Cumulative oesophageal dose and risk of high-grade toxicity in thoracic re-irradiation: a dose/toxicity analysis.
[BACKGROUND AND PURPOSE] Re-irradiation (re-RT) in recurrent thoracic cancer is being performed more often and can cause severe toxicity.
- p-value p < 0.001
- p-value p = 0.013
APA
Rulach R, Harrow S, et al. (2026). Cumulative oesophageal dose and risk of high-grade toxicity in thoracic re-irradiation: a dose/toxicity analysis.. Clinical and translational radiation oncology, 57, 101108. https://doi.org/10.1016/j.ctro.2026.101108
MLA
Rulach R, et al.. "Cumulative oesophageal dose and risk of high-grade toxicity in thoracic re-irradiation: a dose/toxicity analysis.." Clinical and translational radiation oncology, vol. 57, 2026, pp. 101108.
PMID
41583535
Abstract
[BACKGROUND AND PURPOSE] Re-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 METHODS] We performed a literature search for reports of thoracic re-RT and selected studies that quoted cumulative oesophageal maximum dose (cD) 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 cD associated with a 5% ≥G3 toxicity rate. Model performance was assessed using the Pearson correlation coefficient (PCC).
[RESULTS] We identified 21 studies (505 patients), with 49 ≥G3 toxic events. The median oesophageal cD and interval were 84.8 Gy (3.7 - 220.6 Gy EQD2) and 15.5 months (1-162) respectively. Use of conCT and oesophageal cD 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 cD 43.0 Gy (95% CI: -18.5, 108.8) and 94.2 Gy (95% CI: 79.6, 142.8) respectively. The model had a PCC of 0.75 (p = 0.013) suggesting good correlation to the dataset.
[CONCLUSION] The models predict a 5% toxicity at cD 43.0 Gy and 94.2 Gy EQD2 with/without chemotherapy. This supports a cD constraint of <95 Gy EQD2 to limit ≥G3 toxicity to under 5%, consistent with the American Radium Society constraints (<100 Gy 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.
[MATERIALS AND METHODS] We performed a literature search for reports of thoracic re-RT and selected studies that quoted cumulative oesophageal maximum dose (cD) 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 cD associated with a 5% ≥G3 toxicity rate. Model performance was assessed using the Pearson correlation coefficient (PCC).
[RESULTS] We identified 21 studies (505 patients), with 49 ≥G3 toxic events. The median oesophageal cD and interval were 84.8 Gy (3.7 - 220.6 Gy EQD2) and 15.5 months (1-162) respectively. Use of conCT and oesophageal cD 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 cD 43.0 Gy (95% CI: -18.5, 108.8) and 94.2 Gy (95% CI: 79.6, 142.8) respectively. The model had a PCC of 0.75 (p = 0.013) suggesting good correlation to the dataset.
[CONCLUSION] The models predict a 5% toxicity at cD 43.0 Gy and 94.2 Gy EQD2 with/without chemotherapy. This supports a cD constraint of <95 Gy EQD2 to limit ≥G3 toxicity to under 5%, consistent with the American Radium Society constraints (<100 Gy 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.