Mapping the impact of malnutrition as defined by the Global Leadership Initiative on Malnutrition and nutrition impact symptoms on the possibility of returning to work after treatment for head and neck cancer.

PURPOSE: This study aimed to investigate whether malnutrition or nutrition impact symptoms (NIS) affect the possibility of returning to work after treatment for head and neck cancer. METHODS: Patients of working age with head and neck cancer were followed up from treatment initiation to 3 months (n = 238), 1 year (n = 182), and 2 years (n = 130) after treatment completion. The observed decrease in the number of patients over time was due to retirement, lack of follow-up, or death. Returning to work was dichotomised as yes or no. Malnutrition was diagnosed 7 weeks after treatment initiation using the Global Leadership Initiative on Malnutrition (GLIM) criteria. This time-point corresponds to the end of chemoradiotherapy or radiotherapy (with or without prior surgery), except for patients who underwent exclusive surgery. NIS were scored on a Likert scale (1-5) at each follow-up using the Head and Neck Patient Symptom Checklist© (HNSC©). Nonparametric tests were used to analyse the ability of patients with/without malnutrition and high/low NIS scores to return to work. RESULTS: At 3 months, 1 year, and 2 years after treatment completion, 135/238 (56.7%), 49/182 (26.9%), and 23/130 (17.7%) patients had not returned to work. Patients with malnutrition at 7 weeks after treatment initiation were more likely to not return to work at 3 months than those without malnutrition, 70.5% compared to 47.1% (p < 0.001). At all three follow-up time-points, patients reporting high scores for a number of NIS had more often not returned to work, with this pattern being most distinct at 2 years. CONCLUSION: Malnutrition according to the GLIM criteria at 7 weeks after treatment initiation and NIS assessed by the HNSC© at subsequent follow-ups were predictors of the return-to-work process after treatment for up to 2 years. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03343236 (date of registration 17/11/2017).

Loco-Regional Control and Sustained Difference in Serum Immune Protein Expression in Patients Treated for p16-Positive and p16-Negative Head and Neck Squamous Cell Carcinoma.

The main prognostic factors for patients with head and neck cancer are the tumour site and stage, yet immunological and metabolic factors are certainly important, although knowledge is still limited. Expression of the biomarker p16INK4a (p16) in oropharyngeal cancer tumour tissue is one of the few biomarkers for the diagnosis and prognosis of head and neck cancer. The association between p16 expression in the tumour and the systemic immune response in the blood compartment has not been established. This study aimed to assess whether there is a difference in serum immune protein expression profiles between patients with p16+ and p16- head and squamous cell carcinoma (HNCC). The serum immune protein expression profiles, using the Olink® immunoassay, of 132 patients with p16+ and p16- tumours were compared before treatment and one year after treatment. A significant difference in the serum immune protein expression profile was observed both before and one year after treatment. In the p16- group, a low expression of four proteins: IL12RB1, CD28, CCL3, and GZMA before treatment conferred a higher rate of failure. Based on the sustained difference between serum immune proteins, we hypothesise that the immunological system is still adapted to the tumour p16 status one year after tumour eradication or that a fundamental difference exists in the immunological system between patients with p16+ and p16- tumours.

Addressing symptoms that affect patients' eating according to the Head and Neck Patient Symptom Checklist©.

