Abstract
OBJECTIVE: To evaluate the efficacy, safety, and survival impacts of diverse induction chemotherapy regimens (including combination therapy with immune checkpoint inhibitors [ICIs]), radiotherapy modalities, and consolidation therapy in children, adolescents, and young adults (CAYA) with locally advanced or metastatic nasopharyngeal carcinoma (NPC). METHODS: This multicenter retrospective study analyzed 102 CAYA NPC patients (aged 6-24 years; stage III-IVB) from two Chinese centers (January 2011-October 2024). All received induction therapy followed by concurrent chemoradiotherapy (CCRT), radiotherapy combined with concurrent anti-EGFR therapy, or radiotherapy alone, with select cases receiving consolidation (median follow-up: 22 months). RESULTS: GP and TPF induction achieved higher objective response rates (ORR) vs. TP (GP: 68.0% vs. TP: 31.6%, P = 0.005; TPF: 89.5% vs. TP: 68.0%, P < 0.001), though no significant difference in long-term survival was observed. ICIs + chemotherapy (n=15) improved ORR (93.3% vs. 53.3%, P = 0.013) though without a demonstrable difference in survival metrics at this follow-up. In patients achieving partial response (PR) post-induction, CCRT/anti-EGFR therapy + radiotherapy improved 1-year progression-free survival (PFS: 94.5% vs. 50.0%, P < 0.001) and distant metastasis-free survival (DMFS: 97.4% vs. 50.0%, P < 0.001). For stable disease (SD) patients, multimodal therapy increased 5-year overall survival (OS: 100% vs. 66.7%, P = 0.046). Consolidation therapy (n=24) in locally advanced NPC was associated with clinical stage (P = 0.001) but not survival (P > 0.05). CONCLUSION: TPF/GP regimens improved short-term responses with manageable toxicity. The addition of ICIs enhanced objective response rates, though survival benefits were not assessable within the limited follow-up period. CCRT demonstrated survival advantages over radiotherapy alone, especially in PR patients, while consolidation therapy showed limited benefit except in advanced subgroups. These findings, generated from a retrospective analysis, highlight the need for personalized strategies and warrant validation in larger prospective trials.