Late mucosal ulcers in dose-escalated adaptive dose-painting treatments for head-and-neck cancer

Abstract

Background: To identify predictive factors for the development of late grade 4 mucosal ulcers in adaptive dose-escalated treatments for head-and-neck cancer. Material and methods: Patient data of four dose-escalated three-phase adaptive dose-painting by numbers (DPBN) clinical trials were analyzed in this study. Correlations between the development of late grade 4 ulcers and factors related with the treatment, disease characteristics and the patient were investigated. Dosimetrical thresholds were searched among the highest doses received by 1.75 cm3 (D1.75cc) of the primary gross tumor volume (GTVT) and the corresponding normalized isoeffective dose (NID21.75cc, with a reference dose of 2Gy/fraction and α/β of 3 Gy). Results: From 39 studied patients, nine developed late grade 4 mucosal ulcers. The continuation to either smoke or drink alcohol after therapy was the factor that showed a strong (eight out of nine patients) association with the occurrence of grade 4 ulcers. Six of the patients who continued to smoke or/and drink had D1.75cc and NID21.75cc above 84 Gy and 95.5 Gy, respectively. Seven of the patients with grade 4 had the dose levels above these thresholds, but even if the D1.75cc threshold was significant in the prediction of late grade 4 ulcers, it could not be considered as the only contributing factor. Conclusions: The search for patterns provided strong reasons to apply a dosimetrical threshold for the peak-dose volume of 1.75 cm3 as a preventive measure for late grade 4 mucosal ulcers. Also, patients that continue to smoke or drink alcohol after therapy have increased risk to develop late mucosal ulcers.