Use of gEUD for predicting ear and pituitary gland damage following proton and photon radiation therapy

Abstract

Objective: To determine the relationship between the dose to the inner ear or pituitary gland and radiation-induced late effects of skull base radiation therapy.

Methods: 140 patients treated between 2000 and 2008 were considered for this study. Hearing loss and endocrine dysfunction were retrospectively reviewed on pre- and post-radiation therapy audiometry or endocrine assessments. Two normal tissue complication probability (NTCP) models were considered (Lyman-Kutcher-Burman and log-logistic) whose parameters were fitted to patient data using receiver operating characteristics and maximum likelihood analysis. The method provided an estimation of the parameters of a generalized equivalent uniform dose (gEUD)-based NTCP after conversion of dose-volume histograms to equivalent doses.

Results: All 140 patients had a minimum follow up of 26 months. 26% and 44% of patients experienced mild hearing loss and endocrine dysfunction, respectively. The fitted values for TD50 and γ50 ranged from 53.6 to 60.7 Gy and from 1.9 to 2.9 for the inner ear and were equal to 60.6 Gy and 4.9 for the pituitary gland, respectively. All models were ranked equal according to Akaike's information criterion.

Conclusion: Mean dose and gEUD may be used as predictive factors for late ear and pituitary gland late complications after skull base proton and photon radiation therapy.

Advances in knowledge: In this study, we have reported mean dose effects and dose-response relationship of small organs at risk (partial volumes of the inner ear and pituitary gland), which could be useful to define optimal dose constraints resulting in an improved therapeutic ratio.

Figure 1.

Typical treatment plan for a patient with a skull base chondrosarcoma treated up to a total dose of 70.2 Gy-RBE with combined photon–proton therapy (34.2 Gy photons, 36 Gy-RBE protons). ant, anterior; CTV, clinical target volume; IAC, internal auditory canals; L, left; post, posterior; LOBETEMP, temporal lobe; PTV, planning target volume; R, right.

Figure 2.

Cumulative dose–volume histogram (DVH) for patients with (squares) and without (circles) late effects: (a) cochlea, (b) pituitary gland (adults).

Figure 3.

Variation of the area under the receiver operating characteristics (AUROC) curve with standard error for several subvolumes of the ear: (a) inner ear, (b) internal auditory canal, (c) cochlea and (d) pituitary gland (adults). gEUD, generalized equivalent uniform dose.

Figure 4.

Normal tissue complication probability for (a) inner ear, (b) internal auditory canal, (c) cochlea and (d) pituitary gland (adults), and best curves (log-logistic/Lyman–Kutcher–Burman equivalent uniform dose models) fitting the clinical data (lines, models; crosses, experimental incidence). EUD, equivalent uniform dose.