Swallowing Outcomes and Circulating Tumor DNA in Patients With HPV Related Oropharyngeal Cancer Treated With Transoral Surgery and Reduced Intensity Adjuvant Therapy

Inclusion Criteria

• Histologically proven squamous cell carcinoma of the oropharynx
• Clinical stage T1-2, N0-N3, M0 by American Joint Committee on Cancer (AJCC) 8 criteria
• Must have tumors deemed surgically resectable with acceptable morbidity
• Estimated life expectancy of at least 12 weeks
• Must give informed consent
• Must have Eastern Cooperative Oncology Group (ECOG) performance status =< 3
• Must have detectable circulating HPV DNA levels
• Platelets >= 100,000/ul
• Absolute neutrophil count (ANC) >= 1,500/ul
• Hemoglobin > 8 g/dl (use of transfusion to achieve this is acceptable)
• Total bilirubin < 2 X institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 3 X institutional ULN
• Serum creatinine < 2 x institutional ULN or creatinine clearance > 50 ml/min as determined by 24 hour collection or estimated by Cockcroft-Gault formula
• Negative pregnancy test, if applicable

Exclusion Criteria

• Patients may not have received previous therapy for their head and neck squamous cell carcinoma (SCC), including chemotherapy, radiation therapy, or surgery beyond biopsy

• Second primary malignancy. Exceptions are:

  • Patient had a second primary malignancy but has been treated and disease free for at least 3 years
  • In situ carcinoma (e.g. in situ carcinoma of the cervix)
  • Non-melanomatous carcinoma of the skin

• Patients with metastatic disease beyond the neck will be excluded

• Serious concomitant systemic disorders (including active infections) that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator

• Age < 18 years

• Patients with human immunodeficiency virus (HIV) infection are not automatically excluded, but must meet the following criteria: CD4 count is > 499/cu mm and their viral load is < 50 copies/ml. Use of highly active antiretroviral therapy (HAART) is allowed

• Grade 3-4 electrolyte abnormalities (Common Terminology Criteria for Adverse Events [CTCAE], version [v.] 5)

  • Serum calcium (ionized or adjusted for albumin) < 7 mg/dl (1.75 mmol/L) or > 12.5 mg/dl (> 3.1 mmol/L) despite intervention to normalize levels
  • Magnesium < 0.9 mg/dl (< 0.4 mmol/L) or > 3 mg/dl (> 1.23 mmol/L) despite intervention to normalize levels
  • Potassium < 3.0 mmol/L or > 6 mmol/L despite intervention to normalize levels
  • Sodium < 130 mmol/L or > 155 mmol/L despite intervention to normalize levels

• Women who are pregnant, due to the teratogenic effects of radiation therapy and chemotherapy on the unborn fetus. Women of childbearing age must agree to undergo a pregnancy test prior to therapy and to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 6 months after. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

• Tumor deemed unresectable with acceptable morbidity:

  • Tumors > 4 cm in size (T3 or higher)
  • Tumors of the base of tongue < 4 cm but with deep invasion of tongue musculature placing hypoglossal nerve or both lingual arteries at risk
  • Significant extension into hypopharynx
  • Extension into soft palate beyond 1/3 of the width

• Clinically extensive extranodal extension (ENE) e.g. radiologic evidence of invasion of carotid artery, gross extension into sternocleidomastoid muscle or deep neck muscles.

Lymph nodes larger than 6 cm without clinical ENE will be allowed