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Objective: To investigate utilization of mental healthcare among head and neck cancer (HNC) patients from diagnosis to 2 years after treatment, in relation to psychological symptoms, mental disorders, need for mental healthcare, and sociodemographic, clinical and personal factors. Methods: Netherlands Quality of life and Biomedical Cohort study data as measured before treatment, at 3 and 6 months, and at 1 and 2 years after treatment was used (n = 610). Data on mental healthcare utilization (iMCQ), psychological symptoms (Hospital Anxiety and Depression Scale, Cancer Worry Scale), mental disorders (CIDI interview), need for mental healthcare (Supportive Care Needs Survey Short‐Form 34, either as continuous outcome indicating the level of need or dichotomized into unmet need (yes/no)) and several sociodemographic, clinical and personal factors were collected. Factors associated with mental healthcare utilization were investigated using generalized estimating equations (p < 0.05). Results: Of all HNC patients, 5%–9% used mental healthcare per timepoint. This was 4%–14% in patients with mild‐severe psychological symptoms, 4%–17% in patients with severe psychological symptoms, 15%–35% in patients with a mental disorder and 5%–16% in patients with an unmet need for mental healthcare. Among all patients, higher symptoms of anxiety, a higher need for mental healthcare, lower age, higher disease stage, lower self‐efficacy and higher social support seeking were significantly associated with mental healthcare utilization. Conclusion: Mental health care utilization among HNC patients is limited, and is related to psychological symptoms, need for mental healthcare, and sociodemographic, clinical and personal factors. [ABSTRACT FROM AUTHOR]

Simple Summary: Many head and neck cancer patients report sexual problems. A deterioration in sexuality and sexual dysfunction from baseline to 3 months after treatment was observed especially in patients treated with chemoradiation. This effect seems to differ between men and women. Men reported change in erectile function, orgasm, satisfaction with intercourse, and overall satisfaction, while women reported change in desire, arousal, and orgasm. These findings are helpful to improve information on sexuality and sexual care in head and neck cancer patients. The aim of this study was to investigate changes in sexuality and sexual dysfunction in head and neck cancer (HNC) patients in the first two years after treatment, in relation to the type of treatment. Data were used of 588 HNC patients participating in the prospective NETherlands Quality of life and Biomedical Cohort Study (NET-QUBIC) from diagnosis to 3, 6, 12 and 24 months after treatment. Primary outcome measures were the International Index of Erectile Function (IIEF) and the Female Sexual Function Index (FSFI). The total scores of the IIEF and FSFI were dichotomized into sexual (dys)function. In men, type of treatment was significantly associated with change in erectile function, orgasm, satisfaction with intercourse, and overall satisfaction. In women, type of treatment was significantly associated with change in desire, arousal, and orgasm. There were significant differences between treatment groups in change in dysfunctional sexuality. A deterioration in sexuality and sexual dysfunction from baseline to 3 months after treatment was observed especially in patients treated with chemoradiation. Changes in sexuality and sexual dysfunction in HNC patients were related to treatment, with an acute negative effect of chemoradiation. This effect on the various domains of sexuality seems to differ between men and women. [ABSTRACT FROM AUTHOR]

Background: Personalized treatment is increasingly required for oropharyngeal squamous cell carcinoma (OPSCC) patients due to emerging new cancer subtypes and treatment options. Outcome prediction model can help identify low or high‐risk patients who may be suitable to receive de‐escalation or intensified treatment approaches. Purpose: To develop a deep learning (DL)‐based model for predicting multiple and associated efficacy endpoints in OPSCC patients based on computed tomography (CT). Methods: Two patient cohorts were used in this study: a development cohort consisting of 524 OPSCC patients (70% for training and 30% for independent testing) and an external test cohort of 396 patients. Pre‐treatment CT‐scans with the gross primary tumor volume contours (GTVt) and clinical parameters were available to predict endpoints, including 2‐year local control (LC), regional control (RC), locoregional control (LRC), distant metastasis‐free survival (DMFS), disease‐specific survival (DSS), overall survival (OS), and disease‐free survival (DFS). We proposed DL outcome prediction models with the multi‐label learning (MLL) strategy that integrates the associations of different endpoints based on clinical factors and CT‐scans. Results: The multi‐label learning models outperformed the models that were developed based on a single endpoint for all endpoints especially with high AUCs ≥ 0.80 for 2‐year RC, DMFS, DSS, OS, and DFS in the internal independent test set and for all endpoints except 2‐year LRC in the external test set. Furthermore, with the models developed, patients could be stratified into high and low‐risk groups that were significantly different for all endpoints in the internal test set and for all endpoints except DMFS in the external test set. Conclusion: MLL models demonstrated better discriminative ability for all 2‐year efficacy endpoints than single outcome models in the internal test and for all endpoints except LRC in the external set. [ABSTRACT FROM AUTHOR]

