Prediction of Malignant Transformation of Oral Leukoplakia Using a MAGE-A-based Immunoscore

Studien-Informationen Einschlusskriterien Studien-Rationale

Rekrutierend

NCT-Nummer:
NCT03975322

Studienbeginn:
Dezember 2019

Letztes Update:
03.12.2019

Wirkstoff:
-

Indikation (Clinical Trials):
Leukoplakia, Leukoplakia, Oral, Lichen Planus, Oral, Lichen Planus

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
University of Erlangen-Nürnberg Medical School

Collaborator:
-

Studienleiter

Manuel Weber, MD, DMD
Study Chair
Maxillofacial Surgery Erlangen

Falk Wehrhan, MD, DMD
Study Chair
Maxillofacial Surgery Erlangen

Jutta Ries, PhD
Study Chair
Maxillofacial Surgery Erlangen

Kontakt

Manuel Weber, MD, DMD
Kontakt:
Phone: 0049 9131 85 43749
E-Mail: manuel.weber@uk-erlangen.de» Kontaktdaten anzeigen

Falk Wehrhan, MD, DMD
Kontakt:
Phone: 0049 9131 85 43731
E-Mail: falk.wehrhan@uk-erlangen.de» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

Universitätsklinikum Erlangen, FAU Erlangen-Nürnberg
91054 Erlangen
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Manuel Weber, MD, DMD
Phone: 004901318543749
E-Mail: manuel.weber@uk-erlangen.de» Ansprechpartner anzeigen

Studien-Informationen

Detailed Description:

Oral squamous cell carcinomas (OSCC) is among the most common malignancies worldwide. Despite

the introduction of microsurgical reconstruction options and advances in multimodal tumor

therapy, the prognosis has not improved significantly in the last 30 years.

The most important aspect for increasing survival rate is seen in the early detection of OSCC

and its precursor lesions. Up to 67 % of OSCC develop on the basis of oral leukoplakia (OLP),

which frequently occur prior to the diagnosis of carcinoma. OLP treatment depends on the risk

of malignant transformation. Therapeutic approaches range from simple observation to complete

surgical excision of OLP. The scientific evidence regarding the handling of OLP is low.

Current literature outlines missing evidence in therapeutic management of OLP. The early

identification of OLP with a high risk of malignant degeneration is a relevant clinical

question, since approx. 2% of OLPs transform malignantly each year. In lesions with dysplasia

this rate increases to about 17%.

Gold standard for determining the risk of malignant transformation of OLP is the histologic

determination of the degree of dysplasia. As the histological degree of dysplasia increases,

so does the risk of developing PECM on the basis of OLP. The decision for a surgical or a

conservative therapy currently depends on the degree of dysplasia of the OLP. The

histopathological assessment of the degree of dysplasia is subjective and depends on the

experience of the pathologist making the assessment. However, the major disadvantage in

assessing the malignant transformation potential with this method is that many precursor

lesions do not follow the histopathologically determined degree of dysplasia. Thus, 0-3% of

hyperplasias (D0) and up to 30% of mild dysplasias (D1) transform to OSCC. D0 OLP are

lesions, which are usually only observed according to current therapy recommendations. Thus,

an assessment of the dignity of OLP and a long-term prediction of the risk for the

development of OSCC are not reliable. OLP with a histopathologically low malignancy potential

but a cell-biologically probable malignant transformation must be identified in order to

prevent undertreatment of these patients.

The aim of this explorative study is to investigate whether the malignant transformation of

OLP can be reliably predicted using immunohistochemical and molecular biological methods. A

significant association of the expression of MAGE-A expression with the malignant

transformation of OLP to OSCC has already been demonstrated in retrospective studies. It is

now necessary to further develop these available test procedures and evaluate them in a

prospective study in order to transfer them into clinical routine. Sensitivity and

specificity of the investigated markers will be investigated in a prospective, multicenter

setting. A non-selected group of patients will be examined. The aim is to establish a test

procedure that can be used cost-effectively. The MAGE-A expression should serve as an

indicator and for the application of new, innovative therapy concepts such as the

immunotherapy of OLP.

The following questions will be answered:

i) Do OLP with malignant transformation show an increased MAGE-A expression in a time

interval of 3 years (follow-up up to 5 years)? ii) How high is the sensitivity and

specificity of MAGE-A expression as a predictive diagnostic test? Is immunohistochemical or

molecular biological (RT-PCR) detection of MAGE-A better suited as a diagnostic test? iii)

Can MAGE-A be used successfully as a diagnostic test in practice? iv) Is there an association

between MAGE-A expression and immunological changes preceding malignant transformation

(macrophage polarization, T cell infiltration, checkpoint expression, TLR expression)? v) Are

the immunological changes in OLP potentially amenable to immunomodulatory therapy?

