Oral Epithelial Dysplasia (OED), Oral Squamous Cell Carcinoma (SCC)
Conditions
Keywords
p53 mutant, SCC, oral epithelial dysplasia
Brief summary
The goal of this clinical trial is to optimize treatment strategies for patients with p53-mutant oral epithelial dysplasia (OED) and early-stage oral squamous cell carcinoma (OSCC). The main question it aims to answer is what the most optimal treatment is at each diagnostic stage. It is hypothesized that lesions with p53-abnormal low-grade dysplasia (LGD) without surgical intervention will progress to high-grade dysplasia (HGD) or SCC in 4 years. It is also predicted that a clear p53 and severe/CIS excision margins in patients with p53-abnormal HGD will reduce the progression to invasive SCC, compared to clear severe/CIS margins, within 4 years. Finally, it is thought that patients with p53-abnormal cT1N0 and DOI\<4mm receiving an END will have improved disease free and overall survival. This research will elucidate whether or not these hypotheses are correct. Participants in each diagnostic cohort will be assigned to one of two different treatment options, listed below: Cohort 1: A) No intervention, observation only B) Surgical excision with clear margins Cohort 2: A) Surgical excision with clear severe/CIS margins B) Surgical excision with clear severe/CIS and p53 margins Cohort 3: A) Surgical excision and elective neck dissection (END) B) Surgical excision and close follow-up, only salvage ND if development of nodal disease
Interventions
PROCEDURECohort 1 Intervention group
Clear margin excision of the lesion under local anesthetic, with re-excision for p53-positive margins.
PROCEDURECohort 2 severe/CIS margins clear
Clear margin excision of the lesion under local anesthetic, with re-excision until severe/CIS margins are clear
PROCEDURECohort 2 p53 and severe/CIS margins clear
Excision of the lesion ensuring final negative p53 and severe/CIS margins
PROCEDURECohort 3 Excision and END
Excision of primary lesion and immediate elective neck dissection
PROCEDURECohort 3 Excision and Close follow up
Excision of primary lesion and close follow up with salvage neck dissection if development of nodal disease
Sponsors
University of British Columbia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults age 18 or over * No history of head and neck radiation * p53-abnormal IHC patterns (surrogate marker for TP53 mutation) Cohort 1: * Biopsy-confirmed mild/moderate dysplasia Cohort 2: * Biopsy-confirmed severe dysplasia or CIS Cohort 3: * T1 SCC with depth of Invasion (DOI) \<4mm * Clinically and radiologically node-negative (confirmed by contrast-enhanced CT)
Exclusion criteria
* Immunocompromised status * Lesions greater than 3 cm * Presence of Proliferative Verrucous Leukoplakia Cohort 1: * Had prior treatment for oral premalignant lesions Cohort 2: * Presence of invasive SCC on initial biopsy Cohort 3: * Positive nodes on contrast-enhanced CT * DOI \>= 4mm
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression of Disease | 4 years | Study 1: Whether diagnosis progressed from low-grade dysplasia (mild/moderate OED) to high-grade (severe/CIS) dysplasia or OSCC. Study 2: Whether diagnosis progressed from high-grade (severe/CIS) dysplasia to OSCC. |
| Time of Disease Progression | 4 years | Study 1: Time for disease to progress from low-grade dysplasia (mild/moderate OED) to high-grade (severe/CIS) dysplasia or OSCC. Study 2: Time for disease to progress from high-grade (severe/CIS) dysplasia to OSCC. |
| Recurrence of Disease | Study 1 and 2: 4 years, Study 3: 3 years | Study 1: Whether recurrence of low-grade dysplasia is present. Study 2: Whether recurrence of high-grade dysplasia is present. Study 3: Whether recurrence of OSCC is present, and if recurrence pattern is local recurrence or nodal metastasis. All: Time for disease to recur. |
| Disease-free Survival | 3 years | Study 3: If survival is achieved disease-free following treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | Study 1 and 2: 4 years, Study 3: 3 years | Overall survival is measured as survival for 4 years following diagnosis and treatment. Cause of death will be included, if applicable. |
| Patient Reported Outcomes - Quality of Life and Functional Measurements | Study 1 and 2: 4 years, Study 3: 3 years | Patient quality of life: 1. Oral Health Impact Profile-14 (OHIP) - 14 questions on a 5 point Likert scale (0-4), total ranging from 0-56, with higher scores indicating worse quality of life. 2. Hospital Anxiety and Depression Scale (HADS) - 14 questions on a 4 point Likert scale (0-3), total ranging from 0-21, with higher scores indicating increased severity or probability of depression and anxiety. Functional measurement: 1\. MD Anderson Dysphagia Inventory (MDADI) - 20 questions on a 5 point Likert scale (1-5), score total ranging from 20-100, with lower scores indicating more severe limitations. |
Countries
Canada
Contacts
CONTACTEitan Prisman
CONTACTAlan Wei
Outcome results
None listed