Re-Irradiation for Head and Neck Cancer: Cumulative Dose to Organs at Risk and Late Side Effects

Simple Summary Local recurrences of head and neck cancer are unfortunately common and can be difficult to treat. The treatment is challenging, partly due to the location, with several important organs in the head and neck area, but also because recurrence often occurs in an area already treated with radiotherapy. It has been shown that repeat radiotherapy, re-irradiation, can offer long-lasting tumor control and sometimes even cure in selected patients. However, there is a risk of normal tissue close to the tumor being damaged by high cumulative doses of radiotherapy. In this study, we aim to establish levels of cumulative dose to specific organs that could be considered reasonably safe to deliver at re-irradiation without causing high rates of severe side effects. Increased knowledge in dose-response relationships in re-irradiation for head and neck cancer will facilitate a tailored treatment for the individual patient. Re-irradiation in head and neck cancer is challenging, and cumulative dose constraints and dose/volume data are scarce. In this study, we present dose/volume data for patients re-irradiated for head and neck cancer and explore the correlations of cumulative dose to organs at risk and severe side effects. We analyzed 54 patients re-irradiated for head and neck cancer between 2011 and 2017. Organs at risk were delineated and dose/volume data were collected from cumulative treatment plans of all included patients. Receiver-operator characteristics (ROC) analysis assessed the association between dose/volume parameters and the risk of toxicity. The ROC-curve for a logistic model of carotid blowout vs. maximum doses to the carotid arteries showed AUC = 0.92 (95% CI 0.83 to 1.00) and a cut-off value of 119 Gy (sensitivity 1.00/specificity 0.89). The near-maximum dose to bones showed an association with the risk of osteoradionecrosis: AUC = 0.74 (95% CI 0.52 to 0.95) and a cut-off value of 119 Gy (sensitivity 1.00/specificity 0.52). Our analysis showed an association between cumulative dose to organs at risk and the risk of developing osteoradionecrosis and carotid blowout, and our results support the existing dose constraint for the carotid arteries of 120 Gy. The confirmation of these dose-response relationships will contribute to further improvements of re-irradiation strategies.