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Background: To improve the understanding of the thermodynamics and performance of small passive hygroscopic Heat and Moisture Exchangers (HMEs), a computer model simulating HME function is required. Methods: We developed a numerical HME model to calculate the HME's water and heat exchange. The model was tuned and verified with experimental data and validated by applying it to HME design variations. Results: Verification of the model's results to the experimental data shows that the tuned model yields reliable results. The mass of the core, which determines the HME's total heat capacity, is the most important parameter influencing the performance of passive HMEs. Conclusions: Increasing the HME's diameter is an effective way to improve an HME, as it yields higher performance and lowers breathing resistance. HMEs intended for use in warm or dry climates should contain more and those for use in cold humid climates should contain less hygroscopic salt.

Purpose This systematic review aimed to provide a comprehensive overview of the validity and reliability of existing measurement instruments for quantifying head and neck lymphedema. Methods Four databases were searched on January 31st, 2022. The COnsensus-based Standards for selecting health Measurement INstruments (COSMIN) checklists were used for the risk of bias (ROB) assessment. Results Out of 3362 unique records, eight studies examined the reliability and validity of five measurement instruments of which one patient reported outcome. The Patterson scale for internal lymphedema and the patient reported head and neck external lymphedema and fibrosis (LIDS-H&N) demonstrated validity and reliability. For external lymphedema, none of the instruments had good reliability for all measuring points. Conclusion There is a lack of sufficiently reliable and valid measurement instruments for external head and neck lymphedema. The Patterson scale and the patient reported LIDS-H&N seem reliable for clinical practice and research.

Contains fulltext : 273921.pdf (Publisher’s version ) (Open Access) BACKGROUND: T4-classified squamous cell carcinoma (SCC) of external auditory canal (EAC) can potentially involve different anatomical structures, which could translate into different treatment strategies and survival outcomes within one classification. Our aim is to evaluate the clinical added value of T4-subclasses proposed by Lavieille and by Zanoletti. METHODS: Retrospective data, including patients with primary operated cT4-classified EAC SCC, was obtained from 12 international hospitals. We subclassified according to the T4-subclasses. The treatment strategies, disease-free survival (DFS) and overall survival per subclass were calculated. RESULTS: A total of 130 T4-classified EAC SCC were included. We found commonly used treatment strategies per subclass according to Lavieille and the DFS seems also to differ per subclass. Subclass according to Zanoletti showed comparable treatment strategies and survival outcomes per subclass. CONCLUSION: Our study suggests that the subclass according Lavieille might have added value in clinical practice to improve care of T4-classified EAC SCC.

Objective: The objective was to assess swallowing, mouth opening and speech function during the first year after radiation-based treatment (RT(+)) after introduction of a dedicated preventive rehabilitation program for stage III–IV oropharyngeal carcinoma (OPC). Methods: Swallowing, mouth opening and speech function were collected before and at six- and twelve-month follow-up after RT(+) for OPC as part of ongoing prospective assessments by speech-language pathologists. Results: Objective and patient-perceived function deteriorated until 6 months and improved until 12 months after treatment, but did not return to baseline levels with 25%, 20% and 58% of the patients with objective dysphagia, trismus and speech problems, respectively. Feeding tube dependency and pneumonia prevalence was low. Conclusion: Despite successful implementation, a substantial proportion of patients still experience functional limitations after RT(+) for OPC, suggesting room for improvement of the current rehabilitation program. Pretreatment sarcopenia seems associated with worse functional outcomes and might be a relevant new target for rehabilitation strategies.

Simple Summary Immunotherapy may induce early treatment response in head and neck squamous cell carcinoma (HNSCC) for some patients. Routine imaging parameters fail to diagnose these responses; however, magnetic resonance (MR) diffusion-weighted imaging (DWI) may be able to do so. This study sought to correlate DWI parameters with treatment response early after immunotherapy treatment in HNSCC. We analyzed 24 patients with advanced HNSCC with imaging before and after the immunotherapy. We found that rounder tumors that were smaller in diameter before treatment were more likely to respond. A decrease in skewness of the tumor after treatment compared to before treatment, as well as an overall low skewness post-treatment, were linked to better treatment response. Though this study was explorative in nature, these results are promising for the predictive use of MR-DWI in HNSCC treated with immunotherapy. Background: Neoadjuvant immune checkpoint blockade (ICB) prior to surgery may induce early pathological responses in head and neck squamous cell carcinoma (HNSCC) patients. Routine imaging parameters fail to diagnose these responses early on. Magnetic resonance (MR) diffusion-weighted imaging (DWI) has proven to be useful for detecting HNSCC tumor mass after (chemo)radiation therapy. METHODS: 32 patients with stage II-IV, resectable HNSCC, treated at a phase Ib/IIa IMCISION trial (NCT03003637), were retrospectively analyzed using MR-imaging before and after two doses of single agent nivolumab (anti-PD-1) (n = 6) or nivolumab with ipilimumab (anti-CTLA-4) ICB (n = 26). The primary tumors were delineated pre- and post-treatment. A total of 32 features were derived from the delineation and correlated with the tumor regression percentage in the surgical specimen. Results: MR-DWI data was available for 24 of 32 patients. Smaller baseline tumor diameter (p = 0.01-0.04) and higher sphericity (p = 0.03) were predictive of having a good pathological response to ICB. Post-treatment skewness and the change in skewness between MRIs were negatively correlated with the tumor's regression (p = 0.04, p = 0.02). Conclusion: Pre-treatment DWI tumor diameter and sphericity may be quantitative biomarkers for the prediction of an early pathological response to ICB. Furthermore, our data indicate that ADC skewness could be a marker for individual response evaluation.

Objective: Chemoradiotherapy (CRT) for head and neck cancer (HNC) is associated with high toxicity that adversely affects physical functioning, body composition, fatigue, quality of life and treatment outcomes. Exercise interventions during treatment might counteract these negative effects. We therefore assessed the feasibility of an exercise programme for HNC patients during CRT.Methods: Forty patients were offered a tailored 10-week endurance and resistance training with supervised and home-based sessions. Feasibility endpoints were (1) adherence (main outcome): ≥60% attendance; (2) recruitment: ≥30%; (3) retention rate: ≥85% and (4) compliance rate: ≥60%. Physical performance, muscle strength, body composition, quality of life and fatigue were assessed pre- and post-intervention.Results: Overall adherence was 54%. The recruitment rate was 36%, and the retention rate was 65%. Compliance to the supervised intervention protocol was 66%. Statistically significant decreases were found in mean grip strength, fat-free mass and clinically relevant deteriorations on several domains of quality of life, and fatigue subscales were found.Conclusion: We conclude that this exercise programme for HNC patients during CRT in its current form is feasible for only a minority of patients. We suggest adaptations to improve adherence and retention rates for a definitive multicentre trial.Trial registration: This study is registered at the Netherlands Trial Register (NTR7305), 6 June 2018, retrospectively registered.

