Diagnostics for the Treatment of Progressive Mucosal Lesions of the Oral Cavity: a Prospective Study

Study Overview
=================
Brief Summary
-----------------
Despite improvements in therapy, head and neck carcinomas still have a poor prognosis with a 5-year survival of   50%. Malignancies of the head and neck area are (almost) always preceded by precursor lesions. Treatment of these premalignant mucosal abnormalities is generally limited and not very inconvenient for the patient. If this precursor lesion remain untreated, it may develop into a malignancy of the head and neck. Extensive treatment will be necessary. This means loss of function of the mouth, eg chewing, speaking and swallowing. The hypothesis is that chromosomal instability (CIN) detected by fluorescence is situ hybridization (FISH) is a reliable indicator for progression to malignancy. By intensifying the follow up and treatment in premalignant CIN lesions, the incidence of progression to invasive carcinoma is expected to be significantly reduced. If this hypothesis is justified, there will be a place for CIN detection as a risk indicator in the diagnostic work up of premalignant lesions in the head and neck. The investigators second hypothesis is that loss of heterozygosity (LOH) detected bij DNA markers is a reliable indicator for progression to malignancy. By intensifying the outpatient clinic follow up and treatment in premalignant lesions, the incidence of progression to invasive carcinoma is expected to be significantly reduced. If this hypothesis is justified, there will be a place for CIN and LOH detection as a risk indicator in the diagnostic work up of premalignant lesions in the head and neck.

Official Title
-----------------
Chromosomal Instability as an Indicator for the Treatment of Progressive Mucosal Lesions of the Oral Cavity.

Conditions
-----------------
Chromosomal Instability, Low Grade Dysplasia Oral Cavity, Loss of Heterozygostiy, Fluorescence In Situ Hybridization

Intervention / Treatment
-----------------
* Procedure: surgery
* Other: follow up


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: subjects ≥18 years premalignant lesions of the oral cavity, classified as hyperkeratosis, hyperplasia, mild or moderate dysplasia written informed consent Exclusion Criteria: former malignancy or lesion classified as severe dysplasia or carcinoma in situ at the same anatomical localization of the oral cavity lesions within an anatomical field which has been exposed to former treatment (e.g. radiotherapy) insufficient biopsy material to perform additional FISH analysis pregnancy, because of the physical burden (e.g. extra general anesthesia) in this study setting

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: follow up & surgery<br>CIN positive with surgery and intensified follow up | Procedure: surgery<br>* excision or carbondioxide laser evaporation of the mucosal lesion of the oral cavity<br>Other: follow up<br>* Intensified outpatient follow up (16 visits in 5 years)<br>|
| Active Comparator: follow up<br>CIN positive, only intensified outpatient follow up | Other: follow up<br>* Intensified outpatient follow up (16 visits in 5 years)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients (CIN negative and positive) who will show progression to malignancy of the oral cavity. | The primary goal of this prospective study is: Demonstrating the predictive value of the detection of CIN in premalignant lesions of the oral cavity by the use of FISH for the occurrence of progression to severe dysplasia /CIS or invasive carcinoma. The prevention of progression of premalignant lesions of the oral cavity to severe dysplasia / CIS or invasive carcinoma by the treatment of selected high-risk lesions. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients (LOH negative and positive) who will show progression to malignancy of the oral cavity. | The secondary objective of this study is as follows: Demonstrating the predictive value of the detection of LOH in premalignant lesions of the oral cavity by the use of DNA markers for the occurrence of progression to severe dysplasia / CIS or invasive carcinoma. | 1 year |