Safety and Effectiveness of Irreversible Electroporation in Lymph Node Metastases.

PURPOSE: Demonstrating the safety and efficacy of percutaneous irreversible electroporation (IRE) for the treatment of lymph node metastases. MATERIALS AND METHODS: An IRB-approved, single-center retrospective review was performed on patients with lymph node metastases gastrointestinal, and genitourinary primary cancers. Primary objective safety was evaluated by assessing complications graded according to the Clavien-Dindo Classification, and efficacy was determined by tumor response on follow-up imaging and local progression-free survival (LPFS). Secondary outcome measures were technical success (complete ablation with an adequate ablative margin > 5 mm), length of hospital stay and distant progression-free survival (DPFS). RESULTS: Nineteen patients underwent percutaneous IRE between June 2018 and February 2023 for lymph node metastases, close to critical structures, such as vasculature, bowel, or nerves. The technical success was achieved in all cases. Complications occurred in four patients (21.1%), including two self-limiting grade 1 hematomas, a grade 1 abdominal pain, and grade 2 nerve pain treated with medication. Seventeen patients were hospitalized overnight, one patient stayed two nights and another patient stayed fourteen nights. Median follow-up was 25.5 months. Median time to local progression was 24.1 months (95% CI: 0-52.8) with 1-, 2-, and 5-year LPFS of 57.9%, 57.9% and 20.7%, respectively. Median time to distant progression was 4.3 months (95% CI: 0.3-8.3) with 1-, 2-, and 5-year DPFS of 31.6%, 13.2% and 13.2%, respectively. CONCLUSION: IRE is a safe and effective minimally-invasive treatment for lymph node metastases in locations, where temperature dependent ablation may be contraindicated. Care should be taken when employing IRE near nerves.

Irreversible Electroporation as a Valid Treatment Option for Hepatic Epithelioid Hemangioendothelioma: An International Multicenter Experience.

PURPOSE: Hepatic epithelioid hemangioendothelioma (HEHE) is a rare tumor with currently no established standard of care. This international multicenter retrospective study assesses the use of percutaneous irreversible electroporation (IRE) as an ablative tool to treat HEHE and provides a clinical overview of the current management and role of IRE in HEHE treatment. MATERIAL AND METHODS: Between 2017 and 2023, 14 patients with 47 HEHE tumors were treated with percutaneous IRE using CT-scan guidance in 23 procedures. Baseline patient and tumor characteristics were evaluated. Primary outcome measures included safety and effectiveness, analyzed using Common Terminology Criteria for Adverse Events (CTCAE) and treatment response by mRECIST criteria. Secondary outcome measures included technical success, post-treatment tumor sizes and length of hospital stay. Technical success was defined as complete ablation with an adequate ablative margin (intentional tumor free ablation margin > 5 mm). RESULTS: IRE treatment resulted in technical success in all tumors. Following a median follow-up of 15 months, 30 tumors demonstrated a complete response according to mRECIST criteria. The average tumor size pre-treatment was 25.8 mm, accompanied by an average reduction in tumor size by 7.5 mm. In 38 out of 47 tumors, there was no evidence of local recurrence. In nine tumors, residual tumor was present. There were no cases of progressive disease. Median length of hospital stay was one day. Only one grade 3 CTCAE event occurred, a pneumothorax requiring chest tube placement. CONCLUSION: The current study provides evidence that IRE is a safe and efficacious minimally invasive treatment option for HEHE.

Irreversible electroporation as a focal therapy for localized prostate cancer: A systematic review.