PURPOSE: The purpose of this prospective study was to assess which nutritional impact symptoms (NIS) interfere with oral intake in patients with head and neck cancer (HNC) and how the symptoms interfere with body weight loss, up to 1 year after treatment. METHODS: This was a prospective study of 197 patients with HNC planned for treatment with curative intention. Body weight was measured before the start of treatment, at 7 weeks after the start of treatment, and at 6 and 12 months after completion of treatment. NIS and NIS interfering with oral intake at each follow-up were examined with the Head and Neck Patient Symptom Checklist© (HNSC©). RESULTS: At 7 weeks of follow-up, patients experienced the greatest symptom and interference burden, and 12 months after treatment the NIS scorings had not returned to baseline. One year after treatment, the highest scored NIS to interfere with oral intake was swallowing problems, chewing difficulties, and loss of appetite. At all 3 follow-ups, the total cumulative NIS and NIS interfering with oral intake were associated with body weight loss. Factors increasing the risk for a body weight loss of ≥ 10% at 12 months after treatment were pain, loss of appetite, feeling full, sore mouth, difficulty swallowing, taste changes, and dry mouth. Women scored higher than men in NIS and NIS interfering with oral intake. Furthermore, during the study period about half of the population had a body weight loss > 5%. CONCLUSION: Because both nutritional and clinical factors may affect body weight, this study highlights the importance of a holistic approach when addressing the patients' nutritional issues. TRIAL REGISTRATION: ClinicalTrials.gov NCT03343236, date of registration: November 17, 2017.

Serum Proteomics in Patients with Head and Neck Cancer: Peripheral Blood Immune Response to Treatment.

In this real-world study, the aims were to prospectively evaluate the expression of inflammatory proteins in serum collected from head and neck cancer patients before and after treatment, and to assess whether there were differences in expression associated with treatment modalities. The mixed study cohort consisted of 180 patients with head and neck cancer. The most common tumor sites were the oropharynx (n = 81), the oral cavity (n = 53), and the larynx (n = 22). Blood tests for proteomics analysis were carried out before treatment, 7 weeks after the start of treatment, and 3 and 12 months after the termination of treatment. Sera were analyzed for 83 proteins using an immuno-oncology biomarker panel (Olink, Uppsala, Sweden). Patients were divided into four treatment groups: surgery alone (Surg group, n = 24), radiotherapy with or without surgery (RT group, n = 94), radiotherapy with concomitant cisplatin (CRT group, n = 47), and radiotherapy with concomitant targeted therapy (RT Cetux group, n = 15). For the overall cohort, the expression levels of 15 of the 83 proteins changed significantly between the pretreatment sample and the sample taken 7 weeks after the start of treatment. At 7 weeks after the start of treatment, 13 proteins showed lower expression in the CRT group compared to the RT group. The majority of the inflammatory proteins had returned to their pretreatment levels after 12 months. It was clearly demonstrated that cisplatin-based chemoradiation has immunological effects in patients with head and neck cancer. This analysis draws attention to several inflammatory proteins that are of interest for further studies.

A Nordic survey of the management of palliative care in patients with head and neck cancer.

BACKGROUND: The five Nordic countries with a population of 27M people form a rather homogenous region in terms of health care. The management of Head and Neck Cancer (HNC) is centralized to the 21 university hospitals in these countries. Our aim was to survey the current status of organization of palliative care for patients with HNC in the Nordic countries as the field is rapidly developing. MATERIALS AND METHODS: A structured web-based questionnaire was sent to all the Departments of Otorhinolaryngology-Head and Neck Surgery and Oncology managing HNC in the Nordic countries. RESULTS: All 21 (100%) Nordic university hospitals responded to the survey. A majority (over 90%) of the patients are discussed at diagnosis in a multidisciplinary tumor board (MDT), but the presence of a palliative care specialist is lacking in 95% of these MDT's. The patients have access to specialized palliative care units (n = 14, 67%), teams (n = 10, 48%), and consultants (n = 4, 19%) in the majority of the hospitals. CONCLUSION: The present results show that specialized palliative care services are available at the Nordic university hospitals. A major finding was that the collaboration between head and neck surgeons, oncologists and palliative care specialists is not well structured and the palliative care pathway of patients with HNC is not systematically organized. We suggest that early integrated palliative care needs to be included as an addition to the already existing HNC care pathways in the Nordic countries.

An explorative study on energy balance in patients with head and neck cancer.

