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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: p53 mutant mild/moderate dysplasia observational group | No Intervention | Observation only | |
| Cohort 1: p53 mutant mild/moderate dysplasia excision group | Experimental | Clear margin excision of the lesion under local anesthetic, with re-excision for p53-positive margins |
|
| Cohort 2: p53 mutant Severe/CIS dysplasia clear severe/CIS margin group | Active Comparator | Clear margin excision of the lesion under local anesthetic, with re-excision until severe/CIS margins are clear |
|
| Cohort 2: p53 mutant Severe/CIS dysplasia negative p53 and severe/CIS margin group | Experimental | Excision of the lesion ensuring final negative p53 and severe/CIS margins |
|
| Cohort 3: p53 mutant T1 SCC (DOI <4mm) excision and END group | Active Comparator | Excision of primary lesion and immediate elective neck dissection (END) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cohort 1 Intervention group | Procedure | Clear margin excision of the lesion under local anesthetic, with re-excision for p53-positive margins. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression of Disease | 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. | 4 years |
| Time of Disease Progression | 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. | 4 years |
| Recurrence of Disease | 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. | Study 1 and 2: 4 years, Study 3: 3 years |
| Disease-free Survival | Study 3: If survival is achieved disease-free following treatment. | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival | Overall survival is measured as survival for 4 years following diagnosis and treatment. Cause of death will be included, if applicable. | Study 1 and 2: 4 years, Study 3: 3 years |
| Patient Reported Outcomes - Quality of Life and Functional Measurements |
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Inclusion Criteria:
Cohort 1:
Cohort 2:
Cohort 3:
Exclusion Criteria:
Cohort 1:
Cohort 2:
Cohort 3:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Eitan Prisman | Contact | 6048754126 | prisman.eitan@vch.ca | |
| Tayo Steininger | Contact | 6048754111 | 22935 | tayo.steininger@vch.ca |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vancouver General Hospital | Vancouver | British Columbia | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26027881 | Background | D'Cruz AK, Vaish R, Kapre N, Dandekar M, Gupta S, Hawaldar R, Agarwal JP, Pantvaidya G, Chaukar D, Deshmukh A, Kane S, Arya S, Ghosh-Laskar S, Chaturvedi P, Pai P, Nair S, Nair D, Badwe R; Head and Neck Disease Management Group. Elective versus Therapeutic Neck Dissection in Node-Negative Oral Cancer. N Engl J Med. 2015 Aug 6;373(6):521-9. doi: 10.1056/NEJMoa1506007. Epub 2015 May 31. | |
| 27560665 |
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| Cohort 3: p53 mutant T1 SCC (DOI <4mm) excision and follow up group | Experimental | Excision of primary lesion and close follow up with salvage neck dissection if development of nodal disease |
|
| Cohort 2 severe/CIS margins clear | Procedure | Clear margin excision of the lesion under local anesthetic, with re-excision until severe/CIS margins are clear |
|
| Cohort 2 p53 and severe/CIS margins clear | Procedure | Excision of the lesion ensuring final negative p53 and severe/CIS margins |
|
| Cohort 3 Excision and END | Procedure | Excision of primary lesion and immediate elective neck dissection |
|
| Cohort 3 Excision and Close follow up | Procedure | Excision of primary lesion and close follow up with salvage neck dissection if development of nodal disease |
|
Patient quality of life:
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. |
| Study 1 and 2: 4 years, Study 3: 3 years |
| Background |
| Liu KY, Durham JS, Wu J, Anderson DW, Prisman E, Poh CF. Nodal Disease Burden for Early-Stage Oral Cancer. JAMA Otolaryngol Head Neck Surg. 2016 Nov 1;142(11):1111-1119. doi: 10.1001/jamaoto.2016.2241. |
| 33034628 | Background | Durham JS, Brasher P, Anderson DW, Yoo J, Hart R, Dort JC, Seikaly H, Kerr P, Rosin MP, Poh CF. Effect of Fluorescence Visualization-Guided Surgery on Local Recurrence of Oral Squamous Cell Carcinoma: A Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2020 Dec 1;146(12):1149-1155. doi: 10.1001/jamaoto.2020.3147. |
| 36522371 | Background | Hyodo T, Kuribayashi N, Fukumoto C, Komiyama Y, Shiraishi R, Kamimura R, Sawatani Y, Yaguchi E, Hasegawa T, Izumi S, Wakui T, Nakashiro KI, Uchida D, Kawamata H. The mutational spectrum in whole exon of p53 in oral squamous cell carcinoma and its clinical implications. Sci Rep. 2022 Dec 15;12(1):21695. doi: 10.1038/s41598-022-25744-8. |
| 39265952 | Background | Lin TY, Liu KYP, Novack R, Mattu PS, Ng TL, Hoang LN, Prisman E, Poh CF, Ko YCK. Abnormal p53 Immunohistochemical Patterns Are Associated with Regional Lymph Node Metastasis in Oral Cavity Squamous Cell Carcinoma at Time of Surgery. Mod Pathol. 2024 Dec;37(12):100614. doi: 10.1016/j.modpat.2024.100614. Epub 2024 Sep 10. |
| 32797678 | Background | Gleber-Netto FO, Neskey D, Costa AFM, Kataria P, Rao X, Wang J, Kowalski LP, Pickering CR, Dias-Neto E, Myers JN. Functionally impactful TP53 mutations are associated with increased risk of extranodal extension in clinically advanced oral squamous cell carcinoma. Cancer. 2020 Oct 15;126(20):4498-4510. doi: 10.1002/cncr.33101. Epub 2020 Aug 14. |
| 34735529 | Background | Liu KYP, Zhu SY, Harrison A, Chen ZY, Guillaud M, Poh CF. Quantitative nuclear phenotype signatures predict nodal disease in oral squamous cell carcinoma. PLoS One. 2021 Nov 4;16(11):e0259529. doi: 10.1371/journal.pone.0259529. eCollection 2021. |
| 36906072 | Background | Novack R, Zhang L, Hoang LN, Kadhim M, Ng TL, Poh CF, Kevin Ko YC. Abnormal p53 Immunohistochemical Patterns Shed Light on the Aggressiveness of Oral Epithelial Dysplasia. Mod Pathol. 2023 Jul;36(7):100153. doi: 10.1016/j.modpat.2023.100153. Epub 2023 Mar 9. |
| 39265950 | Background | Ko YCK, Liu KYP, Chen E, Zhu SY, Poh CF. p53 Abnormal Oral Epithelial Dysplasias are Associated With High Risks of Progression and Local Recurrence-A Retrospective Study in a Longitudinal Cohort. Mod Pathol. 2024 Dec;37(12):100613. doi: 10.1016/j.modpat.2024.100613. Epub 2024 Sep 10. |
| ID | Term |
|---|---|
| D000077195 | Squamous Cell Carcinoma of Head and Neck |
| ID | Term |
|---|---|
| D002294 | Carcinoma, Squamous Cell |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| D000071063 | Endoglin |
| ID | Term |
|---|---|
| D011956 | Receptors, Cell Surface |
| D008565 | Membrane Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
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