Introduction: Irreversible electroporation (IRE) is a new and promising focal therapy for the treatment of localized prostate cancer. In this systematic review, we summarize the literature on IRE for prostate cancer published over the last decade. Methods: PubMed and EMBASE were searched with the end date of May 2023 to find relevant publications on prostate cancer ablation using IRE. Original studies with focal IRE as the primary curative treatment which reported on functional or oncological outcomes were included. The bibliography of relevant studies was also scanned to identify suitable articles. Results: A total of 14 studies reporting on 899 patients treated with IRE for localized prostate cancer were included. Of all the studies reviewed, 77% reported on recurrence within the zone of ablation, and it ranged from 0% to 38.9% for in-field and 3.6% to 28% for out-of-field recurrence. Although, a standardised follow-up protocol was not followed, all the studies employed serial prostate-specific antigen monitoring, a multiparametric magnetic resonance imaging, and a biopsy (6-12 months post-treatment). Across all the studies, 58% reported that the urinary continence returned to the pretreatment levels and 25% reported a minor decrease in the continence from the baseline at 12-months of follow-up. Erections sufficient for intercourse varied from 44% to 75% at the baseline to 55% to 100% at 12-months of follow-up across all the studies. Conclusion: IRE, as a focal therapy, shows promising results with minimal complications and reasonably effective oncological control, but the data comparing it to the standard of care is still lacking. Future research should focus on randomized definitive comparisons between IRE, radical prostatectomy, and radiation therapy.

Irreversible Electroporation of the Hepatobiliary System: Current Utilization and Future Avenues.

Liver cancer remains a leading cause of cancer-related deaths worldwide despite numerous advances in treatment. While surgical resection remains the gold standard for curative treatment, it is only possible for a minority of patients. Thermal ablation is an effective option for the treatment of smaller tumors; however, its use is limited to tumors that are not located in proximity to sensitive structures due to the heat sink effect and the potential of thermal damage. Irreversible electroporation (IRE) is a non-thermal ablative modality that can deliver targeted treatment and the effective destruction of tumors that are in close proximity to or even surrounding vascular or biliary ducts with minimal damage to these structures. IRE produces short pulses of high-frequency energy which opens pores in the lipid bilayer of cells leading to apoptosis and cell death. IRE has been utilized clinically for over a decade in the treatment of liver cancers with multiple studies documenting an acceptable safety profile and high efficacy rates.

Safety and Efficacy of Percutaneous Liver Microwave Ablation Using a Fully Water-Cooled Choke Ring Antenna: First Multicenter Clinical Report.

INTRODUCTION: The safety and efficacy of a microwave ablation (MWA) system for the liver with novel technologies in field control, antenna cooling through the inner part of the choke ring, and dual temperature monitoring were evaluated in this multicenter retrospective study. MATERIAL AND METHODS: Ablation characteristics and efficacy were assessed on follow-up imaging (computed tomography or magnetic resonance imaging). Safety was evaluated according to CTCAE classification. RESULTS: Eighty-seven liver tumors (65 metastases and 22 hepatocellular carcinomas) measuring 17.8 ± 7.9 mm were treated in 68 patients. Ablation zones measured 35.6 ± 11 mm in longest diameter. The coefficients of variation of the longest and shortest ablation diameters were 30.1% and 26.4%, respectively. The mean sphericity index of the ablation zone was 0.78 ± 0.14. Seventy-one ablations (82%) had a sphericity index above 0.66. At 1 month, all tumors demonstrated complete ablation with margins of 0-5 mm, 5-10 mm, and greater than 10 mm achieved in 22%, 46%, and 31% of tumors, respectively. After a median follow-up of 10 months, local tumor control was achieved in 84.7% of treated tumors after a single ablation and in 86% after one patient received a second ablation. One grade 3 complication (stress ulcer) occurred, but was unrelated to the procedure. Ablation zone size and geometry in this clinical study were in accordance with previously reported in vivo preclinical findings. CONCLUSION: Promising results were reported for this MWA device. The high spherical index, reproducibility, and predictability of the resulting treatment zones translated to a high percentage of adequate safety margins, providing good local control rate.

Causes of Death Among Patients With Initially Inoperable Pancreas Cancer After Induction Chemotherapy and Ablative 5-fraction Stereotactic Magnetic Resonance Image Guided Adaptive Radiation Therapy.