Background: Involuntary body weight loss in head and neck cancer is common. Fundamental for weight loss is an energy imbalance where total energy expenditure exceeds energy intake.Aim: To map energy intake and parameters of energy expenditure at the start of and after radiotherapy, and their relation to weight change, body mass index, and immune markers in patients with head and neck cancer.Materials and Methods: Data from 20 patients on energy intake (24-hour dietary intake recalls), total energy expenditure (SenseWear Armband Pro3), resting energy expenditure (indirect calorimetry), body weight, body mass index, and immune markers in serum (C-reactive protein and Interleukin-6) were collected at the start of and after radiotherapy (median 8 mo, range 5-13).Results: No statistical significance was shown between the two measurement points for energy intake or for the different parameters of energy expenditure. Median values for energy balance were 0.93 and 0.96 for the start of treatment and follow-up, respectively. Twelve and 13 patients had a negative energy balance at the start of radiotherapy and at follow-up, respectively.Conclusion: A negative energy balance was seen for the majority of patients, which stresses the importance of nutritional treatment at the start of and after radiotherapy.

Vitamin D in Head and Neck Cancer: a Systematic Review.

PURPOSE OF REVIEW: Observational studies have shown that serum 25-OH vitamin D [25(OH)D] is inversely associated with overall cancer risk in many malignancies. We performed a systematic literature review to determine whether vitamin D deficiency is related to head and neck cancer (HNC) etiology and outcome. RECENT FINDINGS: The search yielded five prospective studies reporting 25(OH)D levels prior to cancer diagnosis and their effect on the risk of HNC. Eight studies were cross-sectional or case-control studies, in which 25(OH)D levels were only measured after cancer diagnosis. Two studies found an inverse association between 25(OH)D level and HNC risk, while two other prospective cohort studies demonstrated no connection between 25(OH)D and HNC risk. Several studies reported cancer patients to have significantly lower 25(OH)D levels than controls. Associations between 25(OH)D and prognosis and mortality were variable. The link between vitamin D and HNC has so far only been investigated in a few observational, prospective, and case-control studies. Vitamin D deficiency may be more common in HNC patients than in the healthy population. There is no evidence for a causal relationship. Further studies are needed to evaluate whether low 25(OH)D concentrations play a role in the development or outcome of HNCs.

An LCMS-based untargeted metabolomics protocol for cochlear perilymph: highlighting metabolic effects of hydrogen gas on the inner ear of noise exposed Guinea pigs.

INTRODUCTION: Noise-induced hearing loss (NIHL) is an increasing problem in society and accounts for a third of all cases of acquired hearing loss. NIHL is caused by formation of reactive oxygen species (ROS) in the cochlea causing oxidative stress. Hydrogen gas (H2) can alleviate the damage caused by oxidative stress and can be easily administered through inhalation. OBJECTIVES: To present a protocol for untargeted metabolomics of guinea pig perilymph and investigate the effect of H2 administration on the perilymph metabolome of noise exposed guinea pigs. METHODS: The left ear of guinea pigs were exposed to hazardous impulse noise only (Noise, n = 10), noise and H2 (Noise + H2, n = 10), only H2 (H2, n = 4), or untreated (Control, n = 2). Scala tympani perilymph was sampled from the cochlea of both ears. The polar component of the perilymph metabolome was analyzed using a HILIC-UHPLC-Q-TOF-MS-based untargeted metabolomics protocol. Multivariate data analysis (MVDA) was performed separately for the exposed- and unexposed ear. RESULTS: MVDA allowed separation of groups Noise and Noise + H2 in both the exposed and unexposed ear and yielded 15 metabolites with differentiating relative abundances. Seven were found in both exposed and unexposed ear data and included two osmoprotectants. Eight metabolites were unique to the unexposed ear and included a number of short-chain acylcarnitines. CONCLUSIONS: A HILIC-UHPLC-Q-TOF-MS-based protocol for untargeted metabolomics of perilymph is presented and shown to be fit-for-purpose. We found a clear difference in the perilymph metabolome of noise exposed guinea pigs with and without H2 treatment.

Experiences and coping strategies related to food and eating up to two years after the termination of treatment in patients with head and neck cancer.

