This early phase I trial compares sodium fluoride F-18 (F-18 NaF) positron emission tomography (PET)/computed tomography (CT) to the standard of care imaging scan (and fludeoxyglucose F-18 [F-18 FDG] PET/CT) for assessing the effects radiation therapy has on the blood vessels in the neck in patients with head and neck cancers. For people with cancers in the head and neck, doctors often use radiation to target both the tumor and nearby glands. Radiation therapy to this region can affect the blood vessels in the neck that supply blood to the brain. F-18 NaF and F-18 FDG are contrast agents that can be used together with PET/CT imaging to visualize areas inside the body. A PET scan is a procedure in which a small amount of radioactive glucose (sugar) is injected into a vein, and a scanner is used to make detailed, computerized pictures of areas inside the body where the glucose is taken up. A CT scan is a procedure that uses a computer linked to an x-ray machine to make a series of detailed pictures of areas inside the body. The pictures are taken from different angles and are used to create 3-dimensional views of tissues and organs. Combining a PET scan with a CT scan can help make the image easier to interpret. PET/CT scans are hybrid scanners that combine both modalities into a single scan during the same examination. Imaging with F-18 NaF PET/CT may be as effective or more effective than the standard F-18 FDG PET/CT for assessing the effects radiation therapy has on blood vessels in the neck in patients with head and neck cancers.

PRIMARY OBJECTIVES:

I. To determine the role of FDG- and NaF-PET in assessing radiation-induced vascular complications by comparing baseline and follow-up scans in patients with head and neck cancer.

II. To assess the presence and extent of radiation-induced vascular inflammation following proton versus (vs) photon radiation therapy (RT) in patients with head and neck cancer.

III. To determine the correlation between inflammation and actual radiation dose received to the vasculature to assess the effects of dose response.

SECONDARY OBJECTIVE:

I. To determine the effect of radiation-induced vascular inflammation (possibly atherosclerosis) on global brain function as measured by FDG-PET.

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM I: Patients receive F-18 NaF intravenously (IV) and undergo PET/CT within 28 days of each standard of care (SOC) F-18 FDG PET/CT on study, once prior to initiation of SOC intensity-modulated radiation therapy (IMRT) and once 12 weeks after completion of SOC IMRT.

ARM II: Patients receive F-18 NaF IV and undergo PET/CT within 28 days of each SOC F-18 FDG PET/CT on study, once prior to initiation of SOC intensity-modulated proton therapy (IMPT) and once 12 weeks after completion of SOC IMPT.

After completion of study intervention, patients are followed up within one to five business days.

Inclusion Criteria:

• Males and females 18 years of age and older

• Diagnosis of clinical stage III-IVb (American Joint Committee on Cancer [AJCC] 8th edition) squamous cell carcinoma of the oropharynx (human papillomavirus [HPV]-negative), larynx, or hypopharynx, or clinical stage I-III (AJCC 8th edition) HPV-associated squamous cell carcinoma of the oropharynx receiving curative-intent, organ preservation (non-surgical)

• Treatment with concurrent chemoradiotherapy per institutional standard of care at the discretion of Medical Oncology. RT is delivered per institutional standard of care at the discretion of Radiation Oncology

• Patients must give protocol-specific consent on an Institutional Review Board (IRB)-approved consent form prior to completion of protocol-specific testing/procedures

• Women are eligible to participate in the study if they meet one of the following criteria:

  • Females of childbearing potential (FCBP) must have a negative pregnancy test at baseline and follow-up visit. Women of childbearing potential must undergo pregnancy testing during each study visit and agree to use at least one of the following methods of contraception throughout the study duration:

    • Oral contraceptives, transdermal contraceptives, injectable or implantable methods, intrauterine devices, and/or vaginal ring
    • Women who are postmenopausal (for at least one year), sterile, or hysterectomized;
    • Women who have undergone tubal ligation will be required to undergo pregnancy testing during each study visit

Exclusion Criteria:

• Adults who are unable to consent
• Pregnant women
• Prisoners
• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier (i.e., have residual toxicities > grade 1)
• Patients who are receiving any other investigational agents or an investigational device within 21 days before administration of the F-18 NaF for the pre-RT PET/CT imaging
• Patients planned to receive any immunotherapy agent during their radiotherapy or in the interval between radiotherapy and post-RT PET/CT imaging
• History of allergic reactions attributed to compounds of similar chemical or biological composition to F-18 NaF or other agents used in the study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Significant cardiovascular disease (eg, myocardial infarction, arterial thromboembolism, cerebrovascular thromboembolism) within 3 months prior to study entry; angina requiring therapy; symptomatic peripheral vascular disease; New York Heart Association class 3 or 4 congestive heart failure; or uncontrolled grade >= 3 hypertension (diastolic blood pressure >= 100 mmHg or systolic blood pressure >= 160 mmHg) despite antihypertensive therapy

For the purposes of this study, will contour the ascending aorta, arch of the aorta, carotid arteries, and descending aorta but these structures will not be a part of the treatment planning process and will be blinded to the treating physician.