Background: Due to the heat and moisture exchanger's (HME) breathing resistance, laryngectomized patients cannot always use an (optimal) HME during physical exercise. We propose a novel HME cassette concept with adjustable “bypass,” to provide adjustment between different breathing resistances within one device. Methods: Under standardized conditions, the resistance and humidification performance of a high resistance/high humidification HME (XM) foam in a cassette with and without bypass were compared to a lower resistance/lesser humidification HME (XF) foam in a closed cassette. Results: With a bypass in the cassette, the resistance and humidification performance of XM foam were similar to those of XF foam in the closed cassette. Compared to XM foam in the closed cassette, introducing the bypass resulted in a 40% resistance decrease, whereas humidification performance was maintained at 80% of the original value. Conclusions: This HME cassette prototype allows adjustment between substantially different resistances while maintaining appropriate humidification performances.

Nowadays, a substantial number of head and neck cancer patients are treated by organ-preserving chemoradiation (CRT), with a possible increased risk of complications after planned or salvage neck dissections. We try to determine the risk pattern of surgical site complications (SSC) post-CRT.(c) 2020 Elsevier Ltd, BASO -The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Purpose The purpose of this study is to assess the general course of acoustic, patient rated, and clinician-rated voice outcomes from pre- up to 12 months post total laryngectomy. Methods Patients admitted to a total laryngectomy in five participating hospitals in Australia and The Netherlands were included. Assessments took place at pre-, 3 months, 6 months, and 12 months post-surgery. Voice outcomes are evaluated with the Acoustic Voice Quality Index (AVQI), perceptual scales, and patient-reported outcome measures including VHI-10 and EQ-5D-5L. Statistical analyses include descriptive statistics, t tests (pre- to 6 months post-surgery), Linear Mixed Effect models. Results The study included 43 participants. A significant worsening of AVQI is seen from pre- to post-surgery evaluated with t test (p Time as a significant factor in predicting AVQI score (p ≤ 0.001), as well as perceptual rated voice quality by the clinician (p = 0.015) and patient-reported perceptual rated voice quality (p = 0.002). No statistical significance was found in VHI-10 scores over time. Conclusion Successful TE-speech was achieved in most participants, some had to rely on augmentative alternative communication methods. Patient-reported outcomes indicate acceptance of the condition and sufficient coping in the long term. However, acoustic rated voice quality is abnormal at all post-surgery time-points. AVQI proved to be a useful instrument to evaluate TE-speech. There is a need for validation and determination of cut-off values for VHI-10 and AVQI for use in TE-speech.

Objective: Treatment decision-making for patients with laryngeal cancer consists of a complex trade-off between survival and quality of life. For decision makers on coverage and guidelines, costs come in addition to this equation. Our aim was to perform a cost-effectiveness analysis of surgery (laryngectomy with or without radiotherapy) versus organ preservation (OP: radiotherapy, chemo- and/or bioradiation) in advanced laryngeal cancer patients from a healthcare perspective. Methods: A cost-effectiveness analysis was conducted using a Markov model. For each modality, data on survival and quality-adjusted life years (QALYs) were sourced from relevant articles in agreement with experts, and national benchmark cost prices were included regarding treatment, follow-up, adverse events, and rehabilitation. Results: Total QALYs of the surgical approach (6.59) were substantially higher compared to the OP approach (5.44). Total lifetime costs were higher for the surgical approach compared to the OP approach, namely €95,881 versus €47,233. The surgical approach was therefore more effective and more costly compared to OP, resulting in an incremental cost-effectiveness ratio of €42,383/QALY. Conclusion: Based on current literature, surgical treatment was cost-effective compared to OP in advanced laryngeal cancer within most willingness-to-pay thresholds. The study provides information on the survival adjusted for quality of life in combination with costs of two different approaches for advanced laryngeal cancer, relevant for patients, physicians, and policy makers. As financial toxicity is a relevant aspect in this population, collection of real-world data on country-specific costs and utilities is strongly recommended to enable further generalization. Level of Evidence: N/A. Laryngoscope, 131:E509–E517, 2021.

Objectives: Expiratory muscle strength training (EMST) is a threshold based device-driven treatment for improving expiratory pressure. EMST proved to be effective in different patient groups to improve cough function. To date, EMST has not been tested in the total laryngectomy population (TL). Methods: This prospective, randomized case-series study examined feasibility, safety, and compliance of EMST in a group of TL participants and its effects on pulmonary function, physical exertion, fatigue, and vocal functioning. Ten TL participants were included in the study to perform a 4 till 8 weeks of EMST. Objective and subjective outcome measures included manometry, spirometry, cardio pulmonary exercise testing (CPET), voice recordings, and patient reported outcome measures. Group means were reported and estimates of the effect are shown with a 95% confidence interval, using single sample t-tests. Results: Nine participants completed the full study protocol. Compliance to the training program was high. All were able to perform the training, although it requires adjustments of the device and skills of the participants. Maximum expiratory pressure (MEP) and vocal functioning in loudness improved over time. After EMST no changes were seen in other objective and subjective outcomes. Conclusions: EMST appears to be feasible and safe after total laryngectomy. MEP improved over time but no improvement in the clinically relevant outcome measures were seen in this sample of relatively fit participants. Further investigation of the training in a larger group of participants who report specifically pulmonary complaints is recommended to investigate if the increase in MEP results in clinical benefits. Level of Evidence: 4

Background: This study aims to evaluate the cost-effectiveness of using heat and moisture exchangers (HMEs) vs alternative stoma covers (ASCs) following laryngectomy in the United States. Methods: A cost-effectiveness and budget impact analysis were conducted including uncertainty analyses using real-world survey data with pulmonary events and productivity loss. Results: HME use was more effective and less costly compared with ASCs. Quality-adjusted life years were slightly higher for HME-users. Total costs per patient (lifetime) were $59 362 (HME) and $102 416 (ASC). Pulmonary events and productivity loss occurred more frequently in the ASC-users. Annual budget savings were up to $40 183 593. Costs per pulmonary event averted were $3770. Conclusions: HME utilization in laryngectomy patients was cost-effective. Reimbursement of HME devices is thus recommended. Utilities may be underestimated due to the generic utility instrument used and sample size. Therefore, we recommend development of a disease-specific utility tool to incorporate in future analyses.

Contains fulltext : 229418.pdf (Publisher’s version ) (Open Access) BACKGROUND: Squamous cell carcinoma (SCC) of the external auditory canal (EAC) is a rare disease, which is commonly classified with the modified Pittsburgh classification. Our aim was to evaluate the predictive performance of this classification in relation to disease-free survival (DFS). METHODS: We examined retrospective data from a nationwide Dutch cohort study including patients with primary EAC SCC. These data were combined with individual patient data from the literature. Using the combined data, the predictive performances were calculated using the c-index. RESULTS: A total of 381 patients were included, 294 for clinical and 281 for the pathological classification analyses. The c-indices of the clinical and the pathological modified Pittsburgh classification predicting DFS were 0.725 (0.668-0.782) and 0.729 (0.672-0.786), respectively. CONCLUSION: The predictive performance of the modified Pittsburgh classification system as such appears to be acceptable to predict the DFS of EAC SCC. Other factors need to be added to a future model to improve the predicted performance.

