Prediction models for tube feeding dependence in head and neck radiotherapy

Aim of the research presented in this thesis was the development of prediction models that aid in the selection of patients with cancer of the head and neck at high risk for tube feeding dependence after radiotherapy. In head and neck cancer (HNC) the tumour is surrounded by critical structures like the spinal cord, the salivary glands and structures important in swallowing. Radiotherapy in the head and neck region often results in side-effects; examples are xerostomia (dry mouth) and severe swallowing problems. Severe swallowing problems often result in long-term use of tube feedings. Research has shown that this decreases quality of life. Radiotherapy techniques have improved significantly during the last decades. With these improved techniques salivary glands and structures important in swallowing can be spared to a certain degree. Unfortunately, not all structures can be spared since this would result in an unacceptable treatment plan with insufficient radiation dose to the tumour. It is important to know which structures should be spared the most. In previous research structures important for the development of xerostomia have been identified. It is, however, mostly unknown which structures, patient-, tumor- and treatment characteristics are most important for the development of tube feeding dependence. In this thesis prediction models are presented that aid in the selection of patients who are likely to become tube feeding dependent, for preventive measures or new radiation techniques like proton therapy. This thesis also describes how the models can be used in optimizing radiotherapy treatment plans

Acute symptoms during the course of head and neck radiotherapy or chemoradiation are strong predictors of late dysphagia

AbstractPurposeTo determine if acute symptoms during definitive radiotherapy (RT) or chemoradiation (CHRT) are prognostic factors for late dysphagia in head and neck cancer (HNC).Material and methodsThis prospective cohort study consisted of 260 HNC patients who received definitive RT or CHRT. The primary endpoint was grade 2–4 swallowing dysfunction at 6months after completing RT (SWALM6). During treatment, acute symptoms, including oral mucositis, xerostomia and dysphagia, were scored, and the scores were accumulated weekly and entered into an existing reference model for SWALM6 that consisted of dose–volume variables only.ResultsBoth acute xerostomia and dysphagia were strong prognostic factors for SWALM6. When acute scores were added as variables to the reference model, model performance increased as the course of treatment progressed: the AUC rose from 0.78 at the baseline to 0.85 in week 6. New models built for weeks 3–6 were significantly better able to identify patients with and without late dysphagia.ConclusionAcute xerostomia and dysphagia during the course of RT are strong prognostic factors for late dysphagia. Including accumulated acute symptom scores on a weekly basis in prediction models for late dysphagia significantly improves the identification of high-risk and low-risk patients at an early stage during treatment and might facilitate individualized treatment adaptation

Development and validation of a prediction model for tube feeding dependence after curative (chemo-) radiation in head and neck cancer

BACKGROUND: Curative radiotherapy or chemoradiation for head and neck cancer (HNC) may result in severe acute and late side effects, including tube feeding dependence. The purpose of this prospective cohort study was to develop a prediction model for tube feeding dependence 6 months (TUBEM6) after curative (chemo-) radiotherapy in HNC patients. PATIENTS AND METHODS: Tube feeding dependence was scored prospectively. To develop the multivariable model, a group LASSO analysis was carried out, with TUBEM6 as the primary endpoint (n = 427). The model was then validated in a test cohort (n = 183). The training cohort was divided into three groups based on the risk of TUBEM6 to test whether the model could be extrapolated to later time points (12, 18 and 24 months). RESULTS: Most important predictors for TUBEM6 were weight loss prior to treatment, advanced T-stage, positive N-stage, bilateral neck irradiation, accelerated radiotherapy and chemoradiation. Model performance was good, with an Area under the Curve of 0.86 in the training cohort and 0.82 in the test cohort. The TUBEM6-based risk groups were significantly associated with tube feeding dependence at later time points (p<0.001). CONCLUSION: We established an externally validated predictive model for tube feeding dependence after curative radiotherapy or chemoradiation, which can be used to predict TUBEM6

Prognostic factors for tube feeding dependence after curative (chemo-) radiation in head and neck cancer:A systematic review of literature

