Overcoming data scarcity in radiomics/radiogenomics using synthetic radiomic features.

PURPOSE: To evaluate the potential of synthetic radiomic data generation in addressing data scarcity in radiomics/radiogenomics models. METHODS: This study was conducted on a retrospectively collected cohort of 386 colorectal cancer patients (n = 2570 lesions) for whom matched contrast-enhanced CT images and gene TP53 mutational status were available. The full cohort data was divided into a training cohort (n = 2055 lesions) and an independent and fixed test set (n = 515 lesions). Differently sized training sets were subsampled from the training cohort to measure the impact of sample size on model performance and assess the added value of synthetic radiomic augmentation at different sizes. Five different tabular synthetic data generation models were used to generate synthetic radiomic data based on "real-world" radiomics data extracted from this cohort. The quality and reproducibility of the generated synthetic radiomic data were assessed. Synthetic radiomics were then combined with "real-world" radiomic training data to evaluate their impact on the predictive model's performance. RESULTS: A prediction model was generated using only "real-world" radiomic data, revealing the impact of data scarcity in this particular data set through a lack of predictive performance at low training sample numbers (n = 200, 400, 1000 lesions with average AUC = 0.52, 0.53, and 0.56 respectively, compared to 0.64 when using 2055 training lesions). Synthetic tabular data generation models created reproducible synthetic radiomic data with properties highly similar to "real-world" data (for n = 1000 lesions, average Chi-square = 0.932, average basic statistical correlation = 0.844). The integration of synthetic radiomic data consistently enhanced the performance of predictive models trained with small sample size sets (AUC enhanced by 9.6%, 11.3%, and 16.7% for models trained on n_samples = 200, 400, and 1000 lesions, respectively). In contrast, synthetic data generated from randomised/noisy radiomic data failed to enhance predictive performance underlining the requirement of true signal data to do so. CONCLUSION: Synthetic radiomic data, when combined with real radiomics, could enhance the performance of predictive models. Tabular synthetic data generation might help to overcome limitations in medical AI stemming from data scarcity.

Decisional Conflict in Patients with Advanced Laryngeal Carcinoma: A Multicenter Study.

OBJECTIVES: Decision-making for patients with a locally advanced laryngeal carcinoma (T3 and T4) is challenging due to the treatment choice between organ preservation and laryngectomy, both with different and high impact on function and quality of life (QoL). The complexity of these treatment decisions and their possible consequences might lead to decisional conflict (DC). This study aimed to explore the level of DC in locally advanced laryngeal carcinoma patients facing curative decision-making, and to identify possible associated factors. METHODS: In this multicenter prospective cohort study, participants completed questionnaires on DC, level of shared decision-making (SDM), and a knowledge test directly after counseling and 6 months after treatment. Descriptive statistics and Spearman correlation tests were used to analyze the data. RESULTS: Directly after counseling, almost all participants (44/45; 98%) experienced Clinically Significant DC score (CSDC >25, scale 0-100). On average, patients scored 47% (SD 20%) correct on the knowledge test. Questions related to radiotherapy were answered best (69%, SD 29%), whilst only 35% (SD 29%) of the questions related to laryngectomy were answered correctly. Patients' perceived level of SDM (scale 0-100) was 70 (mean, SD 16.2), and for physicians this was 70 (SD 1.7). CONCLUSION: Most patients with advanced larynx cancer experience high levels of DC. Low knowledge levels regarding treatment aspects indicate a need for better patient counseling. LEVEL OF EVIDENCE: Level IV Laryngoscope, 2024.

Organization of head and neck cancer rehabilitation care: a national survey among healthcare professionals in Dutch head and neck cancer centers.