The purpose was to describe how patients with head and neck cancer experience and cope with difficulties related to food and eating up to two years after the termination of treatment. One hundred and thirty-five patients were followed with thematically structured interviews. The patients' responses of nutritional issues were categorised using similarities and differences technique. In the analysis, six categories emerged describing the process of eating and drinking from the end of treatment up to two years after treatment: The constant battle-eating and drinking over time, Food alterations and nutritional support-both pros and cons, Standing aside and not joining in when eating together with others, Finding ways to cope and to make the new a part of everyday life, Relationships and social support-hindrances and facilitators, and Longing for "normality." Results imply that patients struggle with physiological, psychological and social aspects related to food and eating, and use coping mechanisms to facilitate their eating problems. The best practice for rehabilitation and follow-up must be established in order to meet the multifaceted needs of head and neck cancer survivors.

Changes in intimate relationships following treatment for head and neck cancer-A qualitative study.

The aim of this study was to determine how patients with head and neck cancer experience changes within their intimate relationships at the end of treatment and detect detrimental and facilitating factors in the process of resuming intimate relationships. Interviews were conducted with 131 patients. A core category - "being open versus not sharing the cancer journey" - emerged from the patients' narratives and was based on the experiences of engagement/disengagement, openness/fear, and patronizing attitudes/sharing the burden. The findings point to the necessity of patients being open about the disease trajectory and might be understood in the light of theories about potential changes in identity and self-concept.

Super-resolution structured illumination fluorescence microscopy of the lateral wall of the cochlea: the Connexin26/30 proteins are separately expressed in man.

Globally 360 million people have disabling hearing loss and, of these, 32 million are children. Human hearing relies on 15,000 hair cells that transduce mechanical vibrations to electrical signals in the auditory nerve. The process is powered by the endo-cochlear potential, which is produced by a vascularized epithelium that actively transports ions in conjunction with a gap junction (GJ) system. This "battery" is located "off-site" in the lateral wall of the cochlea. The GJ syncytium contains the GJ protein genes beta 2 (GJB2/connexin26 (Cx26)) and 6 (GJB6/connexin30 (Cx30)), which are commonly involved in hereditary deafness. Because the molecular arrangement of these proteins is obscure, we analyze GJ protein expression (Cx26/30) in human cochleae by using super-resolution structured illumination microscopy. At this resolution, the Cx26 and Cx30 proteins were visible as separate plaques, rather than being co-localized in heterotypic channels, as previously suggested. The Cx26 and Cx30 proteins thus seem not to be co-expressed but to form closely associated assemblies of GJ plaques. These results could assist in the development of strategies to treat genetic hearing loss in the future.

Meaning of work and the process of returning after head and neck cancer.

PURPOSE: The purposes of this study were (1) to investigate employment status at diagnosis, sick leave, and returning to work patterns in correlation to quality of life, anxiety, and depression in patients treated for head and neck cancer (HNC) and (2) to explore patients' experiences of the process of returning to work. METHODS: Sixty-six patients with HNC (aged 34-66 years) were repeatedly interviewed over a period of 24 months. Interview responses that concerned the patients' experiences and ideas about work were categorised using the similarities-differences technique. Questionnaires on quality of life, anxiety, and depression were used to describe the patient characteristics and the differences between groups. RESULTS: In total, 53% of the patients had returned to work at 24 months after treatment, and 17% were deceased. Several quality of life parameters were significantly worse for patients not working at 24 months after treatment. Nine categories were found to describe the return-to-work process starting with symptoms causing sick leave, thoughts about the sick leave, and ending with the return to work and/or retirement. CONCLUSIONS: Returning to work is an important part of life because it structures everyday life and strengthens the individual's identity. The quality of life results showed significant differences between workers and non-workers at the 24-month follow-up. The patients need to be both physically and mentally prepared for the process of returning to work. It is important to take an individual rehabilitation approach to guide and support the patients in returning to work and regaining an important aspect of their everyday life. In such an approach, it is vital to understand the patients' overall life context and the patients' own perspective on the process and meaning associated with work.

Motives that head and neck cancer patients have for contacting a specialist nurse - an empirical study.

