Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Diagnosing Osteoradionecrosis in Patients With Head and Neck Cancer That Is Primary, Has Come Back, or Has Spread to Other Places in the Body

PRIMARY OBJECTIVES:

I. To determine whether DCE-MRI following external beam radiation therapy (EBRT) can be used
to reliably predict osteoradionecrosis (ORN).

SECONDARY OBJECTIVES:

I. Define dose-response relationships between DCE-MRI derived imaging biomarkers and
subsequent development of ORN.

II. Evaluate the use of DCE-MRI parameters to monitor ORN response to treatment.

III. Assess the use of DCE-MRI parameters in preoperative planning in advanced ORN subjects.

IV. Develop MRI-based biomarkers inclusive predictive models for development of
radiotherapy-attributable tissue injury within the field of radiation.

V. Determine the association of patient-related outcomes (PROs) to clinical and imaging
findings of tissue damage, such as the onset of ORN.

OUTLINE: Patients are assigned to 1 of 4 cohorts.

COHORT 1: Patients with newly diagnosed tumors undergo DCE-MRI within 4 weeks prior to the
first radiation fraction, within 3-5 weeks after radiation start, and at 2, 6, 12, 24, and 36
months post radiation. Patients who were previously irradiated and are at various stages of
oncologic follow-up undergo DCE-MRI for a total of 2-5 times at baseline and at 6, 12, 24,
36, and/or 48 months post radiation. Patients in the third or subsequent years post treatment
may undergo subsequent yearly imaging studies.

COHORT 2: Patients undergo DCE-MRI within 4 weeks prior to the first re-radiation fraction,
within 3-5 weeks after radiation start, and at 2, 6, 12, 24, and 36 months post radiation.

COHORT 3: Patients undergo DCE-MRI before and at 2 and 6 months post ORN treatment. Patients
may undergo DCE-MRI during the mid-ORN treatment.

COHORT 4: Patients undergo DCE-MRI within 4 weeks prior to and at 5-10 weeks and 12 months
post surgery.

Inclusion Criteria:

- Willing and able to provide informed consent

- Patients must have histologic evidence of malignant neoplasm that may have been
obtained from the primary tumor or metastatic lymph node

- Receipt of external beam radiation therapy (EBRT) with curative intent, with or
without concomitant chemotherapy

- Good performance status (Eastern Cooperative Oncology Group [ECOG] score 0-2)

- Willing to comply with all study procedures; and

- Willing to participate for the duration of the study

- COHORT 1 (LONGITUDINAL) GROUP 1 (PRE-RADIATION): Subjects who are currently undergoing
or scheduled to undergo treatment with radiotherapy with or without chemotherapy
(induction or concurrent) with intent to eradicate the malignancy. Treatment will
include the following: 1) primary or nodal disease adjacent to (within 2 cm) the
mandible (i.e., likely to receive a dose of at least 50 Gy to some portion of the
mandible volumes) and 2) > 60% probability of survival for 3 years after treatment

- COHORT 1 (LONGITUDINAL) GROUP 2 (POST-RADIATION): Subjects who were previously treated
with radiotherapy with or without chemotherapy (induction or concurrent). Treatment
will have included the following: 1) unilateral maximum mandible dose of >= 60 Gy and
a gradient of dose across the mandible of >= 20 Gy, 2) oncological cure and now in
disease surveillance; and 3) no clinically diagnosed ORN at the time of enrollment

- COHORT 2 (ENRICHED): Subjects with recurrent and/or new head and neck cancer disease
who will undergo re-irradiation to the head and neck with intent to eradicate the
malignancy. Treatment will include the following: 1) any mandible dose of at least 50
Gy cumulative (initial and subsequent treatment); and 2) no clinically diagnosed ORN
at the time of enrollment

- COHORT 3 (EARLY ORN INTERVENTION): Subjects with clinically confirmed low-grade/early
stage osteoradionecrosis requiring therapeutic (medical and/or dental surgery)
intervention as diagnosed by a qualified clinician. Clinical staging of developing or
existing ORN will be conducted using the CTCAE 4.0 (Common Terminology Criteria for
Adverse Events)

- COHORT 4 (SURGICAL INTERVENTION FOR ADVANCED ORN): Subjects with clinically confirmed
high grade/high stage osteoradionecrosis requiring surgical intervention. Clinical
staging of ORN will be conducted using the CTCAE 4.0 (Common Terminology Criteria for
Adverse Events)

Exclusion Criteria:

- Unable to tolerate diffusion weighted (DW)-MRI or DCE-MRI

- Having an estimated glomerular filtration rate (GFR) < 60 ml/min/1.73 m^2

- Contraindication to MRI (e.g. non-MRI compatible metallic implants)

- Pregnant females

- Unable or unwilling to give written, informed consent to undergo MRI imaging

- Claustrophobia

- Unable to obtain imaging studies of adequate quality to assess imaging-based
biomarkers

- COHORT 1/GROUP 1: Previously treated with radiotherapy for a malignant neoplasm of the
head and neck, excluding cutaneous lesions. Determination will be made by review of
the radiation therapy plan and dosimetry map to evaluate mandible exposure to
radiation

- COHORT 1/GROUP 2: Previously treated with radiotherapy for a malignant neoplasm of the
head and neck more than one time, excluding cutaneous lesions