PURPOSE: Head and neck cancer (HNC) treatment often leads to physical and psychosocial impairments. Rehabilitation can overcome these limitations and improve quality of life. The aim of this study is to obtain an overview of rehabilitation care for HNC, and to investigate factors influencing rehabilitation provision, in Dutch HNC centers, and to some extent compare it to other countries. METHODS: An online survey, covering five themes: organizational structure; rehabilitation interventions; financing; barriers and facilitators; satisfaction and future improvements, among HNC healthcare- and financial professionals of Dutch HNC centers. RESULTS: Most centers (86%) applied some type of rehabilitation care, with variations in organizational structure. A speech language therapist, physiotherapist and dietitian were available in all centers, but other rehabilitation healthcare professionals in less than 60%. Facilitators for providing rehabilitation services included availability of a contact person, and positive attitude, motivation, and expertise of healthcare professionals. Barriers were lack of reimbursement, and patient related barriers including comorbidity, travel (time), low health literacy, limited financial capacity, and poor motivation. CONCLUSION: Although all HNC centers included offer rehabilitation services, there is substantial practice variation, both nationally and internationally. Factors influencing rehabilitation are related to the motivation and expertise of the treatment team, but also to reimbursement aspects and patient related factors. More research is needed to investigate the extent to which practice variation impacts individual patient outcomes and how to integrate HNC rehabilitation into routine clinical pathways.

Lymphedema and Trismus after Head and Neck Cancer, and the Impact on Body Image and Quality of Life.

BACKGROUND: To assess the prevalence of chronic lymphedema and trismus in patients > 6 months after head and neck cancer (HNC) treatment, and to explore how the severity of these conditions correlates with body image and quality of life. METHODS: The cross-sectional sample included 59 patients, treated for HNC between six months to three years ago. Physical measurements were performed to assess the presence of external lymphedema and trismus (<36 mm). Furthermore, participants completed two questionnaires regarding body image (BIS) and quality of life (UW-QoL V4). RESULTS: Lymphedema prevalence was 94.1% (95% CI 0.86-0.98), with a median severity score of 9 (range 0-24). Trismus prevalence in this sample was 1.2%. The median BIS score was 2, indicating a positive body image. The UW-QoL score showed a good QOL with a median of 100. Only the domain of saliva and overall related health had a lower median of 70 and 60, respectively. There was no correlation between lymphedema and body image (r = 0.08, p = 0.544). Patients with higher lymphedema scores reported poorer speech with a moderate correlation (r = -0.39, p = 0.003). CONCLUSION: Lymphedema is a highly prevalent, but moderately severe late side-effect of HNC with a limited impact on quality of life domains except for speech, in our cohort.

Test-Retest Reliability of a Protocol for Assessment of Local Tissue Water in the Head and Neck Area.

Background: Lymphedema measurement is vital to select appropriate treatment and monitor its progress. Quantifying lymphedema in the head and neck area is challenging. The use of tissue dielectric constant (TDC) measurements has shown promising results in other body areas. This study aims to determine the test-retest reliability of a TDC measurement protocol developed for the head and neck area. Methods and Results: A detailed measurement protocol, including eight measurement points per side, was developed. Subsequently, the reliability of the protocol was tested in a sample of healthy participants (n = 50, 28 males). Using the LymphScanner (Delfin, Finland), participants were subjected to two measurement sessions. Each measurement point was measured three times per session. Test-retest reliability for each point was evaluated using intraclass correlation coefficients (ICCs) and standard errors of measurement (SEMs). Using the average of three measurements, reliability was good to excellent for all points (ICCs 0.81-0.95), with small measurement errors (SEMs 1.51-2.86). The reliability of a single measurement was moderate to excellent for all measurement points (ICCs 0.58-0.87), with larger, but still small, measurement errors (SEMs 1.65-3.39). When using single measurements, the lowest ICCs were found for the temporal (left 0.73 and right 0.67) and submandibular (left 0.58 and right 0.77) locations. Conclusion: Measurements with the LymphScanner, taken according to the developed protocol, are reliable in healthy participants. We recommend using the average of three measurements to optimize reliability. The protocol is fit for further testing in patient populations and for determining normal values in a larger scale study with healthy subjects.

Maximal cardiopulmonary exercise testing in laryngectomised patients using different heat and moisture exchangers - feasibility and exercise responses.

