Outcomes of surgery and postoperative radiation therapy in managing medullary thyroid carcinoma

Background and Objectives We evaluated the outcomes of surgery with or without postoperative radiation therapy (PORT) in the management of medullary thyroid carcinoma (MTC). Methods From two tertiary cancer centers, 297 consecutive patients with MTC treated with PORT (n = 46) between 1990 and 2016 or surgery alone (n = 251) between 2000 and 2016 were reviewed. Results Ten-year cumulative incidences of locoregional and distant failure were 30.2% and 24.9% in the surgery cohort, and 16.9% and 55.2% in the PORT cohort. In the surgery alone cohort, T4 disease, extrathyroidal extension, N1 disease, extranodal extension (ENE), and residual disease after surgery were associated with local failure. The PORT cohort had significantly higher proportions of patients with T4 disease, N1 disease, ENE, and residual disease. Conclusions High-risk clinical features can help identify patients with MTC at high-risk for local failure after surgery alone. Patients with high-risk clinical features had effective locoregional control after PORT

Selection of head and neck cancer patients for adaptive radiotherapy to decrease xerostomia

AbstractBackground and purposeThe aim of this study was to develop and validate a method to select head and neck cancer patients for adaptive radiotherapy (ART) pre-treatment. Potential pre-treatment selection criteria presented in recent literature were included in the analysis.Materials and methodsDeviations from the planned parotid gland mean dose (PG ΔDmean) were estimated for 113 head and neck cancer patients by re-calculating plans on repeat CT scans. Uni- and multivariable linear regression analyses were performed to select pre-treatment parameters, and ROC curve analysis was used to determine cut off values, for selecting patients with a PG dose deviation larger than 3Gy. The patient selection method was validated in a second patient cohort of 43 patients.ResultsAfter multivariable analysis, the planned PG Dmean remained the only significant parameter for PG ΔDmean. A sensitivity of 91% and 80% could be obtained using a threshold of PG Dmean of 22.2Gy, for the development and validation cohorts, respectively. This would spare 38% (development cohort) and 24% (validation cohort) of patients from the labour-intensive ART procedure.ConclusionsThe presented method to select patients for ART pre-treatment reduces the labour of ART, contributing to a more effective allocation of the department resources

Parotid Gland Stem Cell Sparing Radiation Therapy for Patients With Head and Neck Cancer:A Double-Blind Randomized Controlled Trial

BACKGROUND: Radiotherapy for head and neck cancer (HNC) frequently leads to salivary gland damage and subsequent xerostomia. The radiation response of parotid glands of rats, mice, and patients critically depends on dose to its stem cells, mainly located in the gland's main ducts (stem cell rich (SCR) region). Therefore, this double-blind randomized controlled trial aimed to test the hypothesis that parotid gland stem cell sparing radiotherapy preserves parotid gland function better than currently-used whole parotid gland sparing radiotherapy. METHODS: HNC patients (n=102) treated with definitive radiotherapy were randomized between standard parotid sparing and stem cell sparing (SCS) techniques. The primary endpoint was >75% reduction in parotid gland saliva production compared to pretreatment production (FLOW12M). Secondary endpoints were several aspects of xerostomia 12 months after treatment. RESULTS: Fifty-four patients were assigned to the standard arm and 48 to the SCS arm. Only dose to the SCR regions (contralateral 16 and 11 Gy (p=0.004) and ipsilateral 26 and 16 Gy (p=0.001), standard and SCS arm respectively) and pretreatment patient-rated daytime xerostomia (35% and 13% (p=0.01), standard and SCS arm respectively) differed significantly between the arms. In the SCS arm, 1 patient (2.8%) experienced FLOW12M compared to 2 (4.9%) in the standard arm (p=1.00). However, a trend towards better relative parotid gland salivary function in favor of SCS radiotherapy was shown. Moreover, multivariable analysis showed that mean contralateral SCR region dose was the strongest dosimetric predictor for moderate-to-severe patient-rated daytime xerostomia and grade ≥2 physician-rated xerostomia, the latter including complaints of alteration in diet. CONCLUSIONS: No significant better parotid function was observed in SCS radiotherapy. However, additional multivariable analysis showed that dose to the SCR region was more predictive for development of parotid gland function related xerostomia endpoints, than dose to the entire parotid gland

Relationship between videofluoroscopic and subjective (physician- and patient- rated) assessment of late swallowing dysfunction after (chemo) radiation:Results of a prospective observational study