Short summary of the study protocol:

After the patient has been informed and included in the study, the first step is the photo

documentation and then the incision biopsy of the OLP. The treating physician is free to

choose whether to take a sample from one or more sites of the lesion. This procedure complies

with the standard diagnostic guidelines and is not a study-specific measure. Thus, there is

no deviation from the clinical routine for the study and no invasive measure required by the

study. The sample taken is then divided. The total amount of tissue taken corresponds to the

amount taken in the routine outside the study. One part of the sample is conventionally fixed

in formalin. The second part (max. 5x5x2mm) is preserved in RNA later for later PCR analysis.

Both samples will be sent to the study center in Erlangen. There the histological evaluation

of the tissue takes place in the Pathological Institute of the University Hospital Erlangen

within routine diagnostics. The result is communicated to the treating physician and the

study centre. The immunohistochemical and molecular biological analyses are carried out in

the laboratories of the Oral and Maxillofacial Surgery Erlangen. The results of the analyses

are not communicated to the attending physician (blinding). A therapy decision is only made

on the basis of clinical and classical histological parameters (degree of dysplasia). D0 and

D1 lesions are monitored. D2 and D3 lesions are treated surgically or with laser coagulation

depending on the decision of the treating physician and patient. This corresponds to the

current clinical standard. If the patient rejects the treatment of the lesion and wishes to

continue observing its progress, he remains included in the study. The follow-up time during

the study period is 3 years (evaluations also after 2 years). After completion of the study a

further follow-up of 2 years is planned in order to achieve a total follow-up of 5 years.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Adults, consenting male or female patients

- Age 18 - 80 years

- Diagnosis of one or more leukoplakia of the oral cavity

including

- leukoplakia associated wit lichen planus OR

- leukoplakia associated with diseases of the immune system or immunosuppression OR

- leukoplakia associated with a malignoma of other sites (except oral cavity) in the

anamnesis

- Existing consent to participation in the study after clarification has been given

Exclusion Criteria:

- clinical evidence of invasive carcinoma of the oral cavity OR

- carcinoma of the oral cavity in the anamnesis OR

- patients unable to give informed consent OR

- rejection of the patient

Studien-Rationale

Primary outcome:

1. Dependence of malignant transformation on a MAGE-A based immunoscore (Time Frame - 2 years):
Association of OLP malignant transformation with a MAGE-A based immunoscore. Into this score, the following immunohistochemical and molecular biological parameters determined in biopsies will be integrated: MAGE-A expression Macrophage infiltration and polarization (CD68, CD163) T cell infiltration (CD3, CD8) Altered expression of immune checkpoints and TLR receptors (PD-L1, PD-L2, TLR7) These parameters will be aggregated to an immunoscore

2. Dependence of malignant transformation on a MAGE-A based immunoscore (Time Frame - 3 years):
Association of OLP malignant transformation with a MAGE-A based immunoscore. Into this score, the following immunohistochemical and molecular biological parameters determined in biopsies will be integrated: MAGE-A expression Macrophage infiltration and polarization (CD68, CD163) T cell infiltration (CD3, CD8) Altered expression of immune checkpoints and TLR receptors (PD-L1, PD-L2, TLR7) These parameters will be aggregated to an immunoscore

3. Dependence of malignant transformation on a MAGE-A based immunoscore (Time Frame - 5 years):
Association of OLP malignant transformation with a MAGE-A based immunoscore. Into this score, the following immunohistochemical and molecular biological parameters determined in biopsies will be integrated: MAGE-A expression Macrophage infiltration and polarization (CD68, CD163) T cell infiltration (CD3, CD8) Altered expression of immune checkpoints and TLR receptors (PD-L1, PD-L2, TLR7) These parameters will be aggregated to an immunoscore

Secondary outcome:

1. Frequency of malignant transformation (Time Frame - 2 years):
Frequency of malignant transformation of OLP (determination of the incidence of OSCC in OLP cases)

2. Frequency of malignant transformation (Time Frame - 3 years):
Frequency of malignant transformation of OLP (determination of the incidence of OSCC in OLP cases)

3. Frequency of malignant transformation (Time Frame - 5 years):
Frequency of malignant transformation of OLP (determination of the incidence of OSCC in OLP cases)

4. Dependence of malignant transformation on dysplasia (Time Frame - 2 years):
Dependence of malignant transformation on histologically determined degree of dysplasia (D0-D3)

5. Dependence of malignant transformation on dysplasia (Time Frame - 3 years):
Dependence of malignant transformation on histologically determined degree of dysplasia (D0-D3)

6. Dependence of malignant transformation on dysplasia (Time Frame - 5 years):
Dependence of malignant transformation on histologically determined degree of dysplasia (D0-D3)

Quelle: ClinicalTrials.gov

Sie können folgenden Inhalt einem Kollegen empfehlen:

"Prediction of Malignant Transformation of Oral Leukoplakia Using a MAGE-A-based Immunoscore"

Bitte tragen Sie auch die Absenderdaten vollständig ein, damit Sie der Empfänger erkennen kann.

Die mit (*) gekennzeichneten Angaben müssen eingetragen werden!