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 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 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.