before and during thermal ablation (TA). This study aimed to assess the added value of pre-ablation real-time split-dose PET when combined with non-contract CT in the detection of CLM for ablation and the evaluation of the ablation zone and margins. METHODS:A total of 190 CLMs/125 participants from two IRB-approved prospective clinical trials using PET/CT-guided TA were analyzed. Based on detection on pre-TA imaging, CLMs were categorized as detectable, non-detectable, and of poor conspicuity on CT alone, and detectable, non-detectable, and low FDG-avidity on PET/CT after the initial dose. Ablation margins around the targeted CLM were evaluated using a 3D volumetric approach. RESULTS:We found that 129/190 (67.9%) CLMs were detectable on CT alone, and 61/190 CLMs (32.1%) were undetectable or of poor conspicuity, not allowing accurate depiction and targeting by CT alone. Thus, the theoretical 5- and 10-mm margins could not be defined in these tumors (32.1%) using CT alone. When TA intraprocedural PET/CT images are obtained and inspected (fused PET/CT), only 4 CLM (2.1%) remained undetectable or had a low FDG avidity. CONCLUSIONS:The addition of PET to non-contrast CT improved CLM detection for ablation targeting, margin assessments, and continuous depiction of the FDG avid CLMs during the ablation without the need for multiple intravenous contrast injections pre- and intra-procedurally.

PURPOSE/OBJECTIVE:To evaluate a transmission optical spectroscopy instrument for rapid ex vivo assessment of core needle cancer biopsies (CNBs) at the point of care. MATERIALS AND METHODS/METHODS:CNBs from surgically resected renal tumors and nontumor regions were scanned on their sampling trays with a custom spectroscopy instrument. After extracting principal spectral components, machine learning was used to train logistic regression, support vector machines, and random decision forest (RF) classifiers on 80% of randomized and stratified data. The algorithms were evaluated on the remaining 20% of the data set held out during training. Binary classification (tumor/nontumor) was performed based on a decision threshold. Multinomial classification was also performed to differentiate between the subtypes of renal cell carcinoma (RCC) and account for potential confounding effects from fat, blood, and necrotic tissue. Classifiers were compared based on sensitivity, specificity, and positive predictive value (PPV) relative to a histopathologic standard. RESULTS:A total of 545 CNBs from 102 patients were analyzed, yielding 5,583 spectra after outlier exclusion. At the individual spectra level, the best performing algorithm was RF with sensitivities of 96% and 92% and specificities of 90% and 89%, for the binary and multiclass analyses, respectively. At the full CNB level, RF algorithm also showed the highest sensitivity and specificity (93% and 91%, respectively). For RCC subtypes, the highest sensitivity and PPV were attained for clear cell (93.5%) and chromophobe (98.2%) subtypes, respectively. CONCLUSIONS:Ex vivo spectroscopy imaging paired with machine learning can accurately characterize renal mass CNB at the time of tissue acquisition.

Barcelona clinic liver cancer (BCLC) intermediate stage hepatocellular carcinoma is a heterogenous disease. Transarterial chemoembolization is offered as the first line therapy in this disease stage. Recent advances in systemic therapy have markedly improved outcomes even in advanced stage disease. The use of systemic therapy in BCLC intermediate stage disease may now be of therapeutic benefit in selected patients. We will focus on "the up to seven" criteria and its utility in selecting systemic therapy.