ObjectiveTotal laryngectomy (TL) leads to lifelong physical changes which can lead to functional and participation issues. To assess the relationship between self-reported quality of life and functional and participation issues, a large international online questionnaire was used.MethodA questionnaire was sent out to 8119 recipients of whom 1705 (21%) responded. The questionnaire consisted of 26 questions regarding demographic information, product use of the respondents, experienced overall health and independence, and functional and participation issues. Respondents were grouped based on sex, age, time since TL, educational level, and country of residence. Questions were grouped in one measure of reported quality of life (r-QoL) and seven issue themes (“esthetic issues,” “experienced limitations in daily activities,” “avoiding social activities,” “communication issues,” “experienced vulnerability due to environmental factors,” “pulmonary issues,” and “sleep issues”) to assess the underlying relations.ResultsThis study showed that more functional and participation issues and a lower r-QoL are reported in the group of younger respondents (ConclusionThe ability to participate in meaningful and social activities is a major factor in r-QoL. Due to the frequency and strong correlations of pulmonary issues with other issue themes, pulmonary issues might be an underlying cause of many other issues.Level of evidence3b

Contains fulltext : 220434.pdf (Publisher’s version ) (Open Access) BACKGROUND: The prognosis of patients with HPV-negative advanced stage head and neck squamous cell carcinoma (HNSCC) remains poor. No prognostic markers other than TNM staging are routinely used in clinic. Epithelial-to-mesenchymal transition (EMT) has been shown to be a strong prognostic factor in other cancer types. The purpose of this study was to determine the role of EMT in HPV-negative HNSCC outcomes. METHODS: Pretreatment tumor material from patients of two cohorts, totalling 174 cisplatin-based chemoradiotherapy treated HPV-negative HNSCC patients, was RNA-sequenced. Seven different EMT gene expression signatures were used for EMT status classification and generation of HNSCC-specific EMT models using Random Forest machine learning. RESULTS: Mesenchymal classification by all EMT signatures consistently enriched for poor prognosis patients in both cohorts of 98 and 76 patients. Uni- and multivariate analyses show important HR of 1.6-5.8, thereby revealing EMT's role in HNSCC outcome. Discordant classification by these signatures prompted the generation of an HNSCC-specific EMT profile based on the concordantly classified samples in the first cohort (cross-validation AUC > 0.98). The independent validation cohort confirmed the association of mesenchymal classification by the HNSCC-EMT model with poor overall survival (HR = 3.39, p

Item does not contain fulltext BACKGROUND AND PURPOSE: Radiotherapy (RT) with cetuximab is an alternative for advanced-stage head and neck squamous cell carcinoma (HNSCC) patients who are unfit for cisplatin treatment. As 5-year overall survival is below 50%, it is of interest to test PD-L1 immune checkpoint blockade (avelumab) with cetuximab-RT in the curative setting. MATERIALS AND METHODS: Phase-I feasibility trial (planned n=10, NCT02938273) of conventional cetuximab-RT with avelumab (concurrent 10mg/kg Q2W+4months maintenance) for advanced-stage HNSCC patients unfit for cisplatin treatment. RESULTS: One of ten included patients experienced grade 2 cetuximab-related infusion reaction and withdrew from the study before avelumab was administered. One patient discontinued treatment after 2 courses of avelumab and 12x2Gy RT for personal reasons. In 2/8 remaining patients, avelumab was stopped after 4 and 8 courses because of toxicity and tumor progression, respectively. There was no grade 4-5 toxicity. Grade 3 immune-related toxicity was manageable and occurred in 4 patients. One patient was treated with topical steroids for grade 3 maculopapular rash and 3 patients received high-dose prednisone for grade 3 elevated liver enzymes (n=1) and pneumonitis (n=2). Seven patients experienced grade 3 RT-related toxicity with no severe specific cetuximab-related toxicity. Tumor recurrence occurred in 4/8 patients (50%) after a median of 12 (8-26) months follow-up. CONCLUSION: Cetuximab-RT plus avelumab is feasible in patients with advanced-stage HNSCC who are unfit for cisplatin treatment. Immune-related toxicity was transient and manageable and radiotherapy-related toxicity was in accordance with standard of care. This pilot study provides grounds for larger efficacy trials.

OBJECTIVES: To externally validate a pre-treatment MR-based radiomics model predictive of locoregional control in oropharyngeal squamous cell carcinoma (OPSCC) and to assess the impact of differences between datasets on the predictive performance.METHODS: Radiomic features, as defined in our previously published radiomics model, were extracted from the primary tumor volumes of 157 OPSCC patients in a different institute. The developed radiomics model was validated using this cohort. Additionally, parameters influencing performance, such as patient subgroups, MRI acquisition, and post-processing steps on prediction performance will be investigated. For this analysis, matched subgroups (based on human papillomavirus (HPV) status of the tumor, T-stage, and tumor subsite) and a subgroup with only patients with 4-mm slice thickness were studied. Also the influence of harmonization techniques (ComBat harmonization, quantile normalization) and the impact of feature stability across observers and centers were studied. Model performances were assessed by area under the curve (AUC), sensitivity, and specificity.RESULTS: Performance of the published model (AUC/sensitivity/specificity: 0.74/0.75/0.60) drops when applied on the validation cohort (AUC/sensitivity/specificity: 0.64/0.68/0.60). The performance of the full validation cohort improves slightly when the model is validated using a patient group with comparable HPV status of the tumor (AUC/sensitivity/specificity: 0.68/0.74/0.60), using patients acquired with a slice thickness of 4 mm (AUC/sensitivity/specificity: 0.67/0.73/0.57), or when quantile harmonization was performed (AUC/sensitivity/specificity: 0.66/0.69/0.60).CONCLUSION: The previously published model shows its generalizability and can be applied on data acquired from different vendors and protocols. Harmonization techniques and subgroup definition influence performance of predictive radiomics models.KEY POINTS: • Radiomics, a noninvasive quantitative image analysis technique, can support the radiologist by enhancing diagnostic accuracy and/or treatment decision-making. • A previously published model shows its generalizability and could be applied on data acquired from different vendors and protocols.

OBJECTIVE: Patients diagnosed with advanced larynx cancer face a decisional process in which they can choose between radiotherapy, chemoradiotherapy, or a total laryngectomy with adjuvant radiotherapy. Clinicians do not always agree on the best clinical treatment, making the decisional process for patients a complex problem.METHODS: Guided by the International Patient Decision Aid (PDA) Standards, we followed three developmental phases for which we held semi-structured in-depth interviews with patients and physicians, thinking-out-loud sessions, and a study-specific questionnaire. Audio-recorded interviews were verbatim transcribed, thematically coded, and analyzed. Phase 1 consisted of an evaluation of the decisional needs and the regular counseling process; phase 2 tested the comprehensibility and usability of the PDA; and phase 3 beta tested the feasibility of the PDA.RESULTS: Patients and doctors agreed on the need for development of a PDA. Major revisions were conducted after phase 1 to improve the readability and replace the majority of text with video animations. Patients and physicians considered the PDA to be a major improvement to the current counseling process.CONCLUSION: This study describes the development of a comprehensible and easy-to-use online patient decision aid for advanced larynx cancer, which was found satisfactory by patients and physicians (available on www.treatmentchoice.info). The outcome of the interviews underscores the need for better patient counseling. The feasibility and satisfaction among newly diagnosed patients as well as doctors will need to be proven. To this end, we started a multicenter trial evaluating the PDA in clinical practice (ClinicalTrials.gov Identifier: NCT03292341).LEVEL OF EVIDENCE: NA Laryngoscope, 129:2733-2739, 2019.

