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Prospective validation of stringent dose constraints for prostatic stereotactic radiation monotherapy: results of a single-arm phase II toxicity-oriented trial

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Abstract

Purpose

There are no safety-focused trials on stereotactic body radiotherapy (SBRT) for localized prostate cancer. This prospective 3‑year phase II trial used binomial law to validate the safety and efficacy of SBRT with stringent organ at risk dose constraints that nevertheless permitted high planning target volume doses.

Methods

All consecutive ≥ 70-year-old patients with localized prostate adenocarcinoma who underwent SBRT between 2014 and 2018 at the National Radiotherapy Center in Luxembourg were included. Patients with low Cancer of Prostate Risk Assessment (CAPRA) scores (0–2) and intermediate scores (3–5) received 36.25 Gy. High-risk (6–10) patients received 37.5 Gy. Radiation was delivered in 5 fractions over 9 days with Cyberknife-M6™ (Accuray, Sunnyvale, CA, USA). Primary study outcome was Common Terminology Criteria for Adverse Events version 4 (CTCAEv4) genitourinary and rectal toxicity scores at last follow-up. Based on binomial law, SRBT was considered safe in this cohort of 110 patients if there were ≤ 2 severe toxicity (CTCAEv4 grade ≥ 3) cases. Secondary outcomes were biochemical progression-free survival (bPFS) and patient quality of life (QOL), as determined by the IPPS and the Urinary Incontinence QOL questionnaire.

Results

The first 110 patients who were accrued in a total cohort of 150 patients were included in this study and had a median follow-up of 36 months. Acute grade ≥ 3 toxicity never occurred. One transient late grade 3 case was observed. Thus, our SBRT program had an estimated severe toxicity rate of < 5% and was safe at the p < 0.05 level. Overall bPFS was 90%. QOL did not change relative to baseline.

Conclusion

The trial validated our SBRT regimen since it was both safe and effective.

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Acknowledgements

We are grateful to the clinical staff of the Centre François Baclesse, namely Dr Louis Céline, Dr Philippi Sven, Dr Biver Sylvie, Dr Frédérique Bérangère, and Zsusa Bodgal, for monitoring the clinical data. We also thank Prof. Adelin Albert from Liège University in Belgium for the binomial law statistical concept.

Funding

No funds, grants, or other support was received.

Author information

Authors and Affiliations

  1. Department of Radiotherapy, Centre François Baclesse, Rue Emile Mayrisch, 4240, Esch-sur-Alzette, Luxembourg

    Paul Nguyen, Guillaume Vogin & Philippe Nickers

  2. Department of Physics, Centre François Baclesse, Rue Emile Mayrisch, 4240, Esch-sur-Alzette, Luxembourg

    Ludovic Harzée & Stéphane Joseph

  3. Department of Physics, University of Lorraine, Metz Regional Hospital, 1, Allée du Château, 57085, Metz, France

    Paul Retif

  4. CNRS UMR 7365 IMoPA, Université de Lorraine, Biopôle, Vandoeuvre-Lès-Nancy, France

    Guillaume Vogin

  5. Department of Radiotherapy, Metz Regional Hospital, 1, Allée du Château, 57085, Metz, France

    Philippe Nickers

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  1. Paul Nguyen
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Contributions

All authors contributed to study conception and design. Material preparation, data collection, and analysis were performed by Paul Nguyen, Philippe Nickers, Ludovic Harzée, Stéphane Joseph, Paul Rétif, and Guillaume Vogin. The first draft of the manuscript was written by Paul Nguyen and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Paul Nguyen.

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Conflict of interest

P. Nguyen, L. Harzée, P. Retif, S. Joseph, G. Vogin, and P. Nickers declare that they have no competing interests.

Ethical standards

All procedures performed in studies involving human participants or on human tissue were in accordance with the ethical standards of the institutional and/or national research committee (National Review Board of Luxembourg (approval no. 201311/01)) and with the 1975 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

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Nguyen, P., Harzée, L., Retif, P. et al. Prospective validation of stringent dose constraints for prostatic stereotactic radiation monotherapy: results of a single-arm phase II toxicity-oriented trial. Strahlenther Onkol 197, 1001–1009 (2021). https://doi.org/10.1007/s00066-021-01832-y

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