Interobserver Agreement in Acute Toxicity Assessment During Head and Neck Radiotherapy/Chemoradiotherapy: Implications for Endpoint Selection in Clinical Trials.

Authors

Shwetabh Sinha, Anuj Kumar, Samarpita Mohanty, Ashwini Budrukkar, Monali Swain, Amit Joshi, Aditya Dhanawat, Sudhir Nair, Poonam Joshi, Arjun Singh, Rathan Shetty, Imelda Joy, Rozma Ali, Apurva Virkar, Pankaj Chaturvedi, Kumar Prabhash, Sarbani Ghosh Laskar

Published in

International journal of radiation oncology, biology, physics. Aug 01, 2026. Epub Aug 01, 2026.

Abstract

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.
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.
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.
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.

PMID:
42542300
Bibliographic data and abstract were imported from PubMed on 02 Aug 2026.

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