HN-BIO: A Study of Head and Neck MRI and Tumor Microenvironment Biomarkers

Not Applicable

Recruiting

Brief Summary: The purpose of this study is to explore biomarker development in patients with newly diagnosed Head and neck squamous cell carcinoma (HNSCC) receiving curative therapy.

Detailed Description: After being informed about the study and potential risks, all patients giving written informed consent will be assigned to Cohort A or Cohort B.

Cohort A will recruit up to 40 patients planned to receive curative radiotherapy for HNSCC. Patients will undergo a baseline fMRI (Functional Magnetic Resonance Imaging) scan and within 72 hours a biopsy of the primary tumor will be performed in out-patient clinic. In week 2 of radiotherapy a further biopsy of the primary site will be performed with a paired fMRI performed within 72 hours prior to biopsy assess evolving changes in imaging and tumor microenvironment biomarkers during radiotherapy. A further optional biopsy and paired MRI scan in week 4 will be considered for patients who are tolerating therapy without toxicities. 16-24 hours prior to each biopsy the volunteer will take oral pimonidazole.

Cohort B will recruit up to 20 patients planned to receive curative surgery for HNSCC. Each patient will undergo a baseline fMRI scan performed within one week prior to surgery. At time of initial consent they will receive a prescription for oral pimonidazole hydrochloride which they will be asked to take the 16-24 hours before planned surgery. Following surgery whole tumor samples will be processed to permit spatial reconstruction of pimonidazole staining hypoxia to correlate with fMRI imaging.

Recruitment & Eligibility

Inclusion Criteria

Age >/= 18 years
Histologically proven Head and Neck Squamous Cell carcinoma
Primary or nodal disease > 3cm for biomarker imaging
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
Planned for curative surgery or (chemo)radiotherapy
Willingness to undergo repeat MRI imaging
Able to receive and understand verbal and written information regarding study and able to give written informed consent
Adequate renal function: Calculated creatinine clearance >/= 30ml/min
Be able to lie comfortably on back for 1 hour

Exclusion Criteria

As judged by investigator evidence of systemic disease that makes unsuitable for study
Contra-indication for serial MRI scans
Previous solid tumor treated within last 5 years
Pregnancy
History of gadolinium contrast allergy
Non-reversible clotting abnormality

Arm && Interventions

Group	Intervention	Description
Cohort B	Oral Pimonidazole	Participants who are to receive standard of care curative surgery will have an MRI scan within one week prior to surgery. Tumor tissue from the surgery will also be collected for research. Oral pimonidazole will be taken the night before surgery.
Cohort A	Oral Pimonidazole	Participants who are to receive standard of care radiotherapy will have one biopsy and MRI scan before starting radiotherapy and during week two of radiotherapy. Participants will also have an the option to consent to an additional biopsy and MRI scan during week 4 of radiotherapy. Oral pimonidazole will be taken the night before each biopsy.
Cohort A	fMRI	Participants who are to receive standard of care radiotherapy will have one biopsy and MRI scan before starting radiotherapy and during week two of radiotherapy. Participants will also have an the option to consent to an additional biopsy and MRI scan during week 4 of radiotherapy. Oral pimonidazole will be taken the night before each biopsy.
Cohort B	fMRI	Participants who are to receive standard of care curative surgery will have an MRI scan within one week prior to surgery. Tumor tissue from the surgery will also be collected for research. Oral pimonidazole will be taken the night before surgery.

Primary Outcome Measures

Name	Time	Method
Change in tumor microenvironment during radiotherapy	Prior to radiotherapy, week 2 and week 4 of radiotherapy	Repeat biopsy will be analyzed for haematoxylin and eosin (H\&E), pimonidazole (monoclonal IgG1 antibody, Hypoxyprobe MAb1), endogenous proteins associated with hypoxia and/or immune infiltrate, DNA, and RNA.
Change in fMRI during radiotherapy	Prior to radiotherapy, week 2 and week 4 of radiotherapy	Assessed through hypoxic regions visible on imaging scans

Secondary Outcome Measures

Name	Time	Method