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Ajay T Bakas,1 Aniel Sewnaik,1 Jaclyn van Straaten,2 Robert J Baatenburg de Jong,1 Francesco US Mattace-Raso,2 Harmke A Polinder-Bos2 1Department of Otorhinolaryngology, Erasmus MC University Cancer Institute, Rotterdam, the Netherlands; 2Division of Geriatric Medicine, Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, the NetherlandsCorrespondence: Ajay T BakasDepartment of Otorhinolaryngology, Erasmus MC University Cancer, Institute, Rotterdam, the NetherlandsTel +31-10-7040704Email a.bakas@erasmusmc.nlPurpose: The multidimensional prognostic index (MPI) is a prognostic model derived from the comprehensive geriatric assessment (CGA) which can predict 1-year mortality risk in elderly individuals. We hypothesized that the MPI also reflects the degree of frailty and thus will correlate with established measures of frailty. Therefore, the aim of this study is to explore whether the MPI-score is a measure of frailty in older head and neck cancer patients and is associated with several physical functioning measurements.Patients and Methods: From November 2019 to July 2020, a prospective cohort study enrolled patients with head and neck cancer aged ≥ 70 years, and patients < 70 years with an abnormal G8 score. The MPI-score ranged from 0 to 1 and was categorized in MPI-stage 1 (≤ 0.33, non-frail); MPI-stage 2 (0.34– 0.66, mildly frail), and MPI-stage 3 (≥ 0.67, severe frail). Pearson’s correlation coefficient and multivariable linear regression were used to study the association between MPI-score and the physical functioning measurements handgrip strength, gait speed, and the timed up and go test (TUGT).Results: A total of 163 patients were included. One hundred four (63.8%) patients were categorized as non-frail according MPI-stage 1, and 59 (36.2%) patients as mildly or severe frail (n=55 MPI-stage 2; n=4 MPI-stage 3, respectively). A higher MPI-score was significantly associated with lower hand grip strength (B − 0.49 [95% CI − 0.71; − 0.28] p< 0.001), lower gait speed (B − 0.41 [95% CI − 0.55; − 0.25] p< 0.001), and a slower TUGT (B 0.53 [95% CI 0.66; 0.85] p< 0.001).Conclusion: Almost one-third of the included patients with head and neck cancer was mild or severe frail. A higher MPI-score, indicating higher degree of frailty, was associated with worse physical performance by lower handgrip strength, gait speed, and a slower TUGT. Thus, the MPI reflects the degree of frailty.Keywords: comprehensive geriatric assessment, sarcopenia, head and neck cancer, multidimensional prognostic index, elderly

OBJECTIVES: A prospective study of the efficacy and toxicity profile of patients with squamous cell carcinoma of the head and neck (HNSCC) without curative treatment options treated consistently with hypofractionated radiotherapy schedule. PATIENTS AND METHODS: Between 1995 and 2006, 158 patients with HNSCC, unsuitable for curative treatment, were treated with a hypofractionated scheme of radiotherapy consisting of 16 fractions of 3.125 Gy. Endpoints of the study were response rates, loco-regional control, disease-free survival, overall survival, acute and late toxicity, and quality of life (QoL). RESULTS: Seventy four percent of patients were male, 31% had oropharyngeal cancer and 81% stage IV disease. With 45% complete response and 28% partial response an overall response rate of 73% was achieved, 6% had stable disease, and 21% progressed during or directly after completion of treatment. Median survival time was 17 months and 62 patients (40%) survived > or =1 year after RT. The actuarial rates of loco-regional control, disease-free survival and overall survival were 62%, 32% and 40% at 1-year, respectively and 32%, 14% and 17% at 3-years, respectively. Acute grade > or =3 skin and mucosal toxicities were observed in 45% and 65% of patients, respectively. Severe late toxicity was reported in 4.5% of patients. Of patients surviving > or =1 year after RT, retrospective chart review showed that 50% gained weight, pain improved in 77%, performance status in 47% and only 29% of them was still feeding-tube dependent. CONCLUSIONS: Our hypofractionated radiotherapy scheme is an effective, well-tolerated and safe palliative schedule in HNSCC who are unsuitable for curative treatment options. Using 3.125 Gy per fraction (Christie scheme), excellent palliation was achieved resulting in acceptable response rates, excellent symptom control, acceptable toxicity profile, and good QoL of patients surviving > or =1 year after completion of treatment. [ABSTRACT FROM AUTHOR]

Background: Regional lymph node metastasis is an important prognostic factor in head and neck squamous cell carcinoma (HNSCC) and plays a decisive role in the choice of treatment. Here, we present an independent gene expression validation study of metastasized versus non-metastasized HNSCC.Methods: We used a dataset recently published by Roepman et al. as reference dataset and an independent gene expression dataset of 11 metastasized and 11 non-metastasized HNSCC tumors as validation dataset. Reference and validation studies were performed on different microarray platforms with different probe sets and probe content. In addition to a supervised gene-based analysis, a supervised pathway-based analysis was performed, evaluating differences in gene expression for predefined tumorigenesis- and metastasis related gene sets.Results: The gene-based analysis showed 26 significant differentially expressed genes in the reference dataset, 21 of which were present on the microarray platform used in the validation study. 7 of these genes appeared to be significantly expressed in the validation dataset, but failed to pass the correction for multiple testing. The pathway-based analysis revealed 23 significant differentially expressed gene sets, 7 of which were statistically validated. These gene sets are involved in extracellular matrix remodeling (MMPs, MMP regulating pathways and the uPA system), hypoxia and angiogenesis (HIF1alpha regulated angiogenic factors and HIF1alpha regulated invasion).Conclusion: Pathways that are differentially expressed between metastasized and non-metastasized HNSCC are involved in the processes of extracellular matrix remodeling, hypoxia and angiogenesis. A supervised pathway-based analysis enhances the understanding of the biological context of the results, the comparability of results across different microarray studies, and reduces multiple testing problems by focusing on a limited number of pathways of interest instead of analyzing the large number of probes available on the microarray. [ABSTRACT FROM AUTHOR]

