Hypofractionated Radiation Therapy Followed by Surgery in Treating Patients With Advanced Squamous Cell Carcinoma of the Oral Cavity

This phase I/II trial studies how well hypofractionated radiation therapy followed by surgery works in treating patients with squamous cell carcinoma of the oral cavity that has spread to other places in the body. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Giving hypofractionated radiation therapy before surgery may shrink the tumor making it easier to be removed, may reduce the risk of the cancer coming back, and may be a better treatment for squamous cell carcinoma of the oral cavity.

PRIMARY OBJECTIVES: I. 2 year locoregional control for advanced oral cavity squamous cell carcinoma (SCC) treated with preoperative hypofractionated radiation followed by surgical resection. SECONDARY OBJECTIVES: I. Rate of pathologic complete response after preoperative hypofractionated radiation at both the primary site and lymph nodes (LN). II. Rate of radiologic complete and partial response (computed tomography \[CT\] neck with intravenous \[IV\] contrast performed before and after radiation therapy, judged per Response Evaluation Criteria In Solid Tumors \[RECIST\] 1.1 criteria). III. Grade III/IV/V toxicity both short term (from start of radiation to 60 days after surgery) and long term (more than 60 days after surgery). IV. Rate of flap complications: Rate of flap revisions, and complete revisions required. V. Molecular correlates. VI. Quantitative imaging correlates. OUTLINE: Patients undergo hypofractionated intensity-modulated radiation therapy (IMRT) every other day for up to 5 treatments. Patients then undergo surgery 7-14 days after the last radiation treatment. After completion of study treatment, patients are followed up every 3 months for 2 years.