Non-invasive Focal Therapy for Osteoid Osteoma

Treatment of Osteoid Osteoma With MR Guided High Intensity Focused Ultrasound

Non-invasive treatment of Osteoid osteoma using MRI guided high-intensity focused ultrasound. This study is designed as an intention-to-treat using a totally non-invasive approach for pain reduction, quality of life improvement and long-term bone restoration. Procedure is performed in a single session using limited amount of acoustic energy to target the osteoid nidus. Treatment will be performed under anesthesia (peripheral or general according to age and lesion position).

Study Overview

• Status: Unknown
• Conditions: Osteoma, Osteoid
• Intervention / Treatment: Device: MR guided High Intensity focused ultrasound

Detailed Description

An osteoid osteoma is a benign, painful musculoskeletal tumor that usually occurs in young males. The standard of care in the United States is computed tomography (CT)-guided radiofrequency ablation, a minimally invasive percutaneous procedure, with clinical success rates ranging between 85% and 98%.

Percutaneous or surgical therapy can lead to non-negligible side-effects and limited efficacy for pediatric population or young adults with osteoid osteoma. We investigate whether selective focal ablation of osteoid lesions can reduce this treatment burden without compromising long-term clinical efficacy.

Treatments will be performed using a 3.0-T MR unit (Discovery MR 750; GE Medical Systems, Milwaukee,Wis) featuring a Conformité Européenne-approved ExAblate MR-guided focused ultrasound system (InSightec,Tirat-Carmel, Israel) in which the ultrasound transducer is housed in the patient table. Alignment between the lesion and the transducer will be obtained in each patient by using a moistened gel pad and degassed water for acoustic coupling. This approach avoided air- skin interfaces, which can cause energy reflection and skin burns. After patient positioning, the lesion is localized with MR for treatment by using variably orientated non enhanced T1- and T2-weighted acquisitions. In general, an ideal 90° incidental angle between the planned focused ultrasound path and the lesion, relative to the bone long axis, is obtained or at least approximated. The shortest skin-lesion distance is selected for the beam pathway. Care will be taken to avoid multiple interfaces (skin, muscle, fasciae) as much as possible so as to minimize deflection of the focused ultrasound beam. Each lesion will be manually segmented by the operator to precisely delineate the nidus, skin surface, and cortical surface of the bone. Sensitive areas surrounding the target volumes will also be drawn to limit the energy and prevent unwanted thermal damage. The treatment plan is than calculated automatically by the ExAblate software according to previously acquired parameters, including the energy (in joules), the interval between two sonications, the sonication duration, and the spot size, which are modifiable by the operator. Thereafter, a low-energy sonication test will be performed to confirm the path and correct direction of the ultrasound beam into the target area and to confirm the planned energy dose and the effective dose deployed to the lesion.

The increase in tissue temperature is evaluated by using real-time MR thermometry of phase-difference fast spoiled gradient-echo sequences (proton resonant frequency shift method). The sequences are acquired to provide temperature-dependent images and real-time mapping of the thermal dose on a preferred imaging plane. The proton resonant frequency shift method starts simultaneously with each sonication. Similar to other treatments of bone lesions that use MR-guided focused ultrasound, the temperature increase is determined on the adjacent periskeletal tissue. In fact, proton resonant frequency sequences cannot effectively measure the temperature on the bone surface because of the absence of moving protons in the cortical zone. Thus, MR thermometry reveals a temperature increase, which propagates by conductive processes from the bone to the immediately adjacent soft tissues that respond linearly to an increase in bone temperature, thereby allowing an accurate measure of heating. Portions of periosteum and adjacent tumor that are not fully ablated can be re-treated if deemed necessary. The critical temperature threshold for ablation is set at 65°C in the soft tissues adjacent to the targeted bone structures. Postprocedural care includes evaluation of possible skin burns, monitoring of vital signs for 2 hours after treatment in the MR department, and administration of analgesic and/or antiemetic drugs if requested. Treatment-related adverse events will be recorded as minor or major on the basis of medical severity, additional treatment, and long-term consequences for patients. Treatment will be performed on an outpatient basis in the patients who receive only local and peripheral anesthesia; the patient who receives general anesthesia is usually hospitalized for 24 hours after treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Alessandro Napoli, MD, PhD; Phone Number: 3357718114; Email: alessandro.napoli@uniroma1.it

Study Locations

• Italy
  • Rome, Italy, 00100
    • Recruiting
    • Alessandro Napoli
    • Contact: Alessandro Napoli; Phone Number: +393357718114; Email: alessandro.napoli@uniroma1.it
    • Principal Investigator: Alessandro Napoli, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• clinical and imaging diagnosis of osteoid osteoma
• painful non-vertebral location

Exclusion Criteria:

• general contraindication to MRI
• vertebral location of the lesion
• claustrophobia and prior surgery or RFA are not an absolute exclusion criterion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Osteoid Osteoma; MR guided High Intensity focused ultrasound	Device: MR guided High Intensity focused ultrasound; High Intensity Focused Ultrasound is a totally non-invasive procedure that can destroy tumors transcutaneously; safety and efficacy profile are dramatically increased by the MRI guidance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety - Adverse Events (serious and otherwise)	to assess complications	1 year
Efficacy (Symptoms reduction)	Symptoms reduction	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
nidus vascularization (correlation between nidus vascularization reduction and symptoms relieve)	correlation between nidus vascularization reduction and symptoms relieve	4 years

Collaborators and Investigators

• Sponsor: University of Roma La Sapienza
• Investigators: Principal Investigator: Alessandro napoli, MD, PhD, Sapienza University of Rome, Policlinico Umberto I Hospital

Publications and helpful links

General Publications

• Napoli A, Bazzocchi A, Scipione R, Anzidei M, Saba L, Ghanouni P, Cozzi DA, Catalano C. Noninvasive Therapy for Osteoid Osteoma: A Prospective Developmental Study with MR Imaging-guided High-Intensity Focused Ultrasound. Radiology. 2017 Oct;285(1):186-196. doi: 10.1148/radiol.2017162680. Epub 2017 Jun 7.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Anticipated): June 1, 2015
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: November 19, 2014
• First Submitted That Met QC Criteria: November 24, 2014
• First Posted (Estimate): November 27, 2014

Study Record Updates

• Last Update Posted (Estimate): November 27, 2014
• Last Update Submitted That Met QC Criteria: November 24, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: high intensity focused ultrasound; bone tumor; osteoid osteoma
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Osteoma; Osteoma, Osteoid
• Other Study ID Numbers: OO-MC-MRGFUS-002