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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. [ABSTRACT FROM AUTHOR]

The PEARL study is a phase 2 multi-centre trial for good prognosis HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) patients, currently open in the UK. PEARL is investigating the dosimetric impact of re-planning a radical radiotherapy plan midway through a course of treatment, based upon the biological response of the primary GTV on 18 FDG PET-CT. With the wider availability of proton beam therapy in the form of Intensity Modulated Proton Therapy (IMPT) as a potential option for radiotherapy in the management of OPSCC, in addition to substantial cost implications, improving methods to determine the patients who will benefit most from IMPT is required. The organ sparing benefits of IMPT are well documented. This modelling planning study investigated whether the benefits of proton therapy can be improved by applying biological response-based adaptation as per the PEARL study planning method. Objectives: 1. Investigate the dosimetric impact of IMPT by comparing mean dose received by swallowing OARs (SWOARs) between non-adaptive VMAT and non-adapted IMPT plans 2. Investigate the dosimetric impact of adaptation by comparing dose received by SWOARs between non-adaptive IMPT and adapted IMPT plans 3. Investigate the relative dosimetric impact of adaptation by comparing dose received by SWOARs between adaptive VMAT and IMPT plans 4. Identify whether adaptation as per the PEARL Study protocol would influence the delta normal tissue complication probability (ΔNTCP) threshold for proton beam therapy funding in The Netherlands Anonymized patient datasets were used to model VMAT and IMPT plans using RayStation and optimised for SWOARs. The following plans were generated: 1. 'NON-ADAPTIVE': Manually planned non-adapted VMAT 2. 'ADAPTIVE': Manually planned adapted VMAT 3. 'NON-ADAPTIVE_PROTON': Manually planned non-adapted IMPT 4. 'ADAPTIVE_PROTON': Manually planned adapted IMPT NTCP calculations for dysphagia risk we performed using the validated dysphagia model described by Christianen et al (1). Individual calculations were performed on each case comparing adapted and non-adapted VMAT plans to non-adapted IMPT plans to explore whether they reached the threshold for proton beam treatment funding as per The Netherlands scheme. Mean dose to the superior pharyngeal constrictor muscle and the supraglottis was entered into the following calculation: 1/NTCP = (1+ e)– s where s = -6.09 + (mean dose to the superior pharyngeal constrictor muscle x 0.057) + (mean dose to the supraglottis × 0.037) All cases had a reduction in their total mean dose to SWOARs, adapted as per PEARL, and planned with IMPT. The magnitude of impact was ranked in the same order for all cases, with optimisation reducing the total mean dose the least, and adapted IMPT the most. Cases 1 and 2, and Cases 3 and 4, demonstrated similar total mean dose reductions despite having different degrees of biological GTV reduction on the iPET-CT. Adaptation had the greatest impact on Cases 2 and 3 for both VMAT and IMPT plans. [Display omitted] The NTCP differences between non-adaptive VMAT plans and non-adaptive IMPT plans were >10% suggesting these cases would be candidates for IMPT funding as as per the National Indication Protocol Proton therapy (NIPP) - head and neck cancer criteria in The Netherlands. Whilst primarily limited by the small number of cases, we have demonstrated that IMPT markedly reduces doses to SWOARs compared to VMAT planning in line with widely published studies. We have also demonstrated that adaptation based on the biological response to the tumour after 2 weeks of chemoradiotherapy can further improve the tissue sparing already achieved with IMPT. This is the first study to demonstrate that SWOAR sparing by IMPT can be improved with biological response guided adaptive radiotherapy. Our results are in line with published data that IMPT can spare many head and neck SWOARs to a greater extent than VMAT in the treatment of oropharyngeal cancers. In the cases studied here, the impact of IMPT on the mean dose to SWOARs was greater than the impact of adaptation, when compared to standard VMAT planning. However, there may be additional dosimetric benefit when IMPT is adapted to tumour response during a course of radiotherapy treatment, particularly dose to more caudal SWOARs. In this small cohort, adaptation on VMAT plans was unlikely to have affected a decision for IMPT treatment as per the Netherlands NTCP-based algorithm. Further work with a larger cohort of patients, as well as real-time studies to collect prospective clinical data on xerostomia and dysphagia rates, is required to properly investigate the clinical advantages of adaptive IMPT. [ABSTRACT FROM AUTHOR]

Simple Summary: All patients suspected of having head and neck paragangliomas (HNPGLs) undergo magnetic resonance imaging (MRI) or computed tomography (CT) of the head and neck area as the standard imaging according to the Dutch guidelines. However, a relatively new imaging modality, [68Ga]Ga-DOTATOC PET/CT, has shown promising results in the detection of HNPGLs. In this pilot study, we aimed to compare the results of this new modality with the standard imaging. We compared both techniques in 25 patients at the University Medical Center Utrecht, The Netherlands. Twenty-eight percent of the patients had different outcomes between both modalities. In all cases, additional HNPGLs were identified using the [68Ga]Ga-DOTATOC PET/CT, suggesting the need for further prospective research to validate this finding. If confirmed, this modality could potentially be implemented as the standard of care for HNPGL detection in germline variant carriers. The Dutch guideline for patients suspected of head and neck paragangliomas (HNPGLs) recommends magnetic resonance imaging (MRI) and/or computed tomography (CT) of the head and neck area. Additionally, it suggests considering additional nuclear imaging. The aim of this study was to evaluate the outcomes of [68Ga]Ga-DOTATOC PET/CT compared to MRI in patients with suspected HNPGLs and carriers of genetic variations. Methods: In this single-center pilot study, retrospective data were obtained from consecutive patients between 2016 and 2023. Both MRI and [68Ga]Ga-DOTATOC PET/CT were performed within 12 months. The primary outcome was the location of HNPGLs. Results: A total of 25 consecutive patients were included, and 7 patients (28.0%, p = 0.5) showed differences between the imaging modalities, of whom 5 patients had unexpected localizations with additional uptake by somatostatin receptors (SSTR) on the [68Ga]Ga-DOTATOC PET/CT. Conclusions: The authors recommend performing baseline imaging with [68Ga]Ga-DOTATOC PET/CT (if available) in variant carriers and using MRI/CT for follow-up according to the regional protocol, thereby shifting the gold standard for baseline imaging from MRI/CT to [68Ga]Ga-DOTATOC PET/CT. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to quantify sentence-level articulatory kinematics in individuals treated for oral squamous cell carcinoma (ITOC) compared to control speakers while also assessing the effect of treatment site (jaw vs. tongue). Furthermore, this study aimed to assess the relation between articulatory-kinematic measures and self-reported speech problems. Method: Articulatory-kinematic data from the tongue tip, tongue back, and jaw were collected using electromagnetic articulography in nine Dutch ITOC and eight control speakers. To quantify articulatory kinematics, the two-dimensional articulatory working space (AWS; in mm² ), one-dimensional anteroposterior range of motion (AP-ROM; in mm), and superior-inferior range of motion (SIROM in mm) were calculated and examined. Self-reported speech problems were assessed with the Speech Handicap Index (SHI). Results: Compared to a sex-matched control group, ITOC showed significantly smaller AWS, AP-ROM, and SI-ROM for both the tongue tip and tongue back sensor, but no significant differences were observed for the jaw sensor. This pattern was found for both individuals treated for tongue and jaw tumors. Moderate nonsignificant correlations were found between the SHI and the AWS of the tongue back and jaw sensors. Conclusions: Despite large individual variation, ITOC showed reduced one- and two-dimensional tongue, but not jaw, movements compared to control speakers and treatment for tongue and jaw tumors resulted in smaller tongue movements. A larger sample size is needed to establish a more generalizable connection between the AWS and the SHI. Further research should explore how these kinematic changes in ITOC are related to acoustic and perceptual measures of speech. [ABSTRACT FROM AUTHOR]

