Primary objectives:(1) Prevent progression of precursor lesions of the head and neck mucosa by treating selected lesions at risk for malignant outgrowth(2) Demonstrate that the detection of chromosomal instability (CIN) is indeed a powerful tool to…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
- Head and neck therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The endpoint is defined as a biopsy classification as severe dysplasia,
carcinoma in situ or squamous cell carcinoma ( malignant progression).
Primary study parameters:
- % malignant progression in the intervention group (CIN-positive lesions)
- % malignant progression in the control group (CIN-positive lesions)
- % malignant progression in the groep of CIN-negative lesions
Secondary outcome
Secundary study parameters:
Cost-effectiveness
(a) From the hospital perspective concerning the extra costs per prevented case
of cancer.
(b) From a societal perspective concerning costs per gained Quality of Adjusted
Life Year).
Background summary
Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common
malignancy worldwide with an annual incidence of more than 500,000 cases.
Despite advances in treatment modalities that enhance the quality of life,
patient survival rates have not improved resulting in a 5-year survival rate of
approximately 50%. Important factors contributing to this unfavorable prognosis
include the development of (1) multiple precursor lesions (hyperplasia, mild,
moderate and severe dysplasia/carcinoma in situ) in the head and neck mucosa
which may undergo malignant transformation ( 'field cancerization'), and (2)
locoregional recurrences in up to 30% of patients as a result of minimal
residual disease.
Currently used treatment modalities are guided by histopathological examination
and range from watchful waiting (in case of hyperplasia, mild or moderate
dysplasia) to complete resection of precursor lesions or radiotherapy. Because
histopathological examination is troubled by inter-observer variability, more
effective and objective methods for the detection of potentially malignant
precursor lesions are urgently needed.
HNSCC develops through a multistep process which is associated with the
accumulation of multiple (epi)genetic alterations
resulting in chromosomal instability (CIN). CIN can be efficiently detected by
means of fluorescence in situ hybridization (FISH)
and has been defined as chromosome copy number imbalances of chromosomes 1 and
7 and/or chromosome polysomy. Both
literature and our preliminary data show that CIN can predict the progression
of head and neck precursor lesions to carcinoma.
Study objective
Primary objectives:
(1) Prevent progression of precursor lesions of the head and neck mucosa by
treating selected lesions at risk for malignant outgrowth
(2) Demonstrate that the detection of chromosomal instability (CIN) is indeed a
powerful tool to predict malignant outgrowth
Secondary objectives:
(3) Conduct a cost-effectiveness analysis (a) from the hospital perspective
concerning the extra costs per prevented case of
cancer and (b) from a societal perspective concerning costs per gained (quality
adjusted) life year
Study design
This is an open randomised controlled trial with parallel groups.
Intervention
Based on FISH analysis subjects will be assigned to different groups. All
lesions classified as CIN-negative will not receive any treatment and these
subjects will be seen at the outpatient clinic during 5 years (1x/3 months in
the first year, 1x/4 months in the second year, 1x/6 months in the third year
and annual visits during the fourth en fifth year). Subjects with CIN-positive
lesions who are randomly assigned to the control group, will receive the same
follow-up protocol as the CIN-negative subjects. Participants in the
CIN-positive intervention group will receive treatment according to the
guidelines for severe dysplasia/carcinoma in situ. These imply endoscopic
deepithelialisation in larynx lesions and excision or CO2-evaporation in oral
lesions.
Study burden and risks
Burden: If a subject is assigned to the intervention group, he will undergo a(n
extra) surgical procedure under general anesthesia to remove the mucosal
lesion. Several risks apply to this procedure. General anesthesia may lead to
nasea and vomiting after the procedure, or a sore throat from the ventilation
tube. Rare cases of allergic reactions to medicines occur. The surgical
procedure might cause an infection or a bleeding after surgery. Pain or a
temporary voice disability may occur. During 5 years subjects will be seen at
the outpatient clinic, in total eleven visits are scheduled. Physical
examination of the head and neck region will be performed by an
otorhinolaryngologist. This routine examination will not involve taking blood
samples or biopsies.
Benefit: Because of close surveillance of subjects and treatment of
CIN-positive lesions in the intervention group, a decrease in the frequency of
malignant outgrowth will be expected. Therefore, subjects will have less chance
to develop a malignancy at the head and neck region and extensive treatment or
(lifelong) side effects of cancer treatment will be prevented.
Postbus 616
6200 MD Maastricht
NL
Postbus 616
6200 MD Maastricht
NL
Listed location countries
Age
Inclusion criteria
- patient >= 18 years
- premalignant mucosal lesion of larynx or oral cavity, classified as hyperkeratosis, hyperplasia, mild or moderate dysplasia
- written informed consent
Exclusion criteria
- former malignancy or lesion classified as severe dysplasia or CIS at the same anatomical region of the larynx or oral cavity
- former therapy at the same anatomical region
- insufficient biopsy material to perform FISH analysis
- pregnancy
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL31104.068.09 |