Krimsky, William

Background: The AFFINITY trial (NCT05890872) is a prospective, non-randomized, open-label, single-arm study evaluating the safety, immunological impact, and preliminary efficacy of Aliya pulsed electric field ablation in patients with solid tumors. Thirty-one patients were enrolled; thirty received lung lesion ablation prior to continuation on standard-of-care treatment. This manuscript reports six-month local control outcomes and immunological response characteristics. Radiological outcomes were assessed using a modified RECIST 1.1, and immunological impact was evaluated via changes in peripheral blood immunocyte populations and detection of immunoglobulins (Ig) to tumor-associated antigens in serum post-ablation. Methods: Twenty-eight patients underwent radiological assessment of ablated lesions at approximately 1-, 3-, and 6-month post-ablation to evaluate local control. Peripheral blood was collected for immune monitoring using flow cytometry and to detect IgG responses to biopsy-specific and tumor-associated antigens. Results: At 6 months, two cohorts emerged: 12 received ablation only, and 16 received ablation plus systemic and/or focal therapies (radiotherapy or second ablation). In the ablation-only group, imaging showed local control in all ablated lesions (8/12 SD, 4/12 PR), suggesting local efficacy without systemic therapy in those patients. Immunophenotyping showed dynamic changes in circulating immune cells, including T and B cell activation. A subset also exhibited modulation of tumor antigen-specific IgG, indicating a systemic humoral response. Conclusions: This analysis provides preliminary evidence that this form of ablation may promote local tumor control and modulate systemic immune function. These findings support the immunogenic potential of this specialized energy and warrant further investigation. Extended 12-month data for the full cohort will be reported in a future manuscript.

Background: To evaluate the safety of Aliya pulsed electric field (PEF) ablation in lung lesions at the time of biopsy before first-line standard of care (SOC) therapy in patients with metastatic cancer. Methods: Eligible patients requiring diagnostic biopsy for suspected metastatic lung lesions were enrolled. Treatment-naive lesions ≤5 cm were PEF ablated bronchoscopically or percutaneously. Procedure and/or device-related adverse events (AE) or serious adverse events (SAEs) and their effects on subsequent therapy were assessed from PEF ablation through 30 days. Results: Forty-four lesions from 30 enrolled patients were ablated using PEF with 3-dimensional image guidance immediately following diagnostic biopsy under general anesthesia. Ninety percent (27/30) were ablated bronchoscopically with robotic navigation. One to 3 lesions (range: 0.4 to 2.4 cm longest diameter) were ablated per patient, including 17 within 1 cm of the pleura or a fissure. One procedure-related SAE (pneumothorax) occurred at the time of percutaneous biopsy and PEF ablation and resolved without sequelae. No AE impacted planned therapy initiation. Limited changes to the lung parenchyma in and around the PEF ablation zone were observed on CT scans 30 days post-PEF ablation. Conclusion: This study demonstrates PEF ablation of lung lesions at the time of diagnostic biopsy is safe. One PEF-related SAE occurred within 30 days of PEF and resolved without sequelae. Ablation adjacent to sensitive structures was feasible, safe, and without impact on subsequent therapy.

Abstract Rationale Chronic bronchitis (CB) is characterized by productive cough with excessive mucus production, resulting in quality-of-life impairment and increased exacerbation risk. Bronchial rheoplasty uses an endobronchial catheter to apply nonthermal pulsed electrical fields to the airways. Preclinical studies have demonstrated epithelial ablation followed by regeneration of normalized epithelium. Objectives To evaluate the feasibility, safety, and initial outcomes of bronchial rheoplasty in patients with CB. Methods Pooled analysis of two separate studies enrolling 30 patients undergoing bilateral bronchial rheoplasty was conducted. Follow-up through 6 months (primary outcome) and 12 months included assessment of adverse events, airway histology, and changes in symptoms using the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test and St. George’s Respiratory Questionnaire (SGRQ). Measurements and Main Results: Bronchial rheoplasty was performed in all 30 patients (63% male; mean [SD] age, 67 [7.4]; mean [SD] postbronchodilator FEV1, 65% [21%]; mean [SD] COPD Assessment Test score 25.6 [7.1]; mean [SD] SGRQ score, 59.6 [15.3]). There were no device-related and four procedure-related serious adverse events through 6 months, and there were none thereafter through 12 months. The most frequent nonserious, device- and/or procedure-related event through 6 months was mild hemoptysis in 47% (14 of 30) patients. Histologically, the mean goblet cell hyperplasia score was reduced by a statistically significant amount (P < 0.001). Significant changes from baseline to 6 months in COPD Assessment Test (mean, −7.9; median, −8.0; P = 0.0002) and SGRQ (mean, −14.6; median, −7.2; P = 0.0002) scores were observed, with similar observations through 12 months. Conclusions This study provides the first clinical evidence of the feasibility, safety, and initial outcomes of bronchial rheoplasty in symptomatic patients with CB. Clinical trial registered with www.anzctr.org.au (ACTRN 12617000330347) and clinicaltrials.gov (NCT 03107494).