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

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

The Provox Vega High Performance (PVHP) is a newly developed voice prosthesis (VP) with an aim to achieve a longer and more predictable lifetime. This feasibility study aims to assess patient acceptance of the PVHP VP, evaluate adverse events, voice quality, and device lifetime. Laryngectomized patients previously using a Provox Vega or ActiValve Light were included. Acceptance and voice outcomes were evaluated at two-time points with a 2-week interval. Baseline measurements were taken with the standard VP, followed by placement of the PVHP for the 2-week assessment. Fifteen participants completed the study, with thirteen being initial Vega-users. PVHP acceptance was 87% 2 weeks after placement. Median device lifetime for all VPs was 64 d (range 14–370). In the subgroup without periprosthetic leakage, the median device lifetime was 101 d (range 31–370). Acceptance dropped to 40% after device failure. Voice quality did not differ between PVHP and baseline VP. The most reported adverse event was PVHP valve stickiness (46%). Acceptance of the PVHP is largely dependent on device lifetime, decreasing from 87% to 40% after leakage or replacement. Voice quality remains consistent across different VPs. Developing a long-lasting VP remains a challenge. [ABSTRACT FROM AUTHOR]

Simple Summary: Social eating problems may affect lives of people with head and neck cancer (HNC) during and after (chemo)radiotherapy treatment. This study aimed at investigating if people with HNC experience social eating problems from diagnosis up to 24 months after (chemo)radiotherapy and if their change over time is associated with swallowing, oral function, and nutritional status, in addition to the clinical, personal, physical, psychological, social, and lifestyle dimensions. We found that social eating problems worsened three months after treatment and improved to baseline levels up to 24 months. The change in social eating problems over time was associated with swallowing, nutritional status, tumor subsite, age, muscle strength, hearing problems, and depressive symptoms. Results are relevant to research and clinical practice for improving personalized supportive care targeting social eating problems. 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Proton therapy delivers more precise treatment compared with conventional radiotherapy. While this innovation entails investment costs, the information about the treatment costs per patient is limited. This information gap might prevent policymakers from making informed decisions. This study aims to calculate the costs of Proton therapy at a single center during the start-up phase and to provide essential information for the health technology assessment of proton therapy. The total cost of proton therapy varied between EUR 12,062 for eye melanoma and EUR 89,716 for head and neck cancer. Overall, indirect costs were the most significant cost component. The high indirect costs implied the potential of the scale of economics; according to our estimation, the treatment cost could be reduced to 35% of the current cost when maximum treatment capacity is achieved. Nevertheless, to have an estimation that reflects the matured cost of proton therapy which could be used in cost-effectiveness analysis, a follow-up study assessing the full-fledged situation is recommended. However, this study provided insights into the financial situation of a new proton therapy center during its ramp-up period and laid the first stone for future costing studies. Background: Proton therapy (PT) has characteristics that enable the sparing of healthy, non-cancerous tissue surrounding the radiotherapy target volume better from radiation doses than conventional radiotherapy for patients with cancer. While this innovation entails investment costs, the information about the treatment costs per patient, especially during the start-up phase, is limited. This study aims to calculate the costs of PT at a single center during the start-up phase in the Netherlands. Methods: The cost of PT per patient was estimated for the treatment indications, head and neck cancer, breast cancer, brain cancer, thorax cancer, chordoma and eye melanoma. A time-driven activity-based costing analysis (TDABC), a methodology that calculates the costs of consumed healthcare resources by a patient, was conducted in a newly established PT center in the Netherlands (HPTC). Both direct (e.g., the human resource costs for medical staff) and indirect costs (e.g., the operating/interest costs, indirect human resource costs and depreciation costs) were included. A scenario analysis was conducted for short-term (2021), middle-term (till 2024) and long-term (after 2024) predicted patient numbers in the PT center. Results: The total cost of PT in 2020 at the center varied between EUR 12,062 for an eye melanoma course and EUR 89,716 for a head and neck course. Overall, indirect costs were the largest cost component. The high indirect costs implied the potential of the scale of economics; according to our estimation, the treatment cost could be reduced to 35% of the current cost when maximum treatment capacity is achieved. Conclusion: This study estimated the PT cost delivered in a newly operated treatment center. Scenario analysis for increased patient numbers revealed the potential for cost reductions. Nevertheless, to have an estimation that reflects the matured cost of PT which could be used in cost-effectiveness analysis, a follow-up study assessing the full-fledged situation is recommended. [ABSTRACT FROM AUTHOR]

