Phase 2 Trial of Adaptive Radiotherapy Boost for HNSCC

Inclusion Criteria:

* Provision of signed and dated informed consent form
* Stated willingness to comply with all study procedures and availability for the duration of the study
* ECOG performance status of 0, 1
* Patients with histologically or cytologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, nasopharynx, hypopharynx, larynx, or unknown primary in the neck.
* Patients with measurable disease, either at primary site or neck per RECIST 1.1.
* For patients planned to receive chemotherapy, adequate hematologic, hepatic and renal function as outlined in protocol.
* International normalized ratio of prothrombin time (INR) and prothrombin time (PT) within 28 days before randomization must be WNL for the lab. Patients who are therapeutically treated with an agent such as warfarin may participate if they are on a stable dose and no underlying abnormality in coagulation parameters exists per medical history.
* Negative serum pregnancy test within before starting study treatment in woman with childbearing potential.

Exclusion Criteria:

* Pregnancy or lactation
* Patients who have had prior radiotherapy to the head and neck or prior systemic therapy for the index cancer.
* Patients who had undergone definitive surgery for the index cancer.
* Patients with distant metastatic disease
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.