Neck-sparing irradiation reduces toxicity without compromising efficacy in patients with nasopharyngeal carcinoma, according to research published in The Lancet Oncology.

In a phase 3 trial, researchers observed similar regional relapse-free survival (RFS) rates with whole-neck irradiation (WNI) and upper-neck irradiation (UNI) but more late toxicity with WNI.

The trial ( Identifier: NCT02642107) was designed to determine whether irradiation sparing the uninvolved lower neck would impact outcomes in patients with N0-N1 nasopharyngeal carcinoma.

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The trial included 446 patients, 224 who were randomly assigned to UNI and 222 to WNI. Baseline characteristics were similar between the arms. Most patients were men (69% in the UNI arm and 71% in the WNI arm), the median age was 47 and 49 years, respectively, and the most common tumor category was T3 (56% and 57%, respectively).

The median follow-up was 53 months. In the intent-to-treat population, the 3-year regional RFS rates were 97.7% in the UNI arm and 96.3% in the WNI arm (difference, -1.4%; 95% CI, -4.6 to 1.8; P for noninferiority <.0001). The stratified hazard ratio (sHR) was 0.73 (95% CI, 0.25-2.09; P =.85).

The 3-year distant metastasis-free survival rate was 94.6% in the UNI arm and 93.5% in the WNI arm (sHR, 0.85; 95% CI, 0.40-1.78; P =.15). The 3-year local RFS rate was 97.3% and 95.4%, respectively (sHR, 0.88; 95% CI, 0.36-2.16; P =.67).

The 3-year overall survival rate was 99.1% in the UNI arm and 96.4% in the WNI arm (sHR, 0.39; 95% CI, 0.12-1.25; P =.10). There were 14 deaths in the UNI arm and 10 in the WNI arm, but there were no deaths during the treatment period in either arm.

Acute radiation-related adverse events occurred at similar rates in the 2 arms. However, late toxicity occurred less frequently in the UNI arm than in the WNI arm. Late toxicities (in the UNI and WNI arms, respectively) included any-grade hypothyroidism (30% vs 39%), skin toxicity (14% vs 25%), dysphagia (17% vs 32%), and neck tissue damage (23% vs 40%).

“[O]ur 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 patients with N0-N1 nasopharyngeal carcinoma, which will benefit most patients with non­metastatic nasopharyngeal carcinoma,” the researchers wrote.


Tang L-L, Huang C-L, Zhang N, et al. Elective upper-neck versus whole-neck irradiation of the uninvolved neck in patients with nasopharyngeal carcinoma: An open-label, non-inferiority, multicentre, randomised phase 3 trial. Lancet Oncol. Published online February 28, 2022. doi:10.1016/S1470-2045(22)00058-4