Simple Summary: Hearing loss (HL) can be a side effect of paediatric cancer treatment and can be caused by chemotherapy but also local therapies such as radiotherapy and/or surgery of the head and neck region. In this study, the frequency and patterns of HL were assessed in survivors of head and neck rhabdomyosarcoma (HNRMS). Our secondary aim was to look into the dose–effect relationship between radiotherapy dose on the cochlea and the presence of HL. Forty-nine survivors of HNRMS were included in this study, forty-two of them underwent audiological evaluation. HL was found in up to 19% of the survivors. Four survivors had low frequencies HL with normal hearing or milder HL in the higher frequencies. In our series, HL (≥Muenster 2b) was significantly associated with the maximum cochlear irradiation dose (p = 0.047). More research is needed on HL patterns in HNRMS survivors and on the radiotherapy dose–effect relationship. Purpose: The frequency and patterns of HL in a HNRMS survivor cohort were investigated. A dose–effect relationship between the dose to the cochlea and HL was explored. Methods: Dutch survivors treated for HNRMS between 1993 and 2017 with no relapse and at least two years after the end of treatment were eligible for inclusion. The survivors were evaluated for HL with pure-tone audiometry. HL was graded according to the Muenster, Common Terminology Criteria for Adverse Events (CTCAE) v4.03 and International Society for Paediatric Oncology (SIOP) classification. We defined deleterious HL as Muenster ≥ 2b, CTCAE ≥ 2, and SIOP ≥ 2. Mixed-effects logistic regression was used to search for the dose–effect relationship between the irradiation dose to the cochlea and the occurrence of HL. Results: Forty-two HNRMS survivors underwent pure-tone audiometry. The Muenster, CTCAE and SIOP classification showed that 19.0% (n = 8), 14.2% (n = 6) and 11.9% (n = 5) of survivors suffered from HL, respectively. A low-frequency HL pattern with normal hearing or milder hearing loss in the higher frequencies was seen in four survivors. The maximum cochlear irradiation dose was significantly associated with HL (≥Muenster 2b) (p = 0.047). In our series, HL (≥Muenster 2b) was especially observed when the maximum dose to the cochlea exceeded 19 Gy. Conclusion: HL occurred in up to 19% of survivors of HNRMS. More research is needed on HL patterns in HNRMS survivors and on radiotherapy dose–effect relationships. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Although, the 8th edition TNM (TNM8) significantly improved risk stratification of HPV-positive oropharyngeal carcinoma (HPV+ OPC) compared to the 7th edition TNM (TNM7) which was agnostic to tumor HPV status, undesirable heterogeneity still exists within each N category of the TNM8 classification, especially in cN1 disease. Compelling evidence suggests that image-identified extranodal extension (iENE) is prognostic in HPV+ OPC. The International Collaboration of Oropharyngeal cancer Network evaluated its role in refining the TNM8 cN classification in HPV+ OPC (ICON-N-HPV+). Curative-intent HPV+ OPC from 4 institutions in Canada, USA, and the Netherlands were included. cN+ patients were randomly allocated to Training (60%) and Validation (40%) datasets. All cases were staged according to TNM8. Pre-treatment (within 8 weeks of treatment commencement) CT/MRI were reviewed by radiologists for presence/absence of iENE (iENE+/iENE–) and other nodal features, including total lymph node (LN) number, laterality of neck nodes, presence of retropharyngeal LN [RPLN]) using a priori definition. Multivariable analysis (MVA) employing a step-wise approach evaluated the prognostic value of iENE and other nodal features for overall survival (OS) in cN+ patients in both Training and Validation datasets, adjusted for age, smoking, T-categories, N-categories, and treatment. We used the adjusted hazard ratio (AHR) and recursive-partitioning analysis (RPA) methods to derive cN-classifications that included nodal features that were significant in MVA. We evaluated the performance of stage schemas using the refined cN-classifications (including cN0) against TNM8 for hazard consistency, hazard discrimination, outcome prediction, and sample size balance. A total of 1898 cN+ (1139 Training; 759 Validation) and 155 cN0 patients were included. iENE+ patients accounted for 37% (710/1898) of cN+ patients. The Training dataset contained 435 (38%) iENE+ and 704 (62%) iENE– cases. iENE positivity increased with higher cN categories: 33% in N1, 43% in N2, and 82% in N3 diseases. Median follow-up was 5.1 years. The iENE+ cohort (vs iENE–) had inferior 5-year OS (69% vs 86%) vs iENE–. MVA confirmed that iENE was prognostic for both Training (Hazard ratio [HR] 2.72) and Validation (HR 1.90) datasets (p<0.001). RPLN and LN number (5+ vs 1-4) were also significant in univariable analysis but non-significant in MVA. We proposed to reclassify iENE+ cases one-stratum higher than that of the existing TNM8 cN, while iENE– either remained as TNM8 cN categories based on AHR model. To evaluate the performance of the stage schemas on OS and DFS, we reassembled cN+ and cN0 patients to create various stage groupings combining the T-categories with TNM8-N, AHR_N, and RPA_N schemas, respectively. The performance of stage grouping with AHR_N and RPA_N were similarly better than that of TNM8 for OS in both Training (1.23 and 1.17 vs 3.03) and Validation (0.85 and 0.37 vs 4.06) datasets. The 5-year OS for the entire cohort by TNM8 stage I/II/III were 89%/80%/62%, by AHR stage I/II/III were 92% vs 83% vs 64%, and by RPA stage I/II/III were 91%/81%/63%. These survival changes are evident in the relocation of higher risk disease with iENE to the higher stage groupings defined by the AHR_N and RPA_N models. This ICON-N-HPV+ study confirms the prognostic importance of iENE. We propose that iENE+ patients be reclassified one-stratum higher in the N categorization (similar to pN classification in HPV-negative head and neck cancer) while iENE– cases could either remain as per TNM-8 cN (AHR cN schema) or be amalgamated to form a new N1 (RPA cN schema) with consequent modification of the TNM stage groups. Since the AHR2 cN schema retains the TNM8 cN framework and is also consistent with current pN classification for non-viral head and neck cancer, it may be a more practical and less complicated proposal. T1-2_cN+_iENE– patients are potentially more appropriate candidates for deintensification trials while new strategies are needed to address the high risk of disease progression in iENE+ patients. [ABSTRACT FROM AUTHOR]

