Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05841966 |
| Other study ID # |
Unknown Primary Transoral US |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
February 21, 2023 |
| Est. completion date |
March 1, 2024 |
Study information
| Verified date |
May 2024 |
| Source |
Rigshospitalet, Denmark |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Adult patients suspected of Squamous Cell Carcinoma of Unknown Primary (SCCUP) will be
prospectively enrolled at a tertiary head & neck cancer center at Copenhagen University
Hospital - Rigshospitalet, Copenhagen, Denmark. All patients will undergo Magnetic Resonance
Imaging (MRI) and Positron Emission Tomography-Computerized Tomography (PET-CT) prior to
examination in general anesthesia. During general anesthesia, Intraoperative Transoral
Ultrasound (ITUS) will be performed prior to panendoscopy. Detected tumors will be registered
with specified oropharyngeal sub-locations. Blinded to ITUS, a consultant head & neck surgeon
will perform panendoscopy. After examination, the surgeon is unblinded to ultrasound results.
Final histopathology results from location-specified biopsies performed will be used as
reference standard. The overall detection rate will be compared between ITUS, panendoscopy,
PET-CT and MRI with sensitivity and specificity analysis. Oropharynx sub-location specific
detection rate of ITUS vs. panendoscopy will be compared with logistic regression analysis.
Description:
A prospective diagnostic study examining patients with suspected SCCUP will be performed at
the Department of Otorhinolaryngology & Head & Neck Surgery, Copenhagen University Hospital -
Rigshospitalet, Denmark. This specialized cancer center is responsible for the surgical
work-up for approximately half of suspected SCCUP patients in the Danish population of 5.8
million.
Standard work-up of patients with suspected SCCUP in Denmark consists of same-day clinical
examination combined with high resolution video endoscopy with NBI, surgeon-performed neck
ultrasound and fine-needle aspiration cytology (FNAC) of suspected lymph nodes with same-day
results. Cytology results can be further tested for Human Papillomavirus (HPV), and patients
are booked for panendoscopic examination under general anesthesia with frozen section biopsy.
Pre-operative cross-sectional imaging to locate the primary tumor includes MRI and 18-F
Fluordeoxyglucose (FDG) PET-CT.
Intraoperative transoral ultrasound
During general anesthesia and prior to panendoscopy, ITUS will be performed while a
consultant head & neck surgeon performing panendoscopy is blinded. A Fujifilm Arietta 850 or
Arietta 65 (Fujifilm, Tokyo, Japan), BK5000 (BK Medical ApS, Herlev, Denmark), or Samsung
RS85 (Samsung Medison, Seoul, South Korea) ultrasound machines will be used. Small-footprint,
high-frequency transducers such as the Arietta L51K linear-array intraoperative robot
transducer attached to a forceps, the BK5000 "flexible hockey-stick" 18XL5s, or the Samsung
RS85 LA3-22AI "hockeystick" will be used. A Boyle-Davis gag or laryngoscope will be used to
visualize the tonsils (Figure 1), while the transducer is placed onto each tonsil in
transverse and sagittal planes. The tongue base will be scanned by pulling the tongue
anteriorly by an assistant and placing the transducer directly onto the tongue base.
Alternatively, the tongue can be retracted with a video-laryngoscope while revealing the
tongue base. The tongue base will be scanned from side to side in the sagittal plane. The
tongue can then be pulled to either the left or right side to angle the probe obliquely for
transverse imaging. If a tumor is suspected, the tumor location is registered in the
following categories, including indication of right or left side:
- Tonsil cranial.
- Tonsil caudal.
- Glossotonsillar sulcus.
- Anterolateral tongue base.
- Anteromedial tongue base.
- Posterolateral tongue base.
- Posteromedial tongue base.
- "Other" oropharynx sub-locations, including anterior & posterior pharyngeal arches, soft
palate, uvula, posterior oropharynx wall, and vallecula.
B-mode video clips of both tonsils and the tongue base will be recorded. Power doppler for
suspected tumors and the contralateral side will be performed. If a well-defined lesion is
seen, the greatest tumor diameter and if possible, three-dimensional size is measured. The
grade of tumor suspicion will be rated on a 5-point Likert scale ranging from 0 (very low) to
5 (very high).
Panendoscopy Following ITUS, the surgeon will perform standard panendoscopy of the pharynx
including palpation of the oral cavity and oropharynx, and high-resolution video endoscopy
with NBI. If the surgeon suspects a tumor, the location is registered with the same
categories as above. Tumor suspicion will be rated on a 5-point Likert scale ranging from 0
(very low) to 5 (very high). The surgeon will categorize visual findings such as ulcers,
exophytic tumors, asymmetric tissue, vulnerable/bleeding mucosa, suspect vasculature on NBI,
or no suspect visual findings. The surgeon will categorize palpatory findings as soft or
firm. The clinically visualized or palpated greatest tumor diameter will be estimated. The
surgeon is then unblinded to ultrasound results. After unblinding from ultrasound, the
investigators will register whether further directed biopsies from ultrasound suspected
location are performed.
If the primary tumor is not located during panendoscopy, patients will tonsillectomied and
the tonsils will be sliced in 2mm slices by head & neck pathologists in search of the primary
tumor. If the primary tumor is still unknown and the neck metastasis is HPV+, then patients
are offered Transoral Robotic Surgery (TORS) with diagnostic tongue base mucosectomy. These
tongue base specimens will also be sliced in 2mm slices and examined by head & neck
pathologists. If the primary tumor is located in final histopathology from either
tonsillectomies or tongue base mucosectomy, the location of the tumors will be compared to
the initially registered suspected ultrasound locations from panendoscopy.
Medical chart data The patient's age, sex, alcohol, smoking, largest cervical lymph node
size, cervical lymph node side (right/left), date of panendoscopy, date of conclusive
histopathology results, and date of treatment initiation will be obtained from medical
charts.
