Morbidity of head and neck radiotherapyInternal and external generalizability of temporal dose-response relationships for xerostomia following IMRT for head and neck cancer

Background and purposeTo study internal and external generalizability of temporal dose-response relationships for xerostomia after intensity-modulated radiotherapy (IMRT) for head and neck cancer, and to investigate potential amendments of the QUANTEC guidelines.Material and methodsObjective xerostomia was assessed in 121 patients (nCohort1 = 55; nCohort2 = 66) treated to 70 Gy@2 Gy in 2006-2015. Univariate and multivariate analyses (UVA, MVA with 1000 bootstrap populations) were conducted in Cohort1, and generalizability of the best-performing MVA model was investigated in Cohort2 (performance: AUC, p-values, and Hosmer-Lemeshow p-values (pHL)). Ultimately and for clinical guidance, minimum mean dose thresholds to the contralateral and the ipsilateral parotid glands (Dmeancontra, Dmeanipsi) were estimated from the generated dose-response curves.ResultsThe observed xerostomia rate was 38%/47% (3 months) and 19%/23% (11-12 months) in Cohort1/Cohort2. Risk of xerostomia at 3 months increased for higher Dmeancontra and Dmeanipsi (Cohort1: 0.17·Dmeancontra + 0.11·Dmeanipsi-8.13; AUC = 0.90 ± 0.05; p = 0.0002 ± 0.002; pHL = 0.22 ± 0.23; Cohort2: AUC = 0.81; p < 0.0001; pHL = 0.27). The identified minimum Dmeancontra thresholds were lower than in the QUANTEC guidelines (Cohort1/Cohort2: Dmeancontra = 12/19 Gy; Dmeancontra, Dmeanipsi = 16, 25/20, 26 Gy).ConclusionsIncreased Dmeancontra and Dmeanipsi explain short-term xerostomia following IMRT. Our results also suggest decreasing Dmeancontra to below 20 Gy, while keeping Dmeanipsi to around 25 Gy. Long-term xerostomia was less frequent, and no dose-response relationship was established for this follow-up time.