A randomized, double-blind, placebo-controlled trial of antiviral prophylaxis and oral <i>Herpesviridae</i> dynamics during radiotherapy for head and neck cancer.

Abstract

TPS12163 Background: Oral mucositis (OM) is a frequent and debilitating toxicity of radiotherapy (RT) for head and neck cancer (HNC), often leading to pain, nutritional compromise, and treatment interruptions. Reactivation of viruses from the Herpesviridae family has been proposed as a potential contributor to the pathogenesis and severity of OM, but prospective, controlled data remain limited. Antiviral prophylaxis is not standard of care in this setting, and its role in preventing viral reactivation and modulating OM severity during RT has not been systematically evaluated. This randomized trial investigates the association between oral Herpesviridae detection, antiviral prophylaxis, and OM development in patients undergoing RT for HNC. Methods: This is a prospective, randomized, double-blind, placebo-controlled phase II trial conducted across four oncology centers in Brazil. Adult patients (≥18 years) with HNC undergoing intensity-modulated radiotherapy (IMRT), with or without concurrent systemic therapy, are randomized 1:1 to receive antiviral prophylaxis or placebo. Randomization is stratified by age (&lt; 60 vs ≥60 years) and anatomic tumor site (oral cavity/salivary glands; oropharynx/pharynx; nasopharynx/paranasal sinuses). The investigational intervention consists of oral antiviral prophylaxis administered once weekly throughout the course of RT; the control arm receives a matching placebo. Comprehensive dental evaluation and oral care optimization are performed prior to RT initiation in all patients. Serial oral mucosal and saliva samples are collected weekly during RT and after treatment completion. Quantitative real-time PCR is used to detect and quantify viruses from the Herpesviridae family, including HSV-1, HSV-2, VZV, EBV, CMV, HHV-6A/B, HHV-7, and HHV-8. Clinical assessments include OM incidence, severity graded by CTCAE criteria, pain intensity, and timing of OM onset and resolution. Correlative analyses will explore temporal associations between viral detection, viral load, antiviral prophylaxis, and OM outcomes. The planned sample size is 84 patients (42 per arm), providing adequate power to detect differences in viral manifestation and OM-related outcomes. Clinical trial information: NCT07363031 .