AIMS AND OBJECTIVES: The purpose of this study is to systematically explore the motives for patients with head and neck cancer to contact a specialist nurse during two years postdiagnosis. BACKGROUND: Research focusing on the role of specialist nurses in cancer care almost exclusively concern cancers other than head and neck cancer. DESIGN: Qualitative, descriptive study based on the contacts between patients with head and neck cancer and a specialist nurse. METHODS: Patients were invited to contact a specialist nurse by telephone. The specialist nurse took systematic field notes, that is, she registered who contacted her, the nature of the call and the outcome. Sixty patients were included. RESULTS: In descending order, the motives for contact were questions about practical and uncomplicated matters, consultations about medical troubles/worries, presenting a report of the patient's situation, requests for additional information about the treatment plan and requests for medical information. The pattern of the patients' motivations for calling was not related to medical or social factors, suggesting that the initiative to make contact is very much a question of the complexity of individual life circumstances. Very few referrals were sent from the specialist nurse to other professionals. CONCLUSIONS: The specialist nurse turned out to be more than just a coordinator of health-care resources. The findings bring up questions about the potential of the nurse's function as a coordinator, but also as a potential attachment figure, and questions about the nurse's relationships to other professionals. RELEVANCE TO CLINICAL PRACTICE: When implementing a specialist nurse function, it is important to decide whether the function should be inspired by a broader relational perspective. In addition to the indispensible competence and experience in the clinical field of head and neck cancer, training in counselling and acquaintance with object-relational psychology will then be desirable.

Expression of CXCL10 is associated with response to radiotherapy and overall survival in squamous cell carcinoma of the tongue.

Five-year survival for patients with oral cancer has been disappointingly stable during the last decades, creating a demand for new biomarkers and treatment targets. Lately, much focus has been set on immunomodulation as a possible treatment or an adjuvant increasing sensitivity to conventional treatments. The objective of this study was to evaluate the prognostic importance of response to radiotherapy in tongue carcinoma patients as well as the expression of the CXC-chemokines in correlation to radiation response in the same group of tumours. Thirty-eight patients with tongue carcinoma that had received radiotherapy followed by surgery were included. The prognostic impact of pathological response to radiotherapy, N-status, T-stage, age and gender was evaluated using Cox's regression models, Kaplan-Meier survival curves and chi-square test. The expression of 23 CXC-chemokine ligands and their receptors were evaluated in all patients using microarray and qPCR and correlated with response to treatment using logistic regression. Pathological response to radiotherapy was independently associated to overall survival with a 2-year survival probability of 81% for patients showing a complete pathological response, while patients with a non-complete response only had a probability of 42% to survive for 2 years (p = 0.016). The expression of one CXC-chemokine, CXCL10, was significantly associated with response to radiotherapy and the group of patients with the highest CXCL10 expression responded, especially poorly (p = 0.01). CXCL10 is a potential marker for response to radiotherapy and overall survival in patients with squamous cell carcinoma of the tongue.

Radiation-induced trismus in the ARTSCAN head and neck trial.

UNLABELLED: Trismus, a well-known sequelae after treatment of head and neck cancer, decreases a patient's oral function and quality of life. The main objectives of this study were to: 1) investigate the long-term prevalence of radiation-induced trismus in patients treated for head and neck cancer according to two different fractionation schedules; and 2) model a dose-response relationship for trismus. MATERIAL AND METHODS: Patients were recruited from the Swedish ARTSCAN trial, a prospective randomised multicentre study comparing conventional and accelerated fractionation. A total of 124 patients agreed to a clinical ENT examination 21-127 months (median 66 months) after beginning radiation therapy. Trismus-related scores were assessed using the EORTC H&N35 Quality of Life questionnaire. The TheraBite(®) range of motion scale was used to measure maximal interincisal distance. The dose-response relationship for structures important for mastication and the temporomandibular joints was investigated by normal tissue complication probability modelling. RESULTS: No significant differences in patient-reported trismus or maximal interincisal distance were found between the two trial arms. Patient-reported moderate to high scores regarding trismus increased from 3% at the start of radiation therapy to 25% at the long-term follow-up. Maximal interincisal distance correlated significantly with patient-reported scores of trismus. The best dose-response fit to the endpoint data was found for the dose to the ipsilateral masseter. CONCLUSIONS: Trismus is a persistent complication after radiotherapy with 3D-conformal radiation therapy. We found no difference between the severity and prevalence of trismus between conventional and accelerated fractionation, but a significant correlation between the absorbed dose to the mastication structures and opening of the mouth. Further prospective studies may determine whether a reduced dose to structures important for mastication using intensity-modulated radiation therapy will reduce problems with trismus.

