Impact of Preoperative High-Frequency Ultrasound Cutaneous Lesion Extent Assessment on Excision Margin Positivity in Head and Neck Skin Cancer, and the Relationship Between Preoperative Assessment Methods, Inadequate Excision Margins, and Tumor Recurrence

Official title

Impact of Preoperative High-Frequency Ultrasound Cutaneous Lesion Extent Assessment on Excision Margin Positivity in Head and Neck Skin Cancer, and the Relationship Between Preoperative Assessment Methods, Inadequate Excision Margins, and Tumor Recurrence (HFUS-CLEAR)

Overview

Non-melanoma skin cancers (NMSC), particularly basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), are the most common malignancies in Caucasians, with the majority of tumors located in the head and neck due to chronic ultraviolet exposure. Although BCC has very low metastatic potential, while cSCC carries a higher risk of nodal spread, both can cause significant local tissue destruction and functional and cosmetic impairment. Complete excision with histologically clear margins remains the standard treatment; however, incomplete or close excision margins are reported in a substantial proportion of cases and are associated with increased risk of local recurrence, need for additional treatment, and higher healthcare costs. Preoperative dermoscopy improves delineation of lateral tumor borders but does not assess depth of invasion. High-frequency ultrasound (HFUS) is a rapid, non-invasive imaging modality that can visualize superficial skin structures and estimate tumor thickness. Previous studies have suggested good agreement between HFUS and histopathologic depth of invasion, but results are not fully consistent, and HFUS has not yet been incorporated into major guideline recommendations for preoperative assessment of NMSC. Further prospective data are needed to clarify whether HFUS can improve surgical planning and margin control. This prospective study is designed to assess the impact of adding preoperative HFUS to standard dermoscopic evaluation in head and neck BCC and cSCC. The primary objectives are: (1) to compare the frequency of positive or inadequate (\<1 mm) histopathologic excision margins between lesions assessed with dermoscopy alone and those assessed with both dermoscopy and HFUS; and (2) to evaluate 5-year local recurrence rates in relation to preoperative assessment method, histopathologic margin status, and subsequent management of inadequate margins (observation, non-surgical treatment, or scar excision). Secondary and additional objectives include: assessing concordance between HFUS-measured and histopathologic depth of invasion; determining the frequency of residual tumor in scars excised after inadequate margins; evaluating recurrence rate according to the site of inadequate margins (lateral vs deep); and identifying patient-related, tumor-related, surgical, and histopathologic predictors of inadequate margins and recurrence. Approximately 400 lesions (BCC or cSCC of the head and neck) qualified for curative surgical excision will be included. Each lesion will constitute an independent study case. All lesions will undergo preoperative assessment, including clinical evaluation with detailed medical history and dermoscopy; in one cohort, lesions will additionally be evaluated with HFUS. HFUS will be performed with an 18-MHz linear probe, using superficial B-mode and color Doppler. Maximum tumor depth will be recorded from the epidermal surface (or granular layer) to the deepest hypoechoic point, with assessment of potential infiltration of deeper structures when visible. Surgical excision and postoperative care will follow standard clinical practice. Postoperative histopathologic assessment of FFPE tumor samples will record tumor histologic type and subtype, margin status, width, depth of invasion, differentiation, inflammation, elastosis, perineural or vascular invasion, and other routinely assessed diagnostic features. In the event of positive or inadequate excision margins, patients will be referred, after consultation with a dermatologist, for further management (observation, non-surgical treatment, or scar excision), depending on clinical indications and patient preferences. Participation in the study will not influence the primary surgical treatment or any decisions regarding subsequent management. Patients will be followed for at least 5 years according to current clinical guidelines, with dermoscopic skin examination and documentation of local recurrence and its management. The study aims to determine whether incorporating HFUS into preoperative assessment can reduce the frequency of inadequate histologic margins and improve long-term local control in head and neck NMSC.

Interventions

• Diagnostic test High-Frequency Ultrasound
  High-frequency ultrasound examination of the tumor will be performed using a GE LOGIQ S7 Expert system with an L8-18i-D linear probe (18 MHz). Imaging will include superficial-preset B-mode gray-scale assessment and color Doppler evaluation of lesion vascularity. Standard ultrasound gel will be applied; the probe will be positioned perpendicularly to the skin surface without pressure, avoiding direct contact with the tumor. Images and measurements will be obtained in at least two orthogonal plan
• Diagnostic test Dermoscopy
  All lesions will undergo standard preoperative dermoscopic evaluation performed by a consultant dermatologist, including assessment of tumor extent and marking of dermoscopically visible tumor borders.

Primary outcome measures

• Excision Margin Status [Time frame: Postoperative pathology results (within 30 days after excision)]
• Five-Year Tumor Recurrence [Time frame: Up to 5 years after primary tumor excision]

Secondary outcome measures (3)

• Concordance Between HFUS-Measured and Histopathologic Depth of Invasion [Time frame: Preoperative HFUS assessment and postoperative histopathology (within 30 days)]
• Recurrence Rates According to Site of Incomplete Histopathologic Margins [Time frame: Up to 5 years after primary tumor excision]
• Frequency of Residual Tumor Cells in Scar Excision Following Incomplete Margins [Time frame: Scar excision histopathology (within 90 days after primary excision)]

Eligibility criteria

Inclusion criteria

• Cutaneous lesion located in the head and neck region with a preoperative diagnosis of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC), established by dermoscopy or biopsy, and qualified for surgical excision with curative intent.
• patient age of 18 years or older.
• Ability of patient to provide voluntary, informed, written consent for participation in the study.
• Confirmation that the patient has read and understood the Patient Information Sheet.

Exclusion criteria

• Excisional biopsies without radical intent.
• Lack of histopathologic confirmation of BCC or SCC in the postoperative specimen (incorrect dermoscopic qualification).
• Inability to perform radical surgical excision due to excessive tumor extent, poor general condition of the patient, or lack of patient consent for surgery.
• Pregnancy.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Poland · 1 center

• National Medical Institute of the Ministry of the Interior and Administration in Warsaw — Warsaw

Identifiers

NCT: NCT07361666 · 21/BW/2025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