BACKGROUND: Tube feeding dependence is a commonly observed debilitating side-effect of curative (chemo-) radiation in head and neck cancer patients that severely affects quality of life. Prevention of this side-effect can be obtained using advanced radiation techniques, such as IMRT. For radiotherapy treatment plan optimization, it has become increasingly important to develop prediction models that enable clinicians to predict the risk of tube feeding dependence for individual patients. To develop such a tool, information regarding the most relevant prognostic factors for tube feeding dependence is necessary. OBJECTIVES: The primary aim of this systematic review, conducted according to PRISMA guidelines, was to identify prognostic factors that are consistently found to be associated with tube feeding dependence at ≥6months after treatment. The secondary aim was to identify prognostic factors found to be associated with tube feeding placement and use at <6months. DATA SOURCES: Articles were identified through a search in MEDLINE, EMBASE and the Cochrane Library. Approximately 2600 articles were screened and selected by inclusion and exclusion criteria. RESULTS: Fourteen retrospective studies were identified that fulfilled the inclusion criteria and reported on prognostic factors for tube feeding dependence at ≥6months. The studies reported on patient and disease variables, treatment variables and DVH parameters. Two of these studies reported on a model for tube feeding dependence, one including DVH parameters. Additionally, 18 studies were identified that reported on prognostic factors for tube feeding placement and use at <6months. CONCLUSIONS: Prognostic factors that were consistently associated with the risk of tube feeding dependence at ≥6months for head and neck cancer patients treated with (chemo-) radiotherapy were DVH parameters, including dose to the larynx, the pharyngeal constrictor muscle inferior and superior, and the dose to the contralateral parotid gland. Furthermore, advanced tumor and nodal stage, pretreatment weight loss, (concomitant) chemotherapy and prophylactic gastrostomy policy were prognostic for tube feeding dependence ≥6months. For tube feeding use at less than 6months, prognostic DVH parameters included dose and volume to the oral mucosa, dose to the contralateral submandibular gland, and also dose to the larynx and the pharyngeal constrictor muscle inferior and superior. Prognostic patients/disease and treatment factors for tube feeding placement and use at less than 6months were similar to the prognostic factors for tube feeding dependence at ≥6months, but also included several unique variables such as the use of narcotics prior to treatment and living alone at the time of treatment

Variability of NTCP prediction of swallowing organs at risk, due to variation in delineation guidelines

Purpose/Objective: In daily practice, several different delineation guidelines can be used for the delineation of organs at risk that are involved in swallowing (SWOARs). Based on these delineation guidelines, predictive models have been developed for the different aspects of post treatment swallowing dysfunction. This study was performed to test the hypothesis that different guidelines result in different delineated SWOARs and subsequently different NTCP values for swallowing dysfunction. Materials and Methods: Thirty head and neck cancer patients with either laryngeal or pharyngeal carcinoma, treated with swallowing sparing IMRT, were included in this study. Nine SWOAR delineation guidelines derived from literature were compared. The following SWOARs were investigated: superior pharyngeal constrictor muscles (PCM), middle PCM, supraglottic larynx and esophageal inlet muscle (EIM). Especially, differences in description, geometric measures (centre of mass and coefficients of variance for volume), and resulting SWOAR dose-volume parameters were investigated. The results were used to examine the variation in the prediction of normal tissue complication probability (NTCP). For this comparison, five NTCP models for swallowing dysfunction from literature were used with the following endpoints: (1) RTOG grade 2-4; (2) problems with swallowing solid, (3) soft, and (4) liquid food; (5) choking when swallowing. Results: The description of the posterior and anterior borders of the SWOARs in the delineation atlases was similar. However, differences up to several centimeters were seen in the description of the cranial and caudal borders of some of the SWOARs. Mean differences in the position of the centre of mass in cranio-caudal direction were largest for the EIM and superior PCM: 2.2 cm ± 0.4 cm and -1.2 cm ± 0.6 cm respectively. Coefficients of variance of the volume of the SWOARs were largest for the EIM and for the middle PCM: 80% and 45% respectively. The range in differences in NTCP value per tumor location for all models was 0.1 - 18% for oropharynx (18% for endpoint 2), 0.00 - 22.4% for larynx (22.4% for endpoint 5), 0.04 - 7.7% for nasopharynx (7.7% for endpoint 5), 0.20 - 11.7% for hypopharynx (11.7% for endpoint 5), and 0.04 - 1.7% for oral cavity (1.7% for endpoint 2). Thus largest variations were found for tumors situated in the larynx and for NTCP model 'Choking when swallowing' (see figure). (Figure presented). Conclusions: Large variations in the definition of SWOARs were found among published delineation guidelines. This caused considerable variation in delineated volumes and in the position of the SWOARs which in turn resulted in different dose-volume values, and in different NTCP values. Therefore, an NTCP model from a specific group should only be used when SWOARs are delineated according to the corresponding delineation guidelines. Moreover, formulation of generally accepted guidelines for swallowing structures is strongly recommended to improve the generalisability of NTCP models