Surgeon-performed Ultrasound for Real-time Guidance In Oral Cancer Surgeries - A Multicenter Randomized Controlled Trial

NCT ID: NCT07203911

Last Updated: 2025-10-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-09-15

Study Completion Date

2031-08-31

Brief Summary

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The goal of this clinical trial is to improve the surgical treatment of patients with oral cancer. We will explore whether the use of surgeon performed ultrasound during these surgeries result in better tumor removal. We hypothesize that using intraoperative ultrasound to assist the resection results in more frequent clear surgical margins in oral cancer surgeries compared to standard methods. This improvement is associated with a reduced need for post-operative adjuvant therapies such as radiotherapy and reoperation, lower mortality rates, lower cancer recurrence, and enhanced quality of life for patients undergoing surgery for oral cancer.

Participants will be randomized to either the control or intervention group:

* Control group will receive standard treatment for oral cancer.
* Intervention group will in addition to the standard treatment have surgery performed using ultrasound to guide the resection and evaluate resection margins intraoperatively.

Outcomes:

* Number of free surgical margins between control and intervention group.
* Intraoperative surgeon assessed surgical margins compared to final histology report.
* Dysphagia and quality of life questionnaires.
* Recurrence rates.
* Mortality rates.

All participant will be followed-up at 3 months and 12 months with:

* MDADI dysphagia questionnaire
* EORTC head and neck cancer quality of life questionnaire
* Follow-up on recurrrence and mortality.

Detailed Description

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Background:

Surgery is the primary treatment for early-stage oral cancer, aiming to completely remove the tumor along with a margin of healthy tissue to ensure a clear surgical margin. However, in up to 50% of cases, the tumor is not entirely removed, leading to higher rates of cancer recurrence and mortality. This challenge often arises from difficulty distinguishing tumor tissue from healthy tissue during the operation. Studies have shown that ultrasound can effectively make this distinction. This project investigates using B-mode in-vivo and ex-vivo ultrasound to assist surgeons in the resection of the tumor. The objective is to enhance accuracy during these surgeries by use of ultrasound. Consequently, we hope to minimize the need for adjuvant therapies, potentially enhancing patients' quality of life and reducing cancer recurrence and mortality rates.

Study population:

Inclusion criteria

• Patients scheduled for surgical treatment of biopsy-proven T1-T3 oral squamous cell carcinoma.

Exclusion criteria

* Age \< 18 years.
* Oral cancer with suspected bone involvement.
* Unable to understand verbal or written information.
* Prior radiotherapy treatment of oral cavity cancer.
* Tumor not visible on ultrasound.

Methods:

We plan to conduct a multicenter randomized controlled trial at seven otorhinolaryngology-Head and Neck Surgery departments in Europe, USA and Africa. The trial is anchored in Rigshospitalet, Copenhagen (Denmark).

Patients who meet the study´s criteria will be assigned either the control - or intervention group.

* Patients in the control group will have surgery for oral cancer conducted following the current standards for each center. The oral cancer tumor will be excised without having an ultrasound machine available to guide the resection. Then, the surgeon will take additional biopsies either from the in-vivo wound edges or from the specimen depending on local guidelines. Then the biopsies will be sent to the pathology department for frozen-section analysis. The surgeon might revise the resection or terminate the operation based on the frozen-section result. If the frozen-section analysis indicates an inadequate margin, the surgeon will, if possible, excise additional tissue from the wound, and the measured margin will be adjusted accordingly.
* In the intervention group, surgeons will have both in-vivo and ex-vivo ultrasound at their disposal to guide the resection and evaluate surgical margins during the procedure. The in-vivo ultrasound will be employed in real-time on the tumor to guide the resection process. Initially, tumor dimensions are measured using a Fujifilm robotic ultrasound probe or a hockey stick probe, and a 10 mm margin is marked from the tumor's boundaries. The surgeon begins the resection, periodically pausing to obtain real-time images of the resection plane. This is done by repositioning the partially resected specimen, making the resection plane visible as a hyperechoic border on the ultrasound, or by placing a small surgical instrument between the tumor/host interface to visualize the resection plane. Alternatively, the partially resected tumor can be ultrasound scanned from inside-out making the surgical margin visible nearest to the transducer. This is repeated until the tumor is completely removed.

After tumor removal, the specimen will undergo an ex-vivo ultrasound scan. In this phase, we will use a motorized mechanical transducer holder to hold the transducer to obtain standardized and reproducible B-mode cross-sectional images of the resected tissue allowing for margin measurement in the operating room. This imaging along with the margin measurements will help surgeons decide whether to perform an immediate re-resection or to conclude the operation. The use of ultrasound will not replace standard procedures, but should instead be viewed as an add-on tool. Therefore, surgeons in the intervention group will have the possibility to take biopsies for frozen section analyses.

Conditions

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Tongue Cancer Oral Cancer Squamous Cell Carcinoma of the Oral Cavity or Oropharynx

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Patients will randomized to either 1)standard treatment for oral cancer 2) standard treatment for oral cancer + the use of ultrasound during surgery to guide resection process and evaluate resections margins.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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Control

The patients in the control group will have surgery for oral cancer conducted following the current standards for each center.