Purpose To investigate the utility of [18F]FDG-PET as an imaging biomarker for pathological response early upon neoadjuvant immune checkpoint blockade (ICB) in patients with head and neck squamous cell carcinoma (HNSCC) before surgery. Methods In the IMCISION trial (NCT03003637), 32 patients with stage II‒IVb HNSCC were treated with neoadjuvant nivolumab with (n = 26) or without (n = 6) ipilimumab (weeks 1 and 3) before surgery (week 5). [18F]FDG-PET/CT scans were acquired at baseline and shortly before surgery in 21 patients. Images were analysed for SUVmax, SUVmean, metabolic tumour volume (MTV), and total lesion glycolysis (TLG). Major and partial pathological responses (MPR and PPR, respectively) to immunotherapy were identified based on the residual viable tumour in the resected primary tumour specimen (≤ 10% and 11–50%, respectively). Pathological response in lymph node metastases was assessed separately. Response for the 2 [18F]FDG-PET-analysable patients who did not undergo surgery was determined clinically and per MR-RECIST v.1.1. A patient with a primary tumour MPR, PPR, or primary tumour MR-RECIST-based response upon immunotherapy was called a responder. Results Median ΔSUVmax, ΔSUVmean, ΔMTV, and ΔTLG decreased in the 8 responders and were significantly lower compared to the 13 non-responders (P = 0.05, P = 0.002, P P max (median − 3.1, P = 0.04). However, a SUVmax increase (median + 2.1) was observed in 27 lymph nodes (in 11 patients), while only 13 lymph nodes (48%) contained metastases in the corresponding neck dissection specimen. Conclusions Primary tumour response assessment using [18F]FDG-PET-based ΔMTV and ΔTLG accurately identifies pathological responses early upon neoadjuvant ICB in HNSCC, outperforming the EORTC criteria, although pseudoprogression is seen in neck lymph nodes. [18F]FDG-PET could, upon validation, select HNSCC patients for response-driven treatment adaptation in future trials. Trial registration https://www.clinicaltrials.gov/, NCT03003637, December 28, 2016.

Simple Summary Ultrasound-guided fine needle aspiration cytology (USgFNAC) is commonly used for N-staging in head and neck squamous cell carcinoma (HNSCC). The specificity of USgFNAC is always in the order of 100% as false positive cytology is rare. The difference in sensitivity is mainly attributable to selection of the lymph nodes to aspirate and aspiration technique. The aim of this study was to improve the selection criteria of lymph nodes to aspirate. Ultrasound features of nodes such as a short axis diameter, S/L ratio, loss of a fatty hilum sign, resistive index, and peripheral or mixed hilar and peripheral vascularization, obtained by Micro-flow imaging (MFI), which is a new technique to obtain micro-vascularization, were evaluated. To calculate the sensitivity and PPV of each feature, data of sonographic findings and cytological results of all aspirated nodes were statistically analyzed. We found that next to size, peripheral vascularisation obtained by MFI and absent hilum sign have a high predictive value for malignancy and should be added as selection criteria for fine needle aspiration in lymph nodes. Abstract Ultrasound-guided fine needle aspiration cytology (USgFNAC) is commonly used for nodal staging in head and neck squamous cell cancer (HNSCC). Peripheral vascularity is a described feature for node metastasis. Micro-flow imaging (MFI) is a new sensitive technique to evaluate micro-vascularization. Our goal is to assess the additional value of MFI to detect malignancy in lymph nodes. A total of 102 patients with HNSCC were included prospectively. USgFNAC was performed with the Philips eL18–4 transducer. Cytological results served as a reference standard to evaluate the prediction of cytological malignancy depending on ultrasound features such as resistive index (RI), absence of fatty hilum sign, and peripheral vascularization. Results were obtained for all US examinations and for the subgroup of clinically node-negative neck (cN0). USgFNAC was performed in 211 nodes. Peripheral vascularization had a positive predictive value (PPV) of 83% (cN0: 50%) and the absence of a fatty hilum had a PPV of 82% (cN0 50%) The combination of peripheral vascularization and absent fatty hilum had a PPV of 94% (cN0: 72%). RI (threshold: 0.705) had a PPV of 61% (cN0: RI-threshold 0.615, PPV 20%), whereas the PPV of short axis diameter (threshold of 6.5mm) was 59% for all patients and 19% in cN0 necks (threshold of 4 mm). Peripheral vascularization assessed by MFI and absent hilum has a high predictive value for cytological malignancy in neck metastases. Next to size, both features should be used as additional selection criteria for USgFNAC.

Background: Sentinel lymph node (SN) biopsy (SLNB) has proven to be a valuable tool for staging melanoma patients. Since its introduction in the early 1990s, this procedure has undergone several technological refinements, including the introduction of single photon emission computed tomography combined with computed tomography (SPECT/CT) as well as radio- and fluorescence-guidance. The purpose of the current study was to evaluate the effect of this technological evolution on SLNB in the head and neck region. Primary endpoint was the false-negative (FN) rate. Secondary endpoints were number of harvested SNs, overall operation time, operation time per harvested SN and postoperative complications. Patients and Methods: A retrospective database was queried for cutaneous head and neck melanoma patients who underwent SLNB at The Netherlands Cancer Institute between 1993 and 2016. The implementation of new detection techniques was divided in 4 groups: (1) 1993-2005, with preoperative lymphoscintigraphy and intraoperative use of both a gamma ray detection probe and patent blue (n = 30); (2) 2006-2007, with addition of preoperative roadmaps based on SPECT/CT (n = 15); (3) 2008-2009, with intraoperative use of a portable gamma camera (n = 40); and (4) 2010-2016, with the addition of near-infrared fluorescence guidance (n = 192). Results: A total of 277 patients were included. At least one SN was identified in all patients. A tumor-positive SN was found in 59 patients (21.3%), 10 in group 1 (33.3%), 3 in group 2 (20.0%), 6 in group 3 (15.0%) and 40 in group 4 (20.8%). Regional recurrences of patients with tumor-negative SNs resulted in an overall FN rate of 11.9% (FN groups 1: 16.7%; 2: 0%; 3: 14.3%; 4: 11.1%). The number of harvested nodes increased with advancing technologies (P = 0.003) whereas Breslow thickness and operation time per harvested SN decreased (P = 0.003 and P = 0.017, respectively). There was no significant difference in percentage of tumor-positive SNs, overall operation time and complication rate between the different groups. Conclusion: The use of advanced detection technologies led to a higher number of identified SNs without increase in overall operation time, which may indicate an improved surgical efficiency. Operation time per harvested SN decreased, the average FN rate remained 11.9% and unchanged over 23 years. There was no significant change in postoperative complication rate.