Background: Head and neck squamous cell cancer (HNSCC) has a poor prognosis, with approximately 25-30% of patients transitioning into the palliative phase at some point. The length of this phase is relatively short, with a median duration of five months. Patients in this stage often have increased prognostic information needs. Unfortunately, predicting individual life expectancy in this phase is particularly challenging, as physicians and patients tend to overestimate survival. To address this issue, we developed the prognostic model OncologIQ Palliative based on user preferences. In this study, we now aim to assess the clinical impact of utilizing this model during counselling., Methods: This study will employ both quantitative and qualitative approaches. The primary outcome is decisional conflict and satisfaction with the decision-making process after counselling without (cohort 1) and with (cohort 2) OncologIQ Palliative. Therefore, a prospective sequential cohort study will be conducted. Secondary outcomes include the amount of palliative treatment, overall survival rates, and quality of life. These measurements will be collected after the intervention. Additionally, patients' perspectives on the decision-making process and proactive care planning, including end-of-life discussions, will be explored through interviews., Discussion: By offering more personalized prognostic information for HNSCC patients in the palliative phase, we anticipate a shift towards more patient-centred counselling. This approach can facilitate enhanced end-of-life discussions and better proactive care planning. Patients may experience reduced decisional conflict, feel better prepared for what's coming, and find assistance in their decision-making process. This could potentially lead to fewer palliative treatments. Overall, these aspects can contribute to a better quality of life and quality of care for HNSCC patients in the last phase of their lives., Trial Registration: This study was registered November 18, 2024, on ClinicalTrials.gov: NCT06699316., Competing Interests: Declarations. Ethics approval and consent to participate: Ethics approval to start inclusion of patients for cohort 1 was granted by the ethics committee of the Erasmus MC (MEC-number: MEC-2022-0473, version 2.0, dated 13-12-2022). Ethical approval for the initiation of cohort 2 is granted by the ethics committee of the Erasmus MC (MEC-number: MEC-2024-0621, version 1.0, dated 27-08-2024). All participants will be required to provide their informed consent in writing before inclusion in the study. Any protocol modifications will be submitted as an amendment to the ethics committee and updated in Clinical Trial registry. These changes to the research will be made after a favourable opinion by the accredited ethics committee of the Erasmus MC. The study will be conducted according to the principles of the Declaration of Helsinki, Gedragscode Gezondheidsonderzoek 2022 and in accordance with the Erasmus MC Research Code and General Data Protection Regulation. Given the very low-risk nature of this study and that it is classified as Non-WMO, we did not establish a Data Monitoring Committee, report adverse events, or conduct auditing. The METC has approved this approach. Handling of personal data will comply with the Dutch Personal Data Protection Act. All data will be processed digitally, in a protected area. Subjects, and their data will be coded by a serial number (patient identification code), which is not based on the patient initials or birthdate. We will use a subject identification code list to link the data to the subject. Data will be stored in a secured folder and additionally secured by a password. Only the executive researchers and research coordinator will have access to the key. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Patients with limited distant metastatic disease, also known as oligometastasis, show better survival rates than polymetastatic patients, and may be amenable for curative-intent treatment. The definition of oligometastasis, however, is unknown, and no quantitative analyses on the cutoff value for oligometastasis have been performed before. This study aims to derive specific threshold values for the number of metastases and affected locations that defines oligometastatic disease in head and neck squamous cell carcinoma., Methods: A retrospective cohort study was conducted including all patients diagnosed with distant metastases between 2006 and 2021. For each patient, the number of distant metastases and affected locations was recorded on the basis of the available imaging at the time of diagnosis. Cox regression analyses and a machine-learning k-means algorithm were used to determine threshold values., Results: A total of 384 patients untreated for their metastatic foci were analyzed. Most patients (n = 207; 53.9%) had metastasis to one anatomic location, followed by metastases in two anatomic locations (n = 62; 16.1%). The majority of patients had ≥9 metastatic foci (n = 174; 45.3%), followed by one focus (n = 74; 19.3%) and two foci (n = 32; 8.3%). Cox regression and machine-learning k-means models showed that although the number of metastases did not predict survival, the number of affected locations did significantly (p < .001), by identifying a threshold of two locations., Conclusions: Contrary to the prevalent dogma, the definition of oligometastasis should not be defined by the number of metastases but rather by the number of affected locations, with a maximum number of affected locations set at two., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Importance: The Expert Center of Palliative Care for head and neck cancer offers structural attention to patients' complex physical and psychosocial care needs. Patients are offered remote care, including digital monitoring using patient-reported outcome measures, to enable them to stay as long as possible in their trusted home environment. There is limited literature on qualitative feedback and patient-reported experiences with palliative head and neck cancer care, especially for remote care. To provide optimal palliative care, more information on this is needed., Objective: To provide insight into the experiences of patients with head and neck cancer and their next of kin with a hybrid palliative care pathway., Design, Setting, and Participants: A mixed-methods quality improvement study was conducted at a tertiary cancer center. The experiences of patients with head and neck cancer in the palliative phase as of June 2022 and next of kin of patients who had died between June 2021 and March 2022 were evaluated using a patient-reported experience measure that included open-ended questions., Exposures: Hybrid palliative care pathway., Main Outcomes and Measures: Experiences of patients and next of kin., Results: Of 105 included participants, 54 (51.4%) were male, and the mean (SD) age was 67.2 (12.7) years. A total of 56 participants were patients and 49 were next of kin. The face-to-face consultations on the day of the palliative diagnosis were positively experienced by most patients and next of kin. A total of 42 of 102 participants (41%) and 24 of 79 participants (30%) missed at least 1 topic during consultations with their physician and oncology nurse, respectively, such as discussing life expectancy. During the remote follow-up, 71 of 92 (77%) felt safe with this care: they were able to sufficiently clarify their problems, and if necessary, timely action was taken. However, 17 of 48 patients (35%) and 21 of 46 next of kin (46%) considered the provided psychosocial support to be insufficient., Conclusions and Relevance: In this quality improvement study, patients and next of kin were satisfied with most aspects of the hybrid palliative care pathway, and remote care seemed to be a promising means of delivery. Key areas needing attention are discussing life expectancy and providing psychosocial support. These insights represent the initial steps toward gaining a deeper understanding of patients' needs during specific moments in a hybrid palliative trajectory. They may support health care professionals in optimizing personalized and value-based palliative care delivery.

Background: Oral and laryngeal squamous cell carcinoma (OSCC and LSCC) and papillary thyroid carcinoma (PTC) are common head and neck cancers (HNCs) typically treated surgically. Challenges in tumour delineation often lead to inadequate resection margins in OSCC and LSCC, and missed multifocality in PTC. Fluorescence imaging (FLI) using near-infrared tumour-targeting tracers may improve intraoperative identification of malignancy, facilitating precise excision. This study evaluates six potential FLI targets in OSCC, LSCC and PTC., Materials and Methods: Immunohistochemical staining was performed on OSCC (n = 20), LSCC (n = 10) and PTC (n = 10), assessing CEA, c-Met, EpCAM, EGFR, integrin αvβ6 and VEGF-α. Expression was scored (0-12) using the total immunostaining score (TIS) system, and categorized into absent (TIS 0), low (TIS 1-5), moderate (TIS 6-8) or high (TIS 9-12)., Results: Integrin αvβ6 showed significant overexpression in OSCC (TIS: 12; p < 0.001) and LSCC (TIS: 8; p = 0.002), with 80% of OSCC and 90% of LSCC exhibiting moderate-high expression. Similarly, EGFR expression was moderate-high in most OSCC (87.5%; TIS: 8) and universally high in LSCC (100%; TIS: 12). In PTC, EGFR and VEGF-α expressions were low-moderate, but significantly higher than in healthy tissue (TIS: 6; p < 0.006)., Conclusion: This study highlights integrin αvβ6 and EGFR as viable FLI targets in OSCC and LSCC, especially integrin αvβ6 for tumour margin delineation. In PTC, despite lower expressions, the significant overexpression of VEGF-α, c-MET, and EGFR suggests their potential as FLI targets. Our findings support the development of tumour-targeted FLI tracers to improve surgical precision in HNC., (© 2024. The Author(s).)

Cancer is caused by an accumulation of somatic mutations and copy number alterations (CNAs). Besides mutations, these copy number changes are key characteristics of cancer development. Nonetheless, some tumors show hardly any CNAs, a remarkable phenomenon in oncogenesis. Head and neck squamous cell carcinomas (HNSCCs) arise by either exposure to carcinogens, or infection with the human papillomavirus (HPV). HPV-negative HNSCCs are generally characterized by many CNAs and frequent mutations in CDKN2A, TP53, FAT1, and NOTCH1. Here, we present the hallmarks of the distinct subgroup of HPV-negative HNSCC with no or few CNAs (CNA-quiet) by genetic profiling of 802 oral cavity squamous cell carcinomas (OCSCCs). In total, 73 OCSCC (9.1%) are classified as CNA-quiet and 729 as CNA-other. The CNA-quiet group is characterized by wild-type TP53, frequent CASP8 and HRAS mutations, and a less immunosuppressed tumor immune microenvironment with lower density of regulatory T cells. Patients with CNA-quiet OCSCC are older, more often women, less frequently current smokers, and have a better 5-year overall survival compared to CNA-other OCSCC. This study demonstrates that CNA-quiet OCSCC should be considered as a distinct, clinically relevant subclass. Given the clinical characteristics, the patient group with these tumors will rapidly increase in the aging population., (© 2024. The Author(s).)

