Dysphagia Swallowing sparing intensity modulated radiotherapy ( SW-IMRT ) in head and neck cancer : Clinical validation according to the model-based approach q

Purpose: The aim of this study was to clinically validate a multivariable normal tissue complication probability (NTCP) model for grade 2–4 swallowing dysfunction at 6 months after radiotherapy or chemoradiation (SWALM6) in head and neck cancer patients treated with swallowing sparing intensity modulated radiotherapy (SW-IMRT) and to test if SW-IMRT resulted in a reduction of the prevalence of SWALM6. Materials and methods: The primary endpoint was SWALM6. For all 186 patients, a standard IMRT (parotid sparing) and a SW-IMRT plan (additional constraints for swallowing organs at risk) was created. The difference in NTCP for SWALM6 (DNTCPSWALM6 = NTCPstandard NTCPSW-IMRT) was calculated. Patients were treated with SW-IMRT. The external validation of the NTCP model was analyzed by comparing performance measures. Results: The mean DNTCPSWALM6 was 4.9% (range 0.01–17.3%), with a significant lower mean predicted NTCPSW-IMRT of 22.6% (95% CI 20.2–24.9%), compared to NTCPstandard of 27.5% (95% CI 24.9–29.9%) (p < 0.001). There was a perfect correspondence of NTCPSW-IMRT with the observed prevalence of SWALM6 (22.6%). The overall model performance, discrimination and ‘goodness of fit’ were good. Conclusion: We externally validated the multivariable NTCP model for SWALM6 in SW-IMRT treated patients, showing reduced swallowing dysfunction by reducing the dose parameters included in this NTCP model. 2015 The Authors. Published by Elsevier Ireland Ltd. Radiotherapy and Oncology 118 (2016) 298–303 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-ncnd/4.0/). Swallowing dysfunction is one of the most devastating side effects after definitive radiotherapy (RT) or chemoradiation (CHRT) for head and neck cancer (HNC) and has a major impact on health-related quality of life (HRQoL) [1–6]. Recently, we reported on the results of a large multicenter prospective cohort study in which we developed multivariable normal tissue complication probability (NTCP) models for swallowing dysfunction [7]. In that study we identified two independent risk factors for grade 2–4 swallowing dysfunction at 6 months after completion of treatment (SWALM6), including the mean dose to the superior pharyngeal constrictor muscle (superior PCM) and the mean dose to the supraglottic larynx, which is in line with the results reported by other investigators [8–11]. We subsequently showed that swallowing sparing intensity modulated radiotherapy (SW-IMRT) is expected to result in clinically relevant reductions in the risk of swallowing dysfunction in approximately half of the patients. SW-IMRT refers to IMRT with dose constraints for both the parotid glands as well as for the swallowing organs at risk (SWOARs), without compromising the dose to the planning target volumes (PTV) and the parotid glands [12]. However, the clinical validation of SW-IMRT remains to be determined. Therefore, the purpose of this study was to clinically validate a previously developed multivariable NTCP model for SWALM6 in a cohort of patients treated with SW-IMRT and to investigate whether SW-IMRT actually resulted in a reduction of the M.E. M.C. Christianen et al. / Radiotherapy and Oncology 118 (2016) 298–303 299 prevalence of SWALM6 as compared to standard IMRT (parotid gland sparing IMRT). Methods and materials