A Phase 2 Study of De-Intensified Risk-Adapted Postoperative Radiation therapy for Human Papilloma Virus Associated Oropharyngeal Squamous Cell Carcinoma

This research study is studying lowering the standard dose of radiation and chemotherapy
after surgery, to minimize the side effects and improve the quality of life.

Inclusion Criteria:

- Histologically or cytologically confirmed squamous cell carcinoma of the tonsil or
base of tongue (oropharynx) or unknown primary with p16-positive cervical lymph node
metastases

- HPV-associated tumor as defined by: positive p16 immunohistochemistry (>70%) OR in
situ hybridization OR PCR-based methods

- Eligible for curative-intent surgery with anticipated negative margins

- Surgery performed at Brigham & Women's Hospital

- Age 18 or older years.

- ECOG performance status 0-1 (Karnofsky ≥70%, see Appendix A)

- Normal organ and marrow function as defined below:

- leukocytes ≥3,000/mcL

- absolute neutrophil count ≥1,000/mcL

- platelets ≥100,000/mcL

- total bilirubin within normal institutional limits

- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal

- creatinine ≤ 1.5 times the institutional upper limit of normal OR

- creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels
above institutional normal.

- Patients with ≤20 pack-years of cumulative cigarette smoking. Pack-years are
calculated by multiplying the number of years smoked with the pack of cigarettes
smoked per day. One pack is considered to contain 20 cigarettes.

- Tumor clinical stage (AJCC 8th edition): T0 or T1 or T2

- Nodal clinical stage (AJCC 8th edition): N0 or N1

- No distant metastases. Clinical M-stage must be M0 (AJCC 8th edition).

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

Exclusion Criteria:

- Prior history of head and neck cancer within 5 years.

- Prior head and neck radiation

- Clinically fixed or matted nodes

- 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. Note: that HIV positive patients will be eligible.

- Pregnant women are excluded from this study because of the teratogenic risks of
radiation exposure to the developing fetus. Because there is an unknown but potential
risk for adverse events in nursing infants secondary to treatment of the mother with
radiation therapy and supportive care medications required for symptomatic management
of head and neck cancer side effects as well as general anesthesia required for
oncologic head and neck surgery, breastfeeding should be discontinued if the mother is
enrolled in the study. Pregnancy status will be determined by a serum pregnancy test.