Objective: Evidence suggests that distant metastasis in head and neck squamous cell carcinoma is a spectrum of disease. Previous studies show that oligometastasis has favorable survival compared with polymetastasis. The quality of life of patients with oligometastasis remains unknown. To further solidify the position of oligometastasis as a separate entity, we hypothesized that oligometastatic patients experience better quality of life than polymetastatic patients., Methods: Patients with distant metastasis were stratified into three groups: oligometastasis (≤3 metastatic foci in ≤2 anatomic sites), explosive metastasis (≥4 metastatic foci at one anatomic site), and explosive-disseminating metastasis (spread to ≥3 anatomic sites). Quality of life was assessed every 2 months post distant metastasis diagnosis., Results: Between January 1, 2016, and December 31, 2021, a total of 161 patients with distant metastasis were identified, with a total of 397 measurements. In this group, 57 (35.4%) patients had oligometastasis, 35 (21.7%) patients had explosive metastasis, and 69 (42.9%) patients had explosive-disseminating metastasis. Their median post-distant metastasis survivals were 8.5 months, 3.2 months, and 3.2 months respectively (p < 0.001). A significantly better overall quality of life was observed in the oligometastasis group compared with the polymetastatic groups (+0.75 out of 7, p < 0.05). Furthermore, oligometastatic patients performed better in the subdomains of "physical functioning," "fatigue," and "pain.", Conclusion: Results from this study underscore that subgroups exist regarding quality of life and survival within distant metastasis, with polymetastatic patients performing worse than oligometastatic patients. This highlights the significance of tailored interventions that consider the unique challenges faced by each metastatic group of patients., Level of Evidence: 3, retrospective cohort study Laryngoscope, 134:3170-3176, 2024., (© 2024 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Resection margins are an important prognostic factor for patients with head and neck cancer. In general, for head and neck surgery, a margin >5 mm is advised by the Royal College of Pathologists. However, this cannot always be achieved during laryngeal and hypopharyngeal surgery. The aim of this study is to identify the resection surfaces and measure the maximum feasible margins per subsite. The clinical relevance of these maximum feasible resection margins were analyzed in this descriptive anatomical study., Methods: head and neck surgeons and a pathologist from the Erasmus MC performed a total laryngectomy and laryngopharyngectomy on a head and neck specimen specifically available for research., Results: For a total laryngectomy, resection margins >5 mm were not feasible for the ventral and dorsal resection surface. For a total laryngopharyngectomy, resection margins >5 mm were not feasible for the ventral, dorsal and lateral resection surface., Conclusion: Clear resection margins, defined as a margin >5 mm, are not always feasible in laryngeal and hypopharyngeal surgery, due to the anatomy of the larynx and tumor location. However, striving for a maximum feasible margin is still the main goal. We propose a new guideline for maximum feasible but adequate resection margins in larynx and hypopharynx tumor surgery.

Background: Laryngeal and hypopharyngeal cancer is complex and resection margins are therefore constrained. The aim of this study was to investigate the clinical relevance of resection margins in laryngeal and hypopharyngeal surgery., Methods: A retrospective cohort study was performed for patients treated with a total laryngectomy (TL) or laryngopharyngectomy (TLP) for laryngeal or hypopharyngeal squamous cell carcinoma (LSCC and HSCC, respectively). Within the groups primary LSCC, recurrent LSCC, primary HSCC, and recurrent HSCC the relationship between the status of the resection margin according to the Royal Collage of Pathology and the recurrence and survival rates were investigated., Results: Positive resection margins were found in 54% for primary LSCC, 29% for recurrent LSCC, 62% for primary HSCC, and 44% for recurrent HSCC. For primary and recurrent LSCC, there was a linear association between total recurrence and narrowing margins ( p = 0.007 resp. p = 0.008). Multivariate survival analysis for primary and recurrent LSCC showed a significantly worse disease free and disease-specific survival in case of positive margins compared to clear margins., Conclusion: Similar survival rates were recorded for close and clear margins for primary and recurrent LSCC. This may suggest that a margin > 5 mm is not clinically relevant in terms of survival. Therefore, a margin of 1-5 mm should be accepted in certain subsites. Margins < 1 mm are related to significantly worse outcomes and should be avoided.

Purpose: Early stage lip squamous cell carcinoma (lip SCC) can be treated with conventional excision, Mohs micrographic surgery (MMS), or brachytherapy. The aim of this retrospective study was to describe the medical outcomes, patient-reported outcomes, and costs of these treatments., Methods: A retrospective cohort study of T1-T2 lip SSCs treated between 1996 and 2019. Medical outcomes, recurrences, and survival were retrieved from medical records. Facial appearance, facial function, and Quality of Life (QoL) were measured with the Face-Q H&N and EQ-5D-5L questionnaires. Costs were also calculated., Results: Of the 336 lip SCCs, 122 were treated with excision, 139 with MMS, and 75 with brachytherapy. Locally, the recurrence rate was 2.7% and regionally 4.8%. There were 2% disease-related deaths. T2-stage and poor tumor differentiation were associated with recurrences. Posttreatment QoL, facial function, and appearance were rated as good. Brachytherapy was the most expensive treatment modality., Conclusion: Early-stage lip SCC has a good prognosis, with a disease-specific survival of 98.2% after a median follow-up of 36 months, there was a high QoL and satisfaction at long-term follow-up. Based on the costs and the risk of locoregional recurrences, we believe that, for most noncomplex lip SCCs, MMS would be the most logical treatment option., (© 2023 The Authors. Oral Diseases published by Wiley Periodicals LLC.)

Importance: There is limited literature on the exact causes and ways of death in patients with head and neck cancer. To provide optimal care, especially in the palliative phase, more information on this is needed., Objective: To provide insights into the causes and ways of death among patients with head and neck cancer., Design, Setting, and Participants: This retrospective cohort study included a consecutive population of patients who received a diagnosis of primary squamous cell carcinoma of the head and neck between January 2006 and December 2013 who were treated in the Erasmus MC. Patient data were merged with nonpublic microdata from Statistics Netherlands. Follow-up time was specified as the date of diagnosis until death or December 3, 2019, whichever came first. The data were checked and reanalyzed in November 2023., Main Outcomes and Measures: Causes (eg, head and neck cancer, other cancer) and ways (eg, natural death, suicide) of death., Results: A total of 1291 patients (59.2%; 342 women [26.5%]) died during follow-up (median [IQR] follow-up, 2.7 [1.2-5.6] years). The main cause of death was head and neck cancer (557 [43.1%]), followed by the competing cause of other cancers (344 [26.6%]). In total, 240 patients (18.6%) received palliative sedation and 70 patients (5.4%) euthanasia. Compared with patients with head and neck cancer as the underlying cause of death, lower odds ratios (ORs) were observed for receiving palliative sedation (OR, 0.32 vs 0.07; 95% CI, 0.22-0.46 vs 0.03-0.12) and euthanasia (OR, 0.22 vs 0.01; 95% CI, 0.11-0.41 vs 0-0.107) in patients with other causes of death. Patients with a middle and high income had higher ORs for receiving palliative sedation (OR, 1.46 vs 1.86; 95% CI, 1.05-2.04 vs 1.22-2.85) or euthanasia (OR, 2.25 vs 3.37; 95% CI, 1.18-4.3, 1.6-7.12) compared with low-income patients. Retired patients had lower ORs for receiving palliative sedation or euthanasia compared with employed patients (OR, 0.56 vs 0.44; 95% CI, 0.39-0.8 vs 0.24-0.82)., Conclusion and Relevance: The results of this cohort study suggest that more than half of the patients died of competing causes and palliative sedation and euthanasia were more common in patients with head and neck cancer as the underlying cause of death. Patients with a higher socioeconomic status had higher odds of receiving palliative sedation and euthanasia. These insights may support health care professionals in providing patient-centered care, especially for patients in the palliative phase.

