ArticleRadiation oncology (London, England)2026
Induction chemotherapy for locally advanced OPSCC: real-world evidence and HPV-dependent prognostic value of treatment response.
Article in Radiation oncology (London, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundThe clinical value of induction chemotherapy (IC) in stage III-IV oropharyngeal squamous cell carcinoma (OPSCC) remains controversial. While randomized trials have shown limited survival benefit in unselected populations, it remains unclear whether IC provides benefit in high-risk subgroups and whether early treatment response to IC can serve as a prognostic and stratification tool.
methodsWe conducted a two-center retrospective real-world cohort study of 496 patients with stage III-IV OPSCC treated with definitive radiotherapy with or without IC. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics, adjusting for age, sex, smoking, alcohol use, T/N stage (AJCC 7th), tumor subsite, HPV status, clinical extranodal extension (cENE), and use of concurrent chemoradiotherapy. Overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) were compared using Kaplan-Meier and Cox proportional hazards models. A clinical nomogram was developed to predict individual DMFS and estimate IC benefit. In IC-treated patients, analyses were stratified by HPV status and IC response further stratified prognosis across endpoints.
resultsIn IPTW-weighted multivariable Cox analysis, IC was independently associated with improved DMFS (HR = 0.60, 95% CI: 0.43-0.83, p = 0.016) and PFS (HR = 0.66, 95% CI: 0.49-0.90, p = 0.041). Subgroup analysis revealed reduced distant metastasis with IC in N3 patients (HR = 0.43, 95% CI: 0.20-0.93, p = 0.033). The nomogram (C-index = 0.697) suggested IC-associated benefit in patients with higher baseline risk. Among IC-treated patients, treatment response further stratified prognosis in an HPV-dependent manner. In the HPV-negative subgroup, patients achieving a complete or partial response (CR/PR) to IC experienced significantly improved OS compared with non-responders (p = 0.019). In multivariable analysis, IC response (CR/PR) was independently associated with superior PFS and LRFS, whereas no response-associated survival benefit was observed in HPV-positive patients.
conclusionIn this real-world cohort of locally advanced OPSCC, IC was not associated with an overall survival benefit after adjustment, but was associated with improved distant metastasis-free survival, particularly in selected high-risk patients. Early IC response further identified a favorable-risk subgroup among HPV-negative patients. Given the retrospective design and treatment heterogeneity, these findings should be considered hypothesis-generating and require prospective validation.
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