OBJECTIVE: After laryngectomy, the breathing resistance of heat and moisture exchangers may limit exercise capacity. Breathing gas analysis during cardiopulmonary exercise testing is not possible using regular masks. This study tested the feasibility of cardiopulmonary exercise testing with a heat and moisture exchanger in situ, using an in-house designed connector. Additionally, we explored the effect of different heat and moisture exchanger resistances on exercise capacity in this group. METHODS: Ten participants underwent two cardiopulmonary exercise tests using their daily life heat and moisture exchanger (0.3 hPa or 0.6 hPa) and one specifically developed for activity (0.15 hPa). Heat and moisture exchanger order was randomised and blinded. RESULTS: All participants completed both tests. No (serious) adverse events occurred. Only four subjects reached a respiratory exchange ratio of more than 1.1 in at least one test. Maximum exercise levels using heat and moisture exchangers with different resistances did not differ. CONCLUSION: Cardiopulmonary exercise testing in laryngectomees with a heat and moisture exchanger is feasible; however, the protocol does not seem appropriate to reach this group's maximal exercise capacity. Lowering heat and moisture exchanger resistance does not increase exercise capacity in this sample.

Squamous Cell Carcinoma Antigen in the Follow-up of Patients With Head and Neck Cancer.

OBJECTIVE: to determine if the tumor marker squamous cell carcinoma antigen (SCC-Ag) observed over time may contribute to the early detection of recurrence, metastasis, and second primary tumors in the follow-up of patients with head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: A retrospective analysis of patients with HNSCC and at least one SCC-Ag measurement was conducted. Hazard ratios (HRs) were used to determine the correlation between SCC-Ag and an event. SETTING: patients with HNSCC, treated in the Antoni van Leeuwenhoek Hospital in The Netherlands between 2010 and 2020 were used for the analysis. METHODS: Data from 789 patients were used on event-free survival (EFS) with time-dependent Cox models. In addition to current (most recent) SCC-Ag (also dichotomized into high and low as done for clinical practice), average SCC-Ag and change between SCC-Ag measurements (delta SCC-Ag) were considered, using restricted cubic splines to explore nonlinear relationships. RESULTS: Dichotomized SCC-Ag values (HR = 3.01, 95% confidence interval [CI]: 2.17-4.18) and the delta SCC-Ag (HR = 1.15, 95% CI: 1.07-1.22) predicted EFS better than models using the cumulative average or current value of SCC-Ag, also after adjusting for tumor site, stage, age, and gender. A strong association was observed when using delta SCC-Ag as a linear predictor in the subgroup of oropharynx patients (HR = 4.88, 95% CI: 2.71-8.79). CONCLUSION: Dichotomized and delta SCC-Ag values can be important markers for EFS, during the follow-up of patients treated for HNSCC. These results were more evident in patients with oropharyngeal cancer.

The development of a decision aid for patients with operable oropharyngeal carcinoma in the Netherlands - A mixed methods study.

OBJECTIVE: The aim of this project is to create an interactive online patient decision aid (PDA) for oropharyngeal cancer (OPSCC) patients, eligible for transoral (robotic) surgery with an ultimate goal to assist both physicians and patients in making treatment choices. MATERIALS AND METHODS: Following the International Patient Decision Aid Standards, a mixed-methods approach was employed. The study involved semi-structured in-depth interviews with patients and physicians, thinking-out-loud sessions, and study-specific questionnaires. Thematic coding and analysis were conducted on verbatim transcriptions of audio-recorded interviews. RESULTS: The PDA drafts were evaluated by twenty OPSCC survivors and twenty multidisciplinary specialists. Significant revisions were made after phase 1 to enhance readability and reduce text, whilst incorporating videos and graphics. Following all phases, both patients and specialists rated the PDA as comprehensible, feasible, and a valuable addition to regular counseling. CONCLUSION: This study showcases the development of a PDA for early stage oropharyngeal cancer patients considering surgery and radiotherapy options. The decision aid emphasizes the disparities in short- and long-term side effects between the two treatments. Patients and physicians found the decision aid to be understandable, user-friendly, and helpful for future patients. The PDA is available on https://beslissamen.nl/.

