Squamous cell carcinoma of the head and neck
Conditions
Interventions
None listed
Sponsors
Antoni van Leeuwenhoek Ziekenhuis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, a subject must meet all of the following criteria:;* Have a primary mucosal HNSCC (T1-4, N0-3, M0) of any head and neck anatomic subsite. Patients with recurrent HNSCC are eligible only if they have been disease-free *5 years before enrolment. * Be eligible for curative treatment with surgery, radiotherapy, immunotherapy or a combination of these modalities. * Screening laboratory values must meet the following criteria: WBC * 2.0x109/L, Neutrophils * 1.5x109/L, Platelets * 100 x109/L, Hemoglobin * 5.5mmol/L, Creatinine * 1.5x ULN, AST * 3 x ULN, ALT * 3 x ULN, Total Bilirubin *1.5 X ULN (except subjects with Gilbert Syndrome, who can have total bilirubin
Exclusion criteria
Exclusion criteria: * HNSCC patients treated with concomitant chemoradiation therapy. * The presence of any malignancy other than the present HNSCC, unless: o It has been curatively treated *5 years prior to first study-related blood collection; o It is a curatively treated cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, carcinoma in situ of the breast or carcinoma in situ of the bladder. * The presence of active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have: o Vitiligo; o Type I diabetes mellitus; o Residual hypothyroidism due to an autoimmune condition, only requiring hormone replacement; o Psoriasis not requiring systemic treatment; o Conditions not expected to recur in the absence of an external trigger. * The presence of a condition requiring systemic treatment with either corticosteroids (>10mg daily prednisone equivalents) or other immunosuppressive medications. * The presence of active hepatitis B, hepatitis C, active tuberculosis, syphilis, HIV or AIDS. * The presence of any disease or use of medication which, in the investigators* opinion, might significantly influence hematopoiesis.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main study parameter/endpoint * Cytokine detection in pre- and posttreatment peripheral blood samples (26ml) from HNSCC patients will be performed and compared with results obtained in blood samples from healthy volunteers. In case of HNSCC recurrence, we will repeat this analysis on a newly obtained blood sample. Depending on the number of cytokines, optimal detection limits and operability, we will choose between BD* Cytometric Bead Array (at NKI-AVL) and Luminex® Multiplex Assay. The Luminex® analysis will be performed at UMCU. * Pre- and posttreatment blood from HNSCC patients, as well as healthy control blood samples, will be analyzed with flow cytometry in order to characterize the composition and frequency of HSPCs as well as their downstream progenitor and differentiated cells. In case of HNSCC recurrence, we will repeat this analysis on a newly obtained blood sample. * Fresh tumor will be obtained from the surgical specimen in patients who will undergo an operation as standard of care. These will be used for the production of tumor supernatant and tumor pieces, cytokine detection, flow cytometry and cryopreservation. * One or two sections of FFPE pretreatment tumor biopsies, obtained for routine diagnostic purposes, will be stained for the identification of HSPCs, downstream progenitor and differentiated cells using immunohistochemistry and immunofluorescence. In case of HNSCC recurrence, we will repeat these analyses on a newly obtained tumor biopsy (taken for diagnostic purposes). * During the routine biopsy procedure (in case of primary HNSCC or recurrence), patients will be requested (non-mandatory) to donate an additional, non-mandatory tumor 5mm biopsy for cytokine detection, flow cytometry and cryopreservation in order to run future analyses. * Clinical parameters such as disease status and survival data (disease-specific and overall) will be collected for up to two years after treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Once the correlation between the responding progenitor populations and their corresponding lineage cells is made based on previous results. 1. Isolate all corresponding progenitor populations from healthy donor (obtained from Sanquin) and set up an in vitro culture system. By manipulating the cytokine combination (hints got from part I and II) in the medium, study whether the changes of composition and differentiation of certain progenitor populations recapitulate what happens in patients with HNSCC. 2. Culture corresponding progenitor populations from healthy donor, with or without the medium supernatant of HNSCC tumor, then compare the composition and differentiation of the progenitor populations cultured with different conditions. With this approach, the responding progenitor population(s) will be detected. 3. Isolate the responding progenitor populations from the peripheral blood of HNSCC patients and set up an in vitro culture system. By manipulating the cytokine combination in the medium, study whether the changes of composition and differentiation of the responding progenitor populations recapitulate what happens in patients after therapy. 4. Culture the responding progenitor populations from the peripheral blood of HNSCC patient alone, or with the autologous tumor pieces/cells, or with the medium supernatant of the autologous tumor, then compare the composition and differentiation of the responding progenitor populations cultured with different conditions. | — |
Countries
Netherlands
Outcome results
None listed