Patients with metastatic esophagogastric cancer present in 25% with oligometastatic disease. Local treatment of OMD plus systemic therapy was associated with long-term overall survival. [Display omitted] • Patients with metastatic esophagogastric cancer present in 25% with oligometastatic disease (OMD). • Local treatment or systemic therapy for OMD improved overall survival (OS). • OS after local plus systemic therapy was better compared with local or systemic therapy. • Randomized controlled trials are warranted to confirm these results. This multicenter study assessed the incidence and survival of patients with esophagogastric cancer and oligometastatic disease (OMD) in two tertiary referral cancer centers in The Netherlands and Switzerland. Between 2010 and 2021, patients with metastatic esophagogastric cancer were identified. Patients with de-novo OMD were included (first-time diagnosis of ≤5 distant metastases on 18F-FDG-PET/CT). Control of the primary tumor was considered in patients who underwent primary tumor resection or definitive chemoradiotherapy without locoregional recurrence. Treatment of OMD was categorized into (1) systemic therapy, (2) local treatment (stereotactic body radiotherapy or metastasectomy), (3) local plus systemic therapy, or (4) best supportive care. The primary outcomes were overall survival (OS) and independent prognostic factors for OS. Independent prognostic factors for OS were analyzed using multivariable Cox proportional hazard models. In total, 830 patients with metastatic esophagogastric cancer were identified of whom 200 patients with de-novo OMD were included (24%). The majority of included patients had esophageal cancer (73%) with adenocarcinoma histology (79%) and metachronous OMD (52%). The primary tumor was controlled in 68%. Treatment of OMD was systemic therapy (25%), local treatment (43%), local plus systemic therapy (13%), or best supportive care (18%). Median follow-up was 14 months (interquartile range: 7–27). Median OS was 16 months (95% CI: 13–21). Improved OS was independently associated with local plus systemic therapy compared with systemic therapy alone (hazard ratio [HR] 0.47, 95% confidence interval [CI]: 0.25–0.87). Worse OS was independently associated with squamous cell carcinoma (HR 1.70, 95% CI: 1.07–2.74), bone oligometastases (HR 2.44, 95% CI: 1.28–4.68), brain oligometastases (HR 1.98, 95% CI: 1.05–4.69), and two metastatic locations (HR 2.07, 95% CI: 1.04–4.12). Median OS after local plus systemic therapy was 35 months (95% CI: 22-NA) as compared with 13 months (95% CI: 9–21, p < 0.001) after systemic therapy alone for OMD. Patients with metastatic esophagogastric cancer present in 25% with de-novo OMD. Local treatment of OMD plus systemic therapy was independently associated with long-term OS and independently improved OS when compared with systemic therapy alone. Randomized controlled trials are warranted to confirm these results. [ABSTRACT FROM AUTHOR]

Objective: Patients with cancer can experience emotional consequences of reduced ability to eat, their impact is unknown. This study assesses the impact of these emotional consequences, and patients' satisfaction with healthcare professionals' (HCPs) support. Methods: A cross‐sectional survey was conducted among patients with head/neck, lung cancer and lymphoma, who experienced reduced ability to eat in the past year. Patients were recruited through patient organisations and hospitals. The questionnaire encompassed the impact of emotional consequences of reduced ability to eat (scale 1–10) and satisfaction with HCPs' support for reduced ability to eat (scale 1–10). The differences in patient characteristics between unsatisfied (Score < 6) and satisfied patients (score ≥6) were tested using independent t‐tests and the chi‐square or Fishers' exact tests. Results: Overall, 116 patients (48%) responded and 98 were included in the analyses. The most impactful emotional consequences were as follows: disappointment (mean ± SD: 8.31 ± 1.49), grief/sadness (7.90 ± 1.91), and anger (7.87 ± 1.41). Patients were less satisfied when more time had passed since their diagnosis (p < 0.002) and when they expected no improvements regarding their eating problems (p < 0.001). Conclusion: The impact of emotional consequences of reduced ability to eat is high. Support for emotional consequences is needed, especially for patients with reduced ability to eat, which persists in recovery and remission. [ABSTRACT FROM AUTHOR]

• The head and neck cancer incidence was nearly 25% less during the first COVID wave. • The lower incidence was mainly observed in oral cavity and laryngeal cancer. • During COVID, tumor stage and treatment distribution did not differ. • The expected increase in incidence during the remainder of 2020 was not observed. • Time-to-treatment was significantly shorter, regardless of first treatment modality. Inevitably, the emergence of COVID-19 has impacted non-COVID care. Because timely diagnosis and treatment are essential, especially for patients with head and neck cancer (HNC) with fast-growing tumours in a functionally and aesthetically important area, we wished to quantify the impact of the COVID-19 pandemic on HNC care in the Netherlands. This population-based study covered all, in total 8468, newly diagnosed primary HNC cases in the Netherlands in 2018, 2019 and 2020. We compared incidence, patient and tumour characteristics, primary treatment characteristics, and time-to-treatment in the first COVID-19 year 2020 with corresponding periods in 2018 and 2019 (i.e. pre-COVID). The incidence of HNC was nearly 25% less during the first wave (n = 433) than in 2019 (n = 595) and 2018 (n = 598). In April and May 2020, the incidence of oral cavity and laryngeal carcinomas was significantly lower than in pre-COVID years. There were no shifts in tumour stage or alterations in initial treatment modalities. Regardless of the first treatment modality and specific period, the median number of days between first visit to a HNC centre and start of treatment was significantly shorter during the COVID-19 year (26–28 days) than pre-COVID (31–32 days, p < 0.001). The incidence of HNC during the Netherlands' first COVID-19 wave was significantly lower than expected. The expected increase in incidence during the remainder of 2020 was not observed. Despite the overloaded healthcare system, the standard treatment for HNC patients could be delivered within a shorter time interval. [ABSTRACT FROM AUTHOR]

In this presentation, the following topics will be addressed: • Changes in health related quality of life over time from time of diagnosis to 2 years after treatment • Health related quality of life in relation to survival • What is the role of personal, clinical, biological, physical, psychological, social, lifestyle, and HNC-related factors? Data was used of The NETherlands QUality of life and BIomedical Cohort study in head and neck cancer (HNC) (NET-QUBIC) a prospective cohort study including 739 HNC patients and 262 informal caregivers. NET-QUBIC comprises a Data Warehouse and Biobank integrating detailed clinical information and data derived from patient reported outcomes, interviews, and functional tests, and samples of tumour tissue, blood, oral rinse, and saliva. Data and samples are available to researchers worldwide via data releases that are announced on www.kubusproject.nl. In the present study, we used NET-QUBIC data and samples to investigate the course of health related quality of life of HNC patients from diagnosis to 3, 6, 12 and 24 months after treatment. Health related quality of life was operationalised by the EORTC QLQ-C30 global quality of life subscale (2 items) and the summary score. [ABSTRACT FROM AUTHOR]

