Clinical trial NCT05696314: Surgeon-performed Outpatient Transoral and Transcervical Ultrasound of the Oropharynx
Official title: Surgeon-performed Outpatient Transoral and Transcervical Ultrasound Compared to MRI for the Diagnostic Workup of Primary Oropharynx Tumors: the SPOT-US Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Oropharynx Cancer
Tonsil Cancer
Base of the Tongue Tumor
Tonsil Hypertrophy
Tonsil Ulcer
Tonsil Neoplasm
Tonsil Lymphoma
Base of Tongue Carcinoma
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: The Novo Nordic Foundation
First posted: 2023-01-25
Enrollment: 201
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The intervention (transoral and transcervical ultrasound) is performed on all included patients. All patients will also receive a standard MRI of the oropharynx. All tumors will be biopsy verified.
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of the study is to compare the sensitivity and specificity of transoral ultrasound, transcervical ultrasound, Magnetic Resonance Imaging (MRI) and Positron Emission Tomography-Computerized Tomography (PET-CT) in terms of detecting primary oropharynx tumors.

Detailed description: A prospective study will be performed at the head \& neck departments at Copenhagen University Hospital - Rigshospitalet, Zealand University Hospital - Køge, and Aarhus University Hospital in Denmark.

Patients referred with a suspected cancerous lesion of the oropharynx will be invited to participate in this study. With written informed consent, a surgeon-performed outpatient transoral and transcervical examination of the tonsils and tongue base is conducted as an addition to the clinical workup at the head \& neck departments. Clinical work-up includes palpation of the oropharynx, flexible endoscopic exam with narrow-band imaging and neck ultrasound.

Ultrasound of the oropharynx will be performed using small-footprint, high-frequency (minimum 15MHz) transducers for transoral ultrasound. A lower-frequency (between 2-9 MHz) curved transducer will be used for transcervical ultrasound. If a suspected tumor is visualized, the location is noted and the surgeon performing clinical examination is informed.

MRIs will be performed on all patients with cancers, and an expert radiologist blinded to ultrasound results will assess all images for tumor detection, greatest tumor size and T-stage. PET/CTs will be performed in patients with suspected cancer of unknown primary tumor as well as patients with verified cancers. A nuclear medicine physician and an oncoradiologist will separately assess PET/CTs and CTs for tumor detection.

Surgeons performing initial clinical work-up, the ultrasound operators, neuroradiologist and nuclear medicine physician will register tumor detection (sub-location specific) and greatest tumor size immediately and prospectively, blinded to histopathology. Prospective gathered data will be registered on standardized data collection sheets or in REDCap using the same standardized variables. All scanning modalities will be evaluated blinded to each other but not to clinical findings.

Tumor detection: Suspected tumor locations from clinical evaluation with narrowband imaging and palpation, ultrasound, MRI, and PET-CT will be categorized according to the following criteria:

* Right tonsil
* Left tonsil
* Right tongue base
* Left tongue base
* Right overlapping tonsil and tongue base
* Left overlapping tonsil and tongue base
* Other oropharynx (soft palate, uvula, anterior and posterior pharyngeal arches, posterior oropharynx wall, and vallecula)
* Multiple tumor locations The examiners' tumor suspicion confidence will be rated with a 5-point Likert scale ranging from 0, very low suspicion - 5, very high suspicion.

The surgeon will also mark on a pictogram of the oropharynx with the biopsy location(s) numbered according to the histopathology registered biopsy locations.

Tumor size and staging: If a tumor is visualized or palpated, the greatest tumor diameter will be measured in three dimensions with clinical palpation, ultrasound, and MRI. T-staging will be estimated according to the Union for International Cancer Control 8th edition TNM-staging system:

* Tx: Unknown primary tumor.
* T1: Tumor \<20 mm in greatest diameter.
* T2: Tumor 21-40 mm in greatest diameter.
* T3: Greatest size \>40mm or extension to the lingual surface of the epiglottis
* T4: Invasion of the extrinsic tongue muscles, larynx, pterygoid muscles, hard palate, mandible, carotids nasopharynx or skull base (yes, no, indeterminate).

