S534
Clinical – Head & neck
ESTRO 2026
Digital Poster 311
Radiotherapy Dose De-escalation in HPV-Positive Oropharyngeal Carcinoma: A Systematic Review of Efficacy, Toxicity, and Oncologic Outcomes Qashmal Mafazi Syahril, Fahmi Radityamurti Department of Radiotherapy, Ciptomangunkusumo Hospital, Jakarta, Indonesia Purpose/Objective: To evaluate the safety, efficacy, and clinical rationale of radiotherapy dose de-escalation strategies in patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), focusing on oncologic control, treatment toxicity, and selection criteria from major contemporary trials. Material/Methods: A systematic literature search was conducted in PubMed and Scopus up to March 2025 following PRISMA guidelines. Search terms included “HPV- positive oropharyngeal carcinoma,” “de-escalation,” and “radiotherapy.” Randomized controlled trials and prospective cohort studies evaluating reduced-dose radiotherapy or chemoradiotherapy were included. Data were extracted on patient characteristics, radiotherapy dose and fractionation, oncologic outcomes (local control [LC], progression-free survival [PFS], overall survival [OS]), and treatment-related toxicities. Risk stratification criteria and biomarkers were also reviewed. Results: Seven major clinical trials (ECOG-ACRIN E3311, NRG- HN002, NRG-HN005, MC1273/MC1675, PATHOS, MINT, and I-CHOICE-01) were reviewed. Across studies, participants were predominantly younger (<60 years), non-smokers, and p16-positive, reflecting a favorable biological subgroup.In postoperative cohorts, E3311 demonstrated that adjuvant 50 Gy achieved 2-year PFS 95% and OS 99%, with markedly improved swallowing and speech function. PATHOS confirmed comparable disease control at 50 Gy versus 60 Gy, with reduced late dysphagia and xerostomia.In definitive trials, NRG- HN002 reported 60 Gy + cisplatin preserved PFS 90.5% and OS 96.7%, whereas NRG-HN005 failed to establish non-inferiority of 60 Gy regimens, reaffirming the need for careful risk stratification.Ultra-low-dose strategies (MC1273/MC1675) using 30–36 Gy + weekly docetaxel achieved PFS 95%, OS 98%, and minimal long-term toxicity. Biomarker- and response-adapted protocols (MINT, I-CHOICE-01) integrating PET-guided assessment achieved >90% LC/PFS, feeding-tube dependence <5%, and superior patient-reported quality-of-life scores.Across all studies, de-escalation significantly reduced late treatment-related morbidity, including xerostomia, dysphagia, and fatigue, while maintaining robust local control in biologically radiosensitive, low-risk HPV-positive populations.
Conclusion: HypoT-type disorder predicts favorable outcomes in LA-NPC patients receiving PD-1 blockade,warranting close thyroid function monitoring in young, non- smoking, undifferentiated nonkeratinizing females. Reducing adjuvant PD-1 cycles and simplifying pretreatment testing mitigate financial toxicity without compromising survival. References: 1. Xu C, Zhou GQ, Li WF, et al. Nivolumab combined with induction chemotherapy and radiotherapy in nasopharyngeal carcinoma: A multicenter phase 2 PLATINUM trial. Cancer Cell. 2025;43(5):925-936.e4.2. Liu X, Zhang Y, Yang KY, et al. Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial. The Lancet. 2024; 403: 2720-2731.3. The DIAMOND Study Group, Xu C, Liang XY, et al. Toripalimab Combination Therapy Without Concurrent Cisplatin for Nasopharyngeal Carcinoma: The DIAMOND Randomized Clinical Trial. JAMA. 2025;334(11):973-983. Keywords: Nasopharyngeal carcinoma, PD-1, Clinical trials
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