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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Anna Mann Nielsen
  • Katrine Smedegaard Storm
  • Michael R T Laursen
  • Vanja Remberg Gram
  • Laura Ann Rechner
  • Wiviann Ottosson
  • Morten Hiul Suppli
  • Patrik Sibolt
  • Claus F Behrens
  • Vogelius, Ivan
  • Persson, Gitte

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.

Original languageEnglish
JournalActa oncologica (Stockholm, Sweden)
Issue number11
Pages (from-to)1496-1501
Number of pages6
Publication statusPublished - 2023

    Research areas

  • Humans, Quality of Life, Deglutition Disorders, Spinal Cord Compression/radiotherapy, Patient Reported Outcome Measures

ID: 387697693