This is a trial of definitive chemotherapy and radiation therapy in human papilloma virus
positive oropharyngeal cancers, in a population whose cancer is thought to be highly
radio-sensitive. This is a population whose outcomes are already known to be very good with
high rates of local and distant control of the disease. With the long term disease control
and survival of patients with this disease, long term treatment toxicity and resulting
reduction in quality of life poses new problems. This has lead to several studies to examine
the role of radiation dose de-escalation through various strategies in attempt to reduce long
term toxicity from treatment and yet achieve equivalent long term disease control.
This trial specifically hypothesizes that a lower dose of radiation therapy to the clinically
and radiographically uninvolved lymph nodes will no detrimental effect on loco-regional
control or overall survival and will improve the long-term side effect profile, particularly
with regards to xerostomia and dysphagia. The goal of this study is therefore to determine
whether a lower dose to the clinically and radiographically uninvolved lymph nodes can be
done safely and with better long-term toxicity profile and better overall quality of life
without compromising the expected outcomes of progression free survival.
- Patients generally must have the psychological ability and general health that permits
completion of the study requirements and required follow up.
- Women of childbearing potential and men who are sexually active should be willing and
able to use medically acceptable forms of contraception throughout the treatment phase
of the trial and until at least 60 days following the last study treatment.
- Pathologically (histologically or cytologically) proven diagnosis of squamous cell
carcinoma (including the histological variants papillary squamous cell carcinoma and
basaloid squamous cell carcinoma) of the oropharynx (tonsil, base of tongue, soft
palate, or oropharyngeal walls); cytologic diagnosis from a cervical lymph node is
sufficient in the presence of clinical evidence of a primary tumor in the oropharynx.
Clinical evidence should be documented, may consist of palpation, imaging, or
endoscopic evaluation, and should be sufficient to estimate the size of the primary
(for T stage).
- Patients must have clinically or radiographically evident measurable disease at the
primary site or at nodal stations. Tonsillectomy or local excision of the primary
without removal of nodal disease is permitted, as is excision removing gross nodal
disease but with intact primary site. Limited neck dissections retrieving ≤ 4 nodes
are permitted and considered as non-therapeutic nodal excisions.
- Immunohistochemical staining for p16 must be performed on tissue and documented in the
pathology report(s) with reported result positive for p16.
- Clinical stage T1-T3, N0-N2c (AJCC, 7th ed.), which is equal to T1-T3, N0-2 (AJCC, 8th
ed.) including no distant metastases based on the following diagnostic workup:
- General history and physical examination within 30 days prior to registration;
- Fiberoptic exam with laryngopharyngoscopy (mirror and/or fiberoptic and/or direct
procedure) within 60 days prior to registration;
- One of the following combinations of imaging is required within 45 days prior to
1. A CT scan of the neck (with contrast) and a chest CT scan (with or without
2. or an MRI of the neck (with contrast) and a chest CT scan (with or without
3. or a CT scan of neck (with contrast) and a PET/CT of neck and chest (with or
4. or an MRI of the neck (with contrast) and a PET/CT of neck and chest (with
or without contrast).
Note: A CT scan of neck and/or a PET/CT performed for the purposes of radiation planning
may serve as both staging and planning tools.
- Patients will be asked about their personal smoking history prior to enrollment. Only
active smokers with greater than 10 pack years will be excluded from the trial. The
total number of pack years will be collected at baseline. Current smokers who wish to
discontinue will be offered smoking cessation information, and if they are able to
discontinue smoking prior to initiation of radiation therapy, they can remain eligible
for the trial.
Number of pack-years = [Frequency of smoking (number of cigarettes per day) × duration of
cigarette smoking (years)] / 20 Note: Twenty cigarettes is considered equivalent to one
pack. The effect of non-cigarette tobacco products on the survival of patients with
p16-positive oropharyngeal cancers is undefined.
- Zubrod Performance Status of 0-1 within 30 days prior to registration;
- Adequate hematologic function within 14 days prior to registration, defined as
- Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3;
- Platelets ≥ 100,000 cells/mm3;
- Hemoglobin ≥ 8.0 g/dl; Note: The use of transfusion or other intervention to
achieve Hgb ≥ 8.0 g/dl is acceptable.
- Adequate renal function within 14 days prior to registration, defined as follows:
- Serum creatinine < 1.5 mg/dl or creatinine clearance (CC) ≥ 50 ml/min
- Adequate hepatic function within 14 days prior to registration defined as follows:
- Bilirubin < 2 mg/dl;
- AST or ALT < 3 x the upper limit of normal.
- Negative serum pregnancy test within 14 days prior to registration for women of
- Cancers considered to be from an oral cavity site (oral tongue, floor mouth, alveolar
ridge, buccal or lip), or the nasopharynx, hypopharynx, or larynx, even if p16
- Carcinoma of the neck of unknown primary site origin (even if p16 positive);
- T1-T2 N0-1 lateralized squamous cell carcinoma of the tonsil.
- Radiographically matted nodes, that span 6 cm or more; N3 disease
- Supraclavicular nodes, defined as nodes visualized on the same axial imaging slice as
- Definitive clinical or radiologic evidence of metastatic disease or adenopathy below
- Gross total excision of both primary and nodal disease; this includes tonsillectomy,
local excision of primary site, and nodal excision that removes all clinically and
radiographically evident disease.
- Simultaneous primary cancers or separate bilateral primary tumor sites;
- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
for a minimum of 5 years (for example, carcinoma in situ of the breast, oral cavity,
or cervix are all permissible);
- Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a
different cancer is allowable;
- Prior radiotherapy to the region of the study cancer that would result in overlap of
radiation therapy fields;
- Severe, active co-morbidity defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization within
the last 6 months;
- Transmural myocardial infarction within the last 6 months;
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time
- Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy within 30 days of
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
note, however, that laboratory tests for liver function and coagulation
parameters are not required for entry into this protocol other than those
requested in Section 3.2.11 of the protocol.