The Prediction of Biological Features Using Magnetic Resonance Imaging in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

Magnetic resonance imaging (MRI) is an indispensable, routine technique that provides morphological and functional imaging sequences. MRI can potentially capture tumor biology and allow for longitudinal evaluation of head and neck squamous cell carcinoma (HNSCC). This systematic review and meta-analysis evaluates the ability of MRI to predict tumor biology in primary HNSCC. Studies were screened, selected, and assessed for quality using appropriate tools according to the PRISMA criteria. Fifty-eight articles were analyzed, examining the relationship between (functional) MRI parameters and biological features and genetics. Most studies focused on HPV status associations, revealing that HPV-positive tumors consistently exhibited lower ADCmean (SMD: 0.82; p < 0.001) and ADCminimum (SMD: 0.56; p < 0.001) values. On average, lower ADCmean values are associated with high Ki-67 levels, linking this diffusion restriction to high cellularity. Several perfusion parameters of the vascular compartment were significantly associated with HIF-1α. Analysis of other biological factors (VEGF, EGFR, tumor cell count, p53, and MVD) yielded inconclusive results. Larger datasets with homogenous acquisition are required to develop and test radiomic-based prediction models capable of capturing different aspects of the underlying tumor biology. Overall, our study shows that rapid and non-invasive characterization of tumor biology via MRI is feasible and could enhance clinical outcome predictions and personalized patient management for HNSCC.

A systematic review of validated assessments methods for head and neck lymphedema.

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.

Understanding and predicting the performance of passive heat and moisture exchangers using a numerical model.

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.

External validation of an MR-based radiomic model predictive of locoregional control in oropharyngeal cancer.

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.

Does Prophylactic Replacement of Voice Prosthesis Make Sense? A Study to Predict Prosthesis Lifetime.

OBJECTIVE: Voice prosthesis leakage significantly affects the quality of life of patients undergoing laryngectomy, causing insecurity and frequent unplanned hospital visits and costs. In this study, the concept of prophylactic voice prosthesis replacement was explored to prevent leakages. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary hospital. METHODS: This study included all patients who underwent laryngectomy between 2000 and 2012 in the Netherlands Cancer Institute. Device lifetimes and voice prosthesis replacements of a retrospective cohort were used to calculate the number of needed voice prostheses per patient per year to prevent 70% of the leakages by prophylactic replacement. Various strategies for the timing of prophylactic replacement were considered: adaptive strategies based on the individual patient's history of replacement and fixed strategies based on the results of patients with similar voice prosthesis or treatment characteristics. RESULTS: Patients used a median 3.4 voice prostheses per year (range, 0.1-48.1). We found high inter- and intrapatient variability in device lifetime. When prophylactic replacement is applied, this would become a median 9.4 voice prostheses per year, which means replacement every 38 days, implying >6 additional voice prostheses per patient per year. The individual adaptive model showed that preventing 70% of the leakages was impossible for most patients and only a median 25% can be prevented. Monte-Carlo simulations showed that prophylactic replacement is not feasible due to the high coefficient of variation (SD/mean) in device lifetime. CONCLUSION: Based on our simulations, prophylactic replacement of voice prostheses is not feasible due to high inter- and intrapatient variation in device lifetime.

Dutch translation and validation of the Communicative Participation Item Bank (CPIB)-short form.

