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

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.

Overlapping volumes in re-irradiation for head and neck cancer - an important factor for patient selection.

BACKGROUND: There is a lack of consensus concerning the definition of re-irradiation and re-irradiation volumes in head and neck cancer (HNC). The aim of the present study is to introduce a more strict definition of the re-irradiated volume that might better predict the risk of serious side-effects from treatment. METHODS: Fifty-four consecutive patients re-irradiated for HNC cancer were retrospectively analysed. CT images were deformably registered and the dose distributions accumulated after conversion to EQD2. Patients with a cumulative dose of ≥100 Gy in the overlapping volume (V100) were included in the study. Survival data and radiation-related acute and late toxicities were recorded. RESULTS: The overall survival of all included patients at 2 and 5 years was 42.6 and 27.3% respectively and the progression free survival at 2 and 5 years was 32.5 and 28.5% respectively. The overall rate of any event of severe (grade ≥ 3) acute and late toxicity was 26 and 51%, respectively. We found that severe acute toxicity was more common in patients who had a larger overlapping volume (V100 > mean) where 43% of the patients experienced grade ≥ 3 acute toxicity, compared to the patients with smaller overlapping volumes (V100 < mean) where only 11% had severe toxicity (p = 0.02). The seemingly high rates of late toxicity in the present study could be due to the use of a more strict definition of re-irradiation. In previous studies also patients with low dose overlap are included and our results imply that there is a risk that previous studies might have overestimated the risk-benefit ratio in re-irradiation of HNC. CONCLUSIONS: Our study describes the outcome of a patient material where a more strict definition of the re-irradiated volume is used. With this definition, which could better describe the volume of highest risk for serious complications, we found that larger such overlapping volumes result in an increase in severe acute side-effects. A clear definition of re-irradiation and re-irradiation volumes is of utmost importance for future studies of HNC to make results from different studies comparable.