Additional variables: We will prospectively register the study center, date of outpatient ultrasound, ultrasound machine used, doctor performing the ultrasound scan, patient Mallampati 4-point score, Patient mouth opening measured in millimeters between incisors, patient self-reported discomfort from transoral ultrasound and palpation examinations (Supplementary Figure 2), ultrasound scan quality, MRI scan quality and PET-CT scan quality. Quality will be registered on a 5-point Likert scale (1, Very poor quality - 5, excellent quality).

The following data will be registered from medical charts: patient age, sex, tobacco smoking, alcohol consumption, date of first clinical contact, date of MRI scan performed, date of PET/CT scan performed, date of available histopathology results and date of treatment initiation.

Ultrasound video clips and B-mode images will be stored for retrospective descriptive evaluation of the following characteristics:

* Tumor shape (smooth/rounded, irregular/lobular).
* Tumor border delineation (well-circumscribed, unclear).
* Tumor heterogeneity (homogeneous, heterogeneous).
* Doppler flow compared to contralateral side (decreased, equivocal, increased).
* Doppler flow characteristics (peripheral/circumferential, internal organized, internal chaotic)

Reference standard: Final histopathology biopsy results will define the presence of cancer as binary results (no cancer vs. cancer present). An expert head and neck pathologist will re-evaluate biopsies results if inconclusive. The presence of a tumor in a correct sub-location assessed by final Multidisciplinary Team (MDT) conference will be used to define correct tumor location. Greatest tumor size and T-stage will also be determined by final MDT decision, considering the clinical and radiological findings. For patients with available complete tumor resections, a secondary analysis will be performed using the histopathologic reported greatest tumor diameter as reference standard.

Eligibility criteria: Inclusion criteria:

* Initially assessed by a specialist otorhinolaryngologist with clinical suspicion of head and neck cancer and referred to fast-track cancer work-up.
* Any of the following objective or subjective symptoms:

  1. Visible and/or palpable tumors of the oropharynx.
  2. Asymmetry of the tonsils or tongue base.
  3. Symptoms including dysphagia, throat pain, and/or referred otalgia where an oropharynx tumor is suspected but not clinically visible.
  4. Suspected cervical lymph node metastasis with no visible/palpable primary tumor.
  5. Lateral neck cysts in patients aged 40+ years.
* Adult patients aged 18+ years.
* Understands Danish or English and can give written informed consent.

Exclusion criteria:

* Prior radiotherapy to the oropharynx.
* Prior oropharynx cancer.
* MRI of the oropharynx or PET-CT already performed 3 months prior to inclusion.

Primary outcomes:
measure: Tumors detected by clinical evaluation, ultrasound, MRI, CT, and PET/CT compared to the reference standard histopathology results.
timeFrame: 2 weeks.
Secondary outcomes:
measure: Greatest tumor diameter in millimeters estimated with clinical evaluation, ultrasound and MRI, and CT.
timeFrame: 1 minute
measure: Categorical T-stage estimated with clinical evaluation, ultrasound, and MRI, and CT.
timeFrame: 1 minute
measure: Tonsil and tongue base tumor volume estimated with clinical evaluation, ultrasound and MRI, and CT.
timeFrame: 1 minute
Other outcomes:
measure: Comparison of tumor detection and size between MRI and CT
timeFrame: 1 year
measure: MRI and PET-CT scan quality
timeFrame: 1 year
measure: Ultrasound scan quality
timeFrame: 1 minute
measure: Patient mouth opening in millimeters.
timeFrame: 1 minute
measure: 11-point Numeric Rating Scale for Discomfort of oropharynx palpation and transoral ultrasound
timeFrame: 1 minute
measure: Gagging severity index
timeFrame: 1 minute
measure: Patient Mallampati score
timeFrame: 1 minute
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet, Department of Otorhinolaryngology, Head & Neck Surgery & Audiology
city: Køge
country: Denmark
facility: Zealand University Hospital - Køge, Department of Otorhinolaryngology, Head and Neck Surgery
city: Århus
country: Denmark
facility: Århus University Hospital, Department of Otorhinolaryngology, Head & Neck Surgery
Study officials:
affiliation: Rigshospitalet, Denmark
name: Tobias Todsen, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Garset-Zamani M, Norling R, Hahn CH, Agander TK, von Buchwald C, Todsen T. Transoral Ultrasound in the Outpatient Clinic for the Diagnostic Work-Up of Oropharyngeal Cancer: A Feasibility Study. Cancers (Basel). 2023 Nov 4;15(21):5292. doi: 10.3390/cancers15215292.