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

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.

• Clear Margin [Срок оценки: 2 weeks.]
• Dysphagia questionnaire [Срок оценки: 12 months]
• Cancer recurrence [Срок оценки: 24 months]
• Survial [Срок оценки: 24 months]
• Quality of life questionnaire [Срок оценки: 12 months]