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 theprimary site and/or nodal stations. Diagnostic lymph node excision (≤ 2 nodes) isalso allowable.

• Patients may undergo a diagnostic or therapeutic transoral resection for a T1-2tonsil 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 adequatecontraception (hormonal or barrier method of birth control; abstinence) prior tostudy entry, for the duration of study treatment, and for 90 days followingcompletion of therapy. Should a woman become pregnant or suspect she is pregnantwhile participating in this study, she should inform her treating physicianimmediately.

• 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 thefollowing criteria Has not undergone a hysterectomy or bilateral oophorectomy; orHas not been naturally postmenopausal for at least 12 consecutive months (i.e., hashad 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 withcontrast.

• 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, andhypopharynx except for low- and intermediate-risk prostate cancer and synchronouswell-differentiated thyroid cancer; in the latter case, surgery may occur before orafter treatment, provided all other eligibility criteria are met.

• Prior invasive malignancy with an expected disease-free interval of less than 3years.

• Prior systemic chemotherapy for the study cancer; prior chemotherapy for a remotecancer is allowable.

• Prior radiotherapy to the region of the study cancer that would result in overlap ofradiation fields.

• Subjects may not be receiving any other investigational agents.

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to the chemotherapy agents in this study (if necessary).

• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that, in the opinion of theinvestigator, would limit compliance with study requirements.

• History of severe immunosuppression, including HIV, and organ or autologous orallogeneic stem cell transplant.