BACKGROUND: Several conditions and diseases can result in speech problems that can have a negative impact on everyday functioning, referred to as communicative participation. Subjective problems with acquired speech problems are often assessed with the speech handicap index (SHI). To assess generic participation problems, the Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-P) questionnaire is frequently used. The English questionnaire Communicative Participation Item Bank-short form (CPIB short form) is a 10-item valid, reliable instrument that assesses communicative participation. In the absence of a Dutch equivalent, translation and validation of the CPIB short form was required. AIMS: To translate the CPIB short form into Dutch, and to determine its psychometric properties for the group of adults with speech problems resulting from a neurological aetiology or head and neck cancer. METHODS & PROCEDURES: Translation of the CPIB short form was performed following the instructions of the European Organisation for Research and Treatment for Cancer (EORTC). In a cross-sectional multi-centre study, participants completed the Dutch CPIB short form together with the SHI and USER-P, and the CPIB a second time after 2 weeks. We assessed internal consistency and test-retest reliability of the CPIB. Construct validity was assessed based on correlations with SHI, USER-P and speech assessments. OUTCOMES & RESULTS: In the validation study, 122 participants were included: 51 with dysarthria due to different neurological disorders, 48 with speech problems due to head and neck cancer treatment and 23 healthy controls. Internal consistency of the items was high (Cronbach's alpha = 0.962), the intraclass correlation coefficient (ICC) for test-retest reliability was high 0.908 (95% CI = 0.870-0.935). Construct validity was supported by a strong correlation between the Dutch CPIB short form and the SHI total score (SHI total rs = 0.887) and a moderate correlation between the Dutch CPIB-10 and the USER-P subscales (USER-P Frequency rs = 0.365; USER-P restrictions and USER-P satisfaction rs = 0.546). A moderate correlation was found between the Dutch CPIB-10 and the speech performance assessments (degree of distortedness r = -0.0557; p ≤ 0.001; degree of intelligibility r = 0.0562). CONCLUSIONS & IMPLICATIONS: The Dutch CPIB short form provides a valid and reliable tool for clinical practice and research purposes. It allows clinicians to start using this PROM in clinical and research practice to systematically investigate the impact of the speech problems on communicative participation in a Dutch-speaking population. WHAT THIS PAPER ADDS: What is already known on the subject Communicative participation allows people to take part in life situations, but can be affected by acquired speech problems. The CPIB is a patient-reported outcome measure for the assessment of this concept. For the English language the 46-item bank and a 10-item short form is available. What this paper adds to existing knowledge This paper describes the process of translation of the CPIB short form into Dutch, and confirms its reproducibility and validity. What are the potential or actual clinical implications of this work? With this validated Dutch version of the CPIB short form available, professionals can implement this tool in clinical and research practice to systematically evaluate communicative participation.

Quantitative Diffusion-Weighted Imaging Analyses to Predict Response to Neoadjuvant Immunotherapy in Patients with Locally Advanced Head and Neck Carcinoma.

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.

ADC Values of Cytologically Benign and Cytologically Malignant 18 F-FDG PET-Positive Lymph Nodes of Head and Neck Squamous Cell Carcinoma.

Nodal staging (N-staging) in head and neck squamous cell carcinoma (HNSCC) is essential for treatment planning and prognosis. 18F-fluordeoxyglucose positron emission tomography (FDG-PET) has high performance for N-staging, although the distinction between cytologically malignant and reactive PET-positive nodes, and consequently, the selection of nodes for ultrasound-guided fine needle aspiration cytology (USgFNAC), is challenging. Diffusion-weighted magnetic resonance imaging (DW-MRI) can help to detect nodal metastases. We aim to investigate the potential of the apparent diffusion coefficient (ADC) as a metric to distinguish between cytologically reactive and malignant PET-positive nodes in order to improve node selection criteria for USgFNAC. PET-CT, real-time image-fused USgFNAC and DW-MRI to calculate ADC were available for 78 patients offered for routine N-staging. For 167 FDG-positive nodes, differences in the ADC between cytologically benign and malignant PET-positive nodes were evaluated, and both were compared to the ADC values of PET-negative reference nodes. Analyses were also performed in subsets of nodes regarding HPV status. A mild negative correlation between SUVmax and ADC was found. No significant differences in ADC values were observed between cytologically malignant and benign PET-positive nodes overall. Within the subset of non-HPV-related nodes, ADCb0-200-1000 was significantly lower in cytologically malignant PET-positive nodes when compared to benign PET-positive nodes. ADCb0-1000 and ADCb0-200-1000 were significantly lower (p = 0.018, 0.016, resp.) in PET-negative reference nodes than in PET-positive nodes. ADC was significantly higher in PET-negative reference nodes than in PET-positive nodes. The non-HPV-related subgroup showed significantly (p = 0.03) lower ADC values in cytologically malignant than in cytologically benign PET-positive nodes, which should help inform the node selection procedure for puncture.

