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The risk of late effects following pediatric and adult radiotherapy regimens in Hodgkin lymphoma

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Abstract

Purpose

Adolescent young adults (AYA) with Hodgkin lymphoma (HL) are treated according to either pediatric or adult protocols, however, the best strategy has yet to be established. We describe the AYA patients referred for radiotherapy and quantify the risk of radiation-induced late effects and the corresponding life years lost (LYL) following pediatric and adult regimens.

Methods

Patients ≤24 years irradiated for HL were included. For each patient, organs at risk (OARs) were contoured and dosimetric parameters were extracted. Estimated excess hazard ratios of radiation-induced late effects were calculated from dose-response models and LYL attributable to various late effects were estimated.

Results

In total, 77 patients were analyzed (pediatric regimen: 15; adult regimen: 62). Age, clinical stage, and the number of patients enrolled in protocols were significantly different between the groups. Pediatric patients had more advanced disease, which resulted in larger target volumes and higher doses to most OARs, despite a lower prescribed dose compared to adult regimens. LYL estimates were all higher with the pediatric regimens. Total LYL with pediatric and adult treatment regimens were 3.2 years and 2.3 years, respectively. Due to the clinical stage variation and heterogeneity in disease location, a direct comparison of the estimated risks of late effects was only exploratory.

Conclusion

Pediatric regimens selected patients with more advanced disease to radiotherapy resulting in larger target volumes and higher doses to the OARs. Target volume rather than prescribed dose impacted OAR exposure. Consequently, the estimated risk of radiation-induced late effects and corresponding LYL was increased when compared to adult regimens.

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Acknowledgements

This work was supported by the Danish Childhood Cancer Foundation (grant no. 2012‑5, 2015-9) and the Danish Cancer Society (grant no. R150-A10066).

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Authors and Affiliations

  1. Department of Oncology, Rigshospitalet, Unversity of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Anni Young Lundgaard MD, Laura Ann Rechner MSc, PhD, Michael Lundemann MSc, PhD, Morten Joergensen MD, Lena Specht MD, DMSc & Maja Vestmoe Maraldo MD, PhD

  2. Department of Pediatric Haematology and Oncology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Lisa Lyngsie Hjalgrim MD, PhD

  3. Institute for Onco-Physics, Albert Einstein College of Medicine and Montefiore Medical Center, 1300 Morris Park Avenue Bronx, 10461, NY, USA

    N. Patrik Brodin MSc, PhD

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  1. Anni Young Lundgaard MD
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  8. Maja Vestmoe Maraldo MD, PhD
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Correspondence to Anni Young Lundgaard MD.

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Conflict of interest

L. Specht is on advisory boards and received honoraria from Takeda and Kyowa Kirin. She has research grants from Varian and ViewRay. A.Y. Lundgaard, L.L. Hjalgrim, L.A. Rechner, M. Lundemann, N.P. Brodin, M. Joergensen, and M.V. Maraldo declare that they have no competing interests.

Ethical standards

The study was approved by the Danish Patient Safety Authority (3-3013-1953/1) and the Danish Data Protection Agency (RH-2017-28).

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Availability of data and material

The datasets generated during the current study are not publicly available due to regulations on personal data protection but are available from the corresponding author on reasonable request.

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Available from the corresponding author upon request.

Caption Electronic Supplementary Material

Table S1 Pediatric and adult treatment regimens

66_2020_1721_MOESM2_ESM.docx

Table S2 Equations for the excess hazard ratios (HRexcess/Gy) used in the study with 95% confidence intervals (CI) for each value used in the risk models and references. Valve EQD2 was the equivalent dose in 2‑Gy fractions to the aortic or mitral valve, whichever was higher. The aortic valve had the highest EQD2 in most cases

66_2020_1721_MOESM3_ESM.docx

Table S3 Life years lost (LYL) attributable to late effects from radiotherapy for pediatric and adult regimens with the patients’ real age and age 18 years

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Lundgaard, A.Y., Hjalgrim, L.L., Rechner, L.A. et al. The risk of late effects following pediatric and adult radiotherapy regimens in Hodgkin lymphoma. Strahlenther Onkol 197, 711–721 (2021). https://doi.org/10.1007/s00066-020-01721-w

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