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Concordance of the WHO, RTOG, and CTCAE v4.0 grading scales for the evaluation of oral mucositis associated with chemoradiation therapy for the treatment of oral and oropharyngeal cancers

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Abstract

Background

The ability to consistently and accurately assess oral mucositis (OM) is critical to descriptions of its incidence and severity and in evaluating the effectiveness of potential interventions. The lack of a single grading scale compounds outcome interpretation. Consequently, we assessed the concordance of three of the most commonly used OM grading criteria (World Health Organization (WHO), Radiation Therapy Oncology Group (RTOG), and the common terminology criteria for adverse events (CTCAE).

Methods

Data was evaluated from two hundred patients with oropharyngeal or oral cavity cancers who underwent chemoradiation therapy and were enrolled in a double-blind, randomized, placebo-controlled trial in which trained assessors evaluated patients twice weekly. WHO, RTOG, and CTCAE scores were assigned centrally by independent evaluators blinded to the study group. Concordance among the three scales for all OM scores and severe OM scores (score ≥ 3) was defined as the percentage agreement and measured using Cohen’s weighted Kappa.

Results

Of 3,578 OM assessments, 57% had identical scores for all three scales. When any score was considered, the concordance between WHO and RTOG scales was 71% (kappa 0.58; 95%CI: 0.56-0.60), 62% for the WHO and CTCAE scales (kappa 0.46; 95%CI: 0.44-0.48) and 78% for the CTCAE and RTOG scales (kappa 0.69; 95%CI: 0.68-0.71). When patients had severe OM (WHO score ≥ 3), 99.6% (521/523) of the CTCAE OM assessments had scores of 3 or 4 (kappa 0.98; 95%CI: 0.98-0.999) and 97.7% of the RTOG ones (511/523) had scores of 3 or 4 (kappa 0.69; 95%CI: 0.62-0.75). Among patients who had a WHO score of 4, 31.7% (63/199) and 96.0% (196/199) of patients had RTOG or CTCAE scores of 2 or 3, respectively.

Conclusions

Discordance was seen with patients who exhibited mild to moderate OM or most severe OM (grade 4) as described by WHO criteria. Whereas scale selection seems less critical in studies in which general “severe mucositis” is the primary outcome, it is particularly important in accurately describing OM’s clinical trajectory and the frequency and impact in its most severe forms.

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Acknowledgements

We thank Dr. Alan Joslyn and Oragenics for enabling this study by sharing data obtained in their Phase 2 clinical trial.

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This study was supported solely by PES.

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Authors and Affiliations

  1. Primary Endpoint Solutions, Waltham, MA, USA

    Alessandro Villa, Michele Vollemans, Amanda De Moraes & Stephen Sonis

  2. Department of Orofacial Sciences, University of California San Francisco, 513 Parnassus Ave, Suite 512A, San Francisco, CA, 94143, USA

    Alessandro Villa

  3. Divisions of Oral Medicine and Dentistry, Brigham and Women’s Hospital and the Dana-Farber Cancer Institute, Boston, MA, USA

    Stephen Sonis

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  1. Alessandro Villa
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  2. Michele Vollemans
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  3. Amanda De Moraes
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Contributions

All authors whose names appear on the submission (1) made substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data; or the creation of new software used in the work; (2) drafted the work or revised it critically for important intellectual content; (3) approved the version to be published; and (4) agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Michele Vollemans, Amanda De Moraes, and Stephen Sonis. The first draft of the manuscript was written by Alessandro Villa, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Alessandro Villa.

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Ethics approval

The study protocol was approved by the Institutional Review Board at each participating institution.

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Informed consent was obtained for each participant.

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Informed consent was obtained for each participant.

Conflict of interest

Michele Vollemans, Amanda De Moraes, and Stephen Sonis work for Primary Endpoint Solutions (PES), and PES received payments for the clinical trial for which the data was derived. Alessandro Villa is a consultant for PES.

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Villa, A., Vollemans, M., De Moraes, A. et al. Concordance of the WHO, RTOG, and CTCAE v4.0 grading scales for the evaluation of oral mucositis associated with chemoradiation therapy for the treatment of oral and oropharyngeal cancers. Support Care Cancer 29, 6061–6068 (2021). https://doi.org/10.1007/s00520-021-06177-x

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