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Predictors of toxicity after curative reirradiation with intensity modulated radiotherapy or proton therapy for recurrent head and neck carcinoma: new dose constraints for pharyngeal constrictors muscles and oral cavity

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Abstract

Background

Our study aims to identify predictive factors of moderate to severe (grade ≥ 2) late toxicity after reirradiation (reRT) of recurrent head and neck carcinoma (HNC) and explore the correlations between dose organs at risk (OAR) and grade ≥ 2 toxicity.

Material and methods

Between 09/2007 and 09/2019, 55 patients were re-irradiated with IMRT or proton therapy with curative intent for advanced HNC. Our study included all patients for whom data from the first and second irradiations were available. Co-variables, including interval to reRT, size of re-irradiated PTV, and dose to OAR, were analyzed as potential predictors for developing moderate to severe long-term toxicity with death as a competing risk. Receiver-operator characteristics (ROC) analysis assessed the association between dose/volume parameters and the risk of toxicity.

Results

Twenty-three patients participated in our study. After a median follow-up of 41 months, 65% of the patients experienced grade ≥ 2 late toxicity. The average dose to pharyngeal constrictor muscles (PCM) at the time of reRT showed an association with the risk of grade ≥ 2 dysphagia: AUC = 0.78 (95% CI: 0.53–1), optimal cut-off value = 36.7 Gy (sensitivity 62%/specificity 100%). The average dose to the oral cavity at the time of reRT showed an association with the risk of grade ≥ 2 dysgeusia: AUC = 0.96 (0.89–1), optimal cut-off value = 20.5 Gy (sensitivity 100%/specificity 88%).

Conclusion

Our analysis depicted an association between the dose to OAR and the risk of developing moderate to severe dysphagia and dysgeusia and proposed new dose constraints for PCM (36.7 Gy) and oral cavity (20.5 Gy).

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Authors and Affiliations

  1. Radiation Oncology Department, Institut Curie, PSL Research University, 25 rue d’Ulm, 75005, Paris/Orsay, France

    Arnaud Beddok MD, Samar Krhili MD, Anne Chilles MD, Farid Goudjil MSc, Sofia Zefkili PhD, Malika Amessis MSc, Gilles Créhange MD PhD & Valentin Calugaru MD PhD

  2. Institut Curie, PSL Research University, University Paris Saclay, Inserm LITO, 91898, Orsay, France

    Arnaud Beddok MD, Laurence Champion MD, Irene Buvat PhD & Gilles Créhange MD PhD

  3. Biometry Unit, Institut Curie, PSL Research University, Paris, France

    Xavier Maynadier MD & Matthieu Carton MD PhD

  4. Department of Radiology, Institut Curie, Paris, France

    Catherine Ala Eddine MD

  5. Department of Nuclear Medicine, Institut Curie, Saint-Cloud, France

    Laurence Champion MD

  6. Department of Head and Neck Surgery, Institut Curie, Paris, France

    Olivier Choussy MD PhD

  7. Department of Drug Development and Innovation (D3i), INSERM U900 Research unit, Paris-Saclay University, Institut Curie, Paris, France

    Christophe Le Tourneau MD PhD

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  1. Arnaud Beddok MD
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Corresponding author

Correspondence to Arnaud Beddok MD.

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Conflict of interest

A. Beddok, X. Maynadier, S. Krhili, C.A. Eddine, L. Champion, A. Chilles, F. Goudjil, S. Zefkili, M. Amessis, O. Choussy, C.L. Tourneau, I. Buvat, G. Créhange, M. Carton and V. Calugaru declare that they have no competing interests.

Additional information

Author responsible for statistical analysis: Matthieu Carton.

Data availability statement

All data generated and analyzed during this study are included in this published article (and its supplementary information files).

Supplementary Information

66_2023_2080_MOESM1_ESM.docx

Sup. Data 1: Patient and Treatment Characteristics. Sup. Data 2: Impairments before the onset of the reirradiation in relation to the final late toxicity. Sup. Data 3: Time between the two courses of irradiations and risk of toxicity. Sup. Data 4: Volume of PTV (cc) and risk of late toxicity. Sup data 5: Comparison of late toxicity between IMRT and PT groups based on Kaplan Meier curves

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Beddok, A., Maynadier, X., Krhili, S. et al. Predictors of toxicity after curative reirradiation with intensity modulated radiotherapy or proton therapy for recurrent head and neck carcinoma: new dose constraints for pharyngeal constrictors muscles and oral cavity. Strahlenther Onkol 199, 901–909 (2023). https://doi.org/10.1007/s00066-023-02080-y

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