Purpose: Nearly all patients with pancreatic ductal adenocarcinoma (PDAC) eventually die of progressive cancer after exhausting treatment options. Although distant metastases (DMs) are a common cause of death, autopsy studies have shown that locoregional progression may be directly responsible for up to one-third of PDAC-related deaths. Ablative stereotactic magnetic resonance-guided adaptive radiation therapy (A-SMART) is a novel treatment strategy that appears to improve locoregional control compared with nonablative radiation therapy, potentially leading to improved overall survival. Methods and Materials: A single-institution retrospective analysis was performed of patients with nonmetastatic inoperable PDAC treated between 2018 to 2020 using the MRIdian Linac with induction chemotherapy, followed by 5-fraction A-SMART. We identified causes of death that occurred after A-SMART. Results: A total of 62 patients were evaluated, of whom 42 (67.7%) had died. The median follow-up time was 18.6 months from diagnosis and 11.0 months from A-SMART. Patients had locally advanced (72.6%), borderline resectable (22.6%), or resectable but medically inoperable PDAC (4.8%). All patients received induction chemotherapy, typically leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride, and oxaliplatin (69.4%) or gemcitabine/nab-paclitaxel (24.2%). The median prescribed dose was 50 Gy (range, 40-50), corresponding to a median biologically effective dose of 100 Gy10. Post-SMART therapy included surgery (22.6%), irreversible electroporation (9.7%), and/or chemotherapy (51.6%). Death was attributed to locoregional progression, DMs, cancer-related cachexia/malnutrition, surgery/irreversible electroporation complications, other reasons not due to cancer progression, or unknown causes in 7.1%, 45.2%, 11.9%, 9.5%, 11.9%, and 14.3% of patients, respectively. Intra-abdominal metastases of the liver and peritoneum were responsible for 84.2% of deaths from DMs. Conclusions: To our knowledge, this is the first contemporary evaluation of causes of death in patients with PDAC receiving dose-escalated radiation therapy. We demonstrated that the predominant cause of PDAC-related death was from liver and peritoneal metastases; therefore novel treatment strategies are indicated to address occult micrometastatic disease at these sites.

Induction Chemotherapy and Ablative Stereotactic Magnetic Resonance Image-Guided Adaptive Radiation Therapy for Inoperable Pancreas Cancer.

Background: Radiation therapy (RT) dose for inoperable pancreatic ductal adenocarcinoma (PDAC) has historically been non-ablative to avoid injuring gastrointestinal (GI) organs at risk (OARs). Accruing data suggest that dose escalation, in select patients, may significantly improve clinical outcomes. Early results of ablative stereotactic magnetic resonance image-guided adaptive radiation therapy (A-SMART) have been encouraging, although long-term outcomes are not well understood. Methods: A single institution retrospective analysis was performed of inoperable non-metastatic PDAC patients who received induction chemotherapy then 5-fraction A-SMART on a 0.35T-MR Linac from 2018-2021. Results: Sixty-two patients were evaluated with a median age of 66 years (range 35-91) and nearly all achieved Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (96.8%). Locally advanced disease was common (72.6%), otherwise borderline resectable (22.6%), or medically inoperable (4.8%). All received induction chemotherapy for a median 4.2 months (range, 0.2-13.3) most commonly FOLFIRINOX (n=43; 69.4%). Median prescribed dose was 50 Gy (range 40-50); median biologically effective dose (BED10) was 100 Gy10. The median local control (LC), progression-free survival (PFS), and overall survival (OS) from diagnosis were not reached, 20 months, and 23 months, respectively. Also, 2-year LC, PFS, and OS were 68.8%, 40.0%, and 45.5%, respectively. Acute and late grade 3+ toxicity rates were 4.8% and 4.8%, respectively. Conclusions: To our knowledge, this is the largest series of induction chemotherapy followed by ablative 5-fraction SMART delivered on an MR Linac for inoperable PDAC. The potential for this novel treatment strategy is to achieve long-term LC and OS, compared to chemotherapy alone, and warrants prospective evaluation.

