Major Radiation Reduction for HPV+ Oropharyngeal Carcinoma

Inclusion Criteria:

- Pathologically (histologically or cytologically) proven diagnosis of HPV associated
squamous cell carcinoma of the oropharynx (tonsil, base of tongue, or oropharyngeal
walls) from surgical resection or excisional biopsy regardless of margin status.

° Squamous cell carcinoma of the neck of unknown primary is allowed with excision
biopsy of a lymph node (or core biopsy) and consent from the PI or co-PIs (Dr. Nancy
Lee, Dr. Eric Sherman, or Dr. Nadeem Riaz)

- Subjects must have clinically or radiographically evident measurable disease at nodal
stations.

- Clinical stage T1-2, N1-2c without evidence of distant metastasis based on FDG PET/CT.

°Patients who have squamous cell carcinoma of the neck of unknown primary, and thus,
are T0, are allowed with excision biopsy of a lymph node (or core biopsy) or consent
from the PI or co-PI

- CT or MRI of the neck with and without contrast Note: A CT scan of neck and/or a
PET/CT performed for the purposes of radiation planning may serve as planning tools.

- ECOG Performance Status of 0-2

- Age ≥ 18

- Adequate hematologic function within 30 days prior to registration, defined as
follows:

- White Blood Count (WBC) >/= 2 K/mcL

- Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3

- Platelets ≥ 100,000 cells/mm3

- Hemoglobin ≥ 8.0 g/dl; Note: The use of transfusion or other intervention to
achieve Hgb ≥ 8.0 g/dl is acceptable

- Adequate renal function within 30 days prior to registration, defined as follows:

° Serum creatinine ≤ 1.5 mg/dl or creatinine clearance (CC) ≥ 50 ml/min determined by
24-hour collection or estimated by Cockcroft-Gault formula

- Adequate hepatic function within 30 days prior to registration, defined as follows:

- Bilirubin ≤ 2 mg/dl

- AST or ALT ≤ 3 x the upper limit of normal

- Negative serum pregnancy test within 14 days prior to registration for women of
childbearing potential

- The subject must provide study-specific informed consent prior to study entry

Exclusion Criteria:

- Subjects with T3 or higher and N3 disease

- Subjects with prior head and neck radiation therapy

- Subjects with simultaneous primary cancers outside of the oropharynx

- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
for 3 years or if cure rate from treatment at 5 years to be 90% or greater

- Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a
different cancer is allowable

- No particle therapy such as but not limited to proton therapy is allowed

- Severe, active co-morbidity defined as follows:

- Unstable angina and/or congestive heart failure requiring hospitalization within
the last 6 months

- Transmural myocardial infarction within the last 6 months

- Acute bacterial or fungal infection requiring intravenous antibiotics at the time
of registration

- Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy within 30 days of
registration

- Hepatic Insufficiency resulting in clinical jaundice and/or coagulation defects