Background: Proton arc technology has recently shown dosimetric gains for various treatment indications. The increased number of beams and energy layers (ELs) in proton arc plans, increases the degrees of freedom in plan optimization and thereby flexibility to spare dose in organs at risk (OARs).A relationship exists between dosimetric plan quality, delivery efficiency, the number of ELs -and beams in a proton arc plan. Purpose: This work aims to investigate the effect of the number of beams and ELs in a proton arc plan, on toxicity and delivery time for oropharyngeal cancer patients (OPC) selected for intensity modulated proton therapy (IMPT) based on the Dutch model-based approach. Methods: The EL reduction algorithm iteratively selects ELs from beams equidistantly spaced over a 360◦ arc. The beams in the final plan may contain multiple ELs, making them suited for static delivery on the studied treatment machine. The produced plans can therefore be called “step and shoot” proton arc plans. The number of beams and ELs were varied to determine the relationship with the planning cost function value, normal tissue complication probability (NTCP) and delivery time. Proton arc plans with robust target coverage and optimal energy layer reduction (ELR) settings to reduce NTCP, were generated for 10 OPC patients. Proton arc plans were compared to clinical volumetric modulated arc therapy (VMAT) and IMPT plans in terms of integral dose, OAR dose,NTCP for xerostomia and dysphagia and delivery time. Furthermore, dose-weighted average linear energy transfer (LETd) distributions were compared between the IMPT and proton arc plans. A dry run delivery of a plan containing 20 beams and 360 ELs was performed to evaluate delivery time and accuracy. Results: We found 360 ELs distributed over 30 beams generated proton arc plans with near minimal expected plan toxicity. Relative to corresponding IMPT and VMAT plans, an average reduction of 21 ± 3% and 58 ± 10% in integral dose was observed. Dmean was reduced most in the pharyngeal constrictor muscle (PCM) medius structure, with on average 9.0 ± 4.2 Gy(RBE) (p = 0.0002) compared to the clinical IMPT plans. The average NTCP for grade≥2 and grade≥3 xerostomia at 6 months after treatment significantly decreased with 4.7 ± 1.8% (p = 0.002) and 1.7 ± 0.8% (p = 0.002), respectively, while the average NTCP for grade≥2 and grade≥3 dysphagia decreased with 4.4 ± 2.9% (p = 0.002) and 0.9 ± 0.4% (p = 0.002), respectively, increasing the benefit of protons relative to VMAT. For a “step and shoot” proton arc delivery with auto beam sequencing the estimated delivery time is 11 min, similar to the delivery time of a 6-field IMPT treatment. Gamma analysis between the planned and delivered dose distribution resulted in a 99.99% pass rate using 1mm/1% dose difference/distance to agreement criteria. Conclusions: “Step and shoot” proton arc demonstrates potential to further reduce toxicity compared to IMPT and VMAT in OPC treatment. By employing 360 ELs and 30 beams in the proposed ELR method, delivery time can reach clinically acceptable levels without compromising plan toxicity when automatic beam sequencing is available. [ABSTRACT FROM AUTHOR]

Psychoneurological symptoms are commonly reported by newly diagnosed head and neck cancer (HNC) patients, yet there is limited research on the associations of these symptoms with biomarkers of stress and inflammation. In this article, pre-treatment data of a multi-center cohort of HNC patients were analyzed using a network analysis to examine connections between symptoms (poor sleep quality, anxiety, depression, fatigue, and oral pain), biomarkers of stress (diurnal cortisol slope), inflammation markers (c-reactive protein [CRP], interleukin [IL]-6, IL-10, and tumor necrosis factor alpha [TNF-α]), and covariates (age and body mass index [BMI]). Three centrality indices were calculated: degree (number of connections), closeness (proximity of a variable to other variables), and betweenness (based on the number of times a variable is located on the shortest path between any pair of other variables). In a sample of 264 patients, poor sleep quality and fatigue had the highest degree index; fatigue and CRP had the highest closeness index; and IL-6 had the highest betweenness index. The model yielded two clusters: a symptoms—cortisol slope—CRP cluster and a IL-6—IL-10—TNF-α—age—BMI cluster. Both clusters were connected most prominently via IL-6. Our findings provide evidence that poor sleep quality, fatigue, CRP, and IL-6 play an important role in the interconnections between psychoneurological symptoms and biomarkers of stress and inflammation in newly diagnosed HNC patients. [ABSTRACT FROM AUTHOR]

• Optimal timing of re-planning was suggested for a comprehensive set of OARs. • Generic re-planning timing was suggested considering different combinations of OARs. • D mean increase due to anatomical changes were most frequently > 3 Gy in Supraglottic. • The 3rd week is suggested as the optimal timing of re-planning for 10 OARs. • A maximum of 3 re-plannings can guarantee D mean increase below 3 Gy for all OARs. Adaptive radiotherapy (ART) relies on re-planning to correct treatment variations, but the optimal timing of re-planning to account for dose changes in head and neck organs at risk (OARs) is still under investigation. We aimed to find out the optimal timing of re-planning in head and neck ART. A total of 110 head and neck cancer patients were retrospectively enrolled. A semi auto-segmentation method was applied to obtain the weekly mean dose (D mean) to OARs. The K-nearest-neighbour method was used for missing data imputation of weekly D mean. A dose deviation map was built using the planning D mean and weekly D mean values and then used to simulate different ART scenarios consisting of 1 to 6 re-plannings. The difference between accumulated D mean and planning D mean before re-planning (ΔD mean_acc_noART) and after re-planning (ΔD mean_acc_ART) were evaluated and compared. Among all the OARs, supraglottic showed the largest ΔD mean_acc_noART (1.23 ± 3.13 Gy) and most cases of ΔD mean_acc_noART > 3 Gy (26 patients). The 3rd week is suggested in the optimal timing of re-planning for 10 OARs. For all the organs except arytenoid, 2 re-plannings were able to guarantee the ΔD mean_acc_ART below 3 Gy while the average |ΔD mean_acc_ART | was below 1 Gy. ART scenarios of 2_4, 3_4, 3_5 (week of re-planning separated with "_") were able to guarantee ΔD mean_acc_ART of 99 % of patients below 3 Gy simultaneously for 19 OARs. The optimal timing of re-planning was suggested for different organs at risk in head and neck adaptive radiotherapy. Generic scenarios of timing and frequency for re-planning can be applied to guarantee the increase of accumulated mean dose within 3 Gy simultaneously for multiple organs. [ABSTRACT FROM AUTHOR]

Background: To investigate associations between psychological problems and the use of healthcare and informal care and total costs among head and neck cancer (HNC) patients. Method: Data were used of the NETherlands QUality of Life and Biomedical Cohort study. Anxiety and depression disorder (diagnostic interview), distress, symptoms of anxiety and depression (HADS), and fear of cancer recurrence (FCR) and cancer worry scale (CWS) were measured at baseline and at 12-month follow-up. Care use and costs (questionnaire) were measured at baseline, 3-, 6-, 12-, and 24-month follow-up. Associations between psychological problems and care use/costs were investigated using logistic and multiple regression analyses. Results: Data of 558 patients were used. Distress, symptoms of anxiety or depression, FCR, and/or anxiety disorder at baseline were significantly associated with higher use of primary care, supportive care, and/or informal care (odds ratios (ORs) between 1.55 and 4.76). Symptoms of anxiety, FCR, and/or depression disorder at 12-month follow-up were significantly associated with use of primary care, supportive care, and/or informal care (ORs between 1.74 and 6.42). Distress, symptoms of anxiety, and FCR at baseline were associated with higher total costs. Discussion: HNC patients with psychological problems make more use of healthcare and informal care and have higher costs. This is not the result of worse clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: This study assessed the course of fear of cancer recurrence (FCR) in patients newly diagnosed with head and neck cancer (HNC), identified FCR trajectories and factors associated with FCR trajectories. Methods: Six hundred and seventeen HNC patients from the NET‐QUBIC cohort study completed the Cancer Worry Scale‐6 at diagnosis, 3 and 6 months post‐treatment. FCR trajectories were identified using Latent Class Growth Analysis. Associations were explored between FCR trajectories and baseline demographic and medical variables, coping and self‐efficacy. Results: Overall, FCR decreased slightly between baseline and 3 months post‐treatment and remained stable up to 6 months. Two FCR trajectories were identified: "high stable" (n = 125) and "low declining" (n = 492). Patients with high stable FCR were younger, reported more negative adjustment, passive coping, and reassuring thoughts, and less avoidance. Conclusions: The majority of HNC patients have low declining FCR after diagnosis, but one in five patients experience persistent high FCR up to 6 months post‐treatment. [ABSTRACT FROM AUTHOR]

Background: Neurocognition and speech, relevant domains in head and neck cancer (HNC), may be affected pretreatment. However, the prevalence of pretreatment deficits and their possible concurrent predictors are poorly understood. Methods: Using an HNC prospective cohort (Netherlands Quality of Life and Biomedical Cohort Study, N ≥ 444) with a cross‐sectional design, we investigated the estimated prevalence of pretreatment deficits and their relationship with selected demographic, behavioral, and disease‐related factors. Results: Using objective assessments, rates of moderate‐to‐severe neurocognitive deficit ranged between 4% and 8%. From patient‐reported outcomes, 6.5% of patients reported high levels of cognitive failures and 46.1% reported speech deficits. Patient‐reported speech functioning was worse in larynx compared to other subsites. Other nonspeech outcomes were unrelated to any variable. Patient‐reported neurocognitive and speech functioning were modestly correlated, especially in the larynx group. Conclusions: These findings indicate that a subgroup of patients with HNC shows pretreatment deficits, possibly accentuated in the case of larynx tumors. [ABSTRACT FROM AUTHOR]

Background: Most head and neck cancer (HNC) patients receive radiotherapy (RT) and develop toxicities. This genome-wide association study (GWAS) was designed to identify single nucleotide polymorphisms (SNPs) associated with common acute radiation-induced toxicities (RITs) in an HNC cohort.Methods: A two-stage GWAS was performed in 1279 HNC patients treated with RT and prospectively scored for mucositis, xerostomia, sticky saliva, and dysphagia. The area under the curve (AUC) was used to estimate the average load of toxicity during RT. At the discovery study, multivariate linear regression was used in 957 patients, and the top-ranking SNPs were tested in 322 independent replication cohort. Next, the discovery and the replication studies were meta-analyzed.Results: A region on 5q21.3 containing 16 SNPs showed genome-wide (GW) significance association at P-value < 5.0 × 10-8 with patient-rated acute xerostomia in the discovery study. The top signal was rs35542 with an adjusted effect size of 0.17*A (95% CI 0.12 to 0.23; P-value <  = 3.78 × 10-9). The genome wide significant SNPs were located within three genes (EFNA5, FBXL17, and FER). In-silico functional analysis showed these genes may be involved in DNA damage response and co-expressed in minor salivary glands. We found 428 suggestive SNPs (P-value < 1.0 × 10-5) for other toxicities, taken to the replication study. Eleven of them showed a nominal association (P-value < 0.05).Conclusions: This GWAS suggested novel SNPs for patient-rated acute xerostomia in HNC patients. If validated, these SNPs and their related functional pathways could lead to a predictive assay to identify sensitive patients to radiation, which may eventually allow a more individualized RT treatment. [ABSTRACT FROM AUTHOR]

• First time comparison of auto- and human segmentation accuracy using dose and NTCP. • DLC performs better than contour warping by DIR for majority of head and neck OARs. • Human segmentation of parotid glands is needed during adaptive radiotherapy (ART) • Semi auto-segmentation is feasible for accurate dose and NTCP calculation in ART. Accurate segmentation of organs-at-risk (OARs) is crucial but tedious and time-consuming in adaptive radiotherapy (ART). The purpose of this work was to automate head and neck OAR-segmentation on repeat CT (rCT) by an optimal combination of human and auto-segmentation for accurate prediction of Normal Tissue Complication Probability (NTCP). Human segmentation (HS) of 3 observers, deformable image registration (DIR) based contour propagation and deep learning contouring (DLC) were carried out to segment 15 OARs on 15 rCTs. The original treatment plan was re-calculated on rCT to obtain mean dose (D mean) and consequent NTCP-predictions. The average D mean and NTCP-predictions of the three observers were referred to as the gold standard to calculate the absolute difference of D mean and NTCP-predictions (|Δ D mean | and |ΔNTCP|). The average |Δ D mean | of parotid glands in HS was 1.40 Gy, lower than that obtained with DIR and DLC (3.64 Gy, p < 0.001 and 3.72 Gy, p < 0.001, respectively). DLC showed the highest |Δ D mean | in middle Pharyngeal Constrictor Muscle (PCM) (5.13 Gy, p = 0.01). DIR showed second highest |Δ D mean | in the cricopharyngeal inlet (2.85 Gy, p = 0.01). The semi auto-segmentation (SAS) adopted HS, DIR and DLC for segmentation of parotid glands, PCM and all other OARs, respectively. The 90th percentile |ΔNTCP|was 2.19%, 2.24%, 1.10% and 1.50% for DIR, DLC, HS and SAS respectively. Human segmentation of the parotid glands remains necessary for accurate interpretation of mean dose and NTCP during ART. Proposed semi auto-segmentation allows NTCP-predictions within 1.5% accuracy for 90% of the cases. [ABSTRACT FROM AUTHOR]