Irreversible electroporation for colorectal cancer liver metastasis: a review.

Irreversible electroporation (IRE) ablation is gaining popularity over the last decade as a nonthermal alternative to thermal ablation technologies such as radiofrequency ablation (RFA) and Microwave ablation (MWA). This review serves as a practical guide for applying IRE to colorectal cancer liver metastases (CRLM) for interventional radiologists, oncologists, surgeons, and anesthesiologists. It covers patient selection, procedural technique, anesthesia, imaging, and outcomes.

Radioembolization of Secondary Hepatic Malignancies.

Cancer has become the leading cause of mortality in America, and the majority of patients eventually develop hepatic metastasis. As liver metastases are frequently unresectable, the value of liver-directed therapies, such as transarterial radioembolization (TARE), has become increasingly recognized as an integral component of patient management. Outcomes after radioembolization of hepatic malignancies vary not only by location of primary malignancy but also by tumor histopathology. This article reviews the outcomes of TARE for the treatment of metastatic colorectal cancer, metastatic breast cancer, and metastatic neuroendocrine tumors, as well as special considerations when treating metastatic disease with TARE.

Consensus Guidelines for the Definition of Time-to-Event End Points in Image-guided Tumor Ablation: Results of the SIO and DATECAN Initiative.

There is currently no consensus regarding preferred clinical outcome measures following image-guided tumor ablation or clear definitions of oncologic end points. This consensus document proposes standardized definitions for a broad range of oncologic outcome measures with recommendations on how to uniformly document, analyze, and report outcomes. The initiative was coordinated by the Society of Interventional Oncology in collaboration with the Definition for the Assessment of Time-to-Event End Points in Cancer Trials, or DATECAN, group. According to predefined criteria, based on experience with clinical trials, an international panel of 62 experts convened. Recommendations were developed using the validated three-step modified Delphi consensus method. Consensus was reached on when to assess outcomes per patient, per session, or per tumor; on starting and ending time and survival time definitions; and on time-to-event end points. Although no consensus was reached on the preferred classification system to report complications, quality of life, and health economics issues, the panel did agree on using the most recent version of a validated patient-reported outcome questionnaire. This article provides a framework of key opinion leader recommendations with the intent to facilitate a clear interpretation of results and standardize worldwide communication. Widespread adoption will improve reproducibility, allow for accurate comparisons, and avoid misinterpretations in the field of interventional oncology research. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Liddell in this issue.

Multicenter randomized controlled trial and registry study to assess the safety and efficacy of the NanoKnife® system for the ablation of stage 3 pancreatic adenocarcinoma: overview of study protocols.

BACKGROUND: Irreversible electroporation (IRE) is a local ablation technique utilizing high voltage, low energy direct current to create nanopores in cell membrane which disrupt homeostasis and leads to cell death. Previous reports have suggested IRE may have a role in treating borderline resectable and unresectable Stage 3 pancreatic tumors. METHODS: Patients with Stage 3 pancreatic ductal adenocarcinoma (PDAC) will be enrolled in either a randomized, controlled, multicenter trial (RCT) or a multicenter registry study. Subjects enrolled in the RCT must have no evidence of disease progression after 3 months of modified FOLFIRINOX (mFOLFIRINOX) treatment prior to being randomization to either a control or IRE arm. Post-induction and post-IRE treatment for the control and IRE arms, respectively, will be left to the discretion of the treating physician. The RCT will enroll 528 subjects with 264 per arm and include up to 15 sites. All subjects will be followed for at least 24 months or until death. The registry study will include two cohorts of patients with Stage 3 PDAC, patients who received institutional standard of care (SOC) alone and those treated with IRE in addition to SOC. Both cohorts will be required to have undergone at least 3 months of SOC without progression prior to enrollment. The registry study will enroll 532 patients with 266 patients in each arm. All patients will be followed for at least 24 months or until death. The primary efficacy endpoint for both studies will be overall survival (OS). Co-primary safety endpoints will be 1) time from randomization or enrollment in the registry to death or new onset of Grade 4 adverse event (AE), and (2 high-grade complications defined as any AE or serious AE (SAE) with a CTCAE v5.0 grade of 3 or higher. Secondary endpoints will include progression-free survival, cancer-related pain, quality of life, and procedure-related pain for the IRE arm only. DISCUSSION: These studies are intended to provide Level 1 clinical evidence and real-world data demonstrating the clinical utility and safety of the use of IRE in combination with chemotherapy in patients with Stage 3 PDAC. TRIAL REGISTRATION: Clinicaltrials.gov NCT03899636 and NCT03899649. Registered April 2, 2019. Food and Drug Administration (FDA) Investigational Device Exemption (IDE) trial G180278 approved on May 3, 2019.