Buccal squamous cell carcinoma (SCC) appears to behave more aggressively than other oral subsites, in particular with regards to regional disease at presentation and regional recurrence. Adequate management of the neck is of the utmost importance but is still the subject of debate. An international multicentre retrospective review of 101 patients treated for T1-T2 buccal SCC was performed. Twenty-four were staged clinical node positive (cN+) and underwent therapeutic neck dissection, while 77 were node negative (cN0), with 32 undergoing elective neck dissection (END), with an occult nodal metastasis rate of 28.1%. Depth of invasion (DOI) < 4 mm was associated with a significantly lower rate of cervical nodal metastasis (87.5% versus 12.5%; P = 0.033). END demonstrated a non-significantly lower regional recurrence rate compared to observation (6.3% versus 8.9%, P = 0.670). Regional recurrence was more common in pN+ (24%) and undissected cases (8.9%) than in pN0 patients (0%) (P = 0.011) and was associated with DOI > 5 mm (P = 0.002). Regional recurrence resulted in a reduction in survival (24 versus 93 months, P < 0.001). In the pT2cN0 group, END improved survival (123 versus 26 months, P = 0.009). It is suggested that END be performed in cT2N0 buccal SCC, particularly for tumours with DOI > 4 mm., Competing Interests: Competing Interests The authors have no competing or conflicts of interest to declare., (Copyright © 2023 International Association of Oral and Maxillofacial Surgeons. All rights reserved.)

Objective: Timely treatment initiation in head and neck cancer (HNC) care is of great importance regarding survival, oncological, functional, and psychological outcomes. Therefore, waiting times are assessed in the Dutch Head and Neck Audit (DHNA). This audit aims to assess and improve the quality of care through feedback and benchmarking. For this study, we examined how waiting times evolved since the start of the DHNA., Study Design: Prospective cohort study., Setting: National multicentre study., Methods: The DHNA was established in 2014 and reached national coverage of all patients treated for primary HNC in 2019. DHNA data on curative patients from 2015 to 2021 was extracted on national (benchmark) and hospital level. We determined 3 measures for waiting time: (1) the care pathway interval (CPI, first visit to start treatment), (2) the time to treatment interval (TTI, biopsy to start treatment), and (3) CPI-/TTI-indicators (percentage of patients starting treatment ≤30 days). The Dutch national quality norm for the CPI-indicator is 80%., Results: The benchmark median CPI and TTI improved between 2015 and 2021 from 37 to 26 days and 37 to 33 days, respectively. Correspondingly, the CPI- and TTI-indicators, respectively, increased from 39% to 64% and 35% to 40% in 2015 to 2021. Outcomes for all hospitals improved and dispersion between hospitals declined. Four hospitals exceeded the 80% quality norm in 2021., Conclusion: Waiting times improved gradually over time, with 4 hospitals exceeding the quality standard in 2021. On the hospital-level, process improvement plans have been initiated. Systematic registration, auditing, and feedback of data support the improvement of quality of care., (© 2023 The Authors. Otolaryngology-Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Background: Patients with head and neck squamous cell carcinoma (HNSCC) enter the palliative phase when cure is no longer possible or when they refuse curative treatment. The mean survival is five months, with a range of days until years. Realistic prognostic counseling enables patients to make well-considered end-of-life choices. However, physicians tend to overestimate survival. The aim of this study was to develop a prognostic model that calculates the overall survival (OS) probability of palliative HNSCC patients., Methods: Patients diagnosed with incurable HNSCC or patients who refused curative treatment for HNSCC between January 1st 2006 and June 3rd 2019 were included (n = 659). Three patients were lost to follow-up. Patients were considered to have incurable HNSCC due to tumor factors (e.g. inoperability with no other curative treatment options, distant metastasis) or patient factors (e.g. the presence of severe comorbidity and/or poor performance status).Tumor and patients factors accounted for 574 patients. An additional 82 patients refused curative treatment and were also considered palliative. The effect of 17 candidate predictors was estimated in the univariable cox proportional hazard regression model. Using backwards selection with a cut-off P-value < 0.10 resulted in a final multivariable prediction model. The C-statistic was calculated to determine the discriminative performance of the model. The final model was internally validated using bootstrapping techniques., Results: A total of 647 patients (98.6%) died during follow-up. Median OS time was 15.0 weeks (95% CI: 13.5;16.6). Of the 17 candidate predictors, seven were included in the final model: the reason for entering the palliative phase, the number of previous HNSCC, cT, cN, cM, weight loss in the 6 months before diagnosis, and the WHO performance status. The internally validated C-statistic was 0.66 indicating moderate discriminative ability. The model showed some optimism, with a shrinkage factor of 0.89., Conclusion: This study enabled the development and internal validation of a prognostic model that predicts the OS probability in HNSCC patients in the palliative phase. This model facilitates personalized prognostic counseling in the palliative phase. External validation and qualitative research are necessary before widespread use in patient counseling and end-of-life care., (© 2024. The Author(s).)

Purpose: Decision models can be used to support allocation of scarce surgical resources. These models incorporate health-related quality of life (HRQoL) values that can be determined using physician panels. The predominant opinion is that one should use values obtained from citizens. We investigated whether physicians give different HRQoL values to citizens and evaluate whether such differences impact decision model outcomes., Methods: A two-round Delphi study was conducted. Citizens estimated HRQoL of pre- and post-operative health states for ten surgeries using a visual analogue scale. These values were compared using Bland-Altman analysis with HRQoL values previously obtained from physicians. Impact on decision model outcomes was evaluated by calculating the correlation between the rankings of surgeries established using the physicians' and the citizens' values., Results: A total of 71 citizens estimated HRQoL. Citizens' values on the VAS scale were - 0.07 points (95% CI - 0.12 to - 0.01) lower than the physicians' values. The correlation between the rankings of surgeries based on citizens' and physicians' values was 0.96 (p < 0.001)., Conclusion: Physicians put higher values on health states than citizens. However, these differences only result in switches between adjacent entries in the ranking. It would seem that HRQoL values obtained from physicians are adequate to inform decision models during crises., (© 2023. The Author(s).)

Objective: Since the implementation of value-based healthcare, there has been a growing emphasis on utilizing patient-reported experience measures (PREMs) to enhance the quality of care. However, the current PREMs are primarily generic and static, whereas healthcare is constantly evolving and encompasses a wide variety of aspects that impact care quality. To continuously improve care requires a dynamic PREM. The aim of this study was to propose an item bank for the establishment of a dynamic and care-specific patient-reported evaluation., Methods: In co-creation with patients, a mixed methods study was conducted involving: (1) an explorative review of the literature, (2) a focus group analysis with (ex-)patients, (3) qualitative analyses to formulate themes, and (4) a quantitative selection of items by patients and experts through prioritization., Results: Eight existing PREMs were evaluated. After removing duplicates, 141 items were identified. Through qualitative analyses of the focus group in which the patient journey was discussed, eight themes were formulated: "Organization of healthcare," "Competence of healthcare professionals," "Communication," "Information & services," "Patient empowerment," "Continuity & informal care," "Environment," and "Technology." Seven patients and eleven professionals were asked to prioritize what they considered the most important items. From this, an item bank with 76 items was proposed., Conclusion: In collaboration with patients and healthcare professionals, we have proposed a PREM-item bank to evaluate the experiences of patients' receiving cancer care in an outpatient clinic. This item bank is the first step to dynamically assess the quality of cancer care provided in an outpatient setting., (© 2024. The Author(s).)

