Hypofractionated Radiation Therapy Followed by Surgery in Treating Patients With Advanced 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.

Inclusion Criteria:

- Patient is willing to sign study specific informed consent

- Pathologically proven (histologically or cytologically) diagnosis of squamous cell
carcinoma (including histological variants like papillary squamous cell carcinoma and
basaloid squamous cell carcinoma)

- Advanced stage but not metastatic SCC of the oral cavity (III or IVa, b); sites in the
oral cavity include oral tongue, floor of mouth, hard palate, gingiva, buccal mucosa,
retromolar trigone; often, head & neck tumors may involve other adjacent sites, such
as the oropharynx- in these cases, the criteria is that the tumor must appear to have
originated in the oral cavity per ear, nose, and throat (ENT)/radiation oncology

- Patient is deemed to be a surgical candidate by ENT

- Karnofsky performance status (KPS) 0-2

- For women of childbearing potential, a negative serum pregnancy test completed prior
to any radiation therapy

- Patients with human immunodeficiency virus (HIV) infection are not automatically
excluded, but must meet the following criteria: cluster of differentiation 4 (CD4)
count is > 499/cu mm and their viral load is < 50 copies/ml; use of highly active
antiretroviral therapy (HAART) is allowed

- Patient is free of any prior invasive malignancy (except non-melanomatous skin cancer)
for a minimum of the past 3 years

Exclusion Criteria:

- Metastatic disease beyond the neck or supraclavicular area as demonstrated by positron
emission tomography (PET)/CT or biopsy

- KPS 3 or worse

- Gross disease in the retrostyloid (high level II) or retropharyngeal lymph node
regions by CT or PET/CT

- Patients may not have received previous therapy for their head and neck SCC, including
chemotherapy, radiation therapy, or surgery beyond biopsy

- Second primary malignancy; exceptions are 1) patient had a second primary malignancy
but has been treated and disease free for at least 3 years, 2) in situ carcinoma (e.g.
in situ carcinoma of the cervix), 3) non-melanomatous carcinoma of the skin

- 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; this includes scleroderma

- Women who are pregnant; women of childbearing age must agree to undergo a urine
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

- Patient is deemed to not be a surgical candidate by ENT