Ablation in Pancreatic Cancer: Past, Present and Future.

The insidious onset and aggressive nature of pancreatic cancer contributes to the poor treatment response and high mortality of this devastating disease. While surgery, chemotherapy and radiation have contributed to improvements in overall survival, roughly 90% of those afflicted by this disease will die within 5 years of diagnosis. The developed ablative locoregional treatment modalities have demonstrated promise in terms of overall survival and quality of life. In this review, we discuss some of the recent studies demonstrating the safety and efficacy of ablative treatments in patients with locally advanced pancreatic cancer.

Irreversible Electroporation for Hepatic Tumors: Protocol Standardization Using the Modified Delphi Technique.

PURPOSE: A consensus study of panelists was performed to provide a uniform protocol regarding (contra) indications, procedural parameters, perioperative care, and follow-up of irreversible electroporation (IRE) for the treatment of hepatic malignancies. MATERIALS AND METHODS: Interventional radiologists who had 2 or more publications on IRE, reporting at least 1 patient cohort in the field of hepatobiliary IRE, were recruited. The 8 panelists were asked to anonymously complete 3 iterative rounds of IRE-focused questionnaires to collect data according to a modified Delphi technique. Consensus was defined as having reached 80% or greater agreement. RESULTS: Panel members' response rates were 88%, 75%, and 88% in rounds 1, 2, and 3, respectively; consensus was reached on 124 of 136 items (91%). Percutaneous or intraoperative hepatic IRE should be considered for unresectable primary and secondary malignancies that are truly unsuitable for thermal ablation because of proximity to critical structures. Absolute contraindications are ventricular arrhythmias, cardiac stimulation devices, and congestive heart failure of New York Heart Association class 3 or higher. A metal stent outside the ablation zone should not be considered a contraindication. For the only commercially available IRE device, the recommended settings are an inter-electrode distance of 10-20 mm and an exposure length of 20 mm. After 10 test pulses, 90 treatment pulses of 1500 V/cm should be delivered continuously, with a pulse length of 70-90 µs. The first post-procedural follow-up should take place 1 month after IRE and thereafter every 3 months, using cross-sectional imaging plus tumor marker assessment. CONCLUSIONS: This article provides recommendations, created by a modified Delphi consensus study, regarding patient selection, workup, procedure, and follow-up of IRE treatment for hepatic malignancies.

Clinical predictors of arterial extravasation, rebleeding and mortality following angiographic interventions in gastrointestinal bleeding.