• The relation between Time to Treatment Initiation (TTI) and overall survival was confirmed with variation among different sites. • Advanced stage oral cavity cancers had a significantly better hazard of dying when the TTI of 37 days was not exceeded. • Head and neck cancer sites are characterized by considerable heterogeneity. To assess whether there are differences in the effects of time to treatment interval (TTI) on patient survival for head and neck cancer (HNC) sites in order to provide evidence that can support decision-making regarding prioritizing treatment. Patients in the Netherlands with a first primary HNC without distant metastasis between 2010 and 2014 were included for analysis (N = 10,486). TTI was defined as the time from pathologic diagnosis to the start of initial treatment. Overall survival (OS), cox regression analyses and cubic spline hazard models were calculated and visualized. Overall, the hazard of dying was higher (HR = 1.003; 95 % CI 1.001–1.005) with each additional day until treatment initiation. The pattern, as visualized in cubic spline graphs, differed by site the hazard increased more steeply with increasing TTI for oral cavity cancer. For oropharyngeal and laryngeal cancer, a slight increase commenced after a longer TTI than for oral cavity cancer, while there was hardly an increase in hazard with increasing TTI for hypopharyngeal cancer. The relationship between longer TTI and decreased survival was confirmed, but slight variations in the pattern of the hazard of dying by TTI by tumour site were observed. These findings could support decisions on prioritizing treatment. However, other aspects such as extent of treatment and quality of life should be investigated further so this can also be included. [ABSTRACT FROM AUTHOR]

Purpose: Proton therapy is a limited resource that is not available to all patients who may benefit from it. We investigated combined proton-photon treatments, in which some fractions are delivered with protons and the remaining fractions with photons, as an approach to maximize the benefit of limited proton therapy resources at a population level.Methods and Materials: To quantify differences in normal-tissue complication probability (NTCP) between protons and photons, we considered a cohort of 45 patients with head and neck cancer for whom intensity modulated radiation therapy and intensity modulated proton therapy plans were previously created, in combination with NTCP models for xerostomia and dysphagia considered in the Netherlands for proton patient selection. Assuming limited availability of proton slots, we developed methods to optimally assign proton fractions in combined proton-photon treatments to minimize the average NTCP on a population level. The combined treatments were compared with patient selection strategies in which patients are assigned to single-modality proton or photon treatments.Results: There is a benefit of combined proton-photon treatments compared with patient selection, owing to the nonlinearity of NTCP functions; that is, the initial proton fractions are the most beneficial, whereas additional proton fractions have a decreasing benefit when a flatter part of the NTCP curve is reached. This effect was small for the patient cohort and NTCP models considered, but it may be larger if dose-response relationships are better known. In addition, when proton slots are limited, patient selection methods face a trade-off between leaving slots unused and blocking slots for future patients who may have a larger benefit. Combined proton-photon treatments with flexible proton slot assignment provide a method to make optimal use of all available resources.Conclusions: Combined proton-photon treatments allow for better use of limited proton therapy resources. The benefit over patient selection schemes depends on the NTCP models and the dose differences between protons and photons. [ABSTRACT FROM AUTHOR]

Purpose: Evidence-based guidelines on how to prevent or treat cetuximab-related skin reactions are lacking and multiple care and management strategies are used. The main purpose of the present study is to gain information about the different skincare products being used against skin reactions in metastatic colorectal cancer (mCRC) and recurrent/metastatic (R/M) or locally advanced (LA) squamous cell cancer of the head and neck (SCCHN) patients treated with cetuximab.Methods: An open-label, prospective observational study conducted in the Netherlands. The occurrence of skin reactions and the care and management options taken were documented for 16 weeks, starting from the first administration of cetuximab.Results: A total of 103 patients were included in 7 hospitals. 38 patients (37%) developed a grade ≥ 2 skin reaction. Eighty-six patients could be analysed for the primary endpoint (73.3% males, mean age 62.4 years, n = 44 LA SCCHN, n = 16 R/M SCCHN, n = 26 mCRC). The most frequently used skin products at some point during the observation period were moisturizing products (70%), systemic antibiotics (64%), topical antibiotics (58%), lipid-regenerating (28%) and other topical products (28%). The overall use of products gradually increased from baseline to week 6-10, reducing by week 16. Hospital protocols were the primary reason (> 50%) for choice of the skincare products and medications.Conclusion: A variety of skin care products and antibiotics were commonly used. Only few patients developed severe cutaneous reactions. For patients, the occurrence of skin reactions did not influence their willingness to continue cetuximab therapy. [ABSTRACT FROM AUTHOR]

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

• Model-based selection of patients with HNC for proton is clinically feasible. • Around 35% of HNC patients qualify for protons. • Most patients are selected based on ΔNTCP in dysphagia-related models. • Patients with advanced and pharyngeal tumor have higher probability to be selected. In the Netherlands, head and neck cancer (HNC) patients qualify for intensity modulated proton therapy (IMPT) based on model-based selection (MBS). The aim of this study was to evaluate the first experience in MBS of HNC patients. Patients who were subjected to MBS (Jan 2018–Sep 2019) were evaluated. A VMAT plan was created for all patients with optimal sparing of organ at risks (OARs) in normal tissue complication probability (NTCP) models for a number of toxicities. An IMPT plan was created only for those with NTCP difference (ΔNTCP) between VMAT and best-case scenario for proton (assuming 0 Gy dose for all OARs in IMPT plan) that exceeded any ΔNTCP-thresholds defined in Dutch National Indication Protocol. These patients qualified for a robust IMPT-plan creation with similar target doses and subsequent plan comparison. Of 227 patients, 141 (62%) qualified for plan comparison, of which 80 (35%) were eventually selected for proton therapy. Most patients were selected based on the ΔNTCP for dysphagia-related toxicities. The selection rate was higher among patients with advanced disease, pharyngeal tumors, and/or baseline complaints. A significant reduction in all OAR doses and NTCP values was obtained with IMPT compared with VMAT in both selected and non-selected patients, but more pronounced in patients selected for protons. Model-based selection of patients with HNC for proton therapy is clinically feasible. Approximately one third of HNC patients qualify for protons and these patients have the highest probability to benefit from protons in terms of toxicity prevention. [ABSTRACT FROM AUTHOR]