Cancers of the head and neck region often present with nodal involvement. There is a long‐standing convention within the community of head and neck radiation oncology to irradiate both sides of the neck electively in almost all cases to include both macroscopic and microscopic disease extension (so called elective nodal volume). International guidelines for the selection and delineation of the elective lymph nodes were published in the early 2000s and were updated recently. However, diagnostic imaging techniques have improved the accuracy and reliability of nodal staging and as a result, small metastases that used to remain undetected and were thus in the past included in the elective nodal volume, will now be included in high‐dose volumes. Furthermore, the elective nodal areas are situated close to the parotid glands, the submandibular glands and the swallowing muscles. Therefore, irradiation of a smaller, more selected volume of the elective nodes could reduce treatment‐related toxicity. Several researchers consider the current bilateral elective neck irradiation strategies an overtreatment and show growing interest in a unilateral nodal irradiation in selected patients. The aim of this article is to give an overview of the current evidence about the indications and benefits of unilateral nodal irradiation and the use of SPECT/CT‐guided nodal irradiation in squamous cell carcinomas of the head and neck. [ABSTRACT FROM AUTHOR]

Background: Head and neck cancer (HNC) patients often suffer from distress attributed to their cancer diagnosis which may disturb their sleep. However, there is lack of research about poor sleep quality among newly diagnosed HNC patients. Therefore, our aim was to investigate the prevalence and the associated factors of poor sleep quality among HNC patients before starting treatment.Materials and Methods: A cross-sectional study was conducted using the baseline data from NET-QUBIC study, an ongoing multi-center cohort of HNC patients in the Netherlands. Poor sleep quality was defined as a Pittsburgh Sleep Quality Index (PSQI) total score of > 5. Risk factors examined were sociodemographic factors (age, sex, education level, living situation), clinical characteristics (HNC subsite, tumor stage, comorbidity, performance status), lifestyle factors, coping styles, and HNC symptoms.Results: Among 560 HNC patients, 246 (44%) had poor sleep quality before start of treatment. Several factors were found to be significantly associated with poor sleep: younger age (odds ratio [OR] for each additional year 0.98, 95% CI 0.96-1.00), being female (OR 2.6, 95% CI 1.7-4.1), higher passive coping style (OR 1.18, 95% CI 1.09-1.28), more oral pain (OR 1.10, 95% CI 1.01-1.19), and less sexual interest and enjoyment (OR 1.13, 95% CI 1.06-1.20).Conclusion: Poor sleep quality is highly prevalent among HNC patients before start of treatment. Early evaluation and tailored intervention to improve sleep quality are necessary to prepare these patients for HNC treatment and its consequences. [ABSTRACT FROM AUTHOR]

The comparison between intensity-modulated proton therapy (IMPT) and volume-modulated arc therapy (VMAT) plans, based on models of normal tissue complication probabilities (NTCP), can support the choice of radiation modality. IMPT irradiation plans for 50 patients with head and neck tumours originally treated with photon therapy have been robustly optimised against density and setup uncertainties. The dose distribution has been calculated with a Monte Carlo (MC) algorithm. The comparison of the plans was based on dose-volume parameters in organs at risk (OARs) and NTCP-calculations for xerostomia, sticky saliva, dysphagia and tube feeding using Langendijk's model-based approach. While the dose distribution in the target volumes is similar, the IMPT plans show better protection of OARs. Therefore, it is not the high dose confirmation that constitutes the advantage of protons, but it is the reduction of the mid-to-low dose levels compared to photons. This work investigates to what extent the advantages of proton radiation are beneficial for the patient's post-therapeutic quality of life (QoL). As a result, approximately one third of the patients examined benefit significantly from proton therapy with regard to possible late side effects. Clinical data is needed to confirm the model-based calculations. [ABSTRACT FROM AUTHOR]

Abstract Background Consistent delineation of patient anatomy becomes increasingly important with the growing use of highly conformal and adaptive radiotherapy techniques. This study investigates the magnitude and 3D localization of interobserver variability of organs at risk (OARs) in the head and neck area with application of delineation guidelines, to establish measures to reduce current redundant variability in delineation practice. Methods Interobserver variability among five experienced radiation oncologists was studied in a set of 12 head and neck patient CT scans for the spinal cord, parotid and submandibular glands, thyroid cartilage, and glottic larynx. For all OARs, three endpoints were calculated: the Intraclass Correlation Coefficient (ICC), the Concordance Index (CI) and a 3D measure of variation (3D SD). Results All endpoints showed largest interobserver variability for the glottic larynx (ICC = 0.27, mean CI = 0.37 and 3D SD = 3.9 mm). Better agreement in delineations was observed for the other OARs (range, ICC = 0.32-0.83, mean CI = 0.64-0.71 and 3D SD = 0.9-2.6 mm). Cranial, caudal, and medial regions of the OARs showed largest variations. All endpoints provided support for improvement of delineation practice. Conclusions Variation in delineation is traced to several regional causes. Measures to reduce this variation can be: (1) guideline development, (2) joint delineation review sessions and (3) application of multimodality imaging. Improvement of delineation practice is needed to standardize patient treatments.