High expression of p63 is correlated to poor prognosis in squamous cell carcinoma of the tongue.

BACKGROUND: p63 proteins are important in formation of the oral mucosa. Normal oral mucosa shows a balance between the six protein isoforms, whereas an imbalance between them is seen in squamous cell carcinomas (SCC). There is controversy over the clinical impact of p63 in SCC, which may relate to different expression in different areas. In addition, p63 isoforms can act as p53-like molecules (TAp63) or can inhibit p53 functions (ΔNp63) and expression of these isoforms varies in different tumours. Here, we chose to concentrate on the most common intra-oral sub-site, SCC of the mobile tongue. METHODS: Total p63, ΔNp63 and TAp63 were analysed separately using immunohistochemistry. The percentage of cells and intensity of expression of different isoforms of p63 was evaluated using a quick score method and correlated with clinical data in a group of 87 patients with tongue SCC. RESULTS: All tumours expressed p63 in at least 60% of the cells when using two different antibodies detecting all 6 isoforms. p63 expression correlated significantly with 2-year survival (P = 0.018), with fewer patients surviving 2 years if their tumours expressed p63 with strong intensity in at least 80% of the cells (quick score 18). Looking at 5-year survival, this was even more emphasized. ΔNp63 was expressed in all tumours, whereas expression of TAp63 was seen only in 59/87 patients, usually at very low levels. CONCLUSIONS: Based on the present data, we recommend using expression of p63 as an additional factor contributing prognostic information in analysis of SCC in the tongue.

Weight loss and body mass index in relation to aspiration in patients treated for head and neck cancer: a long-term follow-up.

PURPOSE: Persistent severe swallowing dysfunction with aspiration is a common and sometimes overlooked sequelae after treatment for squamous cell carcinoma of the head and neck (SCCHN) and may impact food intake and nutritional status. More knowledge is needed to increase the understanding of severe swallowing dysfunction as a risk factor for persistent nutritional deteriorations in SCCHN survivors. The purpose of the study was to investigate weight loss and body mass index (BMI) in relation to pharyngeal swallowing function in a long-term perspective in patients after SCCHN treatment. METHODS: Data from 101 patients were available for the analyses. Swallowing function was assessed by videofluoroscopy at a mean of 71.6 months after the start of radiotherapy (RT). Percent weight change (calculated with weight at the start of RT as the reference) and BMI at follow-up were the primary nutritional measures. RESULTS: Aspiration was present in 48 of 101 patients (48 %). Patients with aspiration had a significantly higher mean weight loss and a lower BMI (-10.9 % and 23.1, respectively) at follow-up compared with patients without aspiration (-2.8 % and 26.0, respectively). Patients with aspiration were unable to gain weight after 23 months. Only ten of 101 patients (10 %) were underweight at follow-up. CONCLUSIONS: Swallowing dysfunction with aspiration was related to long-term weight loss and reduced BMI. Few patients were underweight despite the high prevalence of swallowing dysfunction.

Critical incidents reveal how patients with head and neck cancer construct their "secure base" as a "helping system".