Permanent hands-free speech with the use of an automatic speaking valve (ASV) is regarded as the optimal voice rehabilitation after total laryngectomy. Due to fixation problems, regular ASV use in patients with a laryngectomy is limited. We have developed an intratracheal fixation device (ITFD) composed of an intratracheal button augmented by hydrophilic foam around its shaft. This study evaluates the short-term effectiveness and experienced comfort of this ITFD during hands-free speech in 7 participants with a laryngectomy. We found that 4 of 7 participants had secure ASV fixation inside the tracheostoma during hands-free speech for at least 30 minutes with the ITFD. The ITFD’s comfort was perceived positively overall. The insertion was perceived as being mildly uncomfortable but not painful. This proof-of-concept study demonstrates the feasibility of the ITFD that might improve stomal attachment of ASVs, and it provides the basis for further development toward a prototype suitable for long-term daily use.

OBJECTIVES: New markers are required to predict chemoradiation response in oropharyngeal squamous cell carcinoma (OPSCC) patients. This study evaluated the ability of magnetic resonance (MR) radiomics to predict locoregional control (LRC) and overall survival (OS) after chemoradiation and aimed to determine whether this has added value to traditional clinical outcome predictors.METHODS: 177 OPSCC patients were eligible for this study. Radiomic features were extracted from the primary tumor region in T1-weighted postcontrast MRI acquired before chemoradiation. Logistic regression models were created using either clinical variables (clinical model), radiomic features (radiomic model) or clinical and radiomic features combined (combined model) to predict LRC and OS 2-years posttreatment. Model performance was evaluated using area under the curve (AUC), 95 % confidence intervals were calculated using 500 iterations of bootstrap. All analyses were performed for the total population and the Human papillomavirus (HPV) negative tumor subgroup.RESULTS: A combined model predicted treatment outcome with a higher AUC (LRC: 0.745 [0.734-0.757], OS: 0.744 [0.735-0.753]) than the clinical model (LRC: 0.607 [0.594-0.620], OS: 0.708 [0.697-0.719]). Performance of the radiomic model was comparable to the combined model for LRC (AUC: 0.740 [0.729-0.750]), but not for OS prediction (AUC: 0.654 [0.646-0.662]). In HPV negative patients, the performance of all models was not sufficient with AUCs ranging from 0.587 to 0.660 for LRC and 0.559 to 0.600 for OS prediction.CONCLUSION: Predictive models that include clinical variables and radiomic tumor features derived from MR images of OPSCC better predict LRC after chemoradiation than models based on only clinical variables. Predictive models that include clinical variables perform better than models based on only radiomic features for the prediction of OS.

Head and neck squamous cell carcinoma (HNSCC) is characterized by the frequent manifestation of DNA crosslink repair defects. We established novel expression-based DNA repair defect markers to determine the clinical impact of such repair defects. Using hypersensitivity to the DNA crosslinking agents, mitomycin C and olaparib, as proxies for functional DNA repair defects in a panel of 25 HNSCC cell lines, we applied machine learning to define gene expression models that predict repair defects. The expression profiles established predicted hypersensitivity to DNA-damaging agents and were associated with mutations in crosslink repair genes, as well as downregulation of DNA damage response and repair genes, in two independent datasets. The prognostic value of the repair defect prediction profiles was assessed in two retrospective cohorts with a total of 180 patients with advanced HPV-negative HNSCC, who were treated with cisplatin-based chemoradiotherapy. DNA repair defects, as predicted by the profiles, were associated with poor outcome in both patient cohorts. The poor prognosis association was particularly strong in normoxic tumor samples and was linked to an increased risk of distant metastasis. In vitro, only crosslink repair–defective HNSCC cell lines are highly migratory and invasive. This phenotype could also be induced in cells by inhibiting rad51 in repair competent and reduced by DNA-PK inhibition. In conclusion, DNA crosslink repair prediction expression profiles reveal a poor prognosis association in HNSCC. Significance: This study uses innovative machine learning-based approaches to derive models that predict the effect of DNA repair defects on treatment outcome in HNSCC.

BACKGROUND: Since 2011, a tailored, interdisciplinary head and neck rehabilitation (IHNR) program, covered by the basic healthcare insurance, is offered to advanced head and neck cancer (HNC) patients in the Netherlands Cancer Institute (NKI). This program is developed to preserve or restore patients' functioning, and to optimize health-related quality of life (HRQoL). It applies an integrated approach to define patients' individual goals and provide rehabilitation care throughout the cancer care continuum. The aim of the current study is to assess the (cost-) effectiveness of the IHNR approach compared to usual supportive care (USC) consisting of monodisciplinary and multidisciplinary care in advanced HNC patients.METHODS: This multicenter prospective observational study is designed to compare (cost-)effectiveness of the IHNR to USC for advanced HNC patients treated with chemoradiotherapy (CRT) or bioradiotherapy (BRT). The primary outcome is HRQoL represented in the EORTC QLQ-C30 summary score. Functional HRQoL, societal participation, utility values, return to work (RTW), unmet needs (UN), patient satisfaction and clinical outcomes are secondary outcomes, assessed using the EORTC QLQ-H&N35, USER-P, EQ-5D-5 L, and study-specific questionnaires, respectively. Both patient groups (required sample size: 64 per arm) are requested to complete the questionnaires at: diagnosis (baseline; T0), 3 months (T1), 6 months (T2), 9 months (T3) and 12 months (T4) after start of medical treatment. Differences in outcomes between the intervention and control group will be analyzed using mixed effects models, Chi-square test and descriptive statistics. In addition, a cost-effectiveness analysis (CEA) will be performed by means of a Markov decision model. The CEA will be performed using a societal perspective of the Netherlands.DISCUSSION: This prospective multicenter study will provide evidence on the effectiveness and cost-effectiveness of IHNR compared to USC. RTW and societal participation, included as secondary outcomes, have not been studied sufficiently yet in cancer rehabilitation. Interdisciplinary rehabilitation has not yet been implemented as usual care in all centers, which offers the opportunity to perform a controlled clinical study. If demonstrated to be (cost-)effective, national provision of the program can probably be advised.TRIAL REGISTRATION: The study has been retrospectively registered in the Netherlands Trial Registry on April 24th 2018 ( NTR7140 ).