Objective: Early-stage glottic cancer (ESGC) is a malignancy of the head and neck. Besides disease control, preservation and improvement of voice quality are essential. To enable expectation management and well-informed decision-making, patients should be sufficiently counseled with individualized information on expected voice quality. This study aims to develop an individualized dynamic prediction model for patient-reported voice quality. This model should be able to provide individualized predictions at every time point from intake to the end of follow-up., Study Design: Longitudinal cohort study., Setting: Tertiary cancer center., Methods: Patients treated for ESGC were included in this study (N = 294). The Voice Handicap Index was obtained prospectively. The framework of mixed and joint models was used. The prognostic factors used are treatment, age, gender, comorbidity, performance score, smoking, T-stage, and involvement of the anterior commissure. The overall performance of these models was assessed during an internal cross-validation procedure and presentation of absolute errors using box plots., Results: The mean age in this cohort was 67 years and 81.3% are male. Patients were treated with transoral CO 2 laser microsurgery (57.8%), single vocal cord irradiation up to (24.5), or local radiotherapy (17.5%). The mean follow-up was 43.4 months (SD 21.5). Including more measurements during prediction improves predictive performance. Including more clinical and demographic variables did not provide better predictions. Little differences in predictive performance between models were found., Conclusion: We developed a dynamic individualized prediction model for patient-reported voice quality. This model has the potential to empower patients and professionals in making well-informed decisions and enables tailor-made counseling., (© 2023 The Authors. Otolaryngology-Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Introduction: During the COVID-19 pandemic, prioritizing certain surgical patients became inevitable due to limited surgical capacity. This study aims to identify which factors patients value in priority setting, and to evaluate their perspective on a decision model for surgical prioritization., Methods: We enacted a qualitative exploratory study and conducted semi-structured interviews with N = 15 patients. Vignettes were used as guidance. The interviews were transcribed and iteratively analyzed using thematic analysis., Results: We unraveled three themes: 1) general attitude towards surgical prioritization: patients showed understanding for the difficult decisions to be made, but demanded greater transparency and objectivity; 2) patient-related factors that some participants considered should, or should not, influence the prioritization: age, physical functioning, cognitive functioning, behavior, waiting time, impact on survival and quality of life, emotional consequences, and resource usage; and 3) patients' perspective on a decision model: usage of such a model for prioritization decisions is favorable if the model is simple, uses trustworthy data, and its output is supervised by physicians. The model could also be used as a communication tool to explain prioritization dilemmas to patients., Conclusion: Support for the various factors and use of a decision model varied among patients. Therefore, it seems unrealistic to immediately incorporate these factors in decision models. Instead, this study calls for more research to identify feasible avenues and seek consensus., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 van Alphen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Patients with head and neck squamous cell carcinoma (HNSCC) can develop second primary tumors (SPTs) in the esophagus. Endoscopic screening could lead to detection of SPTs at early stages and improve survival., Methods: We performed a prospective endoscopic screening study in patients with curably treated HNSCC diagnosed between January 2017-July 2021 in a Western country. Screening was performed synchronously (< 6 months) or metachronously (≥ 6 months) after HNSCC diagnosis. Routine imaging for HNSCC consisted of flexible transnasal endoscopy with positron emission tomography/computed tomography or magnetic resonance imaging, depending on primary HNSCC location. The primary outcome was prevalence of SPTs, defined as presence of esophageal high grade dysplasia or squamous cell carcinoma., Results: 202 patients (mean age 65 years, 80.7 % male) underwent 250 screening endoscopies. HNSCC was located in the oropharynx (31.9 %), hypopharynx (26.9 %), larynx (22.2 %), and oral cavity (18.5 %). Endoscopic screening was performed within 6 months (34.0 %), 6 months to 1 year (8.0 %), 1-2 years (33.6 %), and 2-5 years (24.4 %) after HNSCC diagnosis. We detected 11 SPTs in 10 patients (5.0 %, 95 %CI 2.4 %-8.9 %) during synchronous (6/85) and metachronous (5/165) screening. Most patients had early stage SPTs (90 %) and were treated with curative intent with endoscopic resection (80 %). No SPTs in screened patients were detected with routine imaging for HNSCC before endoscopic screening., Conclusion: In 5 % of patients with HNSCC, an SPT was detected with endoscopic screening. Endoscopic screening should be considered in selected HNSCC patients to detect early stage SPTs, based on highest SPT risk and life expectancy according to HNSCC and comorbidities., Competing Interests: The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Patients with oral cavity cancer are almost always treated with surgery. The goal is to remove the tumor with a margin of more than 5 mm of surrounding healthy tissue. Unfortunately, this is only achieved in about 15% to 26% of cases. Intraoperative assessment of tumor resection margins (IOARM) can dramatically improve surgical results. However, current methods are laborious, subjective, and logistically demanding. This hinders broad adoption of IOARM, to the detriment of patients. Here we present the development and validation of a high-wavenumber Raman spectroscopic technology, for quick and objective intraoperative measurement of resection margins on fresh specimens. It employs a thin fiber-optic needle probe, which is inserted into the tissue, to measure the distance between a resection surface and the tumor. A tissue classification model was developed to discriminate oral cavity squamous cell carcinoma (OCSCC) from healthy oral tissue, with a sensitivity of 0.85 and a specificity of 0.92. The tissue classification model was then used to develop a margin length prediction model, showing a mean difference between margin length predicted by Raman spectroscopy and histopathology of -0.17 mm.

Objective: Patients with palliative head and neck cancer experience many symptoms in a short period of time. Longitudinal data on patient-reported outcomes in this phase are lacking. The aim of this study is to use structurally obtained patient-reported outcome data combined with clinical patient data and obtain insight in patient-reported outcomes, survival, circumstances of death, and interventions and treatment during the palliative phase in order to improve the quality of end-of-life care and patient-centered counseling., Study Design: Longitudinal observational cohort study., Setting: Tertiary cancer center., Method: Quality of life was prospectively collected using the European Organization for Research and Treatment of Cancer QLQ-C15-PAL. Tumor- and patient-specific data were retrospectively collected. Descriptive statistics, linear mixed models, and regression analyses were performed., Results: A significant deterioration was found in global health status, physical functioning, fatigue, dyspnea, appetite loss, and constipation over time. However, emotional functioning improved. Median survival was 5.1 months, and only a low percentage of in-hospital death was observed (7.8%). Higher global health status at intake was associated with prolonged survival., Conclusion: Structural measurement of patient-reported outcome together with clinical outcomes provides unique insight, which enables improvement of patient-centered counseling and care., (© 2022 The Authors. Otolaryngology-Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Purpose: The aim of this prospective cohort study was to estimate the relationship between the course of HRQOL in the first 2 years after diagnosis and treatment of head and neck cancer (HNC) and personal, clinical, psychological, physical, social, lifestyle, HNC-related, and biological factors., Methods: Data were used from 638 HNC patients of the NETherlands QUality of life and BIomedical Cohort study (NET-QUBIC). Linear mixed models were used to investigate factors associated with the course of HRQOL (EORTC QLQ-C30 global quality of life (QL) and summary score (SumSc)) from baseline to 3, 6, 12, and 24 months after treatment., Results: Baseline depressive symptoms, social contacts, and oral pain were significantly associated with the course of QL from baseline to 24 months. Tumor subsite and baseline social eating, stress (hyperarousal), coughing, feeling ill, and IL-10 were associated with the course of SumSc. Post-treatment social contacts and stress (avoidance) were significantly associated with the course of QL from 6 to 24 months, and social contacts and weight loss with the course of SumSc. The course of SumSc from 6 to 24 months was also significantly associated with a change in financial problems, speech problems, weight loss, and shoulder problems between baseline and 6 months., Conclusion: Baseline clinical, psychological, social, lifestyle, HNC-related, and biological factors are associated with the course of HRQOL from baseline to 24 months after treatment. Post-treatment social, lifestyle, and HNC-related factors are associated with the course of HRQOL from 6 to 24 months after treatment., (© 2023. The Author(s).)

Many young people are potentially at risk of noise-induced hearing loss due to unsafe use of personal listening devices. The aim of this cross-sectional study was to examine the association of sociodemographic factors and risk behavior with unsafe use of personal listening devices in adolescents to identify a target group for prevention. A smartphone application was developed to objectively measure music listening habits among 314 adolescents with a mean age of 13 years and 7 months (SD ±5 months). Listening habits were characterized as safe or unsafe based on the weekly noise dose. Data on sociodemographic factors and traditional health risk behaviors were obtained by questionnaires. Within the study group, 10.5% of the participants exceeded the 50%, and 4.8% the 100% recommended weekly noise dose. Adolescents with a lower socioeconomic status were more likely to engage in unsafe listening habits as compared to adolescents with a higher socioeconomic status. Additionally, risk behavior was associated with higher odds of having unsafe listening habits as compared to no risk behavior. Age, sex and educational levels were not significantly associated with unsafe listening habits. The findings of the present study indicate that interventions to promote safe listening habits should target adolescents with a lower socioeconomic status and higher risk behavior. Future research is needed to investigate how these adolescents can be motivated to adopt safe listening habits.