Group Type ACTIVE_COMPARATOR

Standard Treatment

Intervention Type OTHER

Standard surgical treatment of oral cancer

Intervention

In the intervention group, surgeons will have both in-vivo and ex-vivo ultrasound at to guide the resection and evaluate surgical margins during the procedure. The in-vivo ultrasound will be employed in real-time on the tumor to guide the resection process. The surgeon begins the resection, periodically pausing to obtain real-time images of the resection plane using ultrasound. This is done by repositioning the partially resected specimen, making the resection plane visible as a hyperechoic border on the ultrasound, or by placing a small surgical instrument between the tumor/host interface to visualize the resection plane. Alternatively, the partially resected tumor can be ultrasound scanned from inside-out making the surgical margin visible nearest to the transducer. This is repeated until the tumor is completely removed.

Group Type EXPERIMENTAL

Ultrasound imaging

Intervention Type DIAGNOSTIC_TEST

Ultrasound will be performed during surgery in two phases: 1) in-vivo and 2) ex-vivo. In the in-vivo phase surgeons will perform intraoral ultrasound with a small intraoral transducer in order to visualize size and boundaries of tumor. Then the surgeon begins the resection periodically pausing to obtain real-time images of the resection plane and determin if resection is performed at safe distance to the tumor. In the ex-vivo phase the resected tumor will undergo ultrasound by using a motorized mechanical arm designed to hold an ultrasound transducer. This ensures standardized and reproducible scans. The purpose of the ex-vivo scan is to measure the surgical margins at the operating theatre and allow for an immediate re-resection of necessary. Surgeons in the intervention group will also have the possibility of taking biopsies for frozen section analyses.

Interventions

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Ultrasound imaging

Ultrasound will be performed during surgery in two phases: 1) in-vivo and 2) ex-vivo. In the in-vivo phase surgeons will perform intraoral ultrasound with a small intraoral transducer in order to visualize size and boundaries of tumor. Then the surgeon begins the resection periodically pausing to obtain real-time images of the resection plane and determin if resection is performed at safe distance to the tumor. In the ex-vivo phase the resected tumor will undergo ultrasound by using a motorized mechanical arm designed to hold an ultrasound transducer. This ensures standardized and reproducible scans. The purpose of the ex-vivo scan is to measure the surgical margins at the operating theatre and allow for an immediate re-resection of necessary. Surgeons in the intervention group will also have the possibility of taking biopsies for frozen section analyses.

Intervention Type DIAGNOSTIC_TEST

Standard Treatment

Standard surgical treatment of oral cancer

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

• Patients scheduled for surgical treatment of biopsy-proven T1-T3 oral squamous cell carcinoma.

Exclusion Criteria

* Age \< 18 years.
* Oral cancer with suspected bone involvement.
* Unable to understand verbal or written information.
* Prior radiotherapy treatment of oral cavity cancer.
* Tumor not visible on ultrasound.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Karolinska Institutet

OTHER

Sponsor Role collaborator

Emory University

OTHER

Sponsor Role collaborator

Stanford University

OTHER

Sponsor Role collaborator

National Cancer Institute, Milan

OTHER

Sponsor Role collaborator

University of Cape Town

OTHER

Sponsor Role collaborator

Aarhus University Hospital

OTHER

Sponsor Role collaborator

Tobias Todsen

OTHER

Sponsor Role lead

Responsible Party

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Tobias Todsen

MD, PhD, Ass. Prof.

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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Stanford Otolaryngology - Head & Neck Surgery Department

Stanford, California, United States

Site Status NOT_YET_RECRUITING

Emory University Hospital

Atlanta, Georgia, United States

Site Status NOT_YET_RECRUITING

Department of Otorhinolaryngology Head and Neck Surgery

Aarhus, , Denmark

Site Status RECRUITING

Department of Otorhinolaryngology Head and Neck Surgery and Audiology, Rigshospitalet

Copenhagen, , Denmark

Site Status RECRUITING

Istituto Nazionale Tumori of Milan

Milan, , Italy

Site Status NOT_YET_RECRUITING

Groote Schuur

Cape Town, , South Africa

Site Status NOT_YET_RECRUITING

Karolinska Institute

Stockholm, , Sweden

Site Status NOT_YET_RECRUITING

Countries

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United States Denmark Italy South Africa Sweden

Central Contacts

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Daniel J Lauritzen, MD

Role: CONTACT

+4541817574

Facility Contacts

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Lisa A Orloff, MD, FACS, FACE

Role: primary

(650) 736-1680

Michelle Chen, Ass. Prof.

Role: backup

Merry E Sebelik

Role: primary

404-778-3381

Thomas Kjærgaard, MD, PhD

Role: primary

+4578450000

Tobias Todsen, MD, PhD, Ass. Prof.

Role: primary

+4535453545

Alberto Deganello

Role: primary

+39 02 23901

Matthew White

Role: primary

+27 21 404 9111

Mathias von Beckerath

Role: primary

+46 8 524 800 00

Other Identifiers

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p-2024-18099

Identifier Type: -

Identifier Source: org_study_id

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