Omission of Radiation Therapy after Surgery for the Treatment of Patients with HPV-Positive Oropharyngeal Squamous Cell Carcinoma, OPERATION Trial

Inclusion Criteria

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, ≥ 18 years of age (no upper age limit)
• Biopsy proven squamous cell carcinoma
• p16 positive (diffuse ≥ 70% tumor cell expression, with at least moderate [2/3+] staining intensity)
• NavDx positive, HPV16 tumor tissue modified viral (TTMV) only
• American Joint Committee on Cancer (AJCC) 8th edition cT0-2 N1 M0
• Well lateralized tonsil (> 1 cm from midline, tonsil, base of tongue, glossotonsillar sulcus primary tumors)
• ≤ 2 lymph nodes, each ≤ 3cm, -OR- 1 lymph node > 3 but < 6 cm
• ≤ 10 pack-years of cigarette smoking or no cigarette smoking for ≥ 5 years (regardless of pack years)
• Anatomically (e.g. adequate exposure) and physically amenable to transoral robotic surgery (TORS) per the judgement of the operating surgeon
• Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks prior to surgery; at a minimum CT imaging of the chest. PET/CT is acceptable
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• Complete blood count (CBC) with differential obtained within 8 weeks prior to surgery, with adequate bone marrow function
• Platelets ≥ 100,000 cells/mm^3 (obtained within 8 weeks prior to surgery)
• Hemoglobin ≥ 9.0 g/dl (obtained within 8 weeks prior to surgery) (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] ≥ 9.0 g/dl is acceptable. Transfusion must be completed within 2 to 4 weeks prior to enrollment)
• Serum creatinine < 2.0 mg/dl (obtained within 8 weeks prior to surgery)
• Total bilirubin ≤ 1.5 x the institutional upper limit of normal (ULN) (obtained within 8 weeks prior to surgery)
• Negative pregnancy test within 2 weeks prior to surgery for women of childbearing potential
• Eligible for platinum chemotherapy. Chemotherapy drugs allowed: cisplatin, carboplatin/paclitaxel, carboplatin/Abraxane, per treating physician (cisplatin preferred, 2nd preference carboplatin/paclitaxel or carboplatin/Abraxane)
• For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional year after surgery per doctor of medicine (MD) discretion. Acceptable forms of birth control include hormonal contraceptives (such as birth control pills, skin patch, vaginal ring, injection, and/or implant), intrauterine devices (IUDs), and barrier devices (such as condoms, diaphragm, cervical cap, and sponge)

Exclusion Criteria

• Prior history of surgery to the head and neck that in the opinion of the investigators would modify prognostic significance of pathology results
• Prior history of radiation therapy to the head and neck, with the exception of skin cancer treated with a small (≤ 9 cm^3) field with 6 – 9 MeV electron beam or 50 – 250 kVp photon beam
• Prior history within 5 years of cancer with the exception of: * Basal cell carcinoma of the skin * Squamous cell carcinoma of the skin, stage 1-2 * Prostate cancer without distant metastases (stage M0) * Thyroid cancer without distant metastases (stage M0)
• Prior history of squamous cell carcinoma of a mucosal site in the head or neck treated with surgery alone
• Currently taking disease modifying rheumatoid drugs (DMRDs) or immunosuppressive medication, for example as for organ transplant or multiple sclerosis
• Current smoker or tobacco user
• Severe, active co-morbidity, defined as one or more of the following: * Unstable angina and/or congestive heart failure requiring inpatient 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 (COPD) exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects. * Note, however, coagulation parameters are not required for entry into this protocol. * Evidence of active systemic lupus or scleroderma. * Psoriatic arthritis.
• Known HIV positivity. HIV positive patients are known to have worse clinical outcomes especially for local, regional, and distant cancer control. This poorer prognosis is thought to be secondary to a compromised immune system. Thus, de-intensification of radiation and chemotherapy is not justifiable in this population * Note: HIV testing at the time of enrollment is not required
• Subjects of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for the immediate post-op period (1-2 weeks). Females will be determined to be not of child-bearing potential with a history of hysterectomy or with postmenopausal status of > 12 months
• Pregnant or breastfeeding, or expecting to conceive within the projected duration of the study, starting one month prior to screening and for one year after surgery per MD discretion
• Prisoners or subjects who are involuntarily incarcerated, or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness