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Objective: This study aims to determine the added value of a geometrically accurate diffusion-weighted (DW-) MRI sequence on the accuracy of gross tumor volume (GTV) delineations, using pathological tumor delineations as a ground truth., Methods: Sixteen patients with laryngeal or hypopharyngeal carcinoma were included. After total laryngectomy, the specimen was cut into slices. Photographs of these slices were stacked to create a 3D digital specimen reconstruction, which was registered to the in vivo imaging. The pathological tumor (tumor HE ) was delineated on the specimen reconstruction. Six observers delineated all tumors twice: once with only anatomical MR imaging, and once (a few weeks later) when DW sequences were also provided. The majority voting delineation of session one (GTV MRI ) and session two (GTV DW-MRI ), as well as the clinical target volumes (CTVs), were compared to the tumor HE ., Results: The mean tumor HE volume was 11.1 cm 3 , compared to a mean GTV MRI volume of 18.5 cm 3 and a mean GTV DW-MRI volume of 15.7 cm 3 . The median sensitivity (tumor coverage) was comparable between sessions: 0.93 (range: 0.61-0.99) for the GTV MRI and 0.91 (range: 0.53-1.00) for the GTV DW-MRI . The CTV volume also decreased when DWI was available, with a mean CTV MR of 47.1 cm 3 and a mean CTV DW-MRI of 41.4 cm 3 . Complete tumor coverage was achieved in 15 and 14 tumors, respectively., Conclusion: GTV delineations based on anatomical MR imaging tend to overestimate the tumor volume. The availability of the geometrically accurate DW sequence reduces the GTV overestimation and thereby CTV volumes, while maintaining acceptable tumor coverage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Multimodality imaging including 18 F-FDG-PET has improved the detection threshold of nodal metastases in head and neck squamous cell carcinoma (HNSCC). The aim of this retrospective analysis is to investigate the impact of FDG-PET/CT-based nodal target volume definition (FDG-PET/CT-based NTV) on radiotherapy outcomes, compared to conventional CT-based nodal target volume definition (CT-based NTV)., Materials and Methods: Six-hundred-thirty-three patients treated for HNSCC with definitive (chemo)radiotherapy using IMRT/VMAT techniques between 2008 and 2017 were analyzed. FDG-PET/CT-based NTV was performed in 46% of the patients. The median follow-up was 31 months. Diagnostic imaging depicting the regional recurrence was co-registered with the initial CT-scan to reconstruct the exact site of the recurrence. Multivariate Cox regression analysis was performed to identify variables associated with radiotherapy outcome., Results: FDG-PET/CT-based NTV improved control of disease in the CTV elective-nodal (HR: 0.33, p = 0.026), overall regional control (HR: 0.62, p = 0.027) and overall survival (HR: 0.71, p = 0.033) compared to CT-based NTV. The risk for recurrence in the CTV elective-nodal was increased in case of synchronous local recurrence of the primary tumor (HR: 12.4, p < 0.001)., Conclusion: FDG-PET/CT-based NTV significantly improved control of disease in the CTV elective-nodal , overall regional control and overall survival compared to CT-based NTV. A significant proportion of CTV elective-nodal recurrences are potentially new nodal manifestations from a synchronous local recurrent primary tumor. These results support the concept of target volume transformation and give an indication of the potential of FDG-PET to guide gradual radiotherapy dose de-escalation in elective neck treatment in HNSCC., Competing Interests: Declaration of Competing Interest All authors declare having no conflict of interest related to the content of this manuscript., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background/purpose: To report on health-related quality-of-life (HRQoL) of patients with laryngeal cancer, treated in a randomized trial comparing accelerated radiotherapy with carbogen and nicotinamide (ARCON) against accelerated radiotherapy alone (AR)., Material/methods: HRQoL was assessed using the HRQoL Questionnaire-C30 (QLQ-C30) and the Head & Neck cancer module (QLQ-H&N35) at baseline, at completion of radiotherapy and at 6, 12, and 24months post-baseline., Results: From 269/345 patients (AR: 136/174; ARCON: 133/171) data on HRQoL were available for analysis. Moderate to severe clinical impact of the treatment was observed for nearly all items of the QLQ-C30 and QLQ-H&N35 between baseline and end-of-treatment. At 6months, scores returned to baseline level with exception of dry mouth, sticky saliva, and taste/smell. No difference between AR and ARCON was observed. At 2years from baseline, the percentage of patients reporting moderate to severe complaints of dry mouth, sticky saliva, or changes in taste/smell was 30%, 22% and 18%, respectively, while the