A prospective, explorative cohort study to identify biomarkers of treatment response in oropharyngeal cancer.

Rationale: Oropharyngeal cancer (OPC) is most commonly primarily treated with radiotherapy, with or without addition of systemic agents. Treatment outcomes are highly variable, with approximately 40% of patients experiencing locoregional recurrence (LRR) within 2 years after treatment. Human papillomavirus (HPV) status of the tumor has emerged as an important prognostic factor for overall survival (OS), highlighting the influence of tumor biological properties on the treatment outcomes. However, to date no assays exists to allow prediction of tumor response to radiotherapy on the individual patient’s level.
We have developed an ex vivo assay for tumor radiosensitivity for head-and-neck squamous cell carcinoma (HNSCC). We hypothesize that this assay is able to predict clinical outcomes of tumor treatment. Furthermore, we hypothesize that by combining ex vivo sensitivity assay with tumor characteristics, such as circulating tumor DNA (ctDNA), new response biomarkers would be identified that could be implemented in clinical practice. For that, a repository of OPC patient samples needs to be established.
Objective: The main objective of this study is to assess the relation between ex vivo tumor radiosensitivity assay and clinical tumor response. Furthermore, we will build a repository of both tumor material and liquid biopsies to allow future identifications of biomarkers of treatment response.
Study design: This study is a prospective explorative cohort study for OPC patients treated with (chemo-/bio)radiotherapy to assess the correlation between tumor ex vivo radiosensitivity with clinical response and to build a biological database for future biomarker identification.
Study population: All OPC patients >=18 years, who are eligible for curative treatment with radiotherapy with or without the addition of systemic agents.
Intervention (if applicable): All eligible patients will be informed about the study during the first visit at the outpatient clinic of a head-and-neck or maxillofacial surgeon. For patients with OPC accessible during physical examination an additional tumor biopsy will be obtained during their second scheduled visit by a head-an-neck or maxillofacial surgeon. For patients without histology confirmation of OPC and requiring general anaesthesia for tumor approach, an extra biopsy next to the diagnostic one will be obtained during a single procedure. For all patient an additional blood sample will be obtained during their second scheduled visit and during the clinical response evaluation visit. Clinical outcomes will be assessed within the standard follow-up scheme. In case of tumor recurrence, patients will be approached for obtaining additional tumor and blood samples.
Main study parameters/endpoints: The primary study endpoint is establishing the relation of the ex vivo radiosensitivity assay with clinical evaluation of tumor response (physical examination and MRI if indicated) at three months after treatment. The secondary endpoints are: establishing this relation for various treatment groups; describing the effect of known prognostic factors on this relation; establishing the relation between ex vivo radiosensitivity and LRR at two years after treatment; and the predictive value of ctDNA in liquid biopsies of OPC patients.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: This is an explorative prospective cohort study. The burden and risks associated with participation for the patient include those resulting from tumor biopsy (temporary pain and minor local bleeding) and blood sampling (temporary pain and bruising). No additional appointments will be scheduled. The results will be used for research purposes only and will not affect the treatment choices.

We hypothesize that tumor ex vivo radiosensitivity correlates with clinical response to (chemo/bio-)radiotherapy in vivo. The manner of relation will be assessed in this study. Moreover, we postulate that establishing a biobank of OPC tumor and blood samples is crucial for successful biomarker discovery. ctDNA is one of the potential biomarkers and will be investigated in this study. The departments and experts of Erasmus MC involved in this project will furthermore test and validate novel (combinations of) biomarkers to predict and eventually improve treatment outcomes.

Before start of the treatment, 3 months and 2 years after completion of treatment

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