Imaging of Tumour Microenvironment in Patients With Oropharyngeal Head and Neck Squamous Cell Carcinoma Using RGD PET/CT Imaging

Study Overview
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Brief Summary
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Known risk factors inducing squamous cell carcinomas of the head and neck are tabacco and alcohol intake. However, the incidence of human papillomavirus (HPV) related oropharyngeal carcinomas is increasing. It is known that HPV+ and HPV- tumors have a different reaction to (chemo)radiotherapy. The exact mechanisms underlying these differences is not yet known but might be caused by changes in vascularity. Therefore the vasculature is imaged with the help of a study specific Gallium-68-DOTA-(RGD)2 PET/CT scan and a CT perfusion scan.

Detailed Description
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The incidence of Human Papilloma Virus positive (HPV+) oropharyngeal Head and Neck Squamous Cell Carcinoma (HNSCC) is rising and it has become evident that this type of cancer represents a subgroup of HNSCC that is characterized by a more favourable prognosis, mediated by a distinct tumour microenvironment, compared to patients with HPV negative (HPV-) tumours. However, the exact mechanisms underlying this improved treatment outcome and the potential role of the tumour microenvironment are not fully understood yet. Imaging of αvβ3 integrin expression will obtain more insight in the differences in tumour microenvironment between HPV+ and HPV- oropharyngeal HNSCC. CT perfusion provides additional characterisation of this tumour microenvironment. Therefore, these techniques may have the potential to predict response to treatment and might possibly steer treatment decisions in future clinical trials.

Official Title
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Imaging of Tumour Microenvironment in Patients With Oropharyngeal Head and Neck Squamous Cell Carcinoma Using RGD PET/CT Imaging

Conditions
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Oropharyngeal Squamous Cell Carcinoma

Intervention / Treatment
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* Combination Product: RGD PET/CT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Proven squamous cell carcinoma of the oropharynx p-16 immunohistochemistry analysis Tumour lesion of at least 1.0 cm in diameter Planned chemoradiotherapy as primary treatment Ability to provide written informed consent Exclusion Criteria: Contra-indications for PET Contra-indications for administration of iodine-containing contrast agents Other serious illness that can affect the scans

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Imaging results of HPV positive tumours are compared to imaging results of HPV negative tumours.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: HPV Negative tumours<br>Patients will receive four scans. | Combination Product: RGD PET/CT<br>* Patients will receive an RGD PET/CT and a CT perfusion scan prior to treatment and during chemoradiotherapy<br>* Other names: CT perfusion;|
| Active Comparator: HPV positive tumours<br>Patients will receive four scans. | Combination Product: RGD PET/CT<br>* Patients will receive an RGD PET/CT and a CT perfusion scan prior to treatment and during chemoradiotherapy<br>* Other names: CT perfusion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in RGD-tracer uptake between HPV positive and negative tumours | standardized uptake values (SUV) of Ga68-RGD | 1 month | 
| Differences in RGD-tracer uptake between the pre- and per-treatment scan | standardized uptake values (SUV) of Ga68-RGD | 1 month | 
| Differences in CT perfusion flow parameters between HPV positive and negative tumours | Determining the blood flow using ROIs of the tumour drawn on the contrast enhanced CT | 1 month | 
| Differences in CT perfusion parameters between HPV positive and negative tumours | Determining the blood volume using ROIs of the tumour drawn on the contrast enhanced CT | 1 month | 
| Differences in CT perfusion flow parameters between the pre- and per-treatment scan | Determining the blood flow using ROIs of the tumour drawn on the contrast enhanced CT | 1 month | 
| Differences in CT perfusion parameters between the pre- and per-treatment scan | Determining the blood volume using ROIs of the tumour drawn on the contrast enhanced CT | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in RGD-tracer uptake between patients with locoregional control or recurrence within one year | standardized uptake values (SUV) of Ga68-RGD | 1 year | 
| Differences in CT perfusion flow parameters between patients with locoregional control or recurrence within one year | Determining the blood flow using ROIs of the tumour drawn on the contrast enhanced CT | 1 year | 
| Differences in CT perfusion parameters between patients with locoregional control or recurrence within one year | Determining the blood volume using ROIs of the tumour drawn on the contrast enhanced CT | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tumour microenvironment, Chemoradiotherapy, Oropharyngeal squamous cell carcinoma, Human papilloma virus, Positron emission tomography