Background: Knowledge about the efficacy of behavioural intervention technologies that can be used by cancer survivors independently from a health-care provider is scarce. We aimed to assess the efficacy, reach, and usage of Oncokompas, a web-based eHealth application that supports survivors in self-management by monitoring health-related quality of life (HRQOL) and cancer-generic and tumour-specific symptoms and obtaining tailored feedback with a personalised overview of supportive care options.Methods: In this non-blinded, randomised, controlled trial, we recruited patients treated at 14 hospitals in the Netherlands for head and neck cancer, colorectal cancer, breast cancer, Hodgkin lymphoma, or non-Hodgkin lymphoma. Adult survivors (aged ≥18 years) were recruited through the Netherlands Cancer Registry (NCR) and invited by their treating physician through the Patient Reported Outcomes Following Initial Treatment and Long term Evaluation of Survivorship (PROFILES) registry. Participants were randomly assigned (1:1) by an independent researcher to the intervention group (access to Oncokompas) or control group (access to Oncokompas after 6 months), by use of block randomisation (block length of 68), stratified by tumour type. The primary outcome was patient activation (knowledge, skills, and confidence for self-management), assessed at baseline, post-intervention, and 3-month and 6-month follow-up. Linear mixed models (intention-to-treat) were used to assess group differences over time from baseline to 6-month follow-up. The trial is registered in the Netherlands Trial Register, NTR5774 and is completed.Findings: Between Oct 12, 2016, and May 24, 2018, 625 (21%) of 2953 survivors assessed for eligibility were recruited and randomly assigned to the intervention (320) or control group (305). Median follow-up was 6 months (IQR 6-6). Patient activation was not significantly different between intervention and control group over time (difference at 6-month follow-up 1·7 [95% CI -0·8-4·1], p=0·41).Interpretation: Oncokompas did not improve the amount of knowledge, skills, and confidence for self-management in cancer survivors. This study contributes to the evidence for the development of tailored strategies for development and implementation of behavioural intervention technologies among cancer survivors.Funding: Dutch Cancer Society (KWF Kankerbestrijding). [ABSTRACT FROM AUTHOR]

Purpose: To benchmark and improve, through means of a targeted intervention, the quality of intensity modulated radiation therapy treatment planning for locally advanced head and neck cancer (HNC) in the Netherlands. The short and long-term impact of this intervention was assessed.Methods and Materials: A delineated computed tomography-scan of an oropharynx HNC case was sent to all 15 Dutch radiation therapy centers treating HNC. Aims for planning target volume and organ-at-risk (OAR) dosimetry were established by consensus. Each center generated a treatment plan. In a targeted intervention, OAR sparing of all plans was discussed, and centers with the best OAR sparing shared their planning strategies. Impact of the intervention was assessed by (1) short-term (half a year after intervention) replanning of the original case and (2) long-term (1 and 3 years after intervention) planning of new cases.Results: Benchmarking revealed substantial difference in OAR doses. Initial mean doses were 22 Gy (range, 15-31 Gy), 35 Gy (18-49 Gy), and 37 Gy (20-46 Gy) for the contralateral parotid gland, contralateral submandibular gland, and combined swallowing structures, respectively. Replanning after targeted intervention significantly reduced mean doses and variation, but clinically relevant differences still remained: 18 Gy (14-22 Gy), 28 Gy (17-45 Gy), and 29 Gy (18-39 Gy), respectively. One and 3 years later the variation remained stable.Conclusions: Despite many years of HNC intensity modulated radiation therapy experience, initial treatment plans showed surprisingly large variations. The simple targeted intervention used in this analysis improved OAR sparing, and its impact was durable; however, fairly large dose differences still continue to exist. Additional work is needed to understand these variations and to minimize them. A national radiation oncology platform can be instrumental for developing and maintaining high-quality planning protocols. [ABSTRACT FROM AUTHOR]

• Locally advanced head and neck cancer is defined in various ways. • Netherlands Cancer Registry data show an increase of locally advanced oral and oropharynx cancer. • Standardized rates of locally advanced hypopharynx and larynx cancer have declined recent years. • The proportionate share of locally advanced larynx cancer has increased. • There is an urgent need for standardization of the definition locally advanced head and neck cancer. Several reports have indicated that locally advanced head and neck cancer (LAHNC) has increased in the past decade. However, incidence trends cannot be easily compared because slightly different definitions of LAHNC were used. To investigate if the incidence of locally advanced disease (LAD) in the oral cavity, oropharynx, hypopharynx and larynx is indeed increasing over time, considering the growing and ageing population in the Netherlands. Data were obtained from the Netherlands Cancer Registry (NCR). Primary head and neck squamous cell carcinomas of the oral cavity, oropharynx, hypopharynx and larynx diagnosed between 1989 and 2017 were included. Yearly numbers and European standardized incidence rates (ESRs) were reported by extent of disease. The annual percentage change (APC) over time in ESRs was calculated to assess trends. Absolute numbers and ESRs of LAD increased over time for oral cavity and most prominently for oropharynx carcinomas (before 1996, APC: 0.4, 95%CI: 0.1; 0.8 and APC: 5.7 (95%CI: 3.1; 8.4) after 1996: 1.5 (1.0; 2.0) respectively. For hypopharynx cancer the absolute number and ESR of LAD increased until 1997 and declined with 0.8% per year since 1997. Absolute numbers of patients with larynx cancer stayed stable over time, while ESR decreased (APC: −0.8 (95%CI: −1.1; −0.6)). The perception of an increasing trend in LAD in the Netherlands can be attributed to the increasing incidence of oral cavity and oropharynx carcinomas. For LAD of the hypopharynx a decreasing trend was observed. In larynx cancer, the proportional share of LAD of the larynx increased, even though incidence rates declined. [ABSTRACT FROM AUTHOR]

Purpose: To assess cause-specific mortality in a large population-based cohort of 14,393 patients treated for squamous cell carcinoma of the oral cavity (OC) or oropharynx (OP) in The Netherlands between 1989 and 2006.Patients and Methods: Causes of death were obtained for 94.7% of 9620 patients who had died up to January 1, 2009. We assessed standardized mortality ratios (SMR) and absolute excess mortality (AEM), comparing observed cause-specific mortality with expected mortality for our cohort based on general population mortality rates.Results: Median survival was 3.9 years. Overall, the study population experienced a 6-fold higher (95% Confidence Interval (95% CI) 5.9-6.1) mortality risk compared with the general population. After three years, 41% of OP and 29% of OC patients had died due to cancer of the oral cavity and pharynx. Additionally, OC and OP patients experienced high excess mortality from esophageal (SMR 10.6 and 17.9) and lung cancer (SMR 4.6 and 6.3). With regard to non-cancer deaths, the highest AEMs were due to diseases of the circulatory system, with OC patients experiencing an AEM of 11.3 per 10,000 person-years for ischemic heart disease. OP patients experienced excess mortality due to pneumonia (AEM 22.1 per 10,000 person-years). The risk of death due to diseases of the digestive system was for OP and OC patients where about equal (AEM 28.7 and 23.80, respectively). The SMR for death due to pneumonia was more than two times higher (4.4 vs. 1.7) for OP patients than for OC patients (P<0.001). From 15 years after diagnosis, second tumors located outside the head and neck region accounted for most of the excess mortality.Conclusions: Excess mortality in OC and OP patients appears to be dominated by effects of heavy tobacco and alcohol use with high AEM due to second tumors, respiratory, cardiovascular and gastrointestinal diseases. Patients with OP experienced more than two times higher risk of death due to pneumonia than OC patients. Therefore, awareness of this potential complication should be raised along with development of prevention strategies. [ABSTRACT FROM AUTHOR]

