This study will use [18F]-AraG PET/CT scans to monitor patients who have been diagnosed with locally advanced Head and Neck Squamous Cell carcinoma (LA-HNSCC), and are planning to undergo standard of care chemoradiotherapy for treatment.

Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer globally. Definitive chemoradiotherapy (CRT) remains the standard of care (SOC) treatment for LA-HNSCC, yet some patients are unsuccessfully treated. The purpose of this study is to explore the feasibility and possible function of [18F]-AraG PET/CT (a diagnostic procedure that uses a radioactive tracer [A method that uses radioactive substances to make pictures of areas inside the body] to image tumors and assess response to treatment) scans performed before and during treatment to monitor response in patients undergoing chemoradiotherapy.

Inclusion Criteria

1. Patients ≥18 years of age.
2. Ability to provide written informed consent and HIPAA authorization.
3. LA-HNSCC in the larynx, hypopharynx, or human papillomavirus (HPV) negative oropharynx and is planning to receive definitive CRT as the SOC treatment, which includes a total of 70 Gy of radiation dose in 33 fractions, delivered over 5 days a week for 7 weeks, as well as planned weekly cycles of cisplatin (CDDP).
4. Tumor stage III and IV (AJCC 8th edition).
5. Unresectable cases.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
7. Willing and able to maintain the imaging protocol.
8. Patients planning to receive pre-CRT and post-CRT FDG PET/CT scans as part of the standard clinical practice.

Exclusion Criteria

1. Diagnosis of immunodeficiency or receiving systemic steroid therapy or any form of immunosuppressive therapy within 7 days prior to the PET/CT scan.
2. Pregnant or breastfeeding.
3. Patients that will receive definitive induction chemotherapy or surgery.
4. Patients who are unable to complete the radiation therapy.