Abstract
Summary
A novel bipolar cooled radiofrequency ablation probe, optimised for bone metastases applications, is shown in two preclinical models to offer a safe and minimally invasive treatment option that can ablate large tissue volumes and preserve the regenerative ability of bone.
Introduction
Use of radiofrequency ablation (RFA) in treating of skeletal metastases has been rising, yet its impact on bone tissue is poorly understood. 2–11 RF treatment induces frictional heating and effectively necrotises tissue in a local and minimally invasive manner.1 Bipolar cooled RF (BCRF) is a significant improvement to conventional RF whereby larger regions can be safely treated, protecting sensitive neighbouring tissues from thermal effects. This study aimed to evaluate the safety and feasibility of a novel bipolar RFA probe to create large contained lesions within healthy pig vertebrae and its determine its effects on bone and tumour cells in a rabbit long bone tumour model.
Methods
Following a pre-treatment MRI, a BCRF probe was placed transpedicularly into targeted lumbar vertebrae of six Yorkshire pigs. Energy was delivered for 15min at a set temperature of 65°C (n=2 per animal) with a sham control performed at a non-contiguous level (n=1 per animal). Post-treatment neurologic evaluation, MRI and histology were used to characterise the region of effect. Twelve New Zealand White Rabbits received a 200 µl injection of VX2 tumour cells into one femur. On day 14, half of the tumour-bearing and contralateral healthy femora were RF-treated (n=6 per group). RF-treated femora were compared to tumour-bearing and healthy sham groups (n=6 per group) through pre (day 14) and post treatment (day 28) MRI and histology (H&E (for general evaluation), AE1/AE3 (for VX2 tumour cell evaluation), TRAP (for osteoclast evaluation) and TUNEL (for osteocyte evaluation)).
Results
In treated porcine spines there were no neurological complications. MR imaging confirmed a 2cm oval shaped ablative zone. External thermocouple measurements indicated output values in the physiological temperature range suggesting treatment was safely confined within targeted vertebrae. Histological results correlated well with the ablation regions determined using MRI sequences in both models. In rabbit femora, large zones of RF ablation (average volume 12.9±5.5 cm3) extended beyond the femur cortex (corresponding to the probe design for human use) into the surrounding soft tissue. The RFA-treated tumour-involved specimens demonstrated a significant reduction in tumour volume compared to sham femora, however a small number of viable tumour cells remained within the ablation volume. Newly formed trabecular structures were also seen in all treated femora. TRAP staining demonstrated a significant reduction in osteoclast number post-RFA in both the tumour-involved and healthy groups. TUNEL staining revealed areas of patchy cortical osteocyte necrosis within the ablation zone.
Discussion/Conclusions
The large histologic region of effect created by RFA was consistent with MRI findings in both models. Treatment was contained in the porcine vertebrae without collateral damage to neighbouring sensitive structures. In the femora, while osteoclasts were found to be very susceptible to RFA, a small number of tumour cells and osteocytes in the treated regions remained viable. As the treatment zone did not encompass the full extent of the intramedullary lesions, it is possible that the sporadic VX2 cell viability may be explained by local tumour cell migration. Limited destruction of healthy osteocytes by RFA may be desirable in restoring bone health.
