646 POSTER Insights into the mechanism of microtubule stabilization by Taxol

Abstract

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.Objective xerostomia was assessed in 121 patients (nCohort1 = 55; nCohort2 = 66) treated to 70 [email protected] Gy 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.The observed xerostomia rate was 38%/47% (3 months) and 19%/23% (11–12 months) in Cohort1/Cohort2. Risk of xerostomia at 3 months 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 = 12/19 Gy; Dmeancontra, Dmeanipsi = 16, 25/20, 26 Gy).Increased Dmeancontra and Dmeanipsi explain short-term xerostomia following IMRT. Our results also suggest decreasing Dmeancontra to below 20 Gy, while keeping Dmeanipsi to around 25 Gy. Long-term xerostomia was less frequent, and no dose–response relationship was established for this follow-up time.