Pètra M. Braam

Parotid Gland Function after Radiotherapy: The Combined Michigan and Utrecht Experience

PURPOSE To analyze the combined and updated results from the University of Michigan and University Medical Center Utrecht on normal tissue complication probability (NTCP) of the parotid gland 1 year after radiotherapy (RT) for head-and-neck (HN) cancer. PATIENTS AND METHODS A total of 222 prospectively analyzed patients with various HN malignancies were treated with conventional and intensity-modulated RT. Stimulated individual parotid gland flow rates were measured before RT and 1 year after RT using Lashley cups at both centers. A flow ratio <25% of pretreatment was defined as a complication. The data were fitted to the Lyman-Kutcher-Burman model. RESULTS A total of 384 parotid glands (Michigan: 157; Utrecht: 227 glands) was available for analysis 1 year after RT. Combined NTCP analysis based on mean dose resulted in a TD(50) (uniform dose leading to 50% complication probability) of 39.9 Gy and m (steepness of the curve) of 0.40. The resulting NTCP curve had good qualitative agreement with the combined clinical data. Mean doses of 25-30 Gy were associated with 17-26% NTCP. CONCLUSIONS A definite NTCP curve for parotid gland function 1 year after RT is presented, based on mean dose. No threshold dose was observed, and TD(50) was equal to 40 Gy.

Quality of life and salivary output in patients with head-and-neck cancer five years after radiotherapy

BackgroundTo describe long-term changes in time of quality of life (QOL) and the relation with parotid salivary output in patients with head-and-neck cancer treated with radiotherapy.MethodsForty-four patients completed the EORTC-QLQ-C30(+3) and the EORTC-QLQ-H&N35 questionnaires before treatment, 6 weeks, 6 months, 12 months, and at least 3.5 years after treatment. At the same time points, stimulated bilateral parotid flow rates were measured.ResultsThere was a deterioration of most QOL items after radiotherapy compared with baseline, with gradual improvement during 5 years follow-up. The specific xerostomia-related items showed improvement in time, but did not return to baseline. Global QOL did not alter significantly in time, although 41% of patients complained of moderate or severe xerostomia at 5 years follow-up. Five years after radiotherapy the mean cumulated parotid flow ratio returned to baseline but 20% of patients had a flow ratio <25%. The change in time of xerostomia was significantly related with the change in flow ratio (p = 0.01).ConclusionMost of the xerostomia-related QOL scores improved in time after radiotherapy without altering the global QOL, which remained high. The recovery of the dry mouth feeling was significantly correlated with the recovery in parotid flow ratio.

Large cohort dose-volume response analysis of parotid gland function after radiotherapy: intensity-modulated versus conventional radiotherapy.

PURPOSE To compare parotid gland dose-volume response relationships in a large cohort of patients treated with intensity-modulated (IMRT) and conventional radiotherapy (CRT). METHODS AND MATERIALS A total of 221 patients (64 treated with IMRT, 157 with CRT) with various head-and-neck malignancies were prospectively evaluated. The distribution of tumor subsites in both groups was unbalanced. Stimulated parotid flow rates were measured before and 6 weeks, 6 months, and 1 year after radiotherapy. Parotid gland dose-volume histograms were derived from computed tomography-based treatment planning. The normal tissue complication probability (NTCP) model proposed by Lyman was fit to the data. A complication was defined as stimulated parotid flow ratio <25% of the pretreatment flow rate. The relative risk of complications was determined for IMRT vs. CRT and adjusted for the mean parotid gland dose using Poisson regression modeling. RESULTS One year after radiotherapy, NTCP curves for IMRT and CRT were comparable with a TD(50) (uniform dose leading to a 50% complication probability) of 38 and 40 Gy, respectively. Until 6 months after RT, corrected for mean dose, different complication probabilities existed for IMRT vs. CRT. The relative risk of a complication for IMRT vs. CRT after 6 weeks was 1.42 (95% CI 1.21-1.67), after 6 months 1.41 (95% CI; 1.12-1.77), and at 1 year 1.21 (95% CI 0.87-1.68), after correcting for mean dose. CONCLUSIONS One year after radiotherapy, no difference existed in the mean dose-based NTCP curves for IMRT and CRT. Early after radiotherapy (up to 6 months) mean dose based (Lyman) models failed to fully describe the effects of radiotherapy on the parotid glands.

Xerostomia: A day and night difference

PURPOSE To compare patient-reported xerostomia during daytime and during nighttime with objectively measured parotid and submandibular gland function in a cohort of head-and-neck cancer (HNC) patients treated with RT. MATERIALS AND METHODS A cohort of 138 HNC patients underwent objective measurements of parotid (PF) and submandibular (SMF) gland function and completed a xerostomia questionnaire (XQ) before RT, at 6 weeks, 6 months and 1 year after RT. No attempt was made to spare the submandibular gland(s). The XQ contained specific questions concerning the sensation of dry mouth during day- (XD) and nighttime (XN), scored on a 5-point Likert scale. Patients with no or mild (grade 1-3) xerostomia and patients with more severe (grade 4-5) complaints were grouped together. RESULTS Before RT, no association existed between dry mouth complaints and PF or SMF. At 6 weeks, 6 months and 1 year after RT; 37%, 51% and 36% had grade 4-5 XD and 65%, 64% and 56% had grade 4-5 XN, respectively. Patients with grade 4-5 XD and XN had significantly worse SMF at all time points after RT compared to patients with grade 1-3 XD and XN, while PF was significantly worse only at 6 weeks after RT. In multivariate analyses, SMF was consistently the most important factor related to XN after treatment. PF significantly influenced XD at 6 weeks and 1 year after RT. CONCLUSIONS Differentiating between complaints during day- and nighttime in xerostomia research is necessary. Dry mouth at night is a frequent problem after (parotid-sparing) RT for HNC and is explained by submandibular gland dysfunction. Sparing of the contralateral submandibular gland, in addition to parotid gland sparing, may result in improved patient-reported xerostomia.

New insights in the vascular supply of the human parotid gland—Consequences for parotid gland‐sparing irradiation

Xerostomia is caused by irradiation for head and neck cancer, depending on the dose to the parotid gland. To investigate which part of the parotid gland has to be spared with radiotherapy, detailed information about the vascular supply of the parotid gland is necessary.