majority of patients had no or few complaints of swallowing (79%) or speech (64%)., Conclusions: With accelerated radiotherapy, high local tumor control was obtained while maintaining good speech and swallowing function. Long-term dry mouth, sticky saliva and changes in taste/smell are limited to one quarter of patients. (ClinicalTrials.gov number, NCT00147732)., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To investigate changes in head-and-neck cancer (HNC) plan quality following the introduction of new technologies and planning techniques in the last decade., Methods and Materials: Thirty plans were selected from each of four successive periods (P). P1: 7-field static intensity-modulated radiotherapy (IMRT) with parotid gland sparing; P2: dual-arc volumetric-modulated arc therapy (VMAT, similar to P3-P4), including submandibular gland sparing; P3: inclusion of individual swallowing muscles and attempts to further reduce parotid and oral cavity doses through manual interactive optimization; P4: containing the same organs-at-risk (OARs) as P3, but automatically interactively optimized. Plan benchmarking included mean salivary gland/swallowing muscle/oral cavity (Dsal/Dswal/Doc) doses. Differences in mean doses between the periods were analyzed by an ANCOVA, taking geometric differences across periods into account., Results: Compared to P1, P2 plans improved Dsal by 3.4Gy on average. P3 improved Dsal/Dswal/Doc by 6.9/11.5/7.2Gy over P2, showing that Dswal and Dsal could be improved simultaneously. In P4, Doc/Dswal slightly improved over P3 by 1.7/3.8Gy. Improved OAR sparing in P3/P4 did not come at the cost of increased dose deposition elsewhere and planning target volume (PTV) dose homogeneity was similar., Conclusions: New technologies and planning techniques were successfully implemented into routine clinical care and resulting in improved HNC plan quality., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

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 6months 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 (ΔNTCPSWALM6=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 ΔNTCPSWALM6 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., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Objectives: To identify patterns of long-term, radiation-induced swallowing dysfunction after definitive radiotherapy with or without chemotherapy (RT or CHRT) and to determine which factors may explain these patterns over time., Material and Methods: The study population consisted of 238 consecutive head and neck cancer patients treated with RT or CHRT. The primary endpoint was ⩾grade 2 swallowing dysfunction at 6, 12, 18 and 24months after treatment. Cluster analysis was used to identify different patterns over time. The differences between the mean dose to the swallowing organs at risk for each pattern were determined by using dose maps., Results: The cluster analysis revealed five patterns of swallowing dysfunction: low persistent, intermediate persistent, severe persistent, transient and progressive. Patients with high dose to the upper pharyngeal, laryngeal and lower pharyngeal region had the highest risk of severe persistent swallowing dysfunction. Transient problems mainly occurred after high dose to the laryngeal and lower pharyngeal regions, combined with moderate dose to the upper pharyngeal region. The progressive pattern was mainly seen after moderate dose to the upper pharyngeal region., Conclusions: Various patterns of swallowing dysfunction after definitive RT or CHRT can be identified over time. This could reflect different underlying biological processes., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Background and Purpose: Different planning protocols may define varying planning target volume (PTV) dose criteria. We investigated the hypothesis that this could result in differences in organ-at-risk (OAR) sparing., Material and Methods: Volumetric modulated arc therapy plans were created for ten locally advanced head and neck cancer patients following PTV criteria specified by the RTOG, EORTC and institutional (VUmc) protocols. Resulting plans were evaluated on the basis of the homogeneity index, calculated for the boost/elective PTVs as HIB/HIE=100%*(D2%-D98%)/D50% and mean dose to individual and composite salivary (compsal) and swallowing (compswal) OARs., Results: RTOG plans were the most homogeneous, with mean HIB of 8.2±0.9%, compared to 9.5±1.0%/11.6±1.5% for the VUmc/EORTC plans. EORTC plans provided most OAR sparing, with compsal/compswal doses of 24.6±7.7/22.9±4.2Gy, compared to 32.2±9.7/29.9±4.2Gy and 28.4±8.1/24.7±5.3Gy for RTOG and VUmc, respectively. EORTC provided 7.2/7.7Gy mean dose reductions to the contra/ipsilateral parotid glands compared to RTOG., Conclusions: Different planning protocols resulted in different levels of PTV dose homogeneity. We