Feasibility of a supervised and home-based tailored exercise intervention in head and neck cancer patients during chemoradiotherapy.

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.

Largest diameter delineations can substitute 3D tumor volume delineations for radiomics prediction of human papillomavirus status on MRI's of oropharyngeal cancer.

PURPOSE: Laborious and time-consuming tumor segmentations are one of the factors that impede adoption of radiomics in the clinical routine. This study investigates model performance using alternative tumor delineation strategies in models predictive of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Of 153 OPSCC patients, HPV status was determined using p16/p53 immunohistochemistry. MR-based radiomic features were extracted within 3D delineations by an inexperienced observer, experienced radiologist or radiation oncologist, and within a 2D delineation of the largest axial tumor diameter and 3D spheres within the tumor. First, logistic regression prediction models were constructed and tested separately for each of these six delineation strategies. Secondly, the model trained on experienced delineations was tested using these delineation strategies. The latter methodology was repeated with the omission of shape features. Model performance was evaluated using area under the curve (AUC), sensitivity and specificity. RESULTS: Models constructed and tested using single-slice delineations (AUC/Sensitivity/Specificity: 0.84/0.75/0.84) perform better compared to 3D experienced observer delineations (AUC/Sensitivity/Specificity: 0.76/0.76/0.71), where models based on 4 mm sphere delineations (AUC/Sensitivity/Specificity: 0.77/0.59/0.71) show similar performance. Similar performance was found when experienced and largest diameter delineations (AUC/Sens/Spec: 0.76/0.75/0.65 vs 0.76/0.69/0.69) was used to test the model constructed using experienced delineations without shape features. CONCLUSION: Alternative delineations can substitute labor and time intensive full tumor delineations in a model that predicts HPV status in OPSCC. These faster delineations may improve adoption of radiomics in the clinical setting. Future research should evaluate whether these alternative delineations are valid in other radiomics models.

Evaluation Criteria for Chromosome Instability Detection by FISH to Predict Malignant Progression in Premalignant Glottic Laryngeal Lesions.

Background: The definition of objective, clinically applicable evaluation criteria for FISH 1c/7c in laryngeal precursor lesions for the detection of chromosome instability (CI). Copy Number Variations (CNV) for chromosomes 1 and 7 reflect the general ploidy status of premalignant head and neck lesions and can therefore be used as a marker for CI. Methods: We performed dual-target FISH for chromosomes 1 and 7 centromeres on 4 µm formalin-fixed, paraffin-embedded tissue sections of 87 laryngeal premalignancies to detect CNVs. Thirty-five normal head and neck squamous cell samples were used as a control. First, the chromosome 7:1 ratio (CR) was evaluated per lesion. The normal range of CRs (≥0.84 ≤ 1.16) was based on the mean CR +/− 3 x SD found in the normal population. Second, the percentage of aberrant nuclei, harboring > 2 chromosomes of chromosome 1 and/or 7 (PAN), was established (cut-off value for abnormal PAN ≥ 10%). Results: PAN showed a stronger correlation with malignant progression than CR (resp. OR 5.6, p = 0.001 and OR 3.8, p = 0.009). PAN combined with histopathology resulted in a prognostic model with an area under the ROC curve (AUC) of 0.75 (s.e. 0.061, sensitivity 71%, specificity 70%). Conclusions: evaluation criteria for FISH 1c/7c based on PAN ≥ 10% provide the best prognostic information on the risk of malignant progression of premalignant laryngeal lesions as compared with criteria based on the CR. FISH 1c/7c detection can be applied in combination with histopathological assessment.

Evaluation of subclasses for T4-classified squamous cell carcinoma of the external auditory canal.

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.