Purpose: Early detection of residual disease (RD) after (chemo)radiation for oropharyngeal (OPC) is crucial. Surveillance of neck nodes with FDG-PET/CT has been studied extensively, whereas its value for local RD remains less clear. We aim to evaluate the diagnostic value of post-treatment FDG-PET/CT in detecting local RD and the outcome of patients with local RD. Methods: A cohort (n = 352) of consecutively treated OPC patients at our institute between 2010 and 2017 was evaluated. Patients that underwent FDG-PET/CT at 3 months post-treatment (n = 94) were classified as having complete (CMR) or partial metabolic response (PMR). PMR was defined as visually detectable metabolic activity above the background of surrounding normal tissues. Primary endpoint was diagnostic accuracy in detecting local RD. Results: Local RD was seen in 19/352 patients (5%), all of them were HPV negative. The FDG-PET/CT had a sensitivity of 100% (8/8), specificity 85% (73/86), PPV 38% (8/21), NPV 100% (73/73), and accuracy 86%. Patients with local RD had significantly worse OS at 2 years, compared to those without (10 versus 88%, P < 0.001). In multivariable analysis, local RD remained a significant predictive factor for death with a hazard ratio of 11.9 (95% CI 5.8–24.3). The number of patients that underwent PET/CT increased over time (P < 0.001), whereas the number of patients that underwent EUA declined (P = 0.072). Conclusion: FDG-PET/CT has excellent performance for the detection of RD, with the sensitivity and negative predictive value approaching 100%. Due to these excellent results is examination under anaesthesia today in the vast majority of the PET-negative cases not necessary anymore.

BackgroundWith the increasing necessity for total laryngectomy (TL) after prior (chemo)radiotherapy, prosthetic vocal rehabilitation outcomes might have changed.MethodsRetrospective cohort study including all patients laryngectomized between 2000 and 2012 with a voice prosthesis (VP) in the Netherlands Cancer Institute.ResultsMedian device lifetimes of the standard Provox2 and Vega VPs are 63 and 66 days, respectively, and for the problem-solving ActiValve Light and Strong VPs 143 and 186 days, respectively. In multivariable analysis, salvage TL and TL for a dysfunctional larynx (compared to primary TL) were associated with a shorter device lifetime. Almost half of the patients (48%) experienced tracheoesophageal puncture tract-related problems, and this concerned 12% of all VP replacements.ConclusionsCompared to historical cohorts, device lifetimes of regular Provox2 and Vega voice prostheses have decreased. Complications are not occurring more frequently but affect more patients. Nevertheless, the clinical reliability and validity of prosthetic voice rehabilitation is still sound.

Contains fulltext : 203208.pdf (Publisher’s version ) (Closed access) BACKGROUND AND PURPOSE: In recent decades, outcomes of patients with head and neck cancer (HNC) have improved as a result of implementing several strategies, such as chemoradiation. However, these improvements were achieved at the cost of increased toxicity. One way to reduce radiation-related toxicity is by reducing the margins. MATERIALS AND METHODS: Between 2013 and 2016, 206 consecutive patients were treated with CTV-PTV margin of 5mm and subsequently 208 patients with 3mm margin. This study evaluates the impact of reducing clinical target volume (CTV) to planning target volume (PTV) margin on outcome and toxicity. RESULTS: All patients were treated with volumetric modulated arc therapy (VMAT) with daily-image guidance using cone-beam CT (CBCT). Overall acute grade 3 toxicity was significantly lower in 3mm-group, compared to 5mm-group (53.8% vs. 65%, respectively, p=0.032). The same was true for acute grade 3 mucositis (30.8% vs. 42.2%, p=0.008) and for acute grade 3 dysphagia (feeding tube-dependence) (22.1% vs. 33.5%, p=0.026). The incidence of ongoing feeding tube-dependence after 3months of radiotherapy was 11.1% and 20.4%, respectively (p=0.012). The 2-year incidence of late grade >/=2 xerostomia was 15.8% and 19.4% (p=0.8). The 2-year loco-regional control rates of patients treated in 3mm and 5mm-groups were 79.9% and 79.2% (p=1.0). The figures for disease-free survival were 71.5% and 72.7 (p=0.6) and for overall survival were 75.2% and 75.1% (p=0.9). CONCLUSION: Reducing the CTV-PTV margin from 5 to 3mm combined with daily CBCT-guided VMAT reduced the severity, frequency, and duration of radiation-related toxicity without jeopardizing outcome. 7 p.

Approximately 15% of advanced head and neck squamous cell carcinomas (HNSCC) respond to anti-PD-(L)1 monotherapies. Tumor PD-L1 expression and human papillomavirus (HPV) status have been proposed as biomarkers to identify patients likely to benefit from these treatments. We aimed to understand the potential immune effects of HPV in HNSCC and to characterize additional potentially targetable immune-regulatory pathways in primary, treatment-naïve tumors. CD3, CD4, CD8, CD20, CD68, FoxP3, PD-1, PD-L2, LAG-3, IDO-1, and GITR cell densities were determined in 27 HNSCC specimens. IHC for PD-L1 assessed percentage of positive tumor cells and immune cells separately or as a combined positive score (CPS), and whether PD-L1 was expressed in an adaptive or constitutive pattern (i.e., PD-L1+ tumor cells juxtaposed to TILs or in the absence of TILs, respectively). HPV testing with p16 IHC was confirmed by HPV genotyping. When compared to HPV(−) tumors (n = 14), HPV+ tumors (n = 13) contained significantly higher densities of CD3+, CD4+, CD8+, CD20+, and PD-1+ cells (P < 0.02), and there was a trend towards increased density of FoxP3 + cells. PD-L1 expression patterns did not vary by tumor viral status, suggesting possible heterogeneous mechanisms driving constitutive vs adaptive PD-L1 expression patterns in HNSCC. IDO-1 expression was abundant (> 500 IDO-1+ cells/mm2 in 17/27 specimens) and was found on tumor cells as well as immune cells in 12/27 (44%) cases (range 5–80% tumor cells+). Notably, the studied markers varied on a per-patient basis and were not always related to the degree of T cell infiltration. These findings may inform therapeutic co-targeting strategies and raise consideration for a personalized treatment approach.

Permanent hands-free speech with the use of an automatic speaking valve (ASV) is regarded as the optimal voice rehabilitation after total laryngectomy. Due to fixation problems, regular ASV use in laryngectomized patients is limited. We have developed a novel intratracheal fixation device (ITFD), composed of an intratracheal button augmented by a hydrophilic PVA foam exterior around its shaft. The aim of this study was to evaluate the ITFD’s feasibility in vitro, defined as an effective ASV fixation without causing mucosal tissue traumatization. We found that when the expanded PVA foam is compressed less than 60% of its original thickness, it can potentially provide both a safe and effective ASV fixation in a range of tracheostoma morphologies; enough fixation to withstand pressures related to loud speech (approximately 6 kPa) without exerting excessive pressure (>32 mmHg) which could lead to ischemic damage to the tracheal tissue. This study demonstrates the feasibility of the ITFD in vitro that might improve stomal attachment of ASVs. The ITFD’s deformable foam exterior may provide an effective fixation in most laryngectomized patients, compared to commercially available fixation methods, without the need for a user-specific customization. The results of a clinical feasibility study in laryngectomized patients are pending.

