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Prediction of mucositis risk secondary to cancer therapy: a systematic review of current evidence and call to action

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Abstract

Purpose

Despite advances in personalizing the efficacy of cancer therapy, our ability to identify patients at risk of severe treatment side effects and provide individualized supportive care is limited. This is particularly the case for mucositis (oral and gastrointestinal), with no comprehensive risk evaluation strategies to identify high-risk patients. We, the Multinational Association for Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) Mucositis Study Group, therefore aimed to systematically review current evidence on that factors that influence mucositis risk to provide a foundation upon which future risk prediction studies can be based.

Methods

We identified 11,018 papers from PubMed and Web of Science, with 197 records extracted for full review and 113 meeting final eligibility criteria. Data were then synthesized into tables to highlight the level of evidence for each risk predictor.

Results

The strongest level of evidence supported dosimetric parameters as key predictors of mucositis risk. Genetic variants in drug-metabolizing pathways, immune signaling, and cell injury/repair mechanisms were also identified to impact mucositis risk. Factors relating to the individual were variably linked to mucositis outcomes, although female sex and smoking status showed some association with mucositis risk.

Conclusion

Mucositis risk reflects the complex interplay between the host, tumor microenvironment, and treatment specifications, yet the large majority of studies rely on hypothesis-driven, single-candidate approaches. For significant advances in the provision of personalized supportive care, coordinated research efforts with robust multiplexed approaches are strongly advised.

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Acknowledgments

Thanks are given to members of the Multinational Association of Supportive Care in Cancer and International Society for Oral Oncology Mucositis Study Group for supporting this initiative.

Funding

Hannah R Wardill is supported by an NHMRC CJ Martin Biomedical Research Fellowship.

Author information

Authors and Affiliations

  1. Adelaide Medical School, University of Adelaide, Helen Mayo Building (Adelaide Medical School) Frome Road, Adelaide, South Australia, 5005, Australia

    H. R. Wardill & J. M. Bowen

  2. Department of Pediatric Oncology/Hematology, The University of Groningen, University Medical Centre Groningen (Beatrix Children’s Hospital), Groningen, The Netherlands

    H. R. Wardill & E. A. H. Loeffen

  3. Brigham and Women’s Hospital and the Dana-Farber Cancer Institute, Boston, MA, USA

    S. T. Sonis

  4. Primary Endpoint Solutions, LLC, Waltham, MA, USA

    S. T. Sonis

  5. Department of Hematology, Radboud University Medical Centre, Nijmegen, The Netherlands

    N. M. A. Blijlevens

  6. Division of Health Sciences, The University of South Australia, Adelaide, Australia

    Y. Z. A. Van Sebille

  7. Inflammatory Bowel Diseases Center, Division of Gastroenterology, Washington University in Saint Louis, Saint Louis, MO, USA

    M. A. Ciorba

  8. Alice Lee Centre for Nursing Studies, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    K. K. F. Cheng

  9. Department of Medical and Surgical Specialties, Radiological Sciences and Public Health - Medical Oncology, ASST-Spedali Civili, University of Brescia, Brescia, Italy

    P. Bossi

  10. Eastman Institute for Oral Health, Basil G. Bibby Library, Rochester, NY, USA

    L. Porcello

  11. Edward G. Miner Library, University of Rochester Medical Center, Rochester, NY, USA

    D. A. Castillo

  12. Oral Medicine, Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY, USA

    S. Elad

Authors
  1. H. R. Wardill
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  2. S. T. Sonis
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  3. N. M. A. Blijlevens
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  4. Y. Z. A. Van Sebille
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  5. M. A. Ciorba
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  6. E. A. H. Loeffen
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  7. K. K. F. Cheng
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  8. P. Bossi
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  9. L. Porcello
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  10. D. A. Castillo
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  11. S. Elad
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  12. J. M. Bowen
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Consortia

On behalf of The Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO)

Contributions

HRW/JMB/SE/PB/KKFC/STS: conceptualization and project initiation, DAC/LP/SE/HRW/JMB: search strategy and record retrieval, HRW/JMB: record triaging, HRW/JMB/NMAB/YZAVS/EAHL/MAC: record review and data extraction, HRW/JMB: data synthesis/writing, All authors: review and editing of final manuscript.

Corresponding author

Correspondence to H. R. Wardill.

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Dr. Sonis reports personal fees from Biomodels, LLC, personal fees from Primary Endpoint Solutions, LLC, outside of the submitted work. As an employee of Biomodels and PES, he is involved in assisting industry, government and academics in the study and enablement of drugs, biologicals and devices to treat patients for a broad range of indications including cancer and oral toxicities of cancer therapy. He does not have equity or receive payment from any of the companies’ clients.

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Wardill, H.R., Sonis, S.T., Blijlevens, N.M.A. et al. Prediction of mucositis risk secondary to cancer therapy: a systematic review of current evidence and call to action. Support Care Cancer 28, 5059–5073 (2020). https://doi.org/10.1007/s00520-020-05579-7

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