In a Chinese phase III trial reported in The Lancet, You et al found that hyperfractionated vs standard-fractionation intensity-modulated radiotherapy (IMRT) was associated with reduced late severe radiotherapy complications and improved overall survival in patients with locally advanced, recurrent nasopharyngeal carcinoma.
Study Details
In the open-label multicenter trial, 144 patients were randomly assigned between July 2015 and December 2019 to receive hyperfractionated IMRT (n = 72) or standard-fractionation IMRT (n = 72). Hyperfractionated radiotherapy consisted of 65 Gy in 54 fractions given twice daily with an interfractional time interval of at least 6 hours. Standard-fractionation radiotherapy consisted of 60 Gy in 27 fractions given once a day. The two primary endpoints were overall survival in the intention-to-treat population and incidence of severe late complications (defined as grade ≥ 3 late radiation-induced complications occurring 3 months after completion of radiotherapy) in the safety population (patients who received protocol-defined treatment).
Key Findings
Median follow-up was 45.0 months (interquartile range = 37.3–53.3 months).
Hyperfractionated IMRT could significantly decrease the rate of severe late complications and improve overall survival among patients with locally advanced recurrent nasopharyngeal carcinoma. Our findings suggest that hyperfractionated IMRT could be used as the standard of care for these patients.— You et al
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In the safety population, grade ≥ 3 late radiation-induced toxicity occurred in 23 (34%) of 68 patients in the hyperfractionation group vs 39 (57%) of 68 patients in the standard-fractionation group (between-group difference = –23%, 95% confidence interval [CI] = –39% to –7%, P = .023). The most common grade 3 or 4 late adverse events in the hyperfractionation group were hearing impairment (22%) and nasopharyngeal necrosis (19%); the most common in the standard-fractionation group were nasopharyngeal necrosis (29%) and hearing impairment (25%).
Grade 5 late complications occurred in five patients (7%) in the hyperfractionation group, consisting of nasal hemorrhage in all five patients. Grade 5 late complications occurred in 16 patients (24%) in the standard-fractionation group, including nasopharyngeal necrosis in 2 (3%), nasal hemorrhage in 11 (16%), and temporal lobe necrosis in 3 (4%).
Overall survival at 3 years was 74.6% (95% CI = 64.4%–84.8%) in the hyperfractionation group vs 55.0% (95% CI = 43.4%–66.6%) in the standard-fractionation group (hazard ratio = 0.54, 95% CI = 0.33–0.88, P = .014).
The investigators concluded, “Hyperfractionated IMRT could significantly decrease the rate of severe late complications and improve overall survival among patients with locally advanced recurrent nasopharyngeal carcinoma. Our findings suggest that hyperfractionated IMRT could be used as the standard of care for these patients.”
Ming-Yuan Chen, MD, of the Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, is the corresponding author for The Lancet article.
Disclosure: The study was funded by the Key-Area Research and Development of Guangdong Province, National Natural Science Foundation of China, and others. For full disclosures of the study authors, visit thelancet.com.