Introduction: The aim was to analyse prognosticators in acinic cell carcinoma (AciCC) in two head and neck referral centers in Amsterdam, the Netherlands.Materials and Methods: Eighty- nine cases of AciCC treated between 1979 and 2016 were retrospectively reviewed. Five, - 10 -and 20- year estimates of survival were executed as well as univariate analysis of prognosticators.Results: The majority of AciCC were T1-T2; 89%. Two percent had nodal disease (2%). The most affected organ was the parotid gland (84%) with a female preponderance (67%). Mean age was 52 years with most cases diagnosed in the fourth to sixth decade. The majority of patients received adjuvant radiotherapy. Elective neck dissection (END) in the N0 neck showed no metastases. High grade transformation (HGT) was found in 21% of cases. Median follow up was 101.9 months. Median time to recurrence was 26 months. Nine patients developed distant metastases (DM) of whom 6 had HGT-AciCC. Median survival with DM was 7 months. Five,- ten -and twenty- year estimates were 84%, 81% and 81% for recurrence free survival respectively. Negative clinical features were advanced stage disease and tumour size > 2.6 cm. Negative histological features were a high mitotic rate, HGT, close and involved surgical margins and necrosis.Conclusion: AciCC- HGT excluded- of the head and neck has an excellent prognosis and shows acceptable long term results. END can be considered as part of the standard treatment due to the relative high incidence of HGT- AciCC and low accuracy of cytology. [ABSTRACT FROM AUTHOR]

Background: Prospective data on alcohol consumption, cigarette smoking and risk of head-neck cancer (HNC) subtypes, i.e. oral cavity cancer (OCC), oro-/hypopharyngeal cancer (OHPC), and laryngeal cancer (LC), are limited. We investigated these associations within the second largest prospective study on this topic so far, the Netherlands Cohort Study. Methods: 120,852 participants completed a questionnaire on diet and other cancer risk factors in 1986. After 17.3 years of follow-up, 395 HNC (110 OCC, 83 OHPC, and 199 LC) cases and 4288 subcohort members were available for case-cohort analysis using Cox proportional hazards models. Results: For total HNC, the multivariable adjusted incidence rate ratio (RR) was 2.74 (95% confidence interval (CI) 1.85-4.06) for those drinking =30 g ethanol/day compared with abstainers; in subtypes, RRs were 6.39 for OCC, 3.52 for OHPC, and 1.54 for LC. Compared with never cigarette smokers, current cigarette smokers had a RR of 4.49 (95% CI 3.11-6.48) for HNC overall, and 2.11 for OCC, 8.53 for OHPC, and 8.07 for LC. A significant, positive, multiplicative interaction between categories of alcohol consumption and cigarette smoking was found for HNC overall (P interaction 0.03). Conclusions: Alcohol consumption and cigarette smoking were independently associated with risk of HNC overall, with a positive, multiplicative interaction. The strength of these associations differed among HNC-subtypes: OCC was most strongly associated with alcohol consumption but most weakly with cigarette smoking, whereas LC was not statistically significantly associated with alcohol consumption. [ABSTRACT FROM AUTHOR]

Background: Prospective data on alcohol consumption, cigarette smoking and risk of head-neck cancer (HNC) subtypes, i.e. oral cavity cancer (OCC), oro-/hypopharyngeal cancer (OHPC), and laryngeal cancer (LC), are limited. We investigated these associations within the second largest prospective study on this topic so far, the Netherlands Cohort Study. Methods: 120,852 participants completed a questionnaire on diet and other cancer risk factors in 1986. After 17.3 years of follow-up, 395 HNC (110 OCC, 83 OHPC, and 199 LC) cases and 4288 subcohort members were available for case-cohort analysis using Cox proportional hazards models. Results: For total HNC, the multivariable adjusted incidence rate ratio (RR) was 2.74 (95% confidence interval (CI) 1.85-4.06) for those drinking =30 g ethanol/day compared with abstainers; in subtypes, RRs were 6.39 for OCC, 3.52 for OHPC, and 1.54 for LC. Compared with never cigarette smokers, current cigarette smokers had a RR of 4.49 (95% CI 3.11-6.48) for HNC overall, and 2.11 for OCC, 8.53 for OHPC, and 8.07 for LC. A significant, positive, multiplicative interaction between categories of alcohol consumption and cigarette smoking was found for HNC overall (P interaction 0.03). Conclusions: Alcohol consumption and cigarette smoking were independently associated with risk of HNC overall, with a positive, multiplicative interaction. The strength of these associations differed among HNC-subtypes: OCC was most strongly associated with alcohol consumption but most weakly with cigarette smoking, whereas LC was not statistically significantly associated with alcohol consumption. [ABSTRACT FROM AUTHOR]

