S639
Clinical – Head & neck
ESTRO 2026
Purpose/Objective: Cisplatin-induced sensorineural hearing loss (SNHL) is a clinically significant toxicity of chemoradiotherapy for head and neck cancer. Weekly low-dose cisplatin is thought to reduce ototoxicity compared with three- weekly high-dose cisplatin but prospective randomised data are limiting. This secondary analysis of the prospective de-escalation TROG 12.01 trial compared audiometric outcomes in HPV-positive oropharyngeal carcinoma (OPC) treated with weekly cisplatin + RT versus cetuximab + RT. Material/Methods: Of 187 trial participants, audiometric data were available for 101 (cisplatin n=55; cetuximab n=46). Patients were randomized to radiotherapy (70 Gy in 35 fractions) with weekly cisplatin (40 mg/m ² ) or cetuximab (400 mg/m ² loading => 250 mg/m ² weekly). Pure-tone audiometry, measuring hearing thresholds across 500–8000 Hz was performed bilaterally before treatment and 12 months after RT. A random- intercept, linear mixed-effects model assessed threshold shifts at 500–8000 Hz adjusting for gender, laterality, smoking, T-stage, site, and mean cochlear dose. Clinically significant ototoxicity was defined per QUANTEC 2010 criteria as ≥ 10 dB shift at ≥ 2 frequencies or ≥ 20 dB at one frequency. Receiver- operating characteristic (ROC) analyses was used to review cochlear radiation dose thresholds most predictive of clinically significant hearing loss. Results: Across 202 ears, 29 % demonstrated clinically significant treatment-induced SNHL at 12 months — 35 % in the cisplatin + RT arm (39/110 ears) and 22 % in cetuximab + RT arm (20/92 ears). At 8000Hz, cisplatin patients had significantly higher deterioration in hearing threshold than cetuximab patients (mean shift 6.83 dB; 95% CI 1.85–11.81; p = 0.01). On multivariable analysis, low dose cisplatin remained significantly associated with greater high-frequency hearing loss at 8000 Hz (Estimate = 5.58 dB; 95% CI = 0.58, 10.61; p = 0.04). Mean cochlear dose also predicted hearing decline ( β = 0.19 per Gy; p = 0.10 trend). ROC analysis (cetuximab + RT) identified mean > 5.1 Gy (AUC 0.69, sensitivity 0.90) and maximum > 7.2 Gy (AUC 0.70, sensitivity 0.90) as optimal dose thresholds. Higher T-stage and current smoking correlated with greater mid-frequency change in hearing thresholds (p ≤ 0.05). Conclusion: This first prospective randomized audiometric assessment of weekly low-dose cisplatin in HPV- associated OPC demonstrates significant high- frequency hearing decline despite dose de-escalation. These findings support the incorporation of audiological monitoring and cochlear-sparing radiotherapy even in low-dose cisplatin regimens. Keywords: Ototoxicity, Cisplatin, Oropharynx
101.15±1.35% versus 100.77±0.89% (p=0.32), while CTV D1% ≤ 110% of 106.44±1.41% versus 107.55±0.95% (p<0.05). However, under IB-RE with 3 mm inter-beam setup uncertainty, PAT showed significantly degraded worst-case scenarios (D95% IMPT: 100.61±1.34% vs PAT: 98.22±2.00%, p<0.005; D1% IMPT: 106.81±1.28% vs PAT: 112.09±2.56%, p<0.005) and robustness passing rates (D95% IMPT: 97.34±4.95% vs PAT: 52.16±35.82%, p<0.005; D1% IMPT: 100±0% vs PAT: 72.90±30.15%, p<0.05). With 2 mm uncertainty, differences decreased to 18±10% for D95% robustness passing rates (p<0.005). At more clinically realistic 1 mm inter-beam setup uncertainty, robustness passing rates became comparable and clinically acceptable (D95% IMPT: 100±0.0% vs PAT: 99.5±1.8%, p=0.1; D1% IMPT: 100±0.0% vs PAT: 98.8±3.79%, p>0.05), though worst-case scenario differences remained significant (D95% 0.9±0.6%, p<0.05; D1% 1.10±1.2%, p<0.05). Conclusion: This study demonstrates effectiveness of IB-RO methodology for IMPT by implementing comprehensive IB-RE assessment. While PAT optimized with U-RO exhibits greater susceptibility to target underdose under extreme 3 mm inter-beam setup errors, it maintains similar robustness to IB-RO IMPT under clinically realistic 1 mm inter-beam uncertainties. This support clinical implementation of PAT for HN cancer treatment when appropriate setup precision is maintained. Keywords: independent-beam robustness evaluation Sensorineural Hearing Outcomes in HPV-Positive Oropharyngeal Cancer: A Secondary Analysis of the TROG 12.01 Randomized Trial (SHOUT) Julianne O'Shea 1 , Laurelie R. Wishart 2,3 , Danny Rischin 4,5 , June Corry 5,6 , Ben Dixon 5,7 , Stephen O'Leary 5 , Wayne J. Wilson 3 , Syeda Farah Zahir 8,9 , Dominic Hanson 9 , Sandro V. Porceddu 1,9 1 Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia. 2 Centre for Functioning & Health Research, Metro South Hospital & Health Service, Queensland, Australia. 3 School of Health & Rehabilitation Sciences, The University of Queensland, Queensland, Australia. 4 Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia. 5 University of Melbourne, University of Melbourne, Melbourne, Australia. 6 Genesis Care, St Vincent's Hospital, Melbourne, Australia. 7 Department of Otolaryngology, Head and Neck Surgery, St Vincent's Hospital, Melbourne, Australia. 8 Department of Biostatistics, QCIF, Brisbane, Australia. 9 School of Medicine, The University of Queensland, Queensland, Australia Proffered Paper 3830
Made with FlippingBook - Share PDF online