Radiation Therapy Avoiding the Contralateral Neck for the Treatment of Patients with p16-Positive Oropharyngeal Squamous Cell Cancer, SAVER Study

Inclusion Criteria

• Pathologically (histologically or cytologically) proven diagnosis of p16+ squamous cell carcinoma (including the histological variants papillary squamous cell carcinoma and basaloid squamous cell carcinoma) of the oropharynx. Note: Cytologic diagnosis from a cervical lymph node (from a paraffin block, not from smears) is sufficient in the presence of clinical evidence of a primary tumor in the oropharynx. Clinical evidence should be documented, may consist of palpation, imaging, or endoscopic evaluation, and should be sufficient to estimate the size of the primary (for T stage)
• Patient requires elective contralateral radiotherapy in the definitive or adjuvant setting (i.e. base of tongue primary or tonsil with base of tongue invasion, soft palate invasion, or medialized as defined by > 1/3 of the distance from the tonsil to the midline of the soft palate
• Patient has clinical stage T1-4, N0, N1 or N3, and M0 disease (American Joint Committee on Cancer [AJCC] 8th edition) as defined by physical examination and appropriate imaging (positron emission tomography [PET]/computed tomography [CT] preferred, CT neck with IV contrast with CTT chest without contrast as recommended alternative to PET/CT)
• General history and physical examination performed by a radiation oncologist, medical oncologist, or head and neck surgeon within 60 days prior to registration
• Patient’s Zubrod performance status 0-1 within 30 days prior to registration
• Patient >= 18 years of age
• For women of childbearing potential, a serum pregnancy test completed within 2 weeks of initiation or radiotherapy
• Serum pregnancy test negative
• If a woman of child-bearing potential or sexually active male, the patient must be willing to use effective contraception throughout their participation in the treatment phase of the study and at least 180 days following the last study treatment
• Patient provides study specific informed consent prior to study entry, including consent for mandatory submission of tissue for required p16 review

Exclusion Criteria

• Patient has cancer considered to be from an oral cavity site (oral tongue, floor mouth, alveolar ridge, buccal or lip), nasopharynx, hypopharynx, or larynx
• Carcinoma of the neck of unknown primary origin
• Distant metastasis
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years
• Prior systemic chemotherapy for the study cancer (prior chemotherapy for a different cancer is allowable)
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• Prior surgery of the head and neck excluding transoral robotic surgery (TORS) or superficial removal of cutaneous skin malignancies
• Patient is homeless
• Patient has an active drug or alcohol dependency
• Patient is pregnant or nursing (an exception will be made for nursing patients that are not receiving chemotherapy)
• Radiographic evidence of contralateral nodal disease as described below * Max standardized uptake value (SUV) greater than 3.0, or * Short-axis diameter is > 1.5 cm for level II nodes, > 0.8 cm for retropharyngeal node, or > 1.0 cm for level III, IV, or V, or * Central necrosis or heterogeneous enhancement