3628 - Reproducibility of Clinician-Reported Acute Symptom Burden during Head and Neck Chemoradiation: A Prospective Blinded Analysis from a Randomized Trial

Purpose/Objective(s): Clinician-reported acute toxicity grades are widely used as surrogates for symptom severity in Head Neck Squamous Cell Carcinoma (HNSCC); however, their interobserver reliability across the treatment course remains poorly defined. We prospectively evaluated the reproducibility of clinician-reported acute symptom assessment during Radiation Therapy (RT)/ Chemoradiation (CTRT).

Materials/Methods: This was a predefined subgroup analysis of a randomized controlled trial including patients with HNSCC aged =70 years undergoing curative-intent radiotherapy or chemoradiotherapy, of whom 74 out of 100 patients were eligible for the final analysis. Patients who mandated a feeding tube at baseline were excluded as per the study protocol. Acute toxicities were assessed weekly across the entire treatment course (weeks 1–7) using CTCAE 5.0. Assessments were performed independently and in a blinded manner by two experienced head and neck radiation oncologists (>5 years’ experience each).

Results: The most common primary site was the Oral Cavity (n=39, 52.7%), followed by Oropharynx (n=19, 25.7%). Thirty-two (43.2%) patients received RT alone, and 42 (56.8%) received CTRT. Across all weeks and grades, interobserver agreement was moderate to substantial (Table 1). For =Grade 2 events, agreement was highest for mucositis (? = 0.89) and dysphagia (? = 0.60), and moderate for skin (? = 0.51) and xerostomia (? = 0.45). Inter-observer concordance increased progressively during treatment for =Grade 2 events, with the most consistent agreement observed during weeks 5–6, corresponding to peak symptom burden. For severe symptoms (=Grade 3), observed agreement was modest; however, ? estimates were frequently unstable due to the low event prevalence.

Conclusion: Clinician-reported assessment of clinically significant symptom burden (=Grade 2) during RT/ CTRT for HNSCC demonstrated superior reproducibility and interpretability compared with severe (=Grade 3) toxicity. These findings support =Grade 2 toxicity as a more reliable endpoint in clinical trials, and caution against severe toxicity grade comparisons across trials.