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

Background And Purpose: To 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 Methods: Objective xerostomia was assessed in 121 patients (n=55; n=66) treated to 70Gy@2Gy 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 (p)). Ultimately and for clinical guidance, minimum mean dose thresholds to the contralateral and the ipsilateral parotid glands (Dmean, Dmean) were estimated from the generated dose-response curves.

Results: The observed xerostomia rate was 38%/47% (3months) and 19%/23% (11-12months) in Cohort1/Cohort2. Risk of xerostomia at 3months increased for higher Dmean and Dmean (Cohort1: 0.17·Dmean+0.11·Dmean-8.13; AUC=0.90±0.05; p=0.0002±0.002; p=0.22±0.23; Cohort2: AUC=0.81; p<0.0001; p=0.27). The identified minimum Dmean thresholds were lower than in the QUANTEC guidelines (Cohort1/Cohort2: Dmean=12/19Gy; Dmean, Dmean=16, 25/20, 26Gy).

Conclusions: Increased Dmean and Dmean explain short-term xerostomia following IMRT. Our results also suggest decreasing Dmean to below 20Gy, while keeping Dmean to around 25Gy. Long-term xerostomia was less frequent, and no dose-response relationship was established for this follow-up time.