Summary: Objective:: To determine use, appreciation and effectiveness of an electronic health information support system in head and neck (H&N) cancer care. Design:: A prospective evaluation study. The evaluated system has four different functions: (1) communication amongst health care providers and between health care providers and patients, (2) information for health care providers and patients, (3) contact with fellow sufferers and (4) monitoring of discharged patients by means of electronic questionnaires. Evaluation of the system was done both objectively using automatically created log files and stored messages, and subjectively by using paper questionnaires from patients and general practitioners (GPs). Setting:: Department of Otorhinolaryngology and Head and Neck Surgery of a tertiary health care centre in the Netherlands. The system was put at patients’ disposal for a period of 6 weeks following discharge from the hospital after surgery for H&N cancer, and was additional to standard care. Participants:: Head and neck cancer patients, hospital physicians, members of a hospital-based support team, GPs, district nurses and speech therapists. Main outcome measures:: Actual use of the system by patients and health care providers. Patients’ appreciation for each of the system''s four different functions. GPs’ appreciation for the system. Capability to detect potential patient problems with the system. Results:: The system was used by 36 H&N cancer patients, 10 hospital physicians, 2 members of the support team, 8 GPs, 2 district nurses and 2 speech therapists. The total number of patient-sessions was 982: an average of 27.3 sessions per patient during the 6 weeks study period. In total, 456 monitoring questionnaires were completed. The support team in hospital responded with 231 actions. In 16 cases, an extra appointment was made for a patient with the hospital physician. Out of these cases, immediate action was considered necessary eight times. Patients appreciated the system highly, rating it with an average score of 8.0 on a 10-point scale. All patients used the monitoring function, and rated ‘monitoring’ with a mean score of 8.0 on a 10-point scale. Least used and appreciated was the ‘contact with fellow sufferers’ function. Only 8 out of possible 36 GPs used the system, rating it with an average of 5.6 on a 10-point scale. Conclusions:: The electronic health information support system was used intensively and highly appreciated by H&N cancer patients. The system enabled the early detection of occurring health problems that required direct intervention. ICT can play an additional role in the management of patients, also in a relatively elderly and computer illiterate patient population. [Copyright &y& Elsevier]

Following publication of the original article [1], the authors reported the name of R.J. Baatenburg de Jong was incorrectly tagged in the HTML version of the article. [ABSTRACT FROM AUTHOR]

Background: Worldwide, over 500,000 people are diagnosed with head and neck cancer each year, a disease with major impact on life expectancy and quality of life. The purpose of the Netherlands Quality of life and Biomedical Cohort study (NET-QUBIC) is to advance interdisciplinary research that aims to optimize diagnosis, treatment, and supportive care for head and neck cancer patients and their informal caregivers.Methods: Using an extensive assessment protocol (electronic clinical record form, patient reported outcome measures and fieldwork (interviews and physical tests)), clinical data and data on quality of life, demographic and personal factors, psychosocial (depression, anxiety, fatigue, pain, sleep, mental adjustment to cancer, posttraumatic stress), physical (speech, swallowing, oral function, malnutrition, physical fitness, neurocognitive function, sexual function), lifestyle (physical activity, nutrition, smoking, alcohol, drugs), and social factors (social function, social support, work, health care use, and costs) are collected and stored in the data warehouse. A longitudinal biobank is built with tumor tissue, blood and blood components, saliva samples, and oral rinses. An infrastructure for fieldwork and laboratory protocols is established at all participating centers. All patients fill out patient reported outcome measures before treatment and at 3, 6, 12, 24, 36, 48, and 60 months follow-up. The interviews, physical tests and biological sample collection are at baseline and 6, 12, and 24 months follow-up. The protocol for caregivers includes blood sampling and oral rinses at baseline and a tailored list of questionnaires, administered at the same time points as the patients. In total, 739 HNC patients and 262 informal caregivers have been included in 5 out of the 8 HNC centers in the Netherlands.Discussion: By granting access to researchers to the NET-QUBIC data warehouse and biobank, we enable new research lines in clinical (e.g. treatment optimization in elderly patients), biological (e.g. liquid biopsy analysis for relapse detection), health related quality of life (e.g. the impact of toxicity on quality of life), and interrelated research (e.g. health related quality of life in relation to biomarkers and survival). [ABSTRACT FROM AUTHOR]

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

Purpose: HPV-associated cancer in the head-neck region has been reported at high frequencies in certain countries and is considered a separate entity. Since the prevalence of HPV positivity in oropharyngeal squamous cell carcinomas is currently not known in the Northern part of the Netherlands, the aim was to analyze HPV prevalence in oropharyngeal tumours treated at our centre. Material and methods: Based on the Dutch cancer registration, we collected clinical, pathological, and follow-up data and formalin-fixed paraffin embedded samples of a complete cohort of 125 tonsillar and base-of-tongue oropharyngeal tumours treated in our centre from 1997 to 2009. HPV testing was performed using an established algorithm of p16 immunohistochemistry, followed by HPV-PCR of the positive cases. HPV-BRISH was performed as extra control of p16 negative cases. Results: p16 staining could be assessed on 109 cases. 32/109 (29%) were p16+ of these 32 cases 21/32 (66%) were HPV-GP+, 16 cases were found HPV16+ and one HPV18+, three were HPV33+ and one HPV35+. HPV-BRISH showed 83/102 (81%) negativity and 19/102 (19%) positivity. BRISH had a sensitivity of 85% and a specificity of 98%, as only two p16- cases were positive for BRISH. HPV prevalence increased from 11% between 1997 and 2002, to 27% between 2003 and 2009. Conclusions: In the period 1997–2009, 19% of the tonsillar and base-of-tongue tumours in the Northern Netherlands was HPV+. This prevalence is lower than in other regions in the Netherlands (33%) and in Europe (40%). Remarkably, a large increase in prevalence was observed in the more recent years. The relative low incidence in our region might be due to the relative high percentage of smokers, associated with non-HPV related oropharyngeal tumours. Currently HPV testing of a series of 200 oral squamous cell carcinomas from our centre is in progress. [Copyright &y& Elsevier]

Summary: To determine incidence trends of head and neck squamous cell carcinomas (HNSCC), we analyzed site-specific data collected by The Netherlands Cancer Registry by 15years-of-age categories from 1989–2006. The age-standardized annual incidence trends of all sites taken together showed a significant decrease of 0.6% for males and a significant increase of 1.8% for females. The trend for oropharyngeal carcinoma was most remarkable, with a significant increase of 2.5% and 3.0% per year for males and females, respectively. The incidence of oral carcinoma also significantly increased with a more pronounced effect for females than for males (2.0% vs. 0.5% per year). As for hypopharyngeal cancer, a significant annual increase for females (2.5%) and a stable situation for males was observed. Cancer of the larynx was the only site that showed a significant decline for males (2.4% per year), whereas it remained stable for females. In young (<45years) adults incidences decreased for all sites with 0.1–4.7%. In conclusion, recent incidence trends of HNSCC in The Netherlands vary between sites with a considerable increase of oropharyngeal cancer as the most remarkable finding. The reason for the decreasing annual incidence rate at all sites observed for Dutch young adults remains to be explained. [Copyright &y& Elsevier]