Temporally Feathered Radiation Therapy (TFRT) for Head and Neck Squamous Cell Carcinoma

The primary objective of this study is to determine the feasibility of TFRT planning and
delivery for head and neck squamous cell carcinoma. Secondary objectives include estimating
grade 3-5 acute toxicity (within 90 days) and describing patient-reported outcomes (PRO) of
toxicity during and after TFRT. This study is planned as a single arm feasibility trial to
demonstrate clinical delivery of TFRT plans. Five patients will be accrued as a single
cohort.

When using standard-of-care intensity modulated radiation therapy (IMRT), a single radiation
plan is created and delivered on a daily basis Monday-Friday for a total of 7 weeks. In
contrast, when using TFRT, up to 5 different plans are created and delivered each specific
day of the week. Treatments will still occur on a daily basis Monday-Friday for 7 weeks. In
each of these radiation plans used for TFRT, the radiation dose that will be delivered to the
nearby healthy tissues will vary, allowing for increased time for normal tissue to recover
from radiation-induced damage. Once weekly, a slightly higher radiation dose will be
delivered to the "feathered" organ. On the remaining four days of the week, a slightly lower
radiation dose will be delivered to the "feathered" organ. The radiation dose that will be
delivered to the areas of cancer will not be changed. In this study, only the radiation dose
delivered to the normal healthy tissues will be changed.

Inclusion Criteria:

- Subjects must have histologically or cytologically confirmed squamous cell carcinoma
arising from a primary head and neck site (oral cavity, oropharynx,
larynx/hypopharynx, nasopharynx).TX-4, NX-3, MX-0 stages are permitted.

- Subjects must be eligible for definitive radiation therapy (70Gy in 35 fractions) with
or without chemotherapy.

- Karnofsky Performance status ≥80.

- Subjects must have the ability to understand and the willingness to sign a written
informed consent document.

Exclusion Criteria:

- Subjects receiving any other investigational agents.

- Postoperative radiotherapy is not permitted.

- History of prior head and neck radiation therapy.

- Subjects with uncontrolled inter-current illness including, but not limited to ongoing
or active infection, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, or psychiatric illness/social situations that would limit
compliance with study requirements.

- Pregnant or breastfeeding women are excluded from this study because radiation therapy
has the potential for teratogenic or abortifacient effects. Because there is an
unknown, but potential risk for adverse events in nursing infants secondary to
treatment of the mother with radiation therapy, breastfeeding should be discontinued
if the mother is treated with radiation therapy. These potential risks may also apply
to other agents used in this study.

- The patient cannot have distant metastatic disease (or M1 disease by AJCC 8th
edition).