E266: Soundwaves of Hope – Exploring the Safety and Feasibility of Focused Ultrasound Ablation with or without Systemic PD-1 Blockade in Advance Solid Tumors

Introduction: Focused ultrasound (FUS) is an ablative therapy with potential to augment the immune response in solid tumors by inducing heat shock proteins, antigen and cytokine release and T cell activation.  This study tested partial thermal FUS ablation in patients with advanced solid tumors +/- systemic PD-1 blockade. We hypothesized that FUS could be safely administered to diverse advanced solid tumors in variable anatomical locations.

Methods:

Study Population: Patients with metastatic solid tumors accessible to FUS who had either exhausted or were ineligible for all FDA-approved treatment were eligible.

Tumor Assessment

Treatment parameters were ascertained via cross-sectional diagnostic imaging and ultrasound. Lesion size, volume, vascularity, and distance to skin and critical structures were measured.

Ablation Parameters:

Thirty-three percent of the tumor volume was targeted with a maximum ablation of 2cc.  FUS was administered with conscious sedation and local anesthetic in a radiology suite. 

The procedure was executed utilizing an Ultrasound-guided High-Intensity Focused Ultrasound (HIFU) device. The probe was positioned over the lesion and the software algorithm defined the safety margin and ablation zone. A series of HIFU pulses were delivered until the predetermined ablation volume was achieved. Parameters were adjusted to create a discernible hyperechoic mark, signifying tissue coagulation and successful energy delivery (Figure 1).

Treatment Metrics and Safety

Treatment time, number of pulses, treatment volumes, total energy delivered, and effective power were recorded, along with safety data utilizing CTCAE 5.0 criteria.   

Results:

Five participants were treated (2020-2023).  Two patients received combination therapy with PD-1 blockade and FUS.  Three patients received FUS alone. Treated lesions included lymph nodes, subcutaneous or intrabdominal metastasis from diverse primary tumor types. 

The median time required for treatment was 7min (range 4-16), number of pulses delivered was 8 (range 4-12), treatment volume 0.8cc (0.5-1), total energy delivered 2.2 (range 1.4-3.9) and effective power 45W (range 34-48).  There were no major toxicities, and all treatment sessions were completed.

Conclusions:

FUS partial ablation of solid tumors is feasible, well tolerated and can safely be combined with systemic PD-1 blockade.  There is potential to employ FUS as a tool to alter the local immune environment and augment innate immune response or systemic therapy outcomes.