Rulach, R;
Harrow, S;
J. Chalmers, A;
Fenwick, J;
(2026)
Cumulative oesophageal dose and risk of high-grade toxicity in thoracic re-irradiation: a dose/toxicity analysis.
Clinical and Translational Radiation Oncology
, 57
, Article 101108. 10.1016/j.ctro.2026.101108.
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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<inf>max</inf>) 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<inf>max</inf> 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<inf>max</inf> and interval were 84.8 Gy<inf>3</inf> (3.7 – 220.6 Gy<inf>3</inf> EQD2) and 15.5 months (1–162) respectively. Use of conCT and oesophageal cD<inf>max</inf> 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<inf>max</inf> 43.0 Gy<inf>3</inf> (95% CI: −18.5, 108.8) and 94.2 Gy<inf>3</inf> (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<inf>max</inf> 43.0 Gy<inf>3</inf> and 94.2 Gy<inf>3</inf> EQD2 with/without chemotherapy. This supports a cD<inf>max</inf> constraint of <95 Gy<inf>3</inf> EQD2 to limit ≥G3 toxicity to under 5%, consistent with the American Radium Society constraints (<100 Gy<inf>3</inf> 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.
| Type: | Article |
|---|---|
| Title: | Cumulative oesophageal dose and risk of high-grade toxicity in thoracic re-irradiation: a dose/toxicity analysis |
| Location: | Ireland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ctro.2026.101108 |
| Publisher version: | https://doi.org/10.1016/j.ctro.2026.101108 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Intra-thoracic recurrence, Non-small cell lung cancer, Oesophageal cancer, Re-irradiation |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10220869 |
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