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Clinical Studies

Efficacy and toxicity of primary re-irradiation for malignant spinal cord compression based on radiobiological modelling: a phase II clinical trial

Abstract

Background

The efficacy and safety of primary re-irradiation for MSCC are not known. Our aim was to establish the efficacy and safety of biologically effective dose-based re-irradiation.

Methods

Patients presenting with MSCC at a previously irradiated spine segment, and not proceeding with surgical decompression, were eligible. A 3 Gray per fraction experimental schedule (minimum 18 Gy/6 fractions, maximum 30 Gy/10 fractions) was used, delivering a maximum cumulative spinal dose of 100 Gy2 if the interval since the last radiotherapy was within 6 months, or 130 Gy2 if longer. The primary outcome was a change in mobility from week 1 to week 5 post-treatment, as assessed by the Tomita score. The RTOG SOMA score was used to screen for spinal toxicity, and an MRI performed to assess for radiation-induced myelopathy (RIM).

Results

Twenty-two patients were enroled, of whom eleven were evaluable for the primary outcome. Nine of eleven (81.8%) had stable or improved Tomita scores at 5 weeks. One of eight (12.5%) evaluable for late toxicity developed RIM.

Conclusions

Re-irradiation is an efficacious treatment for MSCC. There is a risk of RIM with a cumulative dose of 120 Gy2.

Clinical Trial Registration

Cancer Trials Ireland (ICORG 07-11); NCT00974168.

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Fig. 1: CONSORT flow diagram.

Data availability

Data supporting the results reported in this article can be requested from Cancer Trials Ireland

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Acknowledgements

Cancer Trials Ireland (formerly ICORG), as the study sponsor, was involved in protocol development and approval, study conduct and monitoring/audit, data collection, management, analysis and interpretation, and in the decision to submit the paper for publication. The abstract of this study was presented at ASTRO in October 2020(28).

Funding

This study was funded by Health Research Board under Grant CCT/06/09 (covering Jan. 2006-June 2009), ICORGH/2009 (covering July 2009-June 2012), ICORG/2012 (covering July 2012-Dec 2015) and Grant 2016 HRB/CTI. The funding source had no involvement in study design or conduct; in the collection, management, analysis and interpretation of data; preparation, review or approval of the manuscript; or in the decision to submit the manuscript for publication.

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Contributions

Conception and Design: M Moriarty, PGT, AC-L, OM, CS. Acquisition, collection and assembly of data: OM, CS, AC-L, MP, CDC, JC, DF, MRS, M McCague, M Moriarty, OS, CG, JGA, AMS, PGT. Data analysis and interpretation: AA-I, M McCague, MD, NDW, IP, PGT. Drafting of the work, revising it critically for important intellectual content and Manuscript writing: NDW, PGT, MTD. Final approval of manuscript: All authors. Integrity of the work as a whole, from inception to published article: PGT. Agreement 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: NDW, PGT, MTD.

Corresponding author

Correspondence to Mary T. Dunne.

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The authors declare no competing interests.

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Subjects provided their consent to participate. The trial was approved by the St Luke’s Hospital Ethics and Medical Research Committee and at the Clinical REC Merlin Park Hospital Galway. The trial was carried out in accordance with the International Conference on Harmonization (ICH) for Good Clinical Practice (GCP).

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Wallace, N.D., Dunne, M.T., McArdle, O. et al. Efficacy and toxicity of primary re-irradiation for malignant spinal cord compression based on radiobiological modelling: a phase II clinical trial. Br J Cancer (2022). https://doi.org/10.1038/s41416-022-02078-w

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