Cumulative oesophageal dose and risk of high-grade toxicity in thoracic re-irradiation: a dose/toxicity analysis

Journal article : Review

Background and purposeRe-irradiation (re-RT) in recurrent thoracic cancer is being performed more often and can cause severe toxicity. Information is lacking on safe re-irradiation dose constraints. We modelled the relationship between cumulative oesophageal dose and grade 3 or worse (≥G3) oesophageal toxicity to develop dose constraints.Materials and methodsWe performed a literature search for reports of thoracic re-RT and selected studies that quoted cumulative oesophageal maximum dose (cDmax) in equivalent dose in 2 Gy fractions (EQD2) and ≥G3 toxicity. Additional collected data were inter-treatment interval and concurrent chemotherapy use (conCT) at re-irradiation. Logistic regression analyses were performed. The models were used to predict the cDmax associated with a 5% ≥G3 toxicity rate. Model performance was assessed using the Pearson correlation coefficient (PCC).ResultsWe identified 21 studies (505 patients), with 49 ≥G3 toxic events. The median oesophageal cDmax and interval were 84.8 Gy3 (3.7 - 220.6 Gy3 EQD2) and 15.5 months (1-162) respectively. Use of conCT and oesophageal cDmax were significantly associated with toxicity on univariable and multivariable modelling (both p < 0.001). The maximum likelihood doses associated with 5% risk of ≥G3 toxicity with/without chemotherapy were cDmax 43.0 Gy3 (95% CI: -18.5, 108.8) and 94.2 Gy3 (95% CI: 79.6, 142.8) respectively. The model had a PCC of 0.75 (p = 0.013) suggesting good correlation to the dataset.ConclusionThe models predict a 5% toxicity at cDmax 43.0 Gy3 and 94.2 Gy3 EQD2 with/without chemotherapy. This supports a cDmax constraint of 3 EQD2 to limit ≥G3 toxicity to under 5%, consistent with the American Radium Society constraints (3 EQD2). ConCT with re-irradiation has a large radiosensitising effect. Limitations of this study include the use of old, retrospective data resulting in wide CIs around the predictions and insufficient data to predict a volumetric constraint. Further modelling with more detailed dose data is required to refine and validate these predictions.

Authors: Rulach, R; Harrow, S; J Chalmers, A; Fenwick, J

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Clinical and Translational Radiation Oncology
• Volume: 57
• Pages: 101108
• Publication date: 2026-01-09
• Acceptance date: 2026-01-08
• DOI: 10.1016/j.ctro.2026.101108
• EISSN: 2405-6308
• ISSN: 2405-6308
• Pmid: 41583535
• Language: English
• Keywords: Re-irradiation; Intra-Thoracic Recurrence; Non-small cell lung cancer; Oesophageal Cancer
• Subtype: Review