Involved Field Elective Volume De-Intensification Radiation Therapy for Head and Neck Cancer

This study aims to significantly improve the acute and late morbidity of patients with
oropharyngeal and laryngeal squamous cell carcinoma both by tailoring the elective
irradiation only to regions with a legitimate risk of recurrence (> 5%) and by lowering the
elective dose to 40 Gy. Level IB will not be electively treated unless it is involved with
pathologic or suspicious lymphadenopathy. Level V will not be treated unless two or more
ipsilateral nodal levels are involved (or level V itself has pathologic or suspicious
adenopathy). Levels III and IV will only be irradiated if the immediately proximal level
contains pathologic lymphadenopathy (i.e. level III irradiated if level II is positive; level
IV irradiated if level III is positive). We anticipate that this approach should dramatically
improve the acute and late complication profile.

Inclusion Criteria:

- Pathologically-proven diagnosis of squamous cell carcinoma of the oropharynx or
larynx. 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. Patients may undergo a diagnostic tonsillectomy,
and diagnostic lymph node excision (< 2 nodes) is also allowable.

- Clinical stage I-IVB (AJCC, 7th edition); stages I-II glottic cancer are excluded

- Age ≥ 18 years.

- ECOG Performance Status 0-2

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry.

- 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).

- Negative serum or urine pregnancy test within 2 weeks before registration for women of
childbearing potential.

- Neck CT and/or neck MRI, and whole body PET-CT.

- Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

- Distant metastasis or adenopathy below the clavicles.

- Inability to undergo PET-CT.

- Stage I and II glottic carcinoma.

- Gross total excision of both the primary and nodal disease.

- Synchronous primaries outside of the oropharynx and larynx.

- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease-free
for a minimum of 1 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 would limit compliance with
study requirements.

- Subjects must not be pregnant or nursing due to the potential for congenital
abnormalities and the potential of this regimen to harm nursing infants.

- History of immunosuppression or autoimmunity, including HIV, and organ or stem cell
transplant, or an autoimmune condition previously treated with immunosuppressive
therapy