Adaptive Treatment De-escalation in Favorable Risk HPV-Positive Oropharyngeal Carcinoma

Inclusion Criteria20

• Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma of the oropharynx, which include the sites tonsil, base of tongue, soft palate, or posterior oropharyngeal wall. Histologic variants will be included (papillary squamous cell carcinoma and basaloid squamous cell carcinoma). Cytologic diagnosis from a cervical lymph node is sufficient in the presence of clinical evidence of a primary tumor in the oropharynx.
• If the primary site is biopsied, Patient's tissue must be positive for p16 by immunohistochemical staining (\>70% staining). Fine needle aspiration (FNA) biopsy specimens may be used as the sole diagnostic tissue if formalin-fixed paraffin-embedded cell block material is not available for p16 immunohistochemistry.
• Patients must have detectable HPV ctDNA Score Report at Screening or have a detectable baseline HPV ctDNA Score Report (Naveris test) if no primary site is biopsied. Must have detectable screening plasma HPV DNA (also referred to as ctHPV DNA).
• Clinical stage T1-T3, N1-N2b (AJCC 7th Edition) with no distant metastases based on the following diagnostic workup:
• Fiberoptic exam with laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) within 8 weeks prior to registration.
• One of the following combinations of imaging is required within 8 weeks of registration:
• CT scan of the neck (with contrast) and a PET/CT of neck and chest (with or without contrast);
• Or an MRI of the neck (with contrast) and a PET/CT of neck and chest (with or without contrast)
• Note: A CT scan of the neck and/or a PET/CT performed for the purposes of radiation planning may serve as both staging and planning tools.
• Patients must provide their personal smoking history prior to registration. Patients cannot have a cumulative personal smoking history that exceeds 10 pack-years.
• Number of pack-years = \[Frequency of smoking (number of cigarettes per day) x duration of cigarette smoking (years)\] / 20
• Note: Twenty cigarettes is considered equivalent to one pack. Cigar and pipe tobacco consumption is not included in calculating lifetime pack-years.
• Zubrod Performance Status of 0-1 within 8 weeks prior to registration;
• Adequate hematologic function within 2 weeks prior to registration, defined as follows:
• Absolute neutrophil count (ANC) ≥ 1,500 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 2 weeks prior to registration, defined as follows:
• a.Serum creatinine ≤ 1.5 mg/dl or creatinine clearance (CC) ≥ 50 ml/min determined by 24 hour collection or estimated by Cockcorft-Gault formula: i.CCr male = \[(140 - age) x (wt in kg)\] \[(Serum Cr mg/dl) x (72)\] ii.CCr female = 0.85 x (CrCl male)
• Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential;
• Patients who are HIV positive but who have no prior AIDS-defining illness and have CD4 cells of at least 350/mm3 are eligible. HIV-positive patients must not have multi-drug resistant HIV infection or other concurrent AIDS-defining conditions. Patients must not be sero-positive for Hepatitis B (Hepatitis B surface antigen positive or anti-hepatitis B core antigen positive) or sero-positive for Hepatitis C (anti-Hepatitis C antibody positive). However, patients who are immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B).
• The patient must provide study-specific informed consent prior to study entry.