Most studies of the psychosocial needs of patients with head and neck cancers (HNC) use predefined categories and explicitly ask for specified needs. These studies are important but should be complemented with inductive studies based on patients' own descriptions of experiences. This qualitative study is such a contribution. In repeated interviews positive and negative incidents were collected from 137 patients with HNC, and these experiences were categorized in dimensions expressing needs. A core category--"being included--neglected by a helping system"--emerged from the narrated incidents and was based on the dimensions engagement, competence, and information. The findings are easily related to attachment theory by stressing the significance of establishing trustful relationships with the health care staff, as attachment figures, who respond flexibly and sensitively to the patient's needs. In the constitution of health care as a helping system, all encounters between the patient and health care staff matters. Further research should preferably focus on the creation of guidelines for the constitution of health care as a helping system, that is, how the found factors of a helping system can be operationalized in clinical practice.

Hearing loss and its association with the proteome of perilymph, cerebrospinal fluid, and tumor tissue in patients with vestibular schwannoma.

This study examined the association between hearing loss in sporadic vestibular schwannoma patients and the proteome of perilymph (PL), cerebrospinal fluid (CSF), and vestibular schwannoma. Intraoperative sampling of PL and of CSF, and biopsy of vestibular schwannoma tissue, was performed in 32, 32, and 20 patients with vestibular schwannoma, respectively. Perilymph and CSF in three patients with meningioma and normal hearing were also sampled. The proteomes were identified by liquid chromatography coupled to high-resolution tandem mass spectrometry. Preoperative hearing function of the patients was evaluated with pure tone audiometry, with mean values at frequencies of 500, 1000, 2000, and 4000 Hz (PTA4) in the tumor-affected ear used to delineate three hearing groups. Analysis of the PL samples revealed significant upregulation of complement factor H-related protein 2 (CFHR2) in patients with severe to profound hearing loss after false discovery rate correction. Pathway analysis of biofunctions revealed higher activation scores in the severe/profound hearing loss group of leukocyte migration, viral infection, and migration of cells in PL. Upregulation of CFHR2 and activation of these pathways indicate chronic inflammation in the cochlea of vestibular schwannoma patients with severe to profound hearing loss compared with patients with normal hearing or mild hearing loss.

Six-month mortality has decreased for patients with curative treatment intent for head and neck cancer in Sweden.

BACKGROUND: In general, survival outcomes for patients with Head and Neck Cancer (HNC) has improved over recent decades. However, mortality within six months after diagnosis for curative patients remains at approximately 5%. The aim of this study was to identify risk factors for early death among patients with curative treatment, and furthermore, to analyze whether the risk of early death changed over recent years. MATERIAL AND METHOD: This real-world, population-based, nationwide study from the Swedish Head and Neck Cancer Register (SweHNCR) included all patients ≥18 years diagnosed with HNC with a curative treatment intent at the multidisciplinary tumor board from 2008 to 2020. A total of 16,786 patients were included. RESULTS: During the study period a total of 618 (3.7%) patients with curative-intended treatment died within six months of diagnosis. Patients diagnosed between 2008 and 2012 had a six-month mortality rate of 4.7% compared to 2.5% for patients diagnosed between 2017 and 2020, indicating a risk reduction of 53% (p <0.001) for death within six months. The mean time to radiation therapy from diagnosis in the 2008-2012 cohort was 38 days, compared to 22 days for the 2017-2020 cohort, (p <0.001). The mean time to surgery from diagnosis was 22 days in 2008-2012, compared to 15 days for the 2017-2020 cohort, (p <0.001). Females had a 20% lower risk of dying within six months compared to males (p = 0.013). For every year older the patient was at diagnosis, a 4.8% (p <0.001) higher risk of dying within six months was observed. Patients with a WHO score of 1 had approximately 2.4-times greater risk of early death compared to WHO 0 patients (p <0.001). The risk of early death among WHO 4 patients was almost 28 times higher than for WHO 0 patients (p <0.001). Patients with a hypopharyngeal tumor site had a 2.5-fold higher risk of dying within six months from diagnosis compared to oropharyngeal tumor patients (p <0.001). CONCLUSIONS: We found that the risk of early death decreased significantly from 2008 to 2020. During this period, the mean time to the start of treatment was significantly reduced both for surgery and oncological treatment regimes. Among patients with a curative treatment intention, increased risk of early death was associated with male sex, older age, advanced disease, increased WHO score, and a hypopharyngeal tumor site.