ASTRO Issues Clinical Practice Guideline For Radiation Therapy in HPV-Associated OPSCC

Danielle N. Margalit, MD, MPH

The American Society for Radiation Oncology (ASTRO) has issued a clinical practice guideline to define the role of radiation therapy for patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC).

The guideline, which was published in Practical Radiation Oncology, offers evidence-based recommendations concerning the role of both definitive and postoperative radiation therapy. Patients with HPV-positive OPSCC with either T3 to T4 disease, at least 2 positive nodes, or a single node above 3 cm receiving definitive radiation therapy, were recommended to receive concurrent systemic therapy; this was a strong recommendation with a high quality of evidence. Similar patients who are ineligible for cisplatin received a conditional recommendation for receival of concurrent cetuximab, carboplatin/5-fluorouracil, or taxane-based systemic therapy.

Postoperatively, ASTRO recommended radiation therapy with concurrent cisplatin for patients with positive surgical margins or extranodal extension. Patients with pT3 to pT4 disease, at least 2 positive nodes, or a single node greater than 3 cm were recommended to receive postoperative radiation therapy alone. ASTRO conditionally recommended observation for patients with pT1 to pT2 disease and a single node up to 3 cm in the absence of other risk factors.

“The role and practice of radiation therapy continues to evolve for HPV-associated OPSCC, and these guidelines inform best clinical practice based on the available evidence,” Danielle N. Margalit, MD, MPH, director of Radiation Oncology at the Merkel Cell Cancer Center and a senior physician at Dana-Farber Cancer Institute, as well as an associate professor of Radiation Oncology at Harvard Medical School, in Boston, Massachusetts, and coauthors wrote in the guideline.

To develop the guideline, ASTRO convened a multidisciplinary team of radiation and medical oncologists, head and neck surgeons, a medical physicist, a patient representative, and an information specialist. The guideline was developed via collaboration with the American Society of Clinical Oncology and the American Academy of Otolaryngology-Head and Neck Surgery; these organizations nominated representatives and peer reviewers.

The multidisciplinary team performed a systematic search of human participant studies using the Ovid MEDLINE database and examined English-language publications between January 2000 through May 24, 2023. The search included studies of adult patients with HPV-positive OPSCC; the minimum patient count was 50 for prospective studies and 100 for retrospective studies.

Fourteen official peer reviewers revised the guideline and the modified guideline was posted to the ASTRO website to allow for comments from the public from October to November 2023. The ASTRO Board of Directors approved the final guideline, and it was subsequently endorsed by the European Society for Radiotherapy and Oncology and The Royal Australian and New Zealand College of Radiologists.

The guideline sought to address key questions on the use of radiation therapy to treat patients with HPV-associated OPSCC which included indications for definitive and postoperative radiation therapy and chemoradiation; indications for adjuvant radiation therapy and chemoradiation for patients treated with primary surgery; dose-fractionation regimens and volumes for treatment with definitive and postoperative radiation therapy and chemoradiation; preferred treatment techniques and normal tissue constraints for definitive and postoperative radiation therapy; and initial post-treatment restaging and management of the neck. Notably, the task force did not offer a recommendation on primary surgery vs radiation therapy.

Additional recommendations in the guideline indicated that patients who are treated with definitive radiation therapy with concurrent systemic therapy should receive 7000 cGy in 33 to 35 fractions. Those who are receiving postoperative radiation therapy without positive surgical margins and extranodal extensions are recommended to receive 5600 to 6000 cGy.

All patients being treated with radiation therapy were recommended to receive intensity-modulated radiation therapy over 3D techniques with dose reduction to critical organs at risk. Approximately 3 months after definitive radiation therapy or chemoradiation, reassessment via positron emission tomography-computed tomography (PET-CT) is recommended. Neck dissection is recommended for patients with convincing evidence of residual disease. Patients with convincing evidence of residual disease should receive neck dissection and those with equivocal PET-CT findings are recommended to receive either neck dissection or repeat imaging.

“The competing therapeutic ratios of definitive radiation therapy vs surgery are continuously evolving, as de-escalation approaches may constantly alter the relative risks and benefits of one local therapy over another,” study authors wrote in conclusion. “In the absence of a phase 3 comparison, the optimal choice of local therapy will likely remain highly personalized. Finally, trials of HPV-positive OPSCC have largely enrolled White males….Based on these data, it is unclear how and to what extent these prospective data can be extrapolated to other racial, gender, and socioeconomic settings. Additional work is clearly needed to understand the impact of and optimal treatments for HPV-positive OPSCC in diverse populations.”

Reference

Margalit DN, Anker CJ, Aristophanous M, et al. Radiation therapy for HPV-positive oropharyngeal squamous cell carcinoma: an ASTRO clinical practice guideline. Pract Radiat Oncol. Published online June 18, 2024. doi:10.1016/j.prro.2024.05.007