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

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.

Reduction of oesophageal toxicity with VMAT dose-sparing radiotherapy in thoracic metastatic spinal cord compression: A feasibility study.

Background: Palliative radiotherapy for metastatic spinal cord compression (MSCC) is given to halt disease progression and sustain quality of life for patients with advanced cancer. Radiotherapy can however induce toxicity, contradicting treatment intention. Advanced radiotherapy offers possibility of sparing organs at risk (OARs). The purpose of this dosimetric study is to establish the feasibility and potential benefits of dose sparing of the oesophagus. Materials and methods: 30 patients receiving radiotherapy of 30 Gy/10# for MSCC were retrospectively included and the oesophagus delineated. Two new dose plans were created for each patient (eso-crop and PTV-crop) with the intention of optimising the oesophageal dose. In the eso-crop plan maintaining full target volume coverage was prioritised, for the PTV-crop plan oesophageal dose was further reduced through cropping the planning target volume (PTV) overlapping oesophageal/PTV-area. Time added for delineation was measured. Plans were compared using Wilcoxon signed rank test with p < 0.05 considered statistically significant. Bivariate associations between dose metrics and patient characteristics were quantified using linear regression models. Results: Oesophageal delineation took a mean of 8.6 min. There was significant dose reduction for both V7.7 Gy, D2% and mean oesophageal dose, without significant change in CTV coverage. The mean achievable oesophageal dose reduction was 29.1% and 50.4% for the eso-crop and PTV crop plans, respectively. Minor changes in dose distribution to the lungs was observed, with increased mean and V20Gy for the eso-crop plan and decreased V5Gy to the PTV-crop plan. Conclusion: This study demonstrated the possibility of significant dose sparing of the oesophageal dose using single arc VMAT without impacting on CTV coverage.