Impact of the Common Terminology Criteria for Adverse Events (CTCAE) evolution on toxicity scoring in gynaecological radiotherapy

Abstract

Purpose: The Common Terminology Criteria for Adverse Events (CTCAE) is the established toxicity scoring system that assigns severity grades (G1 = mild to G5 = death) to Adverse Events (AEs). Compared to CTCAE v3.0 (2006), updated versions introduced changes in severity grade definitions. This study evaluated changes between v3.0 and v5.0 (2017) for AEs in gynaecological radiotherapy.

Material and methods: After selecting AEs relevant for gynaecological radiotherapy in v3.0, changes in severity grades were identified using CTCAE v3.0-to-v5.0 mapping tables. Six radiation oncologists (ROs) evaluated severity grade definitions for changes in: clinical interpretation, subjective (patient-reported symptoms) and objective (details on medication/intervention) information, and expected severe (≥G3) events. Agreement was based on at least five (≥5)ROs.

Results: Gastrointestinal, urinary, reproductive, general and injury/musculoskeletal AEs were selected (n = 118). G4 definitions in v5.0 were removed in 22 % of AEs. ≥5ROs agreed on changes affecting clinical interpretation especially for G2 (31 %) and G3 (30 %). For subjective information, 18 % of G2 and 15 % of G3 were judged relying more on patient-reported symptoms. Less objective information was found in 51 % of G3 definitions. Variability in agreement was observed especially for subjective information in G3 and expected ≥G3 events.

Conclusion: This analysis revealed that severity grade definitions in v3.0 and v5.0 for AEs in gynaecological radiotherapy present changes with potential impact on scoring in clinical studies. Notably, 22 % of AEs in v5.0 no longer have G4 defined, and G3 definitions often include fewer details on medication/intervention. Variability in ROs' interpretations is frequently observed, highlighting the need for education to standardise toxicity scoring.

Keywords: Clinical trials; Education in radiation oncology; Patient-reported outcome; Quality of life; Safety; Tolerability; Toxicity scoring.