Single center, non-randomized Phase II study enrolling Stage I-II p16+ oropharyngeal cancer patients to one of two de-escalation treatment paradigms: (1) receive surgery followed by observation or risk-adjusted adjuvant radiation (+/-chemo), or (2) individualized adaptive definitive chemoradiation (CRT).
Patients must have FDG-avid (maximum SUV ≥ 4.0) (from PET scan of any date, any scanner) and histologically or cytologically proven squamous cell carcinoma of the oropharynx (tonsil, base of tongue, oropharyngeal wall, soft palate) or unknown primary that is p16 positive by immunohistochemistry or HPV positive by in situ hybridization
Clinical stage: Stage I-II AJCC 8th edition staging
History/physical examination, including documentation of weight within 4 weeks prior to registration;
For Cohort B, FDG-PET/CT scan for staging within 6 weeks prior to registration. For Cohort A, acceptable imaging for staging can include diagnostic CT neck/chest or PET-CT within 6 weeks prior to registration
cT4, cN3, or cM1 disease (also explained as AJCC 8th edition clinical staging,)
Patients with radiographic ECE or matted lymph nodes, defined as three nodes abutting one another with loss of intervening fat plane that is a replaced with radiologic evidence of extracapsular spread.
Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible);
Any prior therapy for the study cancer; note that prior chemotherapy for a different cancer is allowable if >3 years prior to study;
Parallel
Surgery
Procedure/SurgeryCohort A will undergo initial surgical resection of the primary and neck dissection with pathologic features directing predetermined adjuvant treatment. Pathology of the primary and nodal specimens will then be reviewed as to determine the next intervention per protocol. Based on operative findings including degree of nodal involvement, extracapsular spread, perineural invasion, and lymphovascular involvement, patients will be designated to adjuvant treatment arms consisting of observation, adjuvant radiation, or adjuvant chemoradiation.
Chemoradiation
Combination productPatients will receive an initial plan with a single prescription of 30 Gy in 15 fractions to PTV\_High and PTV\_Low with RT given once daily, 5 days a week (Monday through Friday). After analysis of mid-treatment PET/CT, the remaining radiation treatment will be delivered as a conedown to the gross disease only. Patients will be planned to receive a total dose of 70 Gy, 54 Gy, or 44 Gy to PTV\_High in 2 Gy per fraction.
Observation
Other interventionCohort A will undergo initial surgical resection of the primary and neck dissection with pathologic features directing predetermined adjuvant treatment. Pathology of the primary and nodal specimens will then be reviewed as to determine the next intervention per protocol. Based on operative findings including degree of nodal involvement, extracapsular spread, perineural invasion, and lymphovascular involvement, patients will be designated to adjuvant treatment arms consisting of observation, adjuvant radiation, or adjuvant chemoradiation.
Post-operative radiation
RadiationPatients will receive adjuvant radiation based on pathologic features.Total radiation treatment doses and prescriptions will include 36 Gy in 18 fractions, 50 Gy in 25 fractions and 60 Gy in 30 fractions.
Loco-regional recurrence free survival (LR-RFS) rate
LR-RFS is defined as the difference between the date of the first treatment to the date of the first of the following events: death (any cause) or loco-regional progression. LR-RFS rates will be reported using Kaplan Meier (KM) estimates at 2 years.
Progression free survival (PFS) rate
PFS is defined as the difference between the date of the first therapy to the date of the first of the following events: death (any cause) or disease progression (local, regional, distant, defined as per section 7.1). PFS data will be censored on the date of the last tumor assessment on study for subjects who do not have objective tumor progression and who do not die while on study.
Disease specific survival (DSS) rate
DSS is defined as the difference between the date of the first treatment intake to the date of death due to oropharyngeal cancer.
Overall survival (OS) rate
OS is defined as the difference between the date of the first treatment intake to the date of death (any cause).
Patterns of failure (locoregional relapse versus distant)
Defined as the proportion of patients who progressed in any location and whether the first progression was local, regional or distant or in multiple locations.
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