Browsing by Author "Hall, Timothy"

Now showing 1 - 2 of 2
  • Thumbnail Image
    First-In-DOg HISTotripsy for Intracranial Tumors Trial: The FIDOHIST Study
    Vezza, Christina; Ruger, Lauren; Langman, Maya; Vickers, Elliana; Prada, Francesco; Sukovich, Jonathan; Hall, Timothy; Xu, Zhen; Parker, Rell L.; Vlaisavljevich, Eli; Rossmeisl, John H. (SAGE Publications, 2024-10-17)
    Objective: Brain tumors represent some of the most treatment refractory cancers, and there is a clinical need for additional treatments for these tumors. Domesticated dogs are the only other mammalian species which commonly develop spontaneous brain tumors, making them an ideal model for investigating novel therapies. Histotripsy is a non-thermal ultrasonic ablation method that emulsifies tissue through acoustic cavitation. The primary objectives of this prospective study were to assess the feasibility and safety of histotripsy to ablate naturally occurring canine brain tumors. Secondary endpoints included characterization of magnetic resonance imaging (MRI) responses to histotripsy treatment, and exploratory immunogenomic tumor response analyses. Methods: The study design utilized a treat and resect paradigm, where tumors were approached using craniotomy, partially ablated with histotripsy delivered through the cranial defect, imaged with MRI, and then resected. Dogs were evaluated with clinical, brain MRI, immunopathologic, and genomic examinations before treatment, intraoperatively, and 1, 14, and 42 days post-treatment. Here we report the results of the three dogs with meningiomas, all of which were treated with a custom eight element 1 MHz histotripsy transducer at a pulse repetition frequency of 100 Hz and a treatment dosage of 400 pulses/point. Results: Histotripsy was successfully delivered to all dogs, resulting in histopathologic evidence of ablations that were sharply demarcated from untreated tumor, with measured treatments approximating planned volumes in 2/3 dogs. One dog experienced an adverse event consisting of transient cerebral edema that was possibly attributable to histotripsy. Histotripsy ablations could be grossly visualized and identified on MRI, with features consistent with hemorrhage and necrosis. Significant expression or upregulation of the damage associated molecular pattern HMGB1, cytokine-cytokine receptor interaction, and NF-κb signaling pathways were observed in histotripsy treated tumors. Conclusion: Ablation of canine meningiomas with histotripsy through an open cranial window was feasible and clinically well tolerated.
  • Thumbnail Image
    First-in-man histotripsy of hepatic tumors: the THERESA trial, a feasibility study
    Vidal-Jove, Joan; Serres, Xavier; Vlaisavljevich, Eli; Cannata, Jon; Duryea, Alex; Miller, Ryan; Merino, Xavier; Velat, Manuela; Kam, Yossi; Bolduan, Ryan; Amaral, Joseph; Hall, Timothy; Xu, Zhen; Lee, Fred T., Jr.; Ziemlewicz, Timothy J. (Taylor & Francis, 2022-12-31)
    Rationale Current hepatic locoregional therapies are limited in terms of effectiveness and toxicities. Given promising pre-clinical results, a first in-human trial was designed to assess the technical effectiveness and safety profile of histotripsy, a noninvasive, non-thermal, non-ionizing focused ultrasound therapy that creates precise, predictable tissue destruction, in patients with primary and secondary liver tumors. Methods A multicenter phase I trial (Theresa Study) was performed in a single country with 8 weeks of planned follow-up. Eight of fourteen recruited patients were deemed eligible and enrolled in the study. Hepatic histotripsy, was performed with a prototype system (HistoSonics, Inc., Ann Arbor, MI). Eleven tumors were targeted in the 8 patients who all had unresectable end-stage multifocal liver tumors: colorectal liver metastases (CRLM) in 5 patients (7 tumors), breast cancer metastases in 1 (1 tumor), cholangiocarcinoma metastases in 1 (2 tumors), and hepatocellular carcinoma (HCC) in 1 (1 tumor). The primary endpoint was acute technical success, defined as creating a zone of tissue destruction per planned volume assessed by MRI 1-day post-procedure. Safety (device-related adverse events) through 2 months was a secondary endpoint. Results The 8 patients had a median age of 60.4 years with an average targeted tumor diameter of 1.4cm. The primary endpoint was achieved in all procedures. The secondary safety profile endpoint identified no device-related adverse events. Two patients experienced a continuous decline in tumor markers during the eight weeks following the procedure. Conclusions This first-in-human trial demonstrates that hepatic histotripsy effectively destroys liver tissue in a predictable manner, correlating very well with the planned histotripsy volume, and has a high safety profile without any device-related adverse events. Based on these results, the need for more definitive clinical trials is warranted.