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 (nCohort1=55; nCohort2=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 (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.
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 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=12/19Gy; Dmeancontra, Dmeanipsi=16, 25/20, 26Gy).
CONCLUSIONS: Increased Dmeancontra and Dmeanipsi explain short-term xerostomia following IMRT. Our results also suggest decreasing Dmeancontra to below 20Gy, while keeping Dmeanipsi to around 25Gy. Long-term xerostomia was less frequent, and no dose-response relationship was established for this follow-up time.