observed differences of up to ⩾7Gy in composite and individual mean OAR doses. This could influence rates of toxicity and should be taken into account when comparing clinical studies. A consensus should be reached between major trial groups on appropriate PTV parameters., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: Curative radiotherapy/chemo-radiotherapy 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 multivariable normal tissue complication probability (NTCP) model for tube feeding dependence 6 months (TUBEM6) after definitive radiotherapy, radiotherapy plus cetuximab or concurrent chemoradiation based on pre-treatment and treatment characteristics., Materials and Methods: The study included 355 patients with HNC. TUBEM6 was scored prospectively in a standard follow-up program. To design the prediction model, the penalized learning method LASSO was used, with TUBEM6 as the endpoint., Results: The prevalence of TUBEM6 was 10.7%. The multivariable model with the best performance consisted of the variables: advanced T-stage, moderate to severe weight loss at baseline, accelerated radiotherapy, chemoradiation, radiotherapy plus cetuximab, the mean dose to the superior and inferior pharyngeal constrictor muscle, to the contralateral parotid gland and to the cricopharyngeal muscle., Conclusions: We developed a multivariable NTCP model for TUBEM6 to identify patients at risk for tube feeding dependence. The dosimetric variables can be used to optimize radiotherapy treatment planning aiming at prevention of tube feeding dependence and to estimate the benefit of new radiation technologies., (Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Background and Purpose: To evaluate the course of health-related quality of life (HRQOL) from diagnosis to 2 years follow-up in patients with head and neck cancer (HNSCC) treated with chemoradiation (CRT)., Materials and Methods: 164 patients completed the EORTC QLQ-C30 and QLQ-H&N35 questionnaires 1 week before and 6 weeks and 6, 12, 18, and 24 months after CRT. Patients were compared to a reference group. A linear mixed-model analysis was used to assess changes in HRQOL over time, and whether this was associated with age, gender, comorbidity, and tumor sublocation., Results: Significant differences for the majority of HRQOL scales were observed between patient and reference group at baseline, and follow-up. The course of HRQOL was different for survivors compared to non-survivors. In survivors, improvement over time was observed (in global quality of life, physical, role, and social function, fatigue, pain, swallowing, speech, social eating, and social contacts), while in non-survivors the pattern over time was either no changes in HRQOL or a deterioration (in physical function, social eating and contacts). In both survivors and non-survivors, emotional functioning improved after treatment, but deteriorated in the longer term. Patients with comorbidity reported worse physical function, and patients with oral/oropharyngeal cancer (compared to hypopharyngeal/laryngeal cancer) reported more oral pain and sexual problems, but fewer speech problems., Conclusions: The course of HRQOL of HNSCC patients during the first 2 years after CRT is different for survivors compared to non-survivors and is associated with comorbidity and tumor subsite., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: To retrospectively report changes in gross tumor volume (GTV) and organ-at-risk (OAR) doses after induction chemotherapy (IC) in oropharyngeal cancer using different contouring strategies., Materials and Methods: GTV and OARs were delineated on pre- and post-IC planning CT. Two post-IC GTV contours were made: (1) a 'consensus set' using published guidelines (GTVconsensus), and (2) 'visible set', delineating only visible post-IC GTV (GTVvisible). Pre-IC interactively optimized volumetric modulated arc therapy plans were generated. The pre-IC planning constraints served as the starting point for both post-IC plans. Results reflect pooled data from all 10 patients., Results: Mean reduction in volume post-IC was 24% and 47% for consensus and visible primary tumor and 57% and 60% for consensus and visible nodes. Compared to pre-IC plans, average mean OAR dose for post-IC GTVconsensus plans was significantly lower for CL parotid. For GTVvisible plans both parotids, upper/lower larynx, inferior pharyngeal constrictor and cricopharyngeal muscles were significantly lower. However reductions compared with post-IC GTVconsensus plans were modest (1.6/1.5/1.2/3.7/5.9/2.6Gy, respectively)., Conclusion: IC in patients with oropharyngeal carcinoma results in substantial reductions in GTVs. If post-IC GTVs are used, which is contrary to current consensus, statistically significant but relatively small OAR dose reductions are observed., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: In a phase III trial in patients with advanced stage laryngeal carcinoma comparing ARCON (accelerated radiotherapy with carbogen breathing and nicotinamide) to accelerated radiotherapy alone (AR) the prognostic and predictive value of CAIX, a hypoxia-associated protein, was investigated., Material and Methods: 261 Paraffin embedded tumor biopsies and 79 fresh frozen biopsies from patients entered in the trial were immunohistochemically stained for CAIX. CAIX-fraction and CAIX expression pattern were related to tumor control and patient survival., Results: Low CAIX-fraction was prognostic for worse regional control and overall survival in patients treated with AR. Patients with a low CAIX-fraction treated with ARCON had better regional control and metastasis-free survival compared to AR (RC 97% vs 71%, p < 0.01 and MFS 92% vs 69%, p = 0.06). Patients with a perinecrotic CAIX staining pattern had a significantly worse local control, metastasis-free and overall survival compared to patients with a diffuse pattern (65% vs 84%, p = 0.01, 70% vs 96%, p < 0.01 and 42% vs 71%, p < 0.01 respectively), and this could not be improved with ARCON. After multivariate analysis CAIX pattern and N-stage emerged as significant predictors for metastasis-free survival and overall survival., Conclusions: ARCON improves regional control and metastasis-free survival only in patients with low CAIX expression. The different patterns of CAIX expression suggest different mechanisms of upregulation and have important prognostic value., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The purpose of this study was to investigate the ability of predictive models for patient-rated xerostomia (XER(6M)) and sticky saliva (STIC(6M)) at 6 months after completion of primary (chemo)radiation developed in head and neck cancer patients treated with 3D-conformal radiotherapy (3D-CRT) to predict outcome in patients treated with intensity modulated radiotherapy (IMRT)., Methods and Materials: Recently, we published the results of a prospective study on predictive models for patient-rated xerostomia and sticky saliva in head and neck cancer patients treated with 3D-CRT (3D-CRT based NTCP models). The 3D-CRT based model for XER(6M) consisted of three factors, including the mean parotid dose, age, and baseline xerostomia (none versus a bit). The 3D-CRT based model for STIC(6M) consisted of the mean submandibular dose, age, the mean sublingual dose, and baseline sticky saliva (none versus a bit). In the current study, a population consisting of 162 patients treated with IMRT was used to test the external validity of these 3D-CRT based models. External validity was described by the explained variation (R(2) Nagelkerke) and the Brier score. The discriminative abilities of the models were calculated using the area under the receiver operating curve (AUC) and calibration (i.e. the agreement between predicted and observed outcome) was assessed with the Hosmer-Lemeshow "goodness-of-fit" test., Results: Overall model performance of the 3D-CRT based predictive models for XER(6M) and STIC(6M) was significantly worse in terms of the Brier score and R(2) Nagelkerke among patients treated with IMRT. Moreover the AUC for both 3D-CRT based models in the IMRT treated patients were markedly lower. The Hosmer-Lemeshow test showed a significant disagreement for both models between predicted risk and observed outcome., Conclusion: 3D-CRT based models for patient-rated xerostomia and sticky saliva among head and neck cancer patients treated with primary radiotherapy or chemoradiation turned out to be less valid for patients treated with IMRT. The main message from these findings is that models developed in a population treated with a specific technique cannot be generalised and extrapolated to a population treated with another technique without external validation., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The purpose of this multicentre prospective study was to investigate the significance of the radiation dose in the major and minor salivary glands, and other pre-treatment and treatment factors, with regard to the development of patient-rated xerostomia and sticky saliva among head and neck cancer (HNC) patients treated with primary (chemo-) radiotherapy ((CH)RT)., Methods and Materials: The study population was composed of 167 consecutive HNC patients treated with three-dimensional conformal (3D-CRT) (CH) RT. The primary endpoint was moderate to severe xerostomia (XER6m) as assessed by the EORTC QLQ-H&N35 at 6 months after completing (CH)RT. The secondary endpoint was moderate to severe sticky saliva at 6 months (STIC6m). All organs at risk (OARs) potentially involved in salivary function were delineated on planning-CT, including the parotid, submandibular and sublingual glands and the minor glands in the soft palate, cheeks