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Biomarker-Driven Radiation Therapy Dose Reduction after Transoral Robotic Surgery for the Treatment of HPV-Positive Oropharyngeal Cancer

Cancer Type
Head and Neck Cancer
Unknown Primary
Trial Phase
Phase II
18 Years and older, Male and Female
Study Type
Protocol IDs
WINSHIP5566-22 (primary)
Study Sponsor
Emory University Hospital/Winship Cancer Institute


This phase II trial tests whether reduced dose radiation therapy after transoral robotic surgery works in treating patients with human papillomavirus (HPV)-positive oropharyngeal cancer. HPV positive oropharyngeal cancer has a better prognosis than oropharyngeal cancer not caused by HPV. A standard of care treatment for HPV positive oropharyngeal cancer is transoral robotic surgery followed by radiation therapy. However, this treatment is associated with many long-term side effects including difficulty swallowing. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Giving reduced dose radiation therapy after transoral robotic surgery may improve swallowing outcomes and quality of life compared to standard of care dose radiation therapy after transoral robotic surgery.


I. To evaluate swallow function among post-operative circulating tumor HPV deoxyribonucleic acid (ctHPVDNA)-negative patients treated with reduced intensity adjuvant radiation therapy (RT) doses as compared to historical controls from ECOG 3311.

I. Evaluate progression free survival (PFS), overall survival (OS), and locoreginal control (LRC) among post-operative ctHPVDNA-negative patients treated with reduced adjuvant RT doses.
II. Evaluate PFS among post-operative ctHPVDNA-positive patients treated with standard of care adjuvant therapy.

Patients who are ctHPVDNA negative after surgery undergo reduced dose radiation therapy for 3 weeks (15 treatments). Patients who are ctHPVDNA positive or indeterminate after surgery undergo standard of care radiation therapy.

After completion of study treatment, patients are followed up at 3, 6, 12, 18, and 24 months.


  1. Age >= 18 years.
  2. Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%).
  3. Has diagnosis of HPV-associated squamous cell carcinoma of the oropharynx * HPV positive either via p16 status or via in situ hybridization * This includes patients with HPV positive squamous cell carcinoma of an unknown primary of the head and neck presumed to be of oropharyngeal origin who have undergone ipsilateral palatine and lingual tonsillectomies.
  4. pT1-2, pN0-1, cM0 disease.
  5. Positive ctHPVDNA titer prior to surgery.
  6. =< 10 pack-year smoking history (or < 30 pack-year history and at least 10 years of abstinence).
  7. Completed transoral robotic surgery (TORS) oropharyngectomy and at least ipsilateral neck dissection by an an board-eligible/board-certified otolaryngologist.
  8. Pathology must demonstrate at least one of the follow intermediate risk factors: * Close margin (1 – 4 mm) * Perineural invasion * Lymphovascular space invasion * 2 – 4 positive lymph nodes without extranodal extension (ENE) * A single positive lymph node > 3 cm in size, without ENE
  9. Pathology cannot demonstrate > 4 positive lymph nodes, ENE, or a positive final margin (defined as < 1 mm). Margins that have been subsequently cleared are allowed.
  10. Radiation increases the risk of birth defects. For this reason, females of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to starting therapy.
  11. FCBP and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 12 months after completion of radiation. A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months.
  12. Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions.
  13. Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation.

Treatment Sites in Georgia

Emory University Hospital - Midtown

550 Peachtree Street NE
Atlanta, GA 30308

Winship Cancer Institute of Emory University

1365 Clifton Road NE
Building C
Atlanta, GA 30322

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.