Standard of care radiation therapy (RT) for head and neck squamous cell carcinoma (HNSCC)
involves conventional fractionation delivered over a course of 7 weeks. Although
hypofractionated RT (HFRT) delivering higher dose of RT each day over a shorter overall
treatment time has been studied and adopted as standard of care in many disease sites
including breast and prostate cancers, data on HFRT in HNSCC is limited.
There is a strong radiobiological rationale for HFRT for HNSCC to decrease the overall
treatment time and thus the effects of accelerated repopulation in this disease entity. In
addition, if similar outcomes can be achieved with a reduced number of fractions, cost
effectiveness of care can be improved while minimizing the disruption to the patient's
personal and professional lives. A substantial decrease in treatment time may improve
compliance and financial toxicity associated with the patient's oncologic treatment.
The global COVID-19 pandemic is highlighting the health risk to society at large of having no
viable alternative to a 7 week daily RT course for HNSCC, especially in the setting of
compromised immune systems associated with concurrent chemotherapy frequently used in this
patient population. Thus, the study of HFRT for HNSCC is both timely and potentially paradigm
changing for practices across the United States.
The incidence of human papilloma virus (HPV)-associated oropharynx cancer is increasing in
the United States, now accounting for 70-80% of all oropharynx cancers. It has a favorable
prognosis vs. non-HPV-associated cancers and studies are ongoing to determine the best
strategy to de-intensified therapy while maintaining good oncologic outcomes.
The purpose of this single-arm Phase I study is to assess the tolerability and signal for
efficacy of de-intensified HFRT for favorable HPV-associated oropharynx cancer.
De-intensification will be achieved in two ways. First, the equivalent biologically effective
dose (BED) of HFRT used on trial will be 60 Gy of conventionally fractionationated RT (vs.
the current standard of care of 70 Gy). Second, the elective nodal volume irradiated will be
limited to involved nodal levels and one immediately adjacent level (vs. the current standard
of care of entire bilateral neck nodal regions). Patients will complete RT in 15 fractions (3
weeks) with concurrent weekly cisplatin on dose level 0, and if well tolerated, escalate to
level 1 delivering RT in 12 fractions (3 weeks). If a 3-week regimen is not well-tolerated, a
20 fraction regimen will be used on dose level -1.
Inclusion Criteria:
1. Pathologically-proven diagnosis of T1-3 (up to 6 cm), N0-2 (AJCC 8th edition) p16
positive squamous cell carcinoma of the oropharynx (except T1-2N0 as noted in the
exclusion criteria)
2. ≤10 pack-year smoking history and not actively smoking
3. Age ≥18 years
4. ECOG performance status 0-2 or Karnofsky Performance Status 50-100
5. Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation, and for 90 days following completion of therapy.
Should a woman become pregnant or suspect she is pregnant while participating in this
study, she should inform her treating physician immediately.
A female of child-bearing potential is any woman (regardless of sexual orientation,
marital status, having undergone a tubal ligation, or remaining celibate by choice)
who meets the following criteria: Has not undergone a hysterectomy or bilateral
oophorectomy; or has not been naturally postmenopausal for at least 12 consecutive
months (i.e., has had menses at any time in the preceding 12 consecutive months).
6. Negative serum or urine pregnancy test within 2 weeks before registration for women of
childbearing potential.
7. Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
1. Distant metastasis
2. T1-2N0 (AJCC 8th edition) p16 positive squamous cell carcinoma of the oropharynx
(candidates for definitive RT alone or surgery alone)
3. Inability to receive concurrent weekly cisplatin due to comorbid conditions
4. Synchronous non-skin cancer primaries outside of the oropharynx, oral cavity, larynx,
and hypopharynx except for low- and intermediate-risk prostate cancer and
well-differentiated thyroid cancer. For prostate cancer, patient should not be
receiving active treatment. For thyroid cancer, thyroid surgery may occur before or
after radiation treatment, provided all other eligibility criteria are met.
5. Prior invasive malignancy with an expected disease-free interval of less than 3 years
6. Prior radiotherapy to the region of the study cancer that would result in overlap of
radiation fields
7. Subjects may not be receiving any other investigational agents for the treatment of
the cancer under study.
8. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to the chemotherapy agents in this study
9. 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, in the opinion of the
investigator, would limit compliance with study requirements
10. Subjects must not be pregnant or nursing due to the potential for congenital
abnormalities and the potential of this regimen to harm nursing infants.
11. History of severe immunosuppression, including HIV, organ or autologous or allogeneic
stem cell transplant, or active immunosuppressive medication at the time of enrollment
