Invert-Prospective Phase II Randomized Trial of Involved Nodal Versus Elective Neck RadioTherapy

Inclusion Criteria: * Pathologically-proven diagnosis of squamous cell carcinoma of the oropharynx, larynx, or hypopharynx. Squamous cell carcinoma of unknown primary is not allowed. * Patients must have clinically or radiographically evident measureable disease at the primary site and/or nodal stations. Diagnostic lymph node excision (≤ 2 nodes) is also allowable. * Patients may undergo a diagnostic or therapeutic transoral resection for a T1-2 tonsil or base of tongue cancer. * Clinical stage I-IVB (AJCC, 7th edition); stages I-II glottic cancer are excluded * Age ≥ 18 years. * ECOG Performance Status 0-2 * All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria Has not undergone a hysterectomy or bilateral oophorectomy; or Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). * Neck CT and/or neck MRI, and PET-CT * Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria: * Distant metastasis. * Inability to undergo either a diagnostic CT with contrast or simulation CT with contrast. * Inability to undergo PET-CT. * Stage I and II glottic carcinoma. * Gross total excision of both the primary and nodal disease. * Synchronous non-skin cancer primaries outside of the oropharynx, larynx, and hypopharynx except for low- and intermediate-risk prostate cancer and synchronous well-differentiated thyroid cancer; in the latter case, surgery may occur before or after treatment, provided all other eligibility criteria are met. * Prior invasive malignancy with an expected disease-free interval of less than 3 years. * Prior systemic chemotherapy for the study cancer; prior chemotherapy for a remote cancer is allowable. * Prior radiotherapy to the region of the study cancer that would result in overlap of radiation fields. * Subjects may not be receiving any other investigational agents. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to the chemotherapy agents in this study (if necessary). * 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, in the opinion of the investigator, would limit compliance with study requirements. * History of severe immunosuppression, including HIV, and organ or autologous or allogeneic stem cell transplant.