BACKGROUND AND PURPOSE: Primary (chemo)radiation (CHRT) for HNC may lead to late dysphagia. The purpose of this study was to assess the pattern of swallowing disorders based on prospectively collected objective videofluoroscopic (VF) assessment and to assess the correlations between VF findings and subjective (physician- and patient-rated) swallowing measures. MATERIAL AND METHODS: 189 consecutive HNC patients receiving (CH)RT were included. Swallowing evaluation at baseline and 6 months after treatment (T6) encompassed: CTCAE v.4.0 scores (aspiration/dysphagia), PROMs: SWAL QOL/ EORTC QLQ-H&N35 (swallowing domain) questionnaires and VF evaluation: Penetration Aspiration Scale, semi-quantitative swallowing pathophysiology evaluation, temporal measures and oral/pharyngeal residue quantification. Aspiration specific PROMs (aPROMs) were selected. Correlations between late penetration/aspiration (PA_T6) and: clinical factors, CTCAE and aPROMs were assessed using uni- and multivariable analysis. RESULTS: Prevalence of PA increased from 20% at baseline to 43% after treatment (p<0.001).The most relevant baseline predictors for PA_T6 were: PA_T0, age, disease stage III-IV, bilateral RT and baseline aPROM 'Choking when drinking' (AUC: 0.84). In general aPROMs correlated better with VF-based PA than CTCAE scores. The most of physiological swallowing components significantly correlated and predictive for PA (i.e. Laryngeal Vestibular Closure, Laryngeal Elevation and Pharyngeal Contraction) were prone to radiation damage. CONCLUSION: The risk of RT-induced PA is substantial. Presented prediction models for late penetration/aspiration may support patient selection for baseline and follow-up VF examination. Furthermore, all aspiration related OARs involved in aforementioned swallowing components should be addressed in swallowing sparing strategies. The dose to these structures as well as baseline PROMs should be included in future NTCP models for aspiration

Functional Swallowing Units (FSUs) as organs-at-risk for radiotherapy. PART 2:Advanced delineation guidelines for FSUs

Background and purpose: In a separate article (PART 1), a rationale and explanation of the physiology-and-anatomy-based concept of Functional Swallowing Units (FSUs) was presented. FSUs are swallowing muscles not included in the set of commonly defined swallowing organs at risk (SWOARs). They are involved in three crucial swallowing components: hyolaryngeal elevation (HLE), tongue base retraction (TBR) and tongue motion. This paper is a continuation of PART 1 and it provides detailed computed tomography (CT)-based delineation guidelines for FSUs, which presumably are also at risk of radiationinduced dysphagia. Material and methods: Following analysis of swallowing physiology and human anatomy, presented in PART 1, CT-based delineation guidelines for defined FSUs were created. Delineation was performed by the first author and revised by a panel of experts. Results and conclusions: Detailed delineation guidelines are presented for seven FSUs involved in HLE, TBR and tongue motion. The guidelines are supplemented by CT and MRI-based exemplary illustrations and complete CT/MRI-based delineation atlases (available online). This paper provides information essential to the implementation of the FSU concept in radiation practice, and supports uniform contouring, data collection and further improvement of swallowing sparing radiation-based strategies. (C) 2018 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

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

Multidisciplinary first-day consultation accelerates diagnostic procedures and throughput times of patients in a head-and-neck cancer care pathway, a mixed method study

Abstract Background Head and neck cancers are fast growing tumours that are complex to diagnose and treat. Multidisciplinary input into organization and logistics is critical to start treatment without delay. A multidisciplinary first-day consultation (MFDC) was introduced to reduce throughput times for patients suffering from head and neck cancer in the care pathway. In this mixed method study we evaluated the effects of introducing the MFDC on throughput times, number of patient hospital visits and compliance to the Dutch standard to start treatment within 30 calendar-days. Methods Data regarding ‘days needed for referral’, ‘days needed for diagnostic procedures’, ‘days to start first treatment’, and ‘number of hospital visits’ (process indicators) were retrieved from the medical records and analysed before and after implementation of the MFDC (before implementation: 2007 (n = 21), and after 2008 (n = 20), 2010 (n = 24) and 2013 (n = 24)). We used semi-structured interviews with medical specialists to explore a sample of outliers. Results Comparing 2007 and 2008 data (before and after MFDC implementation), days needed for diagnostic procedures and to start first treatment reduced with 8 days, the number of hospital visits reduced with 1.5 visit on average. The percentage of new patients treated within the Dutch standard of 30 calendar-days after intake increased from 52 to 83%. The reduction in days needed for diagnostic procedures was sustainable. Days needed to start treatment increased in 2013. Semi-structured interviews revealed that this delay could be attributed to new treatment modalities, patients needed more time to carefully consider their treatment options or professionals needed extra preparation time for organisation of more complex treatment due to early communication on diagnostic procedures to be performed. Conclusions A MFDC is efficient and benefits patients. We showed that the MFDC implementation in the care pathway had a positive effect on efficiency in the care pathway. As a consequence, the extra efforts of four specialist disciplines, a nurse practitioner, and a coordinating nurse seeing the patient together during intake, were justified. Start treatment times increased as a result of new treatment modalities that needed more time for preparation

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