A Study of Head and Neck MRI and Tumor Microenvironment Biomarkers

Not Applicable

Not yet recruiting

Interventions: Radiation: Standard of care external beam radiotherapy (single integrated boost)
Radiation: Standard of care external beam radiotherapy (two-phase treatment)

Brief Summary: This is a single centre prospective exploratory study of effects of radiation therapy on biomarker development in patients with newly diagnosed (head and neck squamous cell carcinoma) HNSCC receiving curative therapy. This research is part 2 of the HN-BIO study.

Detailed Description: This study will recruit up to 40 patients planned to receive curative (chemo) radiotherapy for (head and neck squamous cell carcinoma) HNSCC with primary tumor and/or involved lymph node suitable for repeat biopsy in clinic. After being informed about the study and potential risks, patients giving written informed consent will be randomized to receive conventional radiotherapy (single integrated boost or conventional two-phase at clinician discretion) or reversed two-phase treatment with delayed irradiation of elective nodal volumes. Patients will not be informed of their randomization result.

Patients in both arms will undergo a baseline functional magnetic resonance imaging (fMRI) scan and within 72 hours, when possible, a biopsy of the primary tumor +/- lymph node will be performed in an out-patient clinic. If a suitable biopsy has been recently performed as part of diagnostic work up the baseline biopsy on study will be omitted when possible. In week 2 of radiotherapy, patients will have a second fMRI scan and a paired biopsy within 72 hours of the scan, where possible. A further optional biopsy and paired fMRI scan in week 4 will be considered for patients who are tolerating therapy without \>G1 toxicities. 16-24 hours prior to each biopsy the patient will take oral pimonidazole. At the time of each biopsy a blood draw will be performed.

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
Arm 1: Integrated Boost Radiotherapy	Standard of care external beam radiotherapy (single integrated boost)	External beam radiotherapy 70Gy in 35 fractions to head and neck tumour and 56 Gy in 35 fraction to elective nodal regions. This will be given as single integrated boost or two-phase treatment at clinician discretion.
Arm 2: Two Phase Radiotherapy	Standard of care external beam radiotherapy (two-phase treatment)	Standard of care external beam radiotherapy 70 Gy in 35 fractions to head and neck with delayed 40 Gy in 20 fractions to elective nodal regions. This will be given as reversed two-phase treatment.

Primary Outcome Measures

Name	Time	Method
Confirm feasibility of recruitment of HN patients for on treatment repeat biopsy of the primary tumor +/- neck nodes	7 weeks	Achieve a minimum recruitment rate of one patient per month.
Change in fMRI during radiotherapy	7 weeks	Study association of changes in fMRI and tissue biomarkers during radiotherapy. Assessed through hypoxic regions visible on imaging scans.
Assess changes in tumor microenvironment during differing radiotherapy scheduling via repeat biopsy.	7 weeks	Assess effect of varying radiotherapy treatment volumes on changes in tumor microenvironment via repeat biopsy before and during radiotherapy. Quantify effect of delayed treatment of dLN on dynamic changes tumor immune micro-environment and hypoxia status during radiotherapy. Perform exploratory analysis of study data correlating changes in tumor microenvironment and hypoxia status with disease response to therapy.

Secondary Outcome Measures

Name	Time	Method
Validate novel and established fMRI imaging as predictive and prognostic radiotherapy biomarkers for HNSCC	7 weeks	Correlate changes in TME and hypoxia with changes in fMRI on repeat assessment. Correlate fMRI characterized tumor with pathological post-operative specimen.