• Radiomic features improve individual lymph node failure prediction. • Clinical parameters, together with radiomic features showed the best performance in predicting nodal failure risk. • Individual nodal failure prediction could lead to treatment individualization in HNC patients. To develop and validate a pre-treatment radiomics-based prediction model to identify pathological lymph nodes (pLNs) at risk of failures after definitive radiotherapy in head and neck squamous cell carcinoma patients. Training and validation cohorts consisted of 165 patients with 558 pLNs and 112 patients with 467 pLNs, respectively. All patients were primarily treated with definitive radiotherapy, with or without systemic treatment. The endpoint was the cumulative incidence of nodal failure. For each pLN, 82 pre-treatment CT radiomic features and 7 clinical features were included in the Cox proportional-hazard analysis. There were 68 and 23 nodal failures in the training and validation cohorts, respectively. Multivariable analysis revealed three clinical features (T-stage, gender and WHO Performance-status) and two radiomic features (Least-axis-length representing nodal size and gray level co-occurrence matrix based - Correlation representing nodal heterogeneity) as independent prognostic factors. The model showed good discrimination with a c-index of 0.80 (0.69–0.91) in the validation cohort, significantly better than models based on clinical features (p < 0.001) or radiomics (p = 0.003) alone. High- and low-risk groups were defined by using thresholds of estimated nodal failure risks at 2-year of 60% and 10%, resulting in positive and negative predictive values of 94.4% and 98.7%, respectively. A pre-treatment prediction model was developed and validated, integrating the quantitative radiomic features of individual lymph nodes with generally used clinical features. Using this prediction model, lymph nodes with a high failure risk can be identified prior to treatment, which might be used to select patients for intensified treatment strategies targeted on individual lymph nodes. [ABSTRACT FROM AUTHOR]

Objectives: Ambiguous results have been reported on the predictive value of the Ki‐67 proliferation index (Ki‐67 PI) regarding local control (LC) and survival after primary radiotherapy (RT) in early‐stage laryngeal squamous cell cancer (LSCC). Small study size, heterogenic inclusion, variations in immunostaining and cut‐off values are attributing factors. Our aim was to elucidate the predictive value of the Ki‐67 PI for LC and disease‐specific survival (DSS) using a well‐defined series of T1‐T2 LSCC, standardised automatic immunostaining and digital image analysis (DIA). Methods: A consecutive and well‐defined cohort of 208 patients with T1‐T2 LSCC treated with primary RT was selected. The Ki‐67 PI was determined using DIA. Mann‐Whitney U‐tests, logistic and Cox regression analyses were performed to assess associations between Ki‐67 PI, clinicopathological variables, LC and DSS. Results: In multivariate Cox regression analysis, poor tumour differentiation (HR 2.20; 95% CI 1.06‐4.59, P =.04) and alcohol use (HR 2.84, 95% CI 1.20‐6.71; P =.02) were independent predictors for LC. Lymph node positivity was an independent predictor for DSS (HR 3.16, 95% CI 1.16‐8.64; P =.03). Ki‐67 PI was not associated with LC (HR 1.59; 95% CI 0.89‐2.81; P =.11) or DSS (HR 0.98; 95% CI 0.57‐1.66; P =.97). In addition, continuous Ki‐67 PI was not associated with LC (HR 2.03; 95% CI 0.37‐11.14, P =.42) or DSS (HR 0.62; 95% CI 0.05‐8.28; P =.72). Conclusion: The Ki‐67 PI was not found to be a predictor for LC or DSS and therefore should not be incorporated in treatment‐related decision‐making for LSCC. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate whether quantitative CT image-biomarkers (IBMs) can improve the prediction models with only classical prognostic factors for local-control (LC), regional-control (RC), distant metastasis-free survival (DMFS) and disease-free survival (DFS) for head and neck cancer (HNC) patients.Materials and Methods: The cohort included 240 and 204 HNC patients in the training and validation analysis, respectively. Clinical variables were scored prospectively and IBMs of the primary tumor and lymph nodes were extracted from planning CT-images. Clinical, IBM and combined models were created from multivariable Cox proportional-hazard analyses based on clinical features, IBMs, and both for LC, RC, DMFS and DFS.Results: Clinical variables identified in the multivariable analysis included tumor-site, WHO performance-score, tumor-stage and age. Bounding-box-volume describing the tumor volume and irregular shape, IBM correlation representing radiological heterogeneity, and LN_major-axis-length showing the distance between lymph nodes were included in the IBM models. The performance of IBM LC, RC, DMFS and DFS models (c-index(validated):0.62, 0.80, 0.68 and 0.65) were comparable to that of the clinical models (0.62, 0.76, 0.70 and 0.66). The combined DFS model (0.70) including clinical features and IBMs performed significantly better than the clinical model. Patients stratified with the combined models revealed larger differences between risk groups in the validation cohort than with clinical models for LC, RC and DFS. For DMFS, the differences were similar to the clinical model.Conclusion: For prediction of HNC treatment outcomes, image-biomarkers performed as good as or slightly better than clinical variables. [ABSTRACT FROM AUTHOR]

• Head & neck cancer patients can be selected for ART in the first treatment week. • Mean dose change to OARs in week 1 and 2 is predictive for overall BIOΔNTCP. • Comprehensive evaluation of planned vs. actual NTCP in 110 patients. • The proposed strategy could classify all true candidates regarding late toxicity. • The strategy could correctly spare 88.2% patients from ART regarding late toxicity. Adaptive radiotherapy (ART) is workload intensive but only benefits a subgroup of patients. We aimed to develop an efficient strategy to select candidates for ART in the first two weeks of head and neck cancer (HNC) radiotherapy. This study retrospectively enrolled 110 HNC patients who underwent modern photon radiotherapy with at least 5 weekly in-treatment re-scan CTs. A semi auto-segmentation method was applied to obtain the weekly mean dose (D mean) to OARs. A comprehensive NTCP-profile was applied to obtain NTCP's. The difference between planning and actual values of D mean (ΔD mean) and dichotomized difference of clinical relevance (BIOΔNTCP) were used for modelling to determine the cut-off maximum ΔD mean of OARs in week 1 and 2 (maxΔD mean_1 and maxΔD mean_2). Four strategies to select candidates for ART, using cut-off maxΔD mean were compared. The Spearman's rank correlation test showed significant positive correlation between maxΔD mean and BIOΔNTCP (p -value <0.001). For major BIOΔNTCP (>5%) of acute and late toxicity, 10.9% and 4.5% of the patients were true candidates for ART. Strategy C using both cut-off maxΔD mean_1 (3.01 and 5.14 Gy) and cut-off maxΔD mean_2 (3.41 and 5.30 Gy) showed the best sensitivity, specificity, positive and negative predictive values (0.92, 0.82, 0.38, 0.99 for acute toxicity and 1.00, 0.92, 0.38, 1.00 for late toxicity, respectively). We propose an efficient selection strategy for ART that is able to classify the subgroup of patients with >5% BIOΔNTCP for late toxicity using imaging in the first two treatment weeks. [ABSTRACT FROM AUTHOR]

Background Audit and feedback on professional practice and health care outcomes are the most often used interventions to change behaviour of professionals and improve quality of health care. However, limited information is available regarding preferred feedback for patients, professionals and health insurers. Objective Investigate the (differences in) preferences of receiving feedback between stakeholders, using the Dutch Head and Neck Audit as an example. Methods A total of 37 patients, medical specialists, allied health professionals and health insurers were interviewed using semi-structured interviews. Questions focussed on: 'Why,' 'On what aspects' and 'How' do you prefer to receive feedback on professional practice and health care outcomes? Results All stakeholders mentioned that feedback can improve health care by creating awareness, enabling self-reflection and reflection on peers or colleagues, and by benchmarking to others. Patients prefer feedback on the actual professional practice that matches the health care received, whereas medical specialists and health insurers are interested mainly in health care outcomes. All stakeholders largely prefer a bar graph. Patients prefer a pie chart for patient-reported outcomes and experiences, while Kaplan-Meier survival curves are preferred by medical specialists. Feedback should be simple with firstly an overview, and 1-4 times a year sent by e-mail. Finally, patients and health professionals are cautious with regard to transparency of audit data. Conclusions This exploratory study shows how feedback preferences differ between stakeholders. Therefore, tailored reports are recommended. Using this information, effects of audit and feedback can be improved by adapting the feedback format and contents to the preferences of stakeholders. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) is used to treat approximately 80% of patients with cancer of the head and neck. Despite enormous advances in RT planning and delivery, a significant number of patients will experience radiation-associated toxicities, especially those treated with concurrent systemic agents. Many effective management options are available for acute RT-associated toxicities, but treatment options are much more limited and of variable benefit among patients who develop late sequelae after RT. The adverse impact of developing late tissue damage in irradiated patients may range from bothersome symptoms that negatively affect their quality of life to severe life-threatening complications. In the region of the head and neck, among the most problematic late effects are impaired function of the salivary glands and swallowing apparatus. Other tissues and structures in the region may be at risk, depending mainly on the location of the irradiated tumor relative to the mandible and hearing apparatus. Here, we review the available evidence on the use of different therapeutic strategies to alleviate common late sequelae of RT in head and neck cancer patients, with a focus on the critical assessment of the treatment options for xerostomia, dysphagia, mandibular osteoradionecrosis, trismus, and hearing loss. [ABSTRACT FROM AUTHOR]

Objectives: To demonstrate that novice dosimetry planners efficiently create clinically acceptable IMRT plans for head and neck cancer (HNC) patients using a commercially available multicriteria optimization (MCO) system. Methods: Twenty HNC patients were enrolled in this in-silico comparative planning study. Per patient, novice planners with less experience in dosimetry planning created an IMRT plan using an MCO system (RayStation). Furthermore, a conventionally planned clinical IMRT plan was available (Pinnacle3). All conventional IMRT and MCO-plans were blind-rated by two expert radiation-oncologists in HNC, using a 5-point scale (1'5 with 5 the highest score) assessment form comprising 10 questions. Additionally, plan quality was reported in terms of planning time, dosimetric and normal tissue complication probability (NTCP) comparisons. Inter-rater reliability was derived using the intra-class correlation coefficient (ICC). Results: In total, the radiation-oncologists rated 800 items on plan quality. The overall plan score indicated no differences between both planning techniques (conventional IMRT: 3.8 ± 1.2 vs. MCO: 3.6 ± 1.1, p = 0.29). The inter-rater reliability of all ratings was 0.65 (95% CI: 0.57'0.71), indicating substantial agreement between the radiation-oncologists. In 93% of cases, the scoring difference of the conventional IMRT and MCO-plans was one point or less. Furthermore, MCO-plans led to slightly higher dose uniformity in the therapeutic planning target volume, to a lower integral body dose (13.9 ± 4.5 Gy vs. 12.9 ± 4.0 Gy, p < 0.001), and to reduced dose to the contra-lateral parotid gland (28.1 ± 11.8 Gy vs. 23.0 ± 11.2 Gy, p < 0.002). Consequently, NTCP estimates for xerostomia reduced by 8.4 ± 7.4% (p < 0.003). The hands-on time of the conventional IMRT planning was approximately 205 min. The time to create an MCO-plan was on average 43 ± 12 min. Conclusions: MCO planning enables novice treatment planners to create high quality IMRT plans for HNC patients. Plans were created with vastly reduced planning times, requiring less resources and a short learning curve. [ABSTRACT FROM AUTHOR]

Background The impact of primary tumor volume (pTV) on local control after definitive radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC) is unclear. Methods Pertinent literature was reviewed to address the impact of pTV on local control after definitive RT for HNSCC. Results Reproducibility of pTV calculations is probably influenced by interobserver variability and may be reduced by relying on experienced observers. The impact of pTV on local control after definitive RT is probably influenced by primary site. A relatively limited impact of pTV on local control after RT for oropharyngeal squamous cell carcinomas (SCCs) might be attributable to human papillomavirus (HPV) positivity. Conclusion pTV may be a useful parameter to select patients for treatment with definitive RT, particularly for those with laryngeal SCCs. Patients with high-volume primary cancers, in which the probability of local control with a functional larynx is low, are likely better treated with surgery. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1363-1367, 2013 [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate associations between voice quality and swallowing function in patients treated for oral or oropharyngeal cancer. Methods: Recordings of speech and videofluoroscopy of 51 patients after treatment for oral or oropharyngeal cancer were analysed. Acoustic voice parameters (fundamental frequency (F0), perturbation (jitter %, shimmer %), harmonics-to-noise ratio (HNR), and intensity (extracted from the vowels /a/, /i/, and /u/)) were compared to swallowing function parameters as assessed via videofluoroscopy (oral, oropharyngeal, and total transit time; estimated percent of oral, oropharyngeal, and total residue; oropharyngeal swallowing efficiency (OPSE), and the penetration/aspiration (PA-) scale). Results: Stepwise multivariate regression analyses revealed that jitter, shimmer, and HNR were not associated with swallowing function. Higher voice intensity in all three vowels /a/, /i/, and /u/ was significantly associated with a higher score on the PA-scale (more penetration and aspiration). Higher voice intensity and F0 were significantly associated with lower OPSE. Conclusion: Higher voice intensity was significantly associated with higher amount of penetration/aspiration, and higher voice intensity and fundamental frequency were significantly associated with swallowing inefficiency. Possible explanations may be found in overcompensation by increased laryngeal muscular strength resulting in increased intensity and pitch during phonation. However, the physiology of associated voice and swallowing function is yet unclear, and more research is recommended. [ABSTRACT FROM AUTHOR]

Summary: Background & aims: Weight loss is a frequently observed problem in patients with head and neck cancer (HNC) during radiotherapy. It is still to be assessed whether hypermetabolism is contributing to this problem. The aim of this study was to investigate hypermetabolism before radiotherapy, and changes in resting energy expenditure (REE) in HNC patients during radiotherapy. Methods: REE was measured by indirect calorimetry in 71 patients with HNC before radiotherapy, after 3 and 6 weeks of radiotherapy, and 3 months after radiotherapy. The association between REE and tumour stage, CRP, and prior tumour surgery was analyzed by linear regression analyses. Forty healthy control subjects were one-to-one matched to 40 patients by gender, age and fat free mass (FFM) index to compare REE. Results: Before radiotherapy, REE was not significantly different between patients and controls, neither in absolute values (1568 ± 247 vs. 1619 ± 244 kcal/d; p = 0.29), nor after weight-adjustment (22.1 ± 3.5 vs. 21.5 ± 3.3 kcal/kg, p = 0.42) or FFM-adjustment (31.5 ± 4.9 vs. 30.7 ± 4.5 kcal/kg, p = 0.38). REE was independent of tumour stage, CRP, and prior tumour surgery. REE (kcal/d) decreased during radiotherapy and thereafter by 9% from pre-radiotherapy (p < 0.01). Weight and FFM also decreased significantly over time (p < 0.001). REE adjusted for FFM decreased in the first 3 weeks of radiotherapy with 4% (B = −1.39 kcal/kg FFM, p < 0.01), increased at the end of radiotherapy and decreased again 3 months after radiotherapy (B = −1.31 kcal/kg FFM, p = 0.04). Conclusions: Head and neck cancer patients had normal REE before radiotherapy. During radiotherapy, REE decreased continuously with ongoing weight loss. However, weight loss is not the only explaining factor, since REE expressed per kg FFM showed a much more divergent course which is currently unexplained. [Copyright &y& Elsevier]

Abstract: Background and purpose: Radiotherapy, alone or combined with chemotherapy, is a treatment modality used frequently in head and neck cancer. In order to report, compare and interpret the sequelae of radiation treatment adequately, it is important to delineate organs at risk (OARs) according to well-defined and uniform guidelines. The aim of this paper was to present our institutional Computed Tomography (CT)-based delineation guidelines for organs in the head and neck at risk for radiation-induced swallowing dysfunction (SWOARs). Material and methods: After analyses of the human anatomy of the head and neck area and literature review, CT-based guidelines for delineation of the most relevant SWOARs were described by a panel of experts. Results and conclusions: This paper described institutional guidelines for the delineation of potential SWOARs, accompanied by CT-based illustrations presenting examples of the delineated structures and their corresponding anatomic borders. This paper is essential to ensure adequate interpretation of future reports on the relationship between dose distribution in these SWOARs and different aspects of post-treatment swallowing dysfunction. [Copyright &y& Elsevier]

Objective. Investigation of applicability of neural network feature analysis of nasalance in speech to assess hypernasality in speech of patients treated for oral or oropharyngeal cancer. Patients and methods. Speech recordings of 51 patients and of 18 control speakers were evaluated regarding hypernasality, articulation, intelligibility, and patient-reported speech outcome. Feature analysis of nasalance was performed on /a/, /i/, and /u/ and on the entire stretch of speech. Results. Nasalance distinguished significantly between patients and controls. Nasalance in /a/ and /i/ predicted best intelligibility, nasalance in /a/ predicted best articulation, and nasalance in /i/ and /u/ predicted best hypernasality. Conclusion. Feature analysis of nasalance in oral or oropharyngeal cancer patients is feasible; prediction of subjective parameters varies between moderate and poor. [ABSTRACT FROM AUTHOR]