and lips. Patients with moderate to severe xerostomia or sticky saliva at baseline were excluded. The optimum number of variables for a multivariate logistic regression model was determined using a bootstrapping method., Results: The multivariate analysis showed the mean parotid dose, age and baseline xerostomia (none versus a bit) to be the most important predictors for XER6m. The risk of developing xerostomia increased with age and was higher when minor baseline xerostomia was present in comparison with patients without any xerostomia complaints at baseline. Model performance was good with an area under the curve (AUC) of 0.82. For STIC6m, the mean submandibular dose, age, the mean sublingual dose and baseline sticky saliva (none versus a bit) were most predictive for sticky saliva. The risk of developing STIC6m increased with age and was higher when minor baseline sticky saliva was present in comparison with patients without any sticky saliva complaints at baseline. Model performance was good with an AUC of 0.84., Conclusions: Dose distributions in the minor salivary glands in patients receiving 3D-CRT have limited significance with regard to patient-rated symptoms related to salivary dysfunction. Besides the parotid and submandibular glands, only the sublingual glands were significantly associated with sticky saliva. In addition, reliable risk estimation also requires information from other factors such as age and baseline subjective scores. When these selected factors are included in predictive models, instead of only dose volume histogram parameters, model performance can be improved significantly., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The purpose of this multicentre prospective study was to develop multivariable logistic regression models to make valid predictions about the risk of moderate-to-severe patient-rated xerostomia (XER(M6)) and sticky saliva 6 months (STIC(M6)) after primary treatment with intensity modulated radiotherapy (IMRT) with or without chemotherapy for head and neck cancer (HNC)., Methods and Materials: The study population was composed of 178 consecutive HNC patients treated with IMRT. All patients were included in a standard follow up programme in which acute and late side effects and quality of life were prospectively assessed, prior to, during and after treatment. The primary endpoints were XER(M6) and STIC(M6) as assessed by the EORTC QLQ-H&N35 after completing IMRT. Organs at risk (OARs) potentially involved in salivary function were delineated on planning-CT, including the parotid, submandibular and sublingual glands and the minor glands in the soft palate, cheeks and lips. Patients with moderate-to-severe xerostomia or sticky saliva, respectively, at baseline were excluded. The optimal number of variables for a multivariate logistic regression model was determined using a bootstrapping method., Results: Eventually, 51.6% of the cases suffered from XER(M6). The multivariate analysis showed that the mean contralateral parotid gland dose and baseline xerostomia (none vs. a bit) were the most important predictors for XER(M6). For the multivariate NTCP model, the area under the receiver operating curve (AUC) was 0.68 (95% CI 0.60-0.76) and the discrimination slope was 0.10, respectively. Calibration was good with a calibration slope of 1.0. At 6 months after IMRT, 35.6% of the cases reported STIC(M6). The mean contralateral submandibular gland dose, the mean sublingual dose and the mean dose to the minor salivary glands located in the soft palate were most predictive for STIC(M6). For this model, the AUC was 0.70 (95% CI 0.61-0.78) and the discrimination slope was 0.12. Calibration was good with a calibration slope of 1.0., Conclusions: The multivariable NTCP models presented in this paper can be used to predict patient-rated xerostomia and sticky saliva. The dose volume parameters included in the models can be used to further optimise IMRT treatment., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: The purpose of this large multicentre prospective cohort study was to identify which dose volume histogram parameters and pre-treatment factors are most important to predict physician-rated and patient-rated radiation-induced swallowing dysfunction (RISD) in order to develop predictive models for RISD after curative (chemo) radiotherapy ((CH) RT)., Material and Methods: The study population consisted of 354 consecutive head and neck cancer patients treated with (CH) RT. The primary endpoint was grade 2 or more swallowing dysfunction according to the RTOG/EORTC late radiation morbidity scoring criteria at 6 months after (CH) RT. The secondary endpoints were patient-rated swallowing complaints as assessed with the EORTC QLQ-H&N35 questionnaire. To select the most predictive variables a multivariate logistic regression analysis with bootstrapping was