TY - JOUR
T1 - Esophagus-sparing radiotherapy for complicated spinal metastases (ESO-SPARE). A randomized phase III clinical trial
AU - Nielsen, Anna Mann
AU - Laursen, Michael R T
AU - Rechner, Laura A
AU - Krog, Sebastian Moretto
AU - Storm, Katrine S
AU - Ottosson, Wiviann
AU - Gram, Vanja R
AU - Suppli, Morten H
AU - Sibolt, Patrik
AU - Vogelius, Ivan R
AU - Behrens, Claus P
AU - Persson, Gitte
N1 - Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.
PY - 2025/6
Y1 - 2025/6
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Deglutition Disorders/etiology
KW - Esophagus/radiation effects
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Organ Sparing Treatments/methods
KW - Palliative Care/methods
KW - Radiotherapy Dosage
KW - Radiotherapy, Intensity-Modulated/methods
KW - Single-Blind Method
KW - Spinal Neoplasms/radiotherapy
KW - Patient reported outcomes
KW - Palliative radiotherapy
KW - Metastatic spinal cord compression
KW - Spinal metastases
KW - Esophagus-sparing radiotherapy
KW - Dysphagia
KW - phase III trial
UR - https://www.scopus.com/pages/publications/105004299683
U2 - 10.1016/j.radonc.2025.110906
DO - 10.1016/j.radonc.2025.110906
M3 - Journal article
C2 - 40324910
SN - 0167-8140
VL - 207
JO - Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
JF - Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
M1 - 110906
ER -