Personalized, Adaptive Treatment for Locally Advanced Head and Neck Cancer

Inclusion Criteria: * Patients must have pathologically confirmed locally advanced, non-metastatic, human papillomavirus (HPV) negative head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, nasopharynx, larynx, or sinuses. * Stage III or IV disease based on American Joint Committee on Cancer (AJCC) staging 8th edition. * If a primary oropharyngeal squamous cell carcinoma is diagnosed, HPV must be ruled out by immunohistochemistry. * Availability of ≥10 unstained 5 micron slides. Patients who cannot fulfill this requirement will need to undergo a new biopsy prior to enrollment on study. * Patients must be at least 18 years of age. * Measurable disease (either primary site and/or nodal disease) by RECIST 1.1 criteria. * No previous radiation or chemotherapy for a head and neck cancer. * No complete surgical resection for a head and neck cancer within 8 weeks of enrollment (although lymph node biopsy including excision of an individual node with presence of residual nodal disease, or surgical biopsy/excision of the tumor with residual measurable disease is acceptable.) No surgical procedures or core-needle or excisional biopsies will occur after baseline scans are performed and measurable lesions are identified. Fine-needle aspiration can be performed (i.e., to confirm extent of baseline lymph node involvement) following discussion with PI if not performed on a target lesion. * Performance status 0-1 * Normal Organ Function * Leukocytes ≥ 3000/mm…