Simple Summary Delivered radiation dose in the patient during a course of 6–7 weeks of treatment can differ from intended radiation dose in the treatment planning. This study analyzes these dose differences in the target volumes in a set of 188 head-and-neck cancer patients. It was found that large dose deteriorations in targets occur in a minority of patients, although more frequently when smaller margins were used. The correlation to visual estimation of differences based on changing anatomy was poor. Therefore, dosimetric selection tools during treatment to assess differences seem warranted to identify patients at risk for under or overdosage. With such tools, patients at risk can be selected to adjust the treatment plan during treatment (adaptive radiotherapy) to correct the radiation dose. Abstract Delivered radiation dose can differ from intended dose. This study quantifies dose deterioration in targets, identifies predictive factors, and compares dosimetric to clinical patient selection for adaptive radiotherapy in head-and-neck cancer patients. One hundred and eighty-eight consecutive head-and-neck cancer patients treated up to 70 Gy were analyzed. Daily delivered dose was calculated, accumulated, and compared to the planned dose. Cutoff values (1 Gy/2 Gy) were used to assess plan deterioration in the highest/lowest dose percentile (D1/D99). Differences in clinical factors between patients with/without dosimetric deterioration were statistically tested. Dosimetric deterioration was evaluated in clinically selected patients for adaptive radiotherapy with CBCT. Respectively, 16% and 4% of patients had deterioration over 1 Gy in D99 and D1 in any of the targets, this was 5% (D99) and 2% (D1) over 2 Gy. Factors associated with deterioration of D99 were higher baseline weight/BMI, weight gain early in treatment, and smaller PTV margins. The sensitivity of visual patient selection with CBCT was 22% for detection of dosimetric changes over 1 Gy. Large dose deteriorations in targets occur in a minority of patients. Clinical prediction based on patient characteristics or CBCT is challenging and dosimetric selection tools seem warranted to identify patients in need for ART, especially in treatment with small PTV margins.

DNA copy number alterations (CNAs) are frequent in cancer, and recently developed CNA signatures revealed their value in molecular tumor stratification for patient prognosis and platinum resistance prediction in ovarian cancer. Head and neck squamous cell carcinoma (HNSCC) is also characterized by high CNAs. In this study, we determined CNA in 173 human papilloma virus‐negative HNSCC from a Dutch multicenter cohort by low‐coverage whole genome sequencing and tested the prognostic value of seven cancer‐derived CNA signatures for these cisplatin‐ and radiotherapy‐treated patients. We find that a high CNA signature 1 (s1) score is associated with low values for all other signatures and better patient outcomes in the Dutch cohorts and The Cancer Genome Atlas HNSCC data set. High s5 and s7 scores are associated with increased distant metastasis rates and high s6 scores with poor overall survival. High cumulative cisplatin doses result in improved outcomes in chemoradiotherapy‐treated HNSCC patients. Here we find that tumors high in s1 or low in s6 are most responsive to a change in cisplatin dose. High s5 values, however, significantly increase the risk for metastasis in patients with low cumulative cisplatin doses. Together this suggests that the processes causing these CNA signatures affect cisplatin response in HNSCC. In conclusion, CNA signatures derived from a different cancer type were prognostic and associated with cisplatin response in HNSCC, suggesting they represent underlying molecular processes that define patient outcome., What's new? DNA copy number alterations (CNA) reflect the involvement of crucial mutational processes in cancer and has the potential to inform tumor molecular stratification for precision medicine. While CNA signatures have been developed in ovarian cancer, their application in other cancers remains elusive. Here, the authors demonstrate the applicability of ovarian cancer CNA signatures in head and neck squamous cell carcinoma (HNSCC), which is also characterized by high CNA numbers, treated with radiotherapy and cisplatin. Several of the CNA signatures exhibited a prognostic role in two independent HNSCC cohorts that was dependent on cisplatin treatment and the anatomical subsite.

Objectives: To develop and validate a clinical prediction model (CPM) for survival in hypopharynx cancer, thereby aiming to improve individualized estimations of survival. Methods: Retrospective cohort study of hypopharynx cancer patients. We randomly split the cohort into a derivation and validation dataset. The model was fitted on the derivation dataset and validated on the validation dataset. We used a Cox's proportional hazard model and least absolute shrinkage and selection operator (LASSO) selection. Performance (discrimination and calibration) of the CPM was tested. Results: The final model consisted of gender, subsite, TNM classification, Adult Comorbidity Evaluation-27 score (ACE27), body mass index (BMI), hemoglobin, albumin, and leukocyte count. Of these, TNM classification, ACE27, BMI, hemoglobin, and albumin had independent significant associations with survival. The C Statistic was 0.62 after validation. The model could significantly identify clinical risk groups. Conclusions: ACE27, BMI, hemoglobin, and albumin are independent predictors of overall survival. The identification of high-risk patients can be used in the counseling process and tailoring of treatment strategy or follow-up. Level of Evidence: 4 Laryngoscope, 130:2166–2172, 2020.

Background: Single-modality treatment (surgery or radiotherapy [RT]) is a curative treatment option for early-stage oropharyngeal carcinoma (OPC) with comparable (excellent) oncological outcomes. This study aimed to compare self-reported swallowing function. Methods: Participants with a T1-2N0-2bM0 OPC who were offered single-modality treatment and were recruited to the Head and Neck 5000 study were included. Prospectively collected self-reported swallowing function was compared between surgery and RT. Results: Those offered RT (n = 150) had less favorable baseline characteristics than those offered surgery (n = 150). At 12-month follow up, RT participants reported more swallowing problems (35% vs 23%, RR 1.3; 95% CI 0.8-2.3, P =.277) in models adjusted for baseline characteristics. In those allocated to surgery who received adjuvant therapy (n = 78, 52%), the proportion with swallowing problems was similar to those allocated to RT alone. Conclusions: Participants offered surgery alone had similar mortality but improved swallowing, although this was not statistically significant. However, over half of participants offered surgery alone received surgery and adjuvant therapy.

Background: The objective of this study was to explore the 10-year plus outcomes of Intensity Modulated Radiotherapy with concomitant chemotherapy (CRT) combined with preventive swallowing rehabilitation (CRT+) for head and neck cancer (HNC). Methods: Subjective and objective swallowing, trismus, and speech related outcomes were assessed at 10-year plus after CRT+. Outcomes were compared to previously published 6-year results of the same cohort. Results: Fourteen of the 22 patients at 6-year follow-up were evaluable. Although objective swallowing-related outcomes showed no deterioration (eg, no feeding tube dependency and no pneumonia), swallowing-related quality of life slightly deteriorated over time. No patients had or perceived trismus. Voice and speech questionnaires showed little problems in daily life. Overall quality of life (QOL) was good. Conclusions: After CRT with preventive rehabilitation exercises for advanced HNC, swallowing, trismus, and speech related outcomes moderately deteriorated from 6 to 10 years, with an on average good overall QOL after.