used., Results: At 6 months after (CH) RT the bootstrapping procedure revealed that a model based on the mean dose to the superior pharyngeal constrictor muscle (PCM) and mean dose to the supraglottic larynx was most predictive. For the secondary endpoints different predictive models were found: for problems with swallowing liquids the most predictive factors were the mean dose to the supraglottic larynx and radiation technique (3D-CRT versus IMRT). For problems with swallowing soft food the mean dose to the middle PCM, age (18-65 versus >65 years), tumour site (naso/oropharynx versus other sites) and radiation technique (3D-CRT versus IMRT) were the most predictive factors. For problems with swallowing solid food the most predictive factors were the mean dose to the superior PCM, the mean dose to the supraglottic larynx and age (18-65 versus >65 years). And for choking when swallowing the V60 of the oesophageal inlet muscle and the mean dose to the supraglottic larynx were the most predictive factors., Conclusions: Physician-rated and patient-rated RISD in head and neck cancer patients treated with (CH) RT cannot be predicted with univariate relationships between the dose distribution in a single organ at risk and an endpoint. Separate predictive models are needed for different endpoints and factors other than dose volume histogram parameters are important as well., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: The relation between health-related quality of life (HRQOL) and survival was investigated at baseline and 6 months in 80 patients with advanced oral or oropharyngeal cancer after microvascular reconstructive surgery and (almost all) adjuvant radiotherapy., Materials and Methods: Multivariate Cox regression analyses of overall and disease-specific survival were performed including sociodemographic (age, gender, marital status, comorbidity), and clinical (tumor stage and site, radical surgical, metastasis, radiotherapy) parameters, and HRQOL (EORTC QLQ-C30 global quality of life scale)., Results: Before treatment, younger age and having a partner were predictors of disease-specific survival; younger age predicted overall survival. At 6 months post-treatment, disease-specific and overall survival was predicted by (deterioration of) global quality of life solely. Global health-related quality of life after treatment was mainly influenced by emotional functioning., Conclusion: Deterioration of global quality of life after treatment is an independent predictor of survival in patients with advanced oral or oropharyngeal cancer., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: Although patients with early stage (T1/T2) laryngeal cancer (LC) are thought to have a low incidence of malnutrition, severe weight loss is observed in a subgroup of these patients during radiotherapy (RT). The objective of this study was to evaluate weight loss and nutrition-related symptoms in patients with T1/T2 LC during RT and to select predictive factors for early identification of malnourished patients., Methods: Of all patients with T1/T2 LC, who received primary RT between 1999 and 2007, the following characteristics were recorded: sex, age, TNM classification, tumour location, radiation schedule, performance status, quality of life, weight loss, and nutrition-related symptoms. The association between baseline characteristics and malnutrition (>5% weight loss during RT) was investigated by Cox regression analysis., Results: The study population consisted of 238 patients. During RT, 44% of patients developed malnutrition. Tumour location, TNM classification, RT on the neck nodes, RT dose, nausea/vomiting, pain, swallowing, senses problems, trouble with social eating, dry mouth and the use of painkillers were all significantly associated with malnutrition. In the multivariate analysis, RTs on both the neck nodes (HR 4.16, 95% CI 2.62-6.60) and dry mouth (HR 1.72, 95% CI 1.14-2.60) remained predictive. Nevertheless, RT on the neck nodes alone resulted in the best predictive model for malnutrition scores., Conclusions: Patients with early stage laryngeal cancer are at risk of malnutrition during radiotherapy. Radiotherapy on the neck nodes is the best predictor of malnutrition during radiotherapy. Therefore, we suggest to offer nutritional counselling to all the patients who receive nodal irradiation., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Recently, we found that swallowing dysfunction after curative (chemo) radiation (CH) RT has a strong negative impact on health-related quality of life (HRQoL), even more than xerostomia. The purpose of this study was to design a predictive model for swallowing dysfunction after curative radiotherapy or chemoradiation., Materials and Methods: A prospective study was performed including 529 patients with head and neck squamous cell carcinoma (HNSCC) treated