This early phase I trial evaluates the clinical outcome of mucosal sparing adjuvant
radiotherapy after surgical exploration in HPV+ head and neck cancer of unknown primaries.
The purpose of this research is to assess if radiation treatment to the neck only for tumors
with unclear original locations after careful surgical evaluation will lead to historical
rates of disease control while reducing side effects and toxicity from treatment.
PRIMARY OBJECTIVE:
I. To describe the rate of manifestation of an occult primary tumor in the pharyngeal axis or
delayed nodal recurrence in a un-dissected and/or non-irradiated neck at 2 years after study
registration in patients treated with mucosal sparing (and unilateral neck, if applicable)
radiotherapy after resection using transoral surgery for head and neck cancer of unknown
primaries (HNCUP).
SECONDARY OBJECTIVES:
I. To describe the rates and severity of acute and late toxicities and PEG dependence
attributable to mucosal sparing radiotherapy after resection using transoral surgery by
assessment of grade 3 or higher adverse events National Cancer Institute (NCI)-Common
Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0 criteria.
II. To describe the overall survival, recurrence-free survival (manifestation of an occult
primary in the pharyngeal axis, nodal recurrence in a treated (surgery/radiation therapy
[RT]) neck, delayed lymph node metastasis in an untreated neck (surgery/RT), and distant
failure associated with mucosal sparing radiotherapy.
III. To describe swallowing function changes (assessed via swallowing study) associated with
transoral surgery and adjuvant mucosal sparing radiotherapy.
OUTLINE:
Patients who have recurrence or progression during treatment or observation have medical
charts reviewed every 6 months for 5 years. Patients who complete adjuvant treatment are
followed for observation 3 days after radiation therapy, 1 month after radiation therapy,
every 3 months after radiation therapy for 2 years, every 6 months for 1 year, and then
annually for 2 years.
Inclusion Criteria:
- Patients meet criteria for intensity-modulated proton therapy (IMPT) treatment for
oropharyngeal cancer
- If IMPT is declined by patient's insurance, they can be treated with standard of
care IMRT using the same applicable standard of care procedures outlined in the
procedures manual
- Meet criteria for adjuvant chemotherapy (if applicable)
- Histological confirmation of human papillomavirus (HPV)+ squamous cell carcinoma as
defined by neck node pathology. HPV positivity will be defined as positive staining
for p16 and HPV deoxyribonucleic acid (DNA) in situ hybridization (ISH). (If
discordant, ribonucleic acid [RNA] ISH will be run for confirmatory testing)
- Pathologic stage T0 N1-N3 M0 (American Joint Committee on Cancer [AJCC] 8th edition)
with one of the following risk factors:
- Lymph node >= 3 cm
- >= 2 positive lymph nodes
- Presence of extracapsular extension
- > 1 nodal level involved
- Absence of distant metastases on standard diagnostic workup, prior to registration
(chest computed tomography [CT], chest x-ray [CXR], or positron emission tomography
[PET]/CT)
- Able to undergo pre-operative Q-clear series PET/CT head/neck for diagnostic workup of
occult primary and nodal disease
- Able to undergo transoral surgery and neck dissection by their ears, nose, and throat
(ENT) oncologist
- Surgical exploration/sampling of all mucosal sites including ipsilateral wide
field tonsillectomy and base of tongue resection. Additional biopsies or surgical
excision at the surgeon's discretion. Any radiographic or clinically suspicious
areas should be biopsied or removed. Bilateral neck dissection for high risk
patients. Ipsilateral dissection only, for patients with contralateral cN0 necks
and negative preoperative imaging
- Final pathologic evaluation demonstrating all benign samplings without
discernible primary
- Documented smoking history
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- Negative pregnancy test done =< 7 days prior to registration, for women of
childbearing potential only
- Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 35 days prior to
registration)
- Platelet count >= 100,000/mm^3 (obtained =< 35 days prior to registration)
- Hemoglobin >= 8.0 g/dL (obtained =< 35 days prior to registration)
- Creatinine =< 1.5 mg/dL or creatinine clearance >= 50 mL/min (obtained =< 35 days
prior to registration)
- Total or direct bilirubin < 2 x institutional upper limit of normal (ULN) (obtained =<
35 days prior to registration)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) or
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 3 x
institutional ULN (obtained =< 35 days prior to registration)
- Ability to complete questionnaire(s) by themselves or with assistance
- Able to provide written informed consent
- Willing to return to enrolling institution for follow-up (during the Active Monitoring
Phase of the study)
Exclusion Criteria:
- Any patient with positive retropharyngeal nodes on imaging
- Any of the following because this study involves an agent that has known genotoxic,
mutagenic and teratogenic effects:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate
contraception
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
of the investigator, would make the patient inappropriate for entry into this study or
interfere significantly with the proper assessment of safety and toxicity of the
prescribed regimens
- Uncontrolled intercurrent 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
- Other active malignancy =< 5 years prior to registration. EXCEPTIONS: Non-melanotic
skin cancer, breast cancer, prostate cancer, well-differentiated thyroid cancer,
carcinoma-in-situ of the cervix. NOTE: If there is a history or prior malignancy, they
must not be receiving other specific treatment for their cancer
- Immunocompromised patients and patients known to be human immunodeficiency virus (HIV)
positive
- Receiving any other investigational agent which would be considered as a treatment for
the primary neoplasm
- History of connective tissue disorders such as scleroderma, rheumatoid arthritis,
lupus, or Sjogren's disease
- Prior history of radiation therapy to the affected site
