Zi-Xuan Chen, Ye-Hao Zou, Rui-Ling Xie, Ling-Ling Zhang, Chao Lin, Rui Sun
In pediatric and adolescent nasopharyngeal carcinoma, these findings suggest potential feasibility of dose reduction but require prospective validation. However, maintaining adequate chemotherapy intensity could be particularly important for patients with lower pretreatment plasma EBV DNA level. Pretreatment plasma EBV DNA may serve as a potential biomarker to guide individualized adjustment of chemotherapy dose intensity in pNPC, which warrants validation in larger studies.
BACKGROUND: Pediatric and adolescent nasopharyngeal carcinoma (pNPC) is a rare malignancy, and contemporary chemotherapy regimens are largely extrapolated from adult protocols. Adult-intensity chemotherapy is often associated with substantial toxicity in younger patients. Whether chemotherapy dose intensity can be safely reduced in children and adolescents with pNPC remains unclear.
OBJECTIVES: This study aimed to evaluate the association between chemotherapy relative dose intensity (RDI) and survival outcomes in pNPC.
DESIGN: This was a single-center retrospective cohort study of pediatric and adolescent patients with locoregionally advanced nasopharyngeal carcinoma treated between 2006 and 2021.
METHODS: We retrospectively analyzed patients aged ≤21 years with newly diagnosed stage III-IVa (American Joint Committee on Cancer (AJCC) 8th edition) pNPC treated between 2006 and 2021. Relative dose intensity (RDI) of first-line chemotherapy was calculated and categorized as <85% versus ≥85%. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Multivariable Cox regression was used to evaluate the independent prognostic value of RDI and other covariates.
RESULTS: A substantial proportion of patients had an RDI <85%. In the overall cohort, RDI <85% was not significantly associated with worse survival outcomes in survival analyses. Pretreatment plasma Epstein-Barr virus (EBV) DNA level was independently associated with worse survival outcomes. In exploratory analyses, among patients with plasma EBV DNA <4000 copies/mL, RDI <85% suggested an association with worse OS (P for interaction=0.025).
CONCLUSIONS: In pediatric and adolescent nasopharyngeal carcinoma, these findings suggest potential feasibility of dose reduction but require prospective validation. However, maintaining adequate chemotherapy intensity could be particularly important for patients with lower pretreatment plasma EBV DNA level. Pretreatment plasma EBV DNA may serve as a potential biomarker to guide individualized adjustment of chemotherapy dose intensity in pNPC, which warrants validation in larger studies.