with curative (CH) RT. In all patients, acute and late radiation-induced morbidity (RTOG Acute and Late Morbidity Scoring System) was scored prospectively. To design the model univariate and multivariate logistic regression analyses were carried out with grade 2 or higher RTOG swallowing dysfunction at 6 months as the primary (SWALL(6months)) endpoint. The model was validated by comparing the predicted and observed complication rates and by testing if the model also predicted acute dysphagia and late dysphagia at later time points (12, 18 and 24 months)., Results: After univariate and multivariate logistic regression analyses, the following factors turned out to be independent prognostic factors for SWALL(6months): T3-T4, bilateral neck irradiation, weight loss prior to radiation, oropharyngeal and nasopharyngeal tumours, accelerated radiotherapy and concomitant chemoradiation. By summation of the regression coefficients derived from the multivariate model, the Total Dysphagia Risk Score (TDRS) could be calculated. In the logistic regression model, the TDRS was significantly associated with SWALL(6months) ((p<0.001). Subsequently, we defined three risk groups based on the TDRS. The rate of SWALL(6months) was 5%, 24% and 46% in case of low-, intermediate- and high-risk patients, respectively. These observed percentages were within the 95% confidence intervals of the predicted values. The TDRS risk group classification was also significantly associated with acute dysphagia (P<0.001 at all time points) and with late swallowing dysfunction at 12, 18 and 24 months (p<0.001 at all time points)., Conclusion: The TDRS is a simple and validated measure to predict swallowing dysfunction after curative (CH) RT for HNC. This classification system enables identification of patients who may benefit from strategies aiming at prevention of swallowing dysfunction after curative (CH) RT such as preventive swallowing exercises during treatment and/or emerging IMRT techniques aiming at sparing anatomical structures that are involved in swallowing.

Background and Purpose: Reports on shoulder function after non-surgical treatment are not available. In the present study shoulder morbidity after surgical and non-surgical treatment of the neck is determined and compared., Materials and Methods: In 100 head and neck cancer patients 174 neck sides were treated by surgery (n=51) or (chemo)radiation (n=123). Abduction, anteflexion, endorotation and exorotation were assessed. Subjective measurements were performed using the Visual Analogue Scale for pain, the Shoulder Disability Questionnaire (SDQ) and stiffness reporting., Results: Predictive factors for SDQ-score>0 (n=54) were VAS pain score, stiffness, abduction, anteflexion, physiotherapy, low shoulder position and surgical treatment. The SDQ, stiffness and pain scores were significantly higher in the surgically treated group than in the non-surgical group (p<0.01). Anteflexion, abduction and exorotation were less impaired in the non-surgically treated group than in the surgically treated group (p<0.01). No differences between neck dissection and neck dissection with post-operative radiotherapy, and radiotherapy and chemoradiation were found for these movements., Conclusions: Shoulder morbidity is often present after non-surgical treatment of the neck, but to a lesser extent compared to surgical treatment. Radiotherapy adds no morbidity to neck dissection and chemotherapy does not add extra morbidity to primary radiation.

Background and Purpose: To investigate the association between radiation technique with patient-rated moderate and severe xerostomia and sticky saliva., Materials and Methods: One hundred and fifty patients treated with bilateral or unilateral irradiation for head and neck cancer were included. The salivary glands and the oral cavity were delineated on plannings-CT scans. Xerostomia and sticky saliva were assessed using the EORTC QLQ-H&N35 questionnaire at baseline and 6 and 12 months., Results: At 6 months a significant association between radiation technique and the mean parotid dose (MD(parb)) and xerostomia was observed (Odds ratio (OR)-technique: 2.55; p=0.04 and OR-MD(parb): 1.04; p=0.009). Considering the individual salivary glands, only the mean dose in the contralateral parotid gland (MD(parcl)) is associated with xerostomia (OR: 1.04; p<0.0001). Moreover, the threshold dose for a 50% probability (P50) on xerostomia increased from 21 Gy with bilateral to 44 Gy for unilateral irradiation., Conclusions: Both technique and MD(parb) influence the risk of xerostomia in irradiated patients. Of all individual salivary glands, only MD(parcl) is of utmost importance for xerostomia. The shift in the P50 observed for xerostomia suggests that sparing of the contralateral parotid gland is compensated by hyperfunction of the contralateral parotid gland.