Near-infrared (NIR) fluorescence imaging using exogenous fluorescent agents provides whole-field images in real-time to assist the surgeon in the excision of a tumor. Although the method has high sensitivity, the specificity can sometimes be lower than expected. Raman spectroscopy can detect tumors with high specificity. Therefore, a combination of both techniques can be advantageous. A complication that must be addressed is that the NIR spectral region is favored by both techniques for ( in vivo ) tissue analysis. When fluorescence and Raman emissions spectrally overlap, it becomes challenging or impossible to detect the Raman signal. In this paper, by avoiding this overlap, we describe a Raman spectroscopy setup capable of recording high-quality Raman spectra from tissue containing NIR exogenous fluorescent agents. We identify an optimal wavelength interval (900-915 nm) for Raman excitation, which avoids both excitation of fluorescent dyes and Raman signal self-absorption by the tissue. In this way, Raman spectroscopy can be combined with the currently most-used NIR fluorescent dyes. This combined novel setup could pave the way for clinical trials benefiting from both fluorescence imaging and Raman spectroscopy to avoid positive margins in cancer surgery.

Objective: Patient-reported voice quality is an important outcome during counseling in early-stage glottic cancer. However, there is a paucity of adequate longitudinal studies concerning voice outcomes. This study aimed to investigate longitudinal trajectories for patient-reported voice quality and associated risk factors for treatment modalities such as transoral CO 2 laser microsurgery, single vocal cord irradiation, and local radiotherapy., Study Design: A longitudinal observational cohort study., Setting: Tertiary cancer center., Methods: Patients treated for Tcis-T1b, N0M0 glottic cancer were included in this study (N = 294). The Voice Handicap Index was obtained at baseline and during follow-up (N = 1944). Mixed-effects models were used for investigating the different trajectories for patient-reported voice quality., Results: The mean follow-up duration was 43.4 (SD 21.5) months. Patients received transoral CO 2 laser microsurgery (57.8%), single vocal cord irradiation (24.5%), or local radiotherapy (17.5%). A steeper improvement during the first year after treatment for single vocal cord irradiation (-15.7) and local radiotherapy (-12.4) was seen, compared with a more stable trajectory for laser surgery (-6.1). All treatment modalities showed equivalent outcomes during long-term follow-up. Associated risk factors for different longitudinal trajectories were age, tumor stage, and comorbidity., Conclusion: Longitudinal patient-reported voice quality after treatment for early-stage glottic cancer is heterogeneous and nonlinear. Most improvement is seen during the first year of follow-up and differs between treatment modalities. No clinically significant differences in long-term trajectories were found. Insight into longitudinal trajectories can enhance individual patient counseling and provide the foundation for an individualized dynamic prediction model., (© 2023 The Authors. Otolaryngology-Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Cyclin-dependent kinase 2-associated protein 1 (CDK2AP1; also known as deleted in oral cancer or DOC1) is a tumor suppressor gene known to play functional roles in both cell cycle regulation and in the epigenetic control of embryonic stem cell differentiation, the latter as a core subunit of the nucleosome remodeling and histone deacetylation (NuRD) complex. In the vast majority of oral squamous cell carcinomas (OSCC), expression of the CDK2AP1 protein is reduced or lost. Notwithstanding the latter (and the DOC1 acronym), mutations or deletions in its coding sequence are extremely rare. Accordingly, CDK2AP1 protein-deficient oral cancer cell lines express as much CDK2AP1 mRNA as proficient cell lines. Here, by combining in silico and in vitro approaches, and by taking advantage of patient-derived data and tumor material in the analysis of loss of CDK2AP1 expression, we identified a set of microRNAs, namely miR-21-5p, miR-23b-3p, miR-26b-5p, miR-93-5p, and miR-155-5p, which inhibit its translation in both cell lines and patient-derived OSCCs. Of note, no synergistic effects were observed of the different miRs on the CDK2AP1-3-UTR common target. We also developed a novel approach to the combined ISH/IF tissue microarray analysis to study the expression patterns of miRs and their target genes in the context of tumor architecture. Last, we show that CDK2AP1 loss, as the result of miRNA expression, correlates with overall survival, thus highlighting the clinical relevance of these processes for carcinomas of the oral cavity., (© 2023. The Author(s).)

This study aimed at investigating the change in social eating problems from diagnosis to 24 months after primary (chemo)radiotherapy and its associations with swallowing, oral function, and nutritional status, in addition to the clinical, personal, physical, psychological, social, and lifestyle dimensions. Adult patients from the NETherlands QUality of life and BIomedical Cohort (NET-QUBIC) treated with curative intent with primary (chemo)radiotherapy for newly-diagnosed HNC and who provided baseline social eating data were included. Social eating problems were measured at baseline and at 3-, 6-, 12-, and 24-month follow-up, with hypothesized associated variables at baseline and at 6 months. Associations were analyzed through linear mixed models. Included patients were 361 (male: 281 (77.8%), age: mean = 63.3, SD = 8.6). Social eating problems increased at the 3-month follow-up and decreased up to 24 months (F = 33.134, p < 0.001). The baseline-to-24 month change in social eating problems was associated with baseline swallowing-related quality of life (F = 9.906, p < 0.001) and symptoms (F = 4.173, p = 0.002), nutritional status (F = 4.692, p = 0.001), tumor site (F = 2.724, p = 0.001), age (F = 3.627, p = 0.006), and depressive symptoms (F = 5.914, p < 0.001). The 6-24-month change in social eating problems was associated with a 6-month nutritional status (F = 6.089, p = 0.002), age (F = 5.727, p = 0.004), muscle strength (F = 5.218, p = 0.006), and hearing problems (F = 5.155, p = 0.006). Results suggest monitoring social eating problems until 12-month follow-up and basing interventions on patients' features.

