Early vs Routine Oral Nutritional Supplementation During Concurrent Chemoradiotherapy for Nasopharyngeal Carcinoma: A Randomized Clinical Trial

Importance Oral nutritional supplementation (ONS), providing supplementary oral nutrition in addition to usual food, is widely used during concurrent chemoradiotherapy (CCRT) for nasopharyngeal carcinoma (NPC), but its optimal timing and cost utility remain uncertain. Objective To evaluate efficacy and explore cost utility of early ONS in patients with NPC undergoing CCRT. Design, Setting, and Participants This multicenter, open-label, randomized clinical trial was conducted at 6 Chinese tertiary hospitals from July 2021 to May 2025. Eligible patients were aged 18 to 70 years with newly diagnosed stage II to IVA NPC, a Patient-Generated Subjective Global Assessment (PG-SGA) score of 0 to 8, and planned CCRT. Key exclusions included oral intake less than 60% of requirements for 3 days or longer, inability or unwillingness to receive concurrent chemotherapy, and inability to receive oral or enteral nutrition. Data were analyzed from November 2025 to March 2026. Intervention Participants were randomized 1:1 to early ONS at CCRT start or routine ONS after prespecified nutritional decline. Main Outcomes and Measures The primary end point was the incidence of more than 5% weight loss from baseline to CCRT completion. Secondary end points included PG-SGA score, the incidence of grade 3 or higher radiation-induced oral mucositis (RIOM), quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30), and radiotherapy interruption. Cost utility measures included total cost, utility, and incremental cost utility ratio. Results Of 242 patients screened, 236 patients were randomized, and the prespecified modified intention-to-treat population included 216 patients (mean [SD] age, 46.62 [11.19] years; 168 [77.8%] male), with 107 receiving early ONS and 109 receiving routine ONS. More than 5% weight loss occurred in 70 participants (65.4% ) in the early ONS group, compared with 88 participants (80.7%) in the routine ONS group (relative risk [RR], 0.81; 95% CI, 0.68-0.96; P = .01). An intention-to-treat analysis including all randomized participants yielded a similar estimate (RR, 0.78; 95% CI, 0.65-0.93). In the modified intention-to-treat population, grade 3 or higher RIOM occurred in 15 participants (14.0%) in the early ONS group vs 29 participants (26.6%) in the routine ONS group (RR, 0.53; 95% CI, 0.30-0.93). Best-case costs were $9560.56 in the early ONS group vs $9685.23 in the routine ONS group, with quality-adjusted life-years of 0.1144 vs 0.1132, respectively. Conclusions and Relevance This randomized clinical trial found that early ONS reduced clinically meaningful weight loss during CCRT; exploratory analyses suggested potential benefits for severe RIOM and a potentially favorable short-term economic profile. Trial Registration ClinicalTrials.gov Identifier: NCT04823468