Lower Neck-Sparing RT Succeeds in Nasopharyngeal Carcinoma

Use of elective ipsilateral upper-neck irradiation (UNI) in patients with nasopharyngeal carcinoma provided similar regional control as whole-neck irradiation (WNI), and resulted in less late toxicity, according to Chinese researchers.

In an intention-to-treat analysis, the 3-year regional relapse-free survival rate was 97.7% in the UNI group compared with 96.3% in the WNI group (stratified HR 0.73, 95% CI 0.25-2.09, long-rank P=0.85), reported Jun Ma, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China, and colleagues.

There were no substantial differences in acute radiation-related toxic effects between the groups, and UNI patients had a lower incidence of late toxic effects versus the WNI group, including any-grade hypothyroidism (30% vs 39%), skin toxicity (14% vs 25%), dysphagia (17% vs 32%), and neck tissue damage (23% vs 40%).

“We believe that our data could guide practice change in the management of patients with nasopharyngeal carcinoma,” the authors wrote in Lancet Oncology. “Our trial provides high-level evidence supporting lower-neck sparing of the uninvolved neck as a valid option to be considered in future treatment guidelines for N0-N1 nasopharyngeal carcinoma, which will benefit the majority (>70%) of the patient population presenting with nonmetastatic nasopharyngeal carcinoma.”

Ma and colleagues also found that the 3-year overall survival, distant metastasis-free survival, and local relapse-free survival rates were similar between the UNI and WNI groups:

• Overall survival: 99.1% vs 96.4% (stratified HR 0.39, 95% CI 0.12-1.25, P=0.10)
• Distant metastasis-free survival: 94.6% vs 93.5% (HR 0.85, 95% CI 0.40-1.78, P=0.15)
• Local relapse-free survival: 97.3% vs 95.4% (HR 0.88, 95% CI 0.36-2.16, P=0.67)

In a commentary accompanying the study, Quynh-Thu Le, MD, of Stanford Cancer Institute in California, and colleagues suggested that clinicians considering UNI for their patients with N0-N1 nasopharyngeal carcinoma should keep in mind that this trial had a relatively large non-inferiority margin of 8%, which was selected on the basis of expert consensus, data from institutional experiences, and published literature.

They also pointed out that 88% of the patients in the study were enrolled from just one of the three study centers, “and therefore the results might not be generalizable to centers with less robust experience in treating these patients.”

Still, the investigators “should be commended for rapidly accruing this well-designed trial, maintaining excellent protocol adherence, and for completing one of the few randomized trials specifically addressing target volumes in head and neck radiotherapy,” they wrote. “As chemotherapy for nasopharyngeal carcinoma becomes increasingly individualized, it is imperative that lower-risk patients be carefully selected for de-escalation in order not to compromise disease control.”

In this open-label, non-inferiority, randomized, controlled, phase III trial, 446 patients with untreated N0-N1 nasopharyngeal carcinoma were randomly assigned 1:1 to UNI (69% men, median age 47) or WNI (71% men, median age 49) at three Chinese medical centers from January 2016 to May 2018. Patients had a Karnofsky performance status score of 70 or higher and adequate hematologic function. Median follow-up was 53 months.

About 75% of the patients in the study completed quality-of-life (QOL) questionnaires at baseline, and 80% completed the questionnaires at 3 years. Compared with the WNI group, patients in the UNI group had significantly better QOL outcomes for global health status, emotional function, and fatigue, and had clinically significant improvements in swallowing.