Background: p16 INK4a (p16) immunohistochemistry is the most widely used biomarker assay for inferring HPV causation in oropharyngeal cancer in clinical and trial settings. However, discordance exists between p16 and HPV DNA or RNA status in some patients with oropharyngeal cancer. We aimed to clearly quantify the extent of discordance, and its prognostic implications., Methods: In this multicentre, multinational individual patient data analysis, we did a literature search in PubMed and Cochrane database for systematic reviews and original studies published in English between Jan 1, 1970, and Sept 30, 2022. We included retrospective series and prospective cohorts of consecutively recruited patients previously analysed in individual studies with minimum cohort size of 100 patients with primary squamous cell carcinoma of the oropharynx. Patient inclusion criteria were diagnosis with a primary squamous cell carcinoma of oropharyngeal cancer; data on p16 immunohistochemistry and on HPV testing; information on age, sex, tobacco, and alcohol use; staging by TNM 7th edition; information on treatments received; and data on clinical outcomes and follow-up (date of last follow-up if alive, date of recurrence or metastasis, and date and cause of death). There were no limits on age or performance status. The primary outcomes were the proportion of patients of the overall cohort who showed the different p16 and HPV result combinations, as well as 5-year overall survival and 5-year disease-free survival. Patients with recurrent or metastatic disease or who were treated palliatively were excluded from overall survival and disease-free survival analyses. Multivariable analysis models were used to calculate adjusted hazard ratios (aHR) for different p16 and HPV testing methods for overall survival, adjusted for prespecified confounding factors., Findings: Our search returned 13 eligible studies that provided individual data for 13 cohorts of patients with oropharyngeal cancer from the UK, Canada, Denmark, Sweden, France, Germany, the Netherlands, Switzerland, and Spain. 7895 patients with oropharyngeal cancer were assessed for eligibility. 241 were excluded before analysis, and 7654 were eligible for p16 and HPV analysis. 5714 (74·7%) of 7654 patients were male and 1940 (25·3%) were female. Ethnicity data were not reported. 3805 patients were p16-positive, 415 (10·9%) of whom were HPV-negative. This proportion differed significantly by geographical region and was highest in the areas with lowest HPV-attributable fractions (r=-0·744, p=0·0035). The proportion of patients with p16+/HPV- oropharyngeal cancer was highest in subsites outside the tonsil and base of tongue (29·7% vs 9·0%, p<0·0001). 5-year overall survival was 81·1% (95% CI 79·5-82·7) for p16+/HPV+, 40·4% (38·6-42·4) for p16-/HPV-, 53·2% (46·6-60·8) for p16-/HPV+, and 54·7% (49·2-60·9) for p16+/HPV-. 5-year disease-free survival was 84·3% (95% CI 82·9-85·7) for p16+/HPV+, 60·8% (58·8-62·9) for p16-/HPV-; 71·1% (64·7-78·2) for p16-/HPV+, and 67·9% (62·5-73·7) for p16+/HPV-. Results were similar across all European sub-regions, but there were insufficient numbers of discordant patients from North America to draw conclusions in this cohort., Interpretation: Patients with discordant oropharyngeal cancer (p16-/HPV+ or p16+/HPV-) had a significantly worse prognosis than patients with p16+/HPV+ oropharyngeal cancer, and a significantly better prognosis than patients with p16-/HPV- oropharyngeal cancer. Along with routine p16 immunohistochemistry, HPV testing should be mandated for clinical trials for all patients (or at least following a positive p16 test), and is recommended where HPV status might influence patient care, especially in areas with low HPV-attributable fractions., Funding: European Regional Development Fund, Generalitat de Catalunya, National Institute for Health Research (NIHR) UK, Cancer Research UK, Medical Research Council UK, and The Swedish Cancer Foundation and the Stockholm Cancer Society., Competing Interests: Declaration of interests HMe reports grants from UK National Institute of Health research, Cancer Research UK, the UK Medical Research Council, and AstraZeneca; advisory board fees from AstraZeneca, MSD, Merck, Nanobiotix, and Seagen; and is Director of Warwickshire head neck clinic and Docpsert Health. CRL reports a grant from the Dutch Cancer society, consulting fees from Merck & Co, and expenses from the European Head and Neck Society. JPK reports grant funding from MSD (funding for the project Implementation of a German Oropharyngeal Cancer Registry Providing State-of-the-Art-HPV-Diagnostics). Data derived from this project were used in the present study. The funders had no influence on the design of the study, the collection, analysis, or interpretation of the data, the writing of the manuscript, or the decision to publish the results. JPK also declares research grant funding from the European fund for regional development (EFRE) for ImmunPredict (FKZ EFRE EFRE-0801308). LM reports payment to institution from 20200059/Stockholms Läns Landsting. NW reports a grant from Merk, Sharpe, & Dohme (MSD; for the project Implementation of a German Oropharyngeal Cancer Registry Providing State-of-the-Art-HPV-Diagnostics). Data derived from this project were used in the present study. The funders had no influence on the design of the study, the collection, analysis, or interpretation of the data, the writing of the manuscript, or the decision to publish the results. LM is also supported by the Cologne Clinician Scientist Programme, funded by the German Research Council (FI 773/15-1; 50% salary funding for the project Monitoring disease status in patients with oropharyngeal squamous cell carcinoma by detection of cell-free human papillomavirus DNA in liquid biopsies); funding from EFRE (salary funding for the project ImmunPredict FKZ EFRE EFRE-0801308); honoraria for lectures from MSD, and has a patent for CRISPR-based HPV-diagnostics (EP 22197523.8). RHB declares grants from the Dutch Cancer Society to institution; from ZonMW Government to institution; GenMab BV to institution; consulting fees from Nanobiotix; and payment from the Italian Association for Cancer Research as an unpaid board member. SW declares a grant from MSD under the administration of the University of Cologne (for the project Implementation of a German Oropharyngeal Cancer Registry Providing State-of-the-Art-HPV-Diagnostics). Data derived from this project were used in the present study. The funders had no influence on the design of the study, the collection, analysis, or interpretation of the data, the writing of the manuscript, or the decision to publish the results. TD reports a research grant from the Swedish Cancer Foundation. ST reports grants from Merck, Roche, GlaxoSmithKline, Vitro, Hologic, and Seagene and consulting fees from Merck. All other authors declare no other competing interests. HMe is a National Institute for Health Research (NIHR) Senior Investigator. The views expressed in this article are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: To identify risk factors of hearing decline between 9 and 13 years of age. The risk factors examined included sociodemographic, health, and lifestyle-related factors., Methods: This study was embedded within a population-based prospective cohort study from fetal life onwards in the Netherlands. Pure-tone audiometry and tympanometry were performed at the age of 9 and 13 years. The hearing decline was defined as an increase in low-frequency or high-frequency pure-tone average of at least 5 dB in one of both ears. Multivariable logistic regression was performed to examine the association of possible risk factors with hearing decline. The study was conducted from April 2012 to October 2015, and from April 2016 to September 2019., Results: Of the 3,508 participants included, 7.8% demonstrated a hearing decline in the low frequencies, and 11.3% in the high frequencies. Participants who reported alcohol consumption were more likely to have a hearing decline in the low frequencies (OR 1.5, 95% CI 1.1; 2.0). Moreover, a lower educational level was associated with an increased odds of having a hearing decline in the high frequencies (OR 1.4, 95% CI 1.0; 1.8). Age, sex, household income, personal music player use, and body mass index were not associated with hearing decline., Conclusion: Educational level and risky behavior were significantly associated with hearing decline from childhood to early adolescence. The findings of the present study can help in the design of public health interventions to prevent hearing loss at a young age., Level of Evidence: 2 (prospective cohort study) Laryngoscope, 133:389-395, 2023., (© 2022 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: In order to understand how informal caregivers of head and neck cancer (HNC) patients deal with the consequences of the disease, we investigated their self-efficacy and coping style in relation to symptoms of anxiety and depression (distress) and quality of life (QoL) over time. In addition, factors associated with self-efficacy and coping style were investigated., Methods: A total of 222 informal caregivers and their related HNC patients were prospectively followed as part from the multicenter cohort NETherlands QUality of life and Biomedical cohort studies In Cancer (NET-QUBIC). Self-efficacy and coping style were measured at baseline, and distress and QoL at baseline and 3, 6, 12, and 24 months after treatment., Results: Informal caregivers had a high level of self-efficacy comparable with patients. Caregivers used "seeking social support," "passive reacting," and "expression of emotions" more often than patients. Factors associated with self-efficacy and coping were higher age and lower education. Higher self-efficacy was related with better QoL and "active tackling" was associated with less depression symptoms. "Passive reacting" and "expression of emotions" were associated with higher psychological distress and reduced QoL., Conclusion: Among informal caregivers of HNC patients, higher self-efficacy and "active tackling" were associated with better functioning over time, while "passive reacting" and "expression of negative emotions" were associated with worse functioning. Awareness of the differences in self-efficacy skills and coping and their relationship with QoL and psychological distress will help clinicians to identify caregivers that may benefit from additional support that improve self-efficacy and "active tackling" and reduce negative coping styles., (© 2023. The Author(s).)

(1) Background: The aim of this study was to investigate caregiver burden among informal caregivers of head and neck cancer patients, in relation to distress and quality of life (QoL), and the relationship between informal caregivers and patients. (2) Methods: Data of 234 dyads from the multicenter prospective cohort study Netherlands Quality of life and Biomedical Cohort studies in cancer was used. Caregiver burden, psychological distress, global QoL, physical and social functioning were measured from baseline until 24 months after treatment. (4) Conclusions: This prospective cohort study shows the high burden of caring for HNC patients, the impact of this burden and the interaction between caregiver and patient. We suggest that healthcare professionals include caregivers in counseling and support.

