Large-Volume Hyperthermia for Safe and Cost-Effective Targeted Drug Delivery Using a Clinical Ultrasound-Guided Focused Ultrasound Device.

Lyso-thermosensitive liposomes (LTSLs) are specifically designed to release chemotherapy agents under conditions of mild hyperthermia. Preclinical studies have indicated that magnetic resonance (MR)-guided focused ultrasound (FUS) systems can generate well-controlled volumetric hyperthermia using real-time thermometry. However, high-throughput clinical translation of these approaches for drug delivery is challenging, not least because of the significant cost overhead of MR guidance and the much larger volumes that need to be heated clinically. Using an ultrasound-guided extracorporeal clinical FUS device (Chongqing HAIFU, JC200) with thermistors in a non-perfused ex vivo bovine liver tissue model with ribs, we present an optimised strategy for rapidly inducing (5-15 min) and sustaining (>30 min) mild hyperthermia (ΔT <+4°C) in large tissue volumes (≤92 cm3). We describe successful clinical translation in a first-in-human clinical trial of targeted drug delivery of LTSLs (TARDOX: a phase I study to investigate drug release from thermosensitive liposomes in liver tumours), in which targeted tumour hyperthermia resulted in localised chemo-ablation. The heating strategy is potentially applicable to other indications and ultrasound-guided FUS devices.

Ultrasound-Guided High Intensity Focused Ultrasound Ablation for Symptomatic Uterine Fibroids: Preliminary Clinical Experience.

OBJECTIVE: To evaluate the middle-term efficacy and complications of ultrasound-guided high intensity focused ultrasound (USgHIFU) for the treatment of symptomatic uterine fibroids in an NHS population. METHODS: A prospective observational single-center study at a single university hospital in Oxford, UK. Patients with symptomatic uterine fibroids who declined standard surgical/radiological intervention and were referred to the HIFU unit were considered for USgHIFU treatment. Clinical evaluation, adverse event monitoring, uterine fibroid symptoms and health-related quality of life questionnaire (UFS-QOL) and contrast-enhanced pelvic magnetic resonance imaging (MRI) were performed before and at regular intervals after treatment to assess patient outcome. RESULTS: 12 of 22 referred patients underwent one session of USgHIFU ablation of 14 fibroids overall and received a two-year follow-up. No serious adverse events were reported, but a second-degree skin burn was observed in one patient who had a surgical scar from a previous caesarean section. Mean symptom severity scores (SSS-QOL) improved significantly from 56.5 ±â€Š29.1 (SD) at baseline to 33.4 ±â€Š23.3 (p < 0.01) at three months, 45.0 ±â€Š35.4 (p < 0.05) at one year and 40.6 ± 32.7 (p < 0.01) at two years post-treatment. The mean non-perfused volume ratio was 67.7 ±â€Š39.0 % (SD) in the treated fibroids (n = 14) within three months of treatment. The mean volume reduction rates of the treated fibroids were 23.3 ± 25.5 % (SD) at 3 months post-treatment (p < 0.01, n = 14), 49.3 ± 23.7 % at 12 months (p < 0.05, n = 8), and 51.9 ±â€Š11.1 % at 24 months (p < 0.005, n = 8). CONCLUSION: This study demonstrates the clinical efficacy of USgHIFU ablation of uterine fibroids and the low risk of complications. We believe that this noninvasive approach may offer an alternative therapy for women with symptomatic uterine fibroids. While HIFU is fast becoming the standard of care for fibroid ablation in other countries, to our knowledge, this study is the first to present clinical experience of US-guided HIFU ablation of symptomatic uterine fibroids in an NHS population. PLAIN LANGUAGE SUMMARY: High intensity focused ultrasound (HIFU) can be used for the noninvasive ablation of symptomatic uterine fibroids, and MR-guided treatment has already gained FDA approval. Ultrasound-guided HIFU has the advantage of offering practicalities in anesthesia and considerable cost-savings over MR-guided treatments. In this prospective study we have demonstrated the middle-term efficacy and favorable safety profile of ultrasound-guided HIFU for the treatment of symptomatic uterine fibroids for the first time in an NHS population.

Extracorporeal high intensity focused ultrasound for renal tumours: a 3-year follow-up.

OBJECTIVE: To determine whether primary extracorporeal high-intensity focused ultrasound (HIFU) is safe, feasible and effective for managing small renal tumours. PATIENTS AND METHODS: Although surgery currently remains the standard treatment for localized renal cell carcinoma (RCC), the increasing incidence of small renal cancers has led to a shift towards nephron-sparing surgery, with associated morbidity in 20-25% of cases, and minimally invasive ablative therapies present an alternative management. HIFU results in 'trackless' homogenous tissue ablation and when administered via an extracorporeal device, is entirely noninvasive. The study comprised 17 patients (mean tumour size 2.5 cm) with radiologically suspicious renal tumours who underwent extracorporeal HIFU using the Model-JC System (Chongqing HAIFU™, China), under general anaesthesia with one overnight hospital stay. Real-time diagnostic ultrasonography was used for targeting and monitoring. Patients were followed with a clinical review and gadolinium-enhanced magnetic resonance imaging at 12 days and every 6 months for a mean of 36 months. The outcomes measures were patient morbidity and oncological efficacy of HIFU treatment. RESULTS: Of the 17 patients, 15 were treated according to protocol; two procedures were abandoned due to intervening bowel. There were no major complications related to HIFU. Radiological evidence of ablation was apparent at 12 days in seven of the 15 patients. Before the 6-month follow-up one patient had surgery due to persisting central enhancement. Fourteen patients were evaluated at the 6-month follow-up; eight tumours had involuted (mean 12% decrease in tumour area). Four patients had irregular enhancement on imaging and had alternative therapies. Ten patients remain on follow-up at a mean (range) of 36 (14-55) months after HIFU (mean 30% decrease in tumour area). There was central loss of enhancement in all. CONCLUSIONS: Renal HIFU achieves stable lesions in two-thirds of patients, with minimal morbidity, and might be appropriate in selected cases. Further trials with accurate histological follow-up are essential to fully evaluate this novel technique.