Interobserver Agreement in Acute Toxicity Assessment During Head and Neck Radiotherapy/Chemoradiotherapy: Implications for Endpoint Selection in Clinical Trials
In brief
Maximum acute toxicity grades show only fair agreement, mucositis κ≈0.35
In a trial of 74 head-and-neck cancer patients, two blinded radiation oncologists rated weekly toxicities. When looking at the worst toxicity per patient, agreement ranged from fair to moderate (κ 0.23-0.41), with oral mucositis especially discordant (κ 0.35). The authors suggest weekly scoring may be a more reliable endpoint for future studies.
- Journal
- International journal of radiation oncology, biology, physics (Q1)
- Published
- 1 August 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Shwetabh Sinha, Anuj Kumar, Samarpita Mohanty, Ashwini Budrukkar, Monali Swain, Amit Joshi, et al.
- PMID
- 42542300
- DOI
- 10.1016/j.ijrobp.2026.07.036
Why clinicians should know about it
- Picked for Radiology, Radiation Oncology, Nuclear Medicine, Medical Physics and Imaging (top studies of the week, 25 October 2026): Interobserver agreement for acute toxicity shows fair to moderate concordance
Abstract
BACKGROUND: Acute toxicity is a key endpoint in head and neck radiotherapy (RT) and chemoradiotherapy (CRT) trials and is most commonly reported as maximum toxicity per patient. However, the reproducibility of clinician-reported toxicity grading remains incompletely characterized. We evaluated interobserver agreement in acute toxicity assessment, focusing on maximum toxicity as the primary endpoint. METHODS AND MATERIALS: This predefined subgroup analysis was conducted within a prospective randomized controlled trial of patients with head and neck squamous cell carcinoma (HNSCC) undergoing curative-intent RT/CRT. Acute toxicities were assessed weekly using CTCAE v5.0 by two independent, blinded radiation oncologists. Four domains were evaluated: dermatitis, oral mucositis, dysphagia, and xerostomia. The primary endpoint was patient-level maximum toxicity, dichotomized as ≥Grade 2 and ≥Grade 3. Interobserver agreement was assessed using Cohen's κ. RESULTS: Seventy-four patients were included. For maximum ≥Grade 2 toxicity, incidence (O1 vs O2) was: dermatitis 55.4% vs 45.9%, mucositis 91.9% vs 70.2%, dysphagia 95.9% vs 91.9%, and xerostomia 55.4% vs 58.1%, with κ of 0.33, 0.35, 0.41, and 0.23, respectively (fair to moderate). For ≥Grade 3 toxicity, κ values were: dermatitis 0.79, mucositis 0.41, dysphagia 0.63, and xerostomia 0.25. Pooled weekly agreement for ≥Grade 2 toxicity was higher (κ = 0.49-0.89), with peak concordance during weeks 5-6. CONCLUSIONS: Interobserver agreement for maximum acute toxicity was fair to moderate across domains in head and neck RT/CRT, with the largest discordance for oral mucositis even between observers at the same centre. Although maximum toxicity remains a pragmatic and widely used endpoint, caution is warranted in its interpretation, and weekly assessment may offer a more reproducible complementary endpoint, particularly for cross-trial comparisons.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.