Background: The burden of the COVID-19 pandemic resulted in a reduction of available health care capacity for regular care. To guide prioritisation of semielective surgery in times of scarcity, we previously developed a decision model to quantify the expected health loss due to delay of surgery, in an academic hospital setting. The aim of this study is to validate our decision model in a nonacademic setting and include additional elective surgical procedures., Methods: In this study, we used the previously published three-state cohort state-transition model, to evaluate the health effects of surgery postponement for 28 surgical procedures commonly performed in nonacademic hospitals. Scientific literature and national registries yielded nearly all input parameters, except for the quality of life (QoL) estimates which were obtained from experts using the Delphi method. Two expert panels, one from a single nonacademic hospital and one from different nonacademic hospitals in the Netherlands, were invited to estimate QoL weights. We compared estimated model results (disability adjusted life years (DALY)/month of surgical delay) based on the QoL estimates from the two panels by calculating the mean difference and the correlation between the ranks of the different surgical procedures. The eventual model was based on the combined QoL estimates from both panels., Results: Pacemaker implantation was associated with the most DALY/month of surgical delay (0.054 DALY/month, 95% CI: 0.025-0.103) and hemithyreoidectomy with the least DALY/month (0.006 DALY/month, 95% CI: 0.002-0.009). The overall mean difference of QoL estimates between the two panels was 0.005 (95% CI -0.014-0.004). The correlation between ranks was 0.983 (p < 0.001)., Conclusions: Our study provides an overview of incurred health loss due to surgical delay for surgeries frequently performed in nonacademic hospitals. The quality of life estimates currently used in our model are robust and validate towards a different group of experts. These results enrich our earlier published results on academic surgeries and contribute to prioritising a more complete set of surgeries., (© 2022. The Author(s).)

Background: Multidisciplinary decision-making in head and neck cancer care is complex and requires a tradeoff between prolonging survival and optimizing quality of life. To support prognostication and decision-making in head and neck cancer care, an individualized prognostic model for overall survival (OncologIQ) is available., Methods: By quantitative and qualitative research we have studied user value of OncologIQ and its impact on the decision-making process in a multidisciplinary consultation meeting., Results: Healthcare professionals experienced added value upon using prognostic estimates of survival from OncologIQ in half (47.5%) of the measurements. Significant impact on the decision making process was seen when OncologIQ was used for older patients, patients having a WHO performance score ≥ 2, or high tumor stage., Conclusions: The prognostic model OncologIQ enables patient-centered decision-making in a multidisciplinary consultation meeting and was mostly valued in complex patients., (© 2022 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Introduction: Head and neck cancer (HNC) and its treatment often negatively impact swallowing function. The aim was to investigate the course of patient-reported swallowing problems from diagnosis to 3, 6, 12, and 24 months after treatment, in relation to demographic, clinical, and lifestyle factors., Methods: Data were used of the Netherlands Quality of Life and Biomedical Cohort Study in head and neck cancer research (NET-QUBIC). The primary outcome measures were the subscales of the Swallowing Quality of Life Questionnaire (SWAL-QOL). Linear mixed-effects models (LMM) were conducted to investigate changes over time and associations with patient, clinical, and lifestyle parameters as assessed at baseline., Results: Data were available of 603 patients. There was a significant change over time on all subscales. Before treatment, 53% of patients reported swallowing problems. This number increased to 70% at M3 and decreased to 59% at M6, 50% at M12, and 48% at M24. Swallowing problems (i.e., longer eating duration) were more pronounced in the case of female, current smoking, weight loss prior to treatment, and stage III or IV tumor, and were more prevalent at 3 to 6 months after treatment. Especially patients with an oropharynx and oral cavity tumor, and patients receiving (C)RT following surgery or CRT only showed a longer eating duration after treatment, which did not return to baseline levels., Conclusion: Half of the patients with HNC report swallowing problems before treatment. Eating duration was associated with sex, smoking, weight loss, tumor site and stage, and treatment modality, and was more pronounced 3 to 6 months after treatment., (© 2022. The Author(s).)

Psychoneurological symptoms are commonly reported by newly diagnosed head and neck cancer (HNC) patients, yet there is limited research on the associations of these symptoms with biomarkers of stress and inflammation. In this article, pre-treatment data of a multi-center cohort of HNC patients were analyzed using a network analysis to examine connections between symptoms (poor sleep quality, anxiety, depression, fatigue, and oral pain), biomarkers of stress (diurnal cortisol slope), inflammation markers (c-reactive protein [CRP], interleukin [IL]-6, IL-10, and tumor necrosis factor alpha [TNF-α]), and covariates (age and body mass index [BMI]). Three centrality indices were calculated: degree (number of connections), closeness (proximity of a variable to other variables), and betweenness (based on the number of times a variable is located on the shortest path between any pair of other variables). In a sample of 264 patients, poor sleep quality and fatigue had the highest degree index; fatigue and CRP had the highest closeness index; and IL-6 had the highest betweenness index. The model yielded two clusters: a symptoms-cortisol slope-CRP cluster and a IL-6-IL-10-TNF-α-age-BMI cluster. Both clusters were connected most prominently via IL-6. Our findings provide evidence that poor sleep quality, fatigue, CRP, and IL-6 play an important role in the interconnections between psychoneurological symptoms and biomarkers of stress and inflammation in newly diagnosed HNC patients., Competing Interests: The authors declare no conflict of interest.

Background and study aims  Retrospectively, minimally 5% of patients with esophageal squamous cell carcinoma (ESCC) and 11 % with head and neck squamous cell carcinoma (HNSCC) in Western countries developed a second primary tumor (SPT). SPT screening in ESCC and HNSCC patients is not implemented routinely in daily practice in many Western countries. This study aimed to assess medical specialist knowledge and opinions regarding screening for head and neck SPTs (HNSPTs) in ESCC patients and vice versa in the Netherlands. Methods  A nationwide survey among gastroenterologists and head and neck (HN) surgeons was conducted between December 2020 and March 2021. The survey consisted of 27 questions and focused on knowledge of medical specialists of the prevalence and opinions toward implementing screening for HNSPTs in ESCC patients and vice versa. Results  One hundred twenty-eight gastroenterologists (20.5 %) and 31 HN surgeons (50.0 %) completed the survey. The expected median prevalence of HNSPTs in ESCC was 7.0 % (interquartile range [IQR]: 5.0-15.0) among gastroenterologists and 5.0 % (IQR:3.0-8.0) among HN surgeons. For ESPTs in HNSCC, the expected median prevalence was 9.5 % (IQR: 5.0-12.0) among gastroenterologists and 4.0 % (IQR: 2.0-5.0) among HN surgeons. Screening for HNSPTs and ESPTs was considered promising by 35.2 % and 39.6 %, respectively, which increased to 54.7 % of the specialists after providing incidence data on SPTs. Of the HN surgeons, 41.3 % felt they were as capable as gastroenterologists of performing esophageal screening. Conclusions  This Dutch nationwide survey revealed a lack of knowledge and different perspectives among specialists about screening to detect SPTs in ESCC and HNSCC patients. Adequate education seems essential to increase awareness among specialists and improve SPT detection, independent of the need for implementation of screening for SPTs in ESCC and HNSCC patients., Competing Interests: Competing interests Dr. Bruno received research support from and is consultant for Boston Scientific, Cook Medical, InterScope, Mylan, 3 M and Pentax Medical. Dr. Spander received research support from Medtronics, Boston Scientific, Norgine, Informed, Sentinel and Sysmex. Dr. Koch received research support from DrFalk Pharma and consultancy fees from ERBE Elektromedizin and Pentax Medical., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)