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. 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 developdose 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 max ) in equivalent dose in 2 Gy fractions (EQD2) and ≥G3 toxicity. Additional collected data wereinter-treatment interval and concurrent chemotherapy use (conCT) at re-irradiation. Logistic regression analyses were performed. The models were used to predict the cD max 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 max and interval were 84.8 Gy 3 (3.7 – 220.6 Gy 3 EQD2) and 15.5 months (1–162) respectively. Use of conCT and oesophageal cD max 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 max 43.0 Gy 3 (95% CI: −18.5, 108.8) and 94.2 Gy 3 (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% toxicityat cD max 43.0 Gy 3 and 94.2 Gy 3 EQD2 with/without chemotherapy. Thissupports a cD max constraint of