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

Abstract

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_Cohort1=55; n_Cohort2=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_HL)). Ultimately and for clinical guidance, minimum mean dose thresholds to the contralateral and the ipsilateral parotid glands (Dmean_contra, Dmean_ipsi) 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_contra and Dmean_ipsi (Cohort1: 0.17·Dmean_contra+0.11·Dmean_ipsi-8.13; AUC=0.90±0.05; p=0.0002±0.002; p_HL=0.22±0.23; Cohort2: AUC=0.81; p<0.0001; p_HL=0.27). The identified minimum Dmean_contra thresholds were lower than in the QUANTEC guidelines (Cohort1/Cohort2: Dmean_contra=12/19Gy; Dmean_contra, Dmean_ipsi=16, 25/20, 26Gy).

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

Keywords: Dose response; Head and neck; IMRT; QUANTEC; Radiotherapy; Xerostomia.