Randomized Phase II Study of DCE-MRI-based Dose Escalation for Poor-prognosis and Neck Cancer

Inclusion Criteria: * Patients must have pathologically-confirmed, non-metastatic locally/regionally advanced squamous cell carcinoma of the head and neck, stage III/IV, referred for definitive chemo-RT, and meet one of the following six criteria: 1. Primary tumor (T4) with or without metastatic lymph nodes. Tumor or nodes are: unresectable, resection is considered by the treating surgeon or patient to result in unacceptable functional or oncological results, patient refuses surgery, or surgery is not possible due to comorbidities. 2. HPV(-) (Human Papillomavirus) or p16(-) locally/regionally advanced (T3-4 or N2-3) oropharyngeal cancer. 3. HPV(+) or p16(+) locally/regionally advanced (T4 or N3) oropharyngeal cancer. 4. T3 or T4 laryngeal or hypopharyngeal cancer that is locally advanced, bulky (\>40 cc\*), unresectable, or patient declines surgery. 5. Stage III/IV oral cavity or paranasal sinus cancers in patients who refuse surgery or are unfit for surgery. 6. Locally/regionally advanced (stage T3-4 and/or N3) nasopharyngeal cancer which is EBV (-) (Epstein-Barr Virus). * KPS (Karnofsky Performance Status: A measure of general well being and activities of daily living; scores range from 0 to 100 where 100 represents perfect health) \>70 (see Appendix A) within two weeks of enrollment. * Pre-treatment laboratory criteria within four weeks of enrollment: * WBC (White Blood Cell) \> 3500/ul, granulocyte \> 1500/ul. * Platelet count \> 100,000/ul. * Total Bilirubin \< 1.5 X ULN. * AST (Aspartate Aminotransferase) and ALT (Alanine Aminotransferase) \< 2.5 X ULN. * Estimated Creatinine clearance \>30cc/min. * Patients must be able to receive protocol chemotherapy in the judgment of the treating Medical Oncologist. * Patients are adults (Age ≥18). * All patients must be informed of the investigational nature of this study and given written informed consent in accordance with institutional and federal guidelines. Exclusion Criteria: * EBV (+) Nasopharyngeal Carcinoma in the protocol treated tumor. * Prior head and neck radiation. * Documented evidence of distant metastases. * Patients with active infection. * Pregnant women. * Patients should have no contraindications to having a contrast enhanced MRI scan. These contraindications will be assessed at the time of enrollment using the guidelines set up and in clinical use by the Institutional Standard Practice.