BACKGROUND AND AIMS: The aim of this study was to identify clinical and imaging predictors of arterial extravasation, post embolization rebleeding and 30-day mortality in gastrointestinal (GI) bleeding. METHOD: This retrospective study included 114 patients who underwent angiography for upper or lower GI bleeding. Multivariate logistic regression was used to identify clinical and imaging predictors. RESULTS: Angiography demonstrated arterial extravasation in 22 patients (19%) and embolization was performed in 48 (42%) patients including prophylactic embolization in 26 (56%). Fall in hemoglobin level from baseline was an independent predictor of arterial extravasation with 65% increased odds for every unit drop (OR 1.65, 95%CI 1.13-2.40, p=0.01). Age <60 years was a negative predictor of rebleed within 30-days (OR 0.94, 95%CI 0.89-1.00, p=0.04). Patients with a history of malignancy were more likely to rebleed (OR 4.4, 95%CI 1.06-18.36, p=0.04). Hemodynamic instability prior to angiography (OR 13.22, 95%CI 1.65-106.07, p=0.02), history of malignancy (OR 1.36, 95%CI 1.49-10.49, p=0.01), number of units of platelets transfused (OR 1.42, 95%CI 1.02-1.97, p=0.04) and rebleed after angiography (OR 46.8, 95%CI 4.80-456.14, p<0.01) were predictors of 30-day mortality. Prophylactic embolization was not a predictor of rebleed or 30-day mortality. CONCLUSIONS: This paper identified important clinical predictors of arterial extravasation, rebleed and 30-day mortality in GI bleedings, which will assist in patient selection and help to improve the overall angiographic management of GI bleeding.

Ultrasound-Assisted Catheter-Directed Thrombolysis for Submassive Pulmonary Embolism.

PURPOSE: Catheter-directed thrombolysis (CDT) is a relatively new therapy for pulmonary embolism that achieves the superior clot resolution compared to systemic thrombolysis while avoiding the high bleeding risk intrinsically associated with that therapy. In order to examine the efficacy and safety of CDT, we conducted a retrospective cohort study of patients undergoing ultrasound-assisted CDT at our institution. METHODS: The charts of 30 consecutive patients who underwent CDT as a treatment of pulmonary embolism at our institution were reviewed. Risk factors for bleeding during thrombolysis were noted. Indicators of the right heart strain on computed tomography and echocardiogram, as well as the degree of pulmonary vascular obstruction, were recorded before and after CDT. Thirty-day mortality and occurrence of bleeding events were recorded. RESULTS: Nine (30%) patients had 3 or more minor contraindications to thrombolysis and 14 (47%) had major surgery in the month prior to CDT. Right ventricular systolic pressure and vascular obstruction decreased significantly after CDT. There was a significant decrease in the proportion of patients with right ventricular dilation or hypokinesis. Decrease in pulmonary vascular obstruction was associated with nadir of fibrinogen level. No patients experienced major or moderate bleeding attributed to CDT. CONCLUSION: Catheter-directed thrombolysis is an effective therapy in rapidly alleviating the right heart strain that is associated with increased mortality and long-term morbidity in patients with pulmonary embolism with minimal bleeding risk. Catheter-directed thrombolysis is a safe alternative to systemic thrombolysis in patients with risk factors for bleeding such as prior surgery. Future studies should examine the safety of CDT in patients with contraindications to systemic thrombolysis.

Transarterial embolization of a hyperfunctioning aldosteronoma in a patient with bilateral adrenal nodules.

Primary hyperaldosteronism often results in resistant hypertension and hypokalemia, which may lead to cardiovascular and cerebrovascular complications. Although surgery is first line treatment for unilateral functioning aldosteronomas, minimally invasive therapies may be first line for certain patients such as those who cannot tolerate surgery. We present a case of transarterial embolization (TAE) of an aldosteronoma. The patient presented with a cerebrovascular accident, and subsequently developed uncontrolled hypertension, hypokalemia, and a myocardial infarction. Following TAE, potassium returned to normal levels and blood pressure control was improved. There were no postoperative complications. TAE thus may be a safe and effective alternative to surgery.

Role of Urodynamic Studies in Management of Benign Prostatic Obstruction: A Guide for Interventional Radiologists.

Urodynamic testing is the most accurate representation of bladder outlet obstruction physiology. As prostate artery embolization becomes an increasingly common therapy for benign prostatic obstruction, knowledge of urodynamic assessment and reports can assist the interventional radiologist in selecting appropriate patients. This review summarizes the role of urodynamic studies in the management of benign prostatic obstruction, including patient selection, interpretation of urodynamic studies, and their potential to predict patient outcomes.