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TOPLINE:

In patients with human papillomavirus (HPV)-associated oropharyngeal cancer, lower-dose adjuvant radiotherapy (30-36 Gy) reduced chronic toxicities compared with standard care. However, disease control may be poorer for higher-risk patients. 

METHODOLOGY:

• Standard postoperative radiotherapy provides excellent disease control in HPV-associated oropharyngeal squamous cell carcinoma (OPSSC), but can cause significant long-term toxicity, including dysphagia, xerostomia, and osteoradionecrosis. Radiation deintensification may lessen side effects while maintaining disease control rates but requires further study.
• Researchers conducted a phase 3 trial of 194 patients (mean age, 59.4 years; 89% men; 94% White) with stage III-IV HPV-associated OPSCC who had undergone transoral surgery and neck dissection. Patients had either a high-risk factor (pathological extranodal extension) or at least one intermediate risk factor: lymphovascular invasion, perineural invasion, involvement of at least two regional lymph nodes, any node larger than 3 cm, or a pT3 primary tumor.
• Patients were stratified by presence of extranodal extension and were randomly assigned 2:1 to receive either de-escalated adjuvant radiotherapy (n = 130; 30-36 Gy in fractions of 1.5-1.8 Gy twice daily over 2 weeks plus intravenous docetaxel 15 mg/m² on days 1 and 8) or standard of care (n = 64; 60 Gy in 2-Gy fractions once daily over 6 weeks with or without intravenous cisplatin 40 mg/m² weekly).
• The primary endpoint was cumulative chronic toxicity of grade 3 or higher. Secondary endpoints included overall survival, progression-free survival, locoregional disease control, distant metastasis-free survival, and quality of life. Median follow-up was 37.3 months.

TAKEAWAY:

• The cumulative toxicity rate at 3-24 months was significantly lower in the de-escalated group than in the standard-care group (3% vs 11%; P = .042), with fewer percutaneous endoscopic gastric tube placements (2% vs 8%; P = .039). The most common toxicities were dysphagia (2%), esophagitis (1%), and hearing impairment (1%) in the de-escalated group and dysphagia (8%), esophagitis (2%), fatigue (2%), pain (2%), and osteonecrosis (2%) in the standard care group.
• At 2 years, overall survival was similar in the de-escalated and standard care groups (96.9% vs 98.3%; hazard ratio [HR], 1.68; P = .51), as was locoregional disease control (95.9% vs 98.3%; HR, 3.17; P = .26).
• Progression-free survival at 2 years was lower with de-escalated therapy than with standard of care (88.2% vs 96.6%; HR, 4.76; P = .02). This difference was more evident among patients with extranodal extension, with a 2-year progression-free survival of 81.1% vs 97.4% (P = .0049). In this subgroup, 2-year locoregional disease control was 92.9% vs 100% (P = .066), while distant metastasis-free survival was 90% vs 97.4% (P = .077). A similar pattern was seen among patients with pN2 disease, who had a 2-year progression-free survival of 43.8% with de-escalated therapy vs 100% with standard care (P = .014).
• Overall quality-of-life scores were higher among patients in the de-escalated group at 2 years, as were scores related specifically to pain (P = .008) and swallowing (P = .0005).

IN PRACTICE:

Overall, the authors wrote, “The de-escalated adjuvant radiotherapy regimen was superior in both late toxicity and patient quality of life compared with the 60 Gy standard of care.” However, they emphasized, given the findings on disease control, “caution is advised for de-escalating extranodal extension-positive patients, particularly those with pN2 disease.”

SOURCE:

This study, led by Daniel Ma, MD, of the Mayo Clinic in Rochester, Minnesota, was published online in The Lancet Oncology.

LIMITATIONS:

The trial was not blinded due to logistical considerations. Secondly, patient retention was challenging, particularly for those assigned to standard care. Additionally, a considerable proportion of patients lacked presurgery data on quality of life, making it impossible to evaluate pre- vs postsurgery functional status changes.

DISCLOSURES:

This study was funded by the Department of Radiation Oncology, Mayo Clinic, Minnesota and Arizona; the Braillier Family Research Fund; and the Matteson Family Research Fund. Ma reported intellectual property with EXACT Sciences, In Situ Biologics, and CurrentHealth. Several authors reported having ties with various sources. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.