Background. The purpose of this study was to test whether nutritional status of patients with head and neck cancer changes during and after treatment. Methods. Nutritional status (including body weight, lean mass, and fat mass) and dietary intake were assessed in 29patients with head and neck cancer. Patients were assessed 1 week before, and 1 and 4 months after treatment (radiotherapy, either alone or combined with chemotherapy or surgery). Results. During treatment, body weight (-3.6 ⩾ 5.3 kg; p ¼ .019) and lean mass (-2.43 ± 2.81 kg; p ¼ .001) significantly declined. Patients with sufficient intake (⩾35 kcal and ⩾1.5 grams protein/kg body weight) lost less body weight and lean mass than patients with insufficient intake (mean difference, ⩾4.0 ± 1.9 kg; p ¼ 0.048 and ⩾2.1 ± 1.0 kg; p ¼ .054, respectively). After treatment, only patients with sufficient intake gained body weight (2.3 ± 2.3 kg) and lean mass (1.2 ± 1.3 kg). Conclusion. Patients with head and neck cancer fail to maintain or improve nutritional status during treatment, despite sufficient intake. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To synthesize and compare available evidence considering the effectiveness of carbon-ion, proton and photon radiotherapy for head and neck cancer. Methods: A systematic review and meta-analyses were performed to retrieve evidence on tumor control, survival and late treatment toxicity for carbon-ion, proton and the best available photon radiotherapy. Results: In total 86 observational studies (74 photon, 5 carbon-ion and 7 proton) and eight comparative in-silico studies were included. For mucosal malignant melanomas, 5-year survival was significantly higher after carbon-ion therapy compared to conventional photon therapy (44% versus 25%; P-value 0.007). Also, 5-year local control after proton therapy was significantly higher for paranasal and sinonasal cancer compared to intensity modulated photon therapy (88% versus 66%; P-value 0.035). No other statistically significant differences were observed. Although poorly reported, toxicity tended to be less frequent in carbon-ion and proton studies compared to photons. In-silico studies showed a lower dose to the organs at risk, independently of the tumor site. Conclusions: For carbon-ion therapy, the increased survival in mucosal malignant melanomas might suggest an advantage in treating relatively radio-resistant tumors. Except for paranasal and sinonasal cancer, survival and tumor control for proton therapy were generally similar to the best available photon radiotherapy. In agreement with included in-silico studies, limited available clinical data indicates that toxicity tends to be lower for proton compared to photon radiotherapy. Since the overall quantity and quality of data regarding carbon-ion and proton therapy is poor, we recommend the construction of an international particle therapy register to facilitate definitive comparisons. [Copyright &y& Elsevier]

Purpose. Clinical studies concerning head and neck cancer patients treated with protons reporting on radiation- induced side effects are scarce. Therefore, we reviewed the literature regarding the potential benefits of protons compared with the currently used photons in terms of lower doses to normal tissue and the potential for fewer subsequent radiation-induced side effects, with the main focus on in silico planning comparative (ISPC) studies. Materials and Methods. A literature search was performed by two independent researchers on ISPC studies that included proton-based and photon-based irradiation techniques. Results. Initially, 877 papers were retrieved and 14 relevant and eligible ISPC studies were identified and included in this review. Four studies included paranasal sinus cancer cases, three included nasopharyngeal cancercases, and seven included oropharyngeal, hypopharyngeal, and/or laryngeal cancer cases. Seven studiescompared the most sophisticated photon and proton techniques: intensity-modulated photon therapy versus intensity-modulated proton therapy (IMPT). Four studies compared different proton techniques. All studies showed that protons had a lower normal tissue dose, while keeping similar or better target coverage. Two studies found that these lower doses theoretically translated into a significantly lower incidence of salivary dysfunction. Conclusion. The results of ISPC studies indicate that protons have the potential for a significantly lower normal tissue dose, while keeping similar or better target coverage. Scanned IMPT probably offers the most advantage and will allow for a substantially lower probability of radiation-induced side effects. The results of these ISPC studies should be confirmed in properly designed clinical trials. The Oncologist 2011;16:366-377 [ABSTRACT FROM AUTHOR]

Summary: This review discusses the role of adjuvant treatment after curative surgery for patients with head and neck squamous cell carcinoma (HNSCC). In general, patients with unfavourable prognostic factors have a high-risk of loco-regional recurrence and subsequent worse survival after surgery alone and are therefore considered proper candidates for adjuvant treatment by either postoperative radiotherapy alone or postoperative chemoradiation. Selection of the most optimal adjuvant treatment strategy should be based on the most important prognostic factors. In this review, the different treatment strategies will be discussed in general. More specifically, we will discuss the role of the interval between surgery and radiotherapy, the overall treatment time of radiation, the selection of target volumes for radiation and the value of adding concomitant chemotherapy to postoperative radiation. [Copyright &y& Elsevier]

Background. Clinical outcome of endoscopic CO2 laser surgery and radiotherapy in early-stage glottic laryngeal carcinoma is difficult to compare because of differences in treatment selection and patient groups. Therefore, we compared local control, overall survival, and laryngeal preservation in a homogenous group of patients with T1a glottic carcinoma with normal/diminished mucosal wave treated with either CO2 laser surgery or radiotherapy. Methods. Retrospective survival analysis was performed on 100 patients with T1a glottic carcinoma treated with CO2 laser surgery (n = 49) or radiotherapy (n = 51), diagnosed at the University Medical Center Groningen between 1990 and 2004. Results. No significant differences in local control and overall survival were found. Ultimate 5-year laryngeal preservation was significantly better in the CO2 laser surgery group (95% vs 77%, p = .043). Conclusion. Patients with T1a glottic carcinoma with normal/diminished mucosal wave treated with CO2 laser surgery had a significantly better laryngeal preservation rate than patients treated with radiotherapy. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [ABSTRACT FROM AUTHOR]

Abstract: 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 (SWALL6months) 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 SWALL6months: 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 SWALL6months ((p <0.001). Subsequently, we defined three risk groups based on the TDRS. The rate of SWALL6months 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. [Copyright &y& Elsevier]

Background. The aim of this study was to analyze swallowing outcome in advanced oral/oropharyngeal cancer patients treated with microvascular reconstructive surgery and adjuvant radiotherapy. Methods. Eighty patients were included. Patient, tumor, and treatment factors were assessed. Postoperative videofluoroscopic swallowing studies (VFSS) and scintigraphy tests were performed at 6 (n = 54 vs 44) and 12 (n = 32 vs 37) months. Swallowing parameters such as the oropharyngeal swallow efficiency and the Penetration/Aspiration Scale were analyzed. Results. Impaired swallowing status was found at 6 months, which remained stationary at 12 months. Comorbid condition, larger tumors (T3-T4 vs T2), and resections of the base of tongue and soft palate combined (vs defects of other dynamic structures) were associated with most profound swallowing problems (p < .05). Conclusions. Swallowing difficulties are relatively frequent and can to a large extent be predicted. With the knowledge of this study, better counseling and vigilance as to swallowing difficulties may be possible. © 2007 Wiley Periodicals, Inc. Head Neck 2007 [ABSTRACT FROM AUTHOR]

Abstract: 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 46Gy was applied to elective areas with a boost up to 60Gy 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. [Copyright &y& Elsevier]