A picture is emerging in which advanced laryngeal cancers (LCs) are potentially not homogeneous and may be characterized by subpopulations which, if identified, could allow selection of patients amenable to organ preservation treatments in contrast to those to be treated with total laryngectomy (TL). This work aims to analyze a multicentric cohort of T3-T4a LCs treated by upfront TL, investigating the clinical and pathological features that can best predict oncologic outcomes. A total of 149 previously untreated patients who underwent TL for T3-T4a LC at four institutions were analyzed. Survival and disease-control were considered as the main outcomes. A secondary end-point was the identification of covariates associated with nodal status, investigating also the tumor thickness. T and N categories were significantly associated with both overall and disease-specific survival. The number of positive nodes and tracheal involvement were associated with loco-regional failure, post-cricoid area invasion and extra-nodal extension with distant failure. Posterior laryngeal compartment involvement was not a significant prognostic feature, by either univariable and multivariable analyses. These results support the conclusion that laryngeal compartmentalization has no impact on survival in patients treated by upfront TL and the current TNM staging system remains a robust prognosticator in advanced LC.

IntroductionIn this study, we investigate the role of radiomics for prediction of overall survival (OS), locoregional recurrence (LRR) and distant metastases (DM) in stage III and IV HNSCC patients treated by chemoradiotherapy. We hypothesize that radiomic analysis of (peri-)tumoral tissue may detect invasion of surrounding tissues indicating a higher chance of locoregional recurrence and distant metastasis.MethodsTwo comprehensive data sources were used: the Dutch Cancer Society Database (Alp 7072, DESIGN) and "Big Data To Decide" (BD2Decide). The gross tumor volumes (GTV) were delineated on contrast-enhanced CT. Radiomic features were extracted using the RadiomiX Discovery Toolbox (OncoRadiomics, Liege, Belgium). Clinical patient features such as age, gender, performance status etc. were collected. Two machine learning methods were chosen for their ability to handle censored data: Cox proportional hazards regression and random survival forest (RSF). Multivariable clinical and radiomic Cox/ RSF models were generated based on significance in univariable cox regression/ RSF analyses on the held out data in the training dataset. Features were selected according to a decreasing hazard ratio for Cox and relative importance for RSF.ResultsA total of 444 patients with radiotherapy planning CT-scans were included in this study: 301 head and neck squamous cell carcinoma (HNSCC) patients in the training cohort (DESIGN) and 143 patients in the validation cohort (BD2DECIDE). We found that the highest performing model was a clinical model that was able to predict distant metastasis in oropharyngeal cancer cases with an external validation C-index of 0.74 and 0.65 with the RSF and Cox models respectively. Peritumoral radiomics based prediction models performed poorly in the external validation, with C-index values ranging from 0.32 to 0.61 utilizing both feature selection and model generation methods.ConclusionOur results suggest that radiomic features from the peritumoral regions are not useful for the prediction of time to OS, LR and DM.

Purpose: Most people are familiar with the expression ‘laughter is the best medicine’. By enhancing cognitive flexibility and strengthening relationships, laughter can be considered a holistic care-approach. Yet, in medical oncology, especially the palliative phase, using humour can be considered inappropriate or taboo. We aimed to explore the acceptability and functions of humour and laughter in patients with prolonged incurable cancer. Methods: This study was performed in a Dutch Comprehensive Cancer Centre. We included four short conversations with patients, eighteen in-depth patient-interviews and eleven observational fieldnotes in which humour was a major topic of the conversation. We further administered an online questionnaire to thirty-three oncology clinicians about their experiences with humour. Qualitative data were thematically analysed. We specifically distinguished between humour and laughter. Results: Nearly all specialists reported using humour (97%), and all reported sometimes laughing during consultations; 83% experienced a positive effect of laughter. These results were in line with patients’ experiences: Patients noted that humour always stayed alive despite medical difficulties. Apart from this human aspect, patients also used humour to broach difficult topics and downplay challenges. Patients and specialists acknowledged that using humour is sometimes inappropriate, partly because they did not always share the same humour. Laughter, in contrast, was regarded as ‘lighter’ than humour, and could, accordingly, more easily be implemented. Specialists cautioned against patients using laughter to avoid broaching difficult topics. Conclusion: Many conversations were full of laughter. Hierarchy as usually experienced between healthcare professionals and patients/relatives seemed to disappear when using laughter. If applied appropriately, adding shared laughter may help optimize shared decision-making.

Background Dysphagia is a common and serious complication after (chemo)radiotherapy (CRT) for head-and-neck cancer (HNC) patients. Prophylactic swallowing exercises (PSE) can have a significantly positive effect on post-treatment swallowing function. However, low adherence rates are a key issue in undermining this positive effect. This current randomized trial will investigate the effect of adherence-improving measures on patients’ swallowing function, adherence and quality of life (QOL). Methods This ongoing trial will explore the difference in adherence and swallowing-related outcome variables during and after PSE in HNC patients performing the same therapy schedule, receiving different delivery methods. One hundred and fifty patients treated in various hospitals will be divided into three groups. Group 1 performs PSE at home, group 2 practices at home with continuous counseling through an app and group 3 receives face-to-face therapy by a speech and language pathologist. The exercises consist of tongue-strengthening exercises and chin-tuck against resistance with effortful swallow. The Iowa Oral Performance Instrument and the Swallowing Exercise Aid are used for practicing. Patients are evaluated before, during and after treatment by means of strength measurements, swallowing and QOL questionnaires. Discussion Since low adherence rates undermine the positive impact of PSE on post-treatment swallowing function, there is need to develop an efficient PSE protocol maximizing adherence rates. Trial registration ISRCTN, ID: ISRCTN98243550. Registered retrospectively on 21 December 2018.

Background: Physical and psychosocial challenges are common after total laryngectomy. The surgery leads to lifelong changes in communication, airway, swallowing and appearance. As we move towards health models driven by patient-centred care, understanding the differential impacts of surgical procedures on subgroups of patients can help improve our care models, patient education and support systems. This paper discusses the experiences of women following total laryngectomy.Aims: To gain an insight into the impact of total laryngectomy on women's daily life while identifying their specific rehabilitation needs.Methods & Procedures: This paper is based on in-depth, semi-structured interviews with eight women who had undergone total laryngectomy. These interviews were conducted with women at least 1 year after they had undergone total laryngectomy, and the participants did not have recurrent disease. Using an interview guide, participants were encouraged to discuss their everyday experiences, while also focusing on issues typical to women. The transcribed interview data were analysed by thematic analysis, taking interpretative phenomenological analysis as a lead.Outcomes & Results: The interviews revealed three main themes: disease and treatment as a turning point, re-establishing meaningful everyday activities, and persistent vulnerability. Participants reported experiencing challenges in their rehabilitation process due to physical disabilities, dependency on others and experienced stigma. Women-specific challenges arose in dealing with the altered appearance and voice, performing care activities, and the spousal relationship (including intimacy).Conclusions & Implications: Women who undergo total laryngectomy are likely to experience issues in returning to work, the performance of informal care-work, the spousal relationship, intimacy and social interaction due to stigmatization. Medical pretreatment counselling and multidisciplinary rehabilitation programmes should help patients form realistic expectations and prepare them for the changes they will face. A gender- and age-matched laryngectomized patient visitor can contribute to this process. Rehabilitation programmes should incorporate the partner and offer psychosocial support for women following total laryngectomy to return to their former roles in family life, social life and work-related activities.