A prospective, explorative cohort study to assess the value of an ex vivo radiosensitivity assay as a BIOmarker of treatment Response in Oropharyngeal Cancer (BIO-ROC).

Radiotherapy with or without addition of systemic agents is the primary
treatment choice for oropharyngeal cancer (OPC). Despite large heterogeneity in
treatment response within OPC tumors, currently all patients receive an
identical treatment. Currently there is no clinicaly validated test of a
biomarker predictive of the therapy response. Consequently, patient with a good
response receive potentially too intensive treatment, resulting in unnecessary
toxicity. On the other hand, patients with resistent tumors require intensified
treatment for tumor control. Ability to predict tumor response early in the
treatment would have a major impact on the treatment choices of patients with
OPC.

Within Erasmus MC a novel experimental assay has recently been developed, in
which biopsy tissue of head-and-neck cancer is irradiated ex vivo to predict
radiosensitivity of an individual tumor. This assay revelaed large differences
in treatment response between investigated tumors. Within this study we want to
perform a prospective cohort study to investigate the relation between the ex
vivo radiosensitivity and clinical treatment respons of OPC patients.
Furthermore, we want to establisch a biobank of OPC patients for future
research on new biomarkers of treatment respons, such as circulating tumor DNA
(ctDNA).

Primary objective: to assess the relation of an ex vivo functional assay for
tumor radiosensitivity with clinical tumor response of OPC patients treated
with (chemo/bio-)radiotherapy at 3 months after treatment.

Secondary objectives:
- to assess the above mentioned relation in various treatment groups (such as:
radiation only, chemo-radiotherapy, bioradiation with cetuximab, radiotherapy
with protons instead of photons)
- to investigate the effect of known prognostic factors (smoking, HPV-status,
age, comorbidities) on the above mentioned relation
- to assess the relation of the of ex vivo functional assay for tumor
radiosensitivity with locoregional tumor control of OPC patients treated with
(chemo/bio-)radiotherapy at 2 years after treatment
- to assess the prognostic value, specificity and sensitivity of ctDNA as
biomarkers of treatment response
- to build a repository of tumor biopsies and blood samples of OPC patients for
future testing and validation of new (combinations of) biomarkers to predict
treatment outcomes

Prospective explorative cohort study

Burden of the study consist of an additional biopsy of the tumor and four
additional blood samplings. Those procedures will be integrated within the
diagnostic workflow of the head-and-neck cancer patients and will require no
additional hospital and/or outpatient clinic visits. The risk and impact on the
patient*s quality of life are minimal and include a temporary bruising in the
arm and moderate pain and/or minimal bleeding at the site of biopsy for a very
short time.