Esophagus-sparing radiotherapy for complicated spinal metastases (ESO-SPARE). A randomized phase III clinical trial

Background: Patients receiving palliative radiotherapy (RT) for complicated spinal metastases in the cervical and thoracic spine may develop dysphagia due to esophageal and pharyngeal irradiation. This phase III trial investigated if esophagus/pharynx-sparing VMAT/IMRT could reduce patient-reported peak dysphagia without affecting ambulatory function compared to standard VMAT/IMRT. Methods: This dual-center, single-blind, phase III trial (NCT05109819) randomized adult patients with complicated spinal metastases (C1-T12) receiving 1–10 fraction RT to either conventional or esophagus/pharynx-sparing VMAT/IMRT. Patient-reported outcomes (PRO-CTCAE) were collected daily for five weeks, and EQ-5D-5L, EORTC-QLQ-C30, weight, and analgesic use were assessed weekly for nine weeks. Co-primary endpoints were peak dysphagia (first five weeks) and ambulatory function (EQ-5D-5L mobility) at nine weeks, analyzed by Wilcoxon rank-sum test. The association between esophageal dosimetric parameters and “severe-or-worse” dysphagia was assessed. Results: From May 2021–April 2024, 188 patients were randomized (standard: 92 included, 60 analyzed; esophagus-sparing: 96 included, 70 analyzed). Fourteen esophagus-sparing patients did not receive the intended intervention. These patients were recategorized as standard for per-protocol analysis. Dysphagia (any grade) occurred in 64 % (standard) and 55 % (esophagus-sparing) of patients. Intention-to-treat analysis found no differences in peak dysphagia (p = 0.20) or ambulatory status (p = 0.30). Per-protocol analysis found significant difference in peak dysphagia (p = 0.50). Dosimetric parameters (D0.027 cc-D5cc, V15Gy–V25Gy) correlated with “severe-or-worse” dysphagia. Conclusion: Esophagus-sparing VMAT/IMRT did not reduce peak dysphagia in the intention-to-treat analysis but showed a significant benefit in the per-protocol analysis. Higher esophageal dose and larger irradiated volumes correlated with risk of “severe-or-worse” dysphagia, suggesting that esophagus/pharynx-sparing RT may particularly benefit patients receiving high-dose, large-field radiation.