Interim analysis of patient-reported outcome compliance and dosimetry in a phase 3 randomized clinical trial of oesophagus-sparing spinal radiotherapy

Authors

  • Anna Mann Nielsen a Department of Oncology, Copenhagen University Hospital – Herlev and Gentofte, Copenhagen, Denmark
  • Katrine Smedegaard Storm a Department of Oncology, Copenhagen University Hospital – Herlev and Gentofte, Copenhagen, Denmark
  • Michael R. T. Laursen a Department of Oncology, Copenhagen University Hospital – Herlev and Gentofte, Copenhagen, Denmark
  • Vanja Remberg Gram a Department of Oncology, Copenhagen University Hospital – Herlev and Gentofte, Copenhagen, Denmark
  • Laura Ann Rechner a Department of Oncology, Copenhagen University Hospital – Herlev and Gentofte, Copenhagen, Denmark
  • Wiviann Ottosson a Department of Oncology, Copenhagen University Hospital – Herlev and Gentofte, Copenhagen, Denmark
  • Morten Hiul Suppli b Department of Oncology, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
  • Patrik Sibolt a Department of Oncology, Copenhagen University Hospital – Herlev and Gentofte, Copenhagen, Denmark
  • Claus F. Behrens a Department of Oncology, Copenhagen University Hospital – Herlev and Gentofte, Copenhagen, Denmark;c Department of Health Technology, Technical University of Denmark, Lyngby, Denmark
  • Ivan R. Vogelius b Department of Oncology, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark; d Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
  • Gitte F. Persson a Department of Oncology, Copenhagen University Hospital – Herlev and Gentofte, Copenhagen, Denmark; d Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

DOI:

https://doi.org/10.1080/0284186X.2023.2251083

Keywords:

Metastatic spinal cord compression, patient-reported outcome measures, oesophagus-sparing radiotherapy, phase III clinical trial

Abstract

Background

The randomized clinical trial ESO-SPARE investigates if oesophagus-sparing radiotherapy (RT) can reduce dysphagia in patients with metastatic spinal cord compression (MSCC). Patient-reported outcome (PRO) is the only follow-up measure. Due to the fragile patient population, low respondent compliance was anticipated. We performed a planned interim analysis of dosimetry and respondent compliance, to ensure that the protocol requirements were met.

Methods

Patients >18 years referred for cervical/thoracic MSCC radiotherapy in 1-10 fractions were included from two centres. Patients were randomized (1:1) to standard RT or oesophagus-sparing RT, where predefined oesophageal dose constraints were prioritized over target coverage. Patients completed a trial diary with daily reports of dysphagia for 5 weeks (PRO-CTC-AE) and weekly quality of life reports for 9 weeks (QLQ-C30, EQ-5D-5L). According to power calculation, 124 patients are needed for primary endpoint analysis. The sample size was inflated to 200 patients to account for the fragile patient population. The co-primary endpoints, peak patient-reported dysphagia, and preserved ability to walk (EQ-5D-5L), are analysed at 5 and 9 weeks, respectively. The interim analysis was conducted 90 days after the inclusion of patient no 100. Respondent compliance was assessed at 5 and 9 weeks. In all RT plans, oesophagus and target doses were evaluated regarding adherence to protocol constraints.

Results

From May 2021 to November 2022, 100 patients were included. Fifty-two were randomized to oesophagus-sparing RT. In 23% of these plans, oesophagus constraints were violated. Overall, the dose to both target and oesophagus was significantly lower in the oesophagus-sparing plans. Only 51% and 41% of the patients were evaluable for co-primary endpoint analysis at five and nine weeks, respectively. Mortality and hospitalization rates were significantly larger in patients who completed <4 days PRO questionnaires.

Conclusion

Compliance was lower than anticipated and interventions to maintain study power are needed.

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Additional Files

Published

2023-11-02

How to Cite

Mann Nielsen, A., Smedegaard Storm, K., Laursen, M. R. T., Remberg Gram, V., Ann Rechner, L., Ottosson, W., … Persson, G. F. (2023). Interim analysis of patient-reported outcome compliance and dosimetry in a phase 3 randomized clinical trial of oesophagus-sparing spinal radiotherapy. Acta Oncologica, 62(11), 1496–1501. https://doi.org/10.1080/0284186X.2023.2251083

Issue

Vol. 62 No. 11 (2023): Acta Oncologica

Section

Articles