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 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.