Background and Purpose: In the present study, prognostic values of several CT-based pre-treatment nodal and treatment-related characteristics were evaluated among patients with squamous cell head and neck cancer treated with non-surgical modalities., Patients and Methods: Included were 79 patients with 210 pathological nodes, who underwent primary irradiation or chemoradiation. Several nodal characteristics were assessed on the planning CT scan. In addition, the 3D-dose distribution in the nodes was calculated by the planning system to allow for evaluation of underdosage in the pathological nodes and to correlate these results with control in the neck. Analysis was done on patient level (regional control) and node level (nodal control)., Results: For regional control, total nodal volume and the use of chemotherapy in addition to radiation were significant prognostic factors. For nodal control, also the presence of central necrosis and radiological extranodal spread were of importance. In case of radiotherapy alone, a minimal dose <95% of the prescribed dose was associated with worse control. In case of combined modality treatment, the minimal radiation dose was of less importance., Conclusions: Nodal volume and chemotherapy are the most important prognostic factors to control pathological nodes in the neck. Radiological central necrosis and extranodal growth, nodal volume and chemotherapy were significant prognostic factors for nodal control. Additionally, it appears that regional control in patients treated with primary radiation alone or with chemoradiation in case of a total nodal volume of more than 3.0 cm(3) results in an unacceptable high risk on regional recurrence.

Background and Purpose: In this prospective study, the effect of a second course of primary radiotherapy on locoregional control, survival and toxicity was investigated, in patients who underwent a second course of high dose irradiation for second primary or locoregional recurrent squamous cell head and neck carcinoma (HNSCC) in a previously irradiated area., Patients and Methods: A total of 34 patients with second primary (n=26) or locoregional recurrent (n=8) tumours were treated with a second course of high dose radiotherapy. Patients were selected for re-irradiation in case of inoperable and/or unresectable tumours. In most cases, the target volume for re-irradiation was confined to the gross tumour volume (GTV). No elective radiotherapy was applied in the former high-dose area. A total dose of 46 Gy was applied to elective areas with a boost up to 60 Gy with conventional fractionation. The median follow-up period was 32 months., Results: The locoregional control rate after 2 years was 27%. The 3-year overall survival was 22%. The most frequently reported acute side-effect was acute mucositis resulting in swallowing complaints. Pharyngeal and oesophageal late morbidity was also the most important late side-effect. In general, acute and late radiation-induced morbidity remained within acceptable limits., Conclusions: In conclusion, primary re-irradiation appears to be feasible in terms of acute and late radiation-induced toxicity. To improve outcome in terms locoregional control and survival, future studies should be focussed on optimising radiation schedules and the addition of concomitant chemotherapy.

Background and Purpose: To investigate the association between the mean salivary gland and oral cavity dose, with patient-rated moderate and severe xerostomia and sticky saliva., Patients and Methods: One hundred and fifty-seven patients treated with bilateral irradiation for head and neck cancer were included. The parotid and submandibular glands and the oral cavity were delineated on plannings-CT scans. At baseline and 6 and 12 months self-reported xerostomia and sticky saliva were assessed using the EORTC QLQ-H&N35 questionnaire., Results: At 6 months a significant association between the mean parotid (MD(par)) and mean submandibular dose (MD(subm)) and xerostomia was observed (OR - MD(par): 1.17; P=0.002 and OR - MD(subm): 1.08; P = 0.02). Between MD(par) and MD(subm), a significant interaction term was present. No significant association was found with the oral cavity dose. Xerostomia was reversible depending on MD(par) and MD(subm). Considering Sticky saliva, a significant association was found at 6 and 12 months with MD(subm) (OR: 1.03; P < 0.001). The P50 for sticky saliva increased with elapsing time., Conclusions: Both MD(par) and MD(subm) influence the risk of xerostomia in irradiated patients at 6 months. This probability as a function of the mean parotid dose significantly depended on the mean dose in the submandibular glands. Sticky saliva mainly depends on MD(subm).