Objective : Robotically-assisted sonic therapy (RAST) is the automated treatment of a defined volume of tissue utilizing histotripsy, the first non-thermal, non-ionizing, non-invasive ablation modality. To date RAST has been successfully applied in pre-clinical porcine liver models. A Phase I trial was initiated to evaluate the safety and efficacy of RAST in patients with liver tumors.
Methods : The phase I, open-label, non-randomized trial had a primary endpoint of technical success, defined as creation of an ablation zone per the planned volume as assessed by MRI 1 day post-procedure. Secondary endpoints included safety (adverse events graded per CTCAE v4.0), local tumor progression, involution of the ablation zone, and analgesic requirements. All RAST procedures (VORTX RX system, Histosonics, Inc. Ann Arbor, MI) were performed with the patient under general anesthesia. Follow-up MRI, laboratory draws, and clinical visit were planned at 1 day, 1 week, 1 month, and 2 months.
Results : To date 5 patients (mean 59, range 46 to 87 years) have had a single tumor treated under the protocol. All patients had multifocal liver malignancy with primary disease of colorectal metastases in 3 patients, hepatocellular carcinoma in 1 patient, and breast cancer in 1 patient. Average targeted tumor largest diameter is 1.5 cm (range 0.5 to 2.3 cm) and tumor volume is 2.5 mL (range 0.1 to 6.4 mL). Planned treatment volumes averaged 10.5 mL (range 7.5 to 16.3 mL). All procedures were successfully completed with average energy delivery time of 23.0 minutes (range 15 to 34 minutes) and achieved volume of 13.0 mL (range 9.2 to 20.2 mL). Achieved volume was within 25% of planned volume in each case, with larger volume attributable to ablation elongation in the cranio-caudal dimension due to respiratory motion. The axial dimensions of each resultant ablation zone averaged within 0.1 cm of planned (range 0 to 0.2 cm). Craniocaudal dimensions averaged 0.5 cm larger than planned (range 0.2 to 0.9 cm). Median clinical follow-up is 8 weeks (range 8-24 weeks) and imaging follow-up is 8 weeks (range 4-8 weeks). Contraction of the diameter and volume of the ablation zone averaged 15.0% and 36.7% at 1 week, 34.6% and 71.9% at 1 month, and 50.0% and 87.3% at 2 months respectively. One patient was admitted to the hospital 22 days post-procedure with Grade 4 hypocalcemia and hypomagnesemia, both attributed to underlying Crohn’s disease by the admitting service. A second patient was admitted to the hospital 32 days post-procedure with Grade 2 fever which was treated supportively. No device related adverse event has occurred. The ablation created for the 0.5 cm tumor was mis-targeted immediately adjacent to this tumor due to poor ultrasound visualization and will undergo a second procedure for local control. No definitive local tumor progression has occurred. The patient with multifocal hepatocellular carcinoma had decreasing alpha-fetoprotein at the 1 and 2 month timepoints when compared with baseline.
Conclusions : Preliminary results of a Phase I trial demonstrate that RAST can create a planned ablation volume without significant device-related adverse event. Elongation of the ablation zone in the craniocaudal plane and relatively rapid involution of the ablation zone are consistent with previous laboratory work and areas for future research. Short term local control is noted in appropriately targeted tumors.