The effect of internet-administered support (carer eSupport) on preparedness for caregiving in informal caregivers of patients with head and neck cancer compared with support as usual: a study protocol for a randomized controlled trial.

BACKGROUND: Informal caregivers (ICs) of patients with cancer provide essential and mainly uncompensated care. A self-perceived preparedness to care for the patient is associated with a lower caregiver burden, described as the extent to which caregiving is perceived as having adverse effects on IC functioning and well-being. ICs' well-being is associated with patient-perceived quality of care, suggesting that interventions to optimize ICs' health are essential in order to improve patient care. Head and neck cancer (HNC) is the seventh most common malignant disease in the world. The disease and its treatment have a significant negative impact on the patient's health and quality of life. Symptoms usually interfere with swallowing, food and fluid intake, breathing, speaking, and communication. ICs frequently manage patients' symptoms and side effects, especially problems related to nutrition and oral pain, without being properly prepared. Carer eSupport is an Internet-administered intervention, based on focus group discussions with ICs, developed in collaboration with ICs and healthcare professionals, tested for feasibility, and deemed feasible. This study protocol outlines the methods of investigating the effects of Carer eSupport plus support as usual (SAU) on self-reported preparedness for caregiving, caregiver burden, and well-being in the ICs of patients with HNC, compared with ICs receiving SAU only. METHODS AND ANALYSIS: In this randomized controlled trial, 110 ICs of patients with HNC, undergoing radiotherapy combined with surgery and/or medical oncological treatment, will be randomized (1:1) to Carer eSupport plus SAU or SAU only. Data will be collected at baseline (before randomization), post-intervention (after 18 weeks), and 3 months after post-intervention. The primary outcome is self-reported preparedness for caregiving. Secondary outcomes are self-reported caregiver burden, anxiety, depression, and health-related quality of life. The effect of Carer eSupport plus SAU on preparedness for caregiving and secondary outcomes, compared with SAU only, will be evaluated by intention to treat analyses using linear regression models, mixed-model regression, or analysis of covariance. DISCUSSION: If proven effective, Carer eSupport has the potential to significantly improve ICs' preparedness for caregiving and their wellbeing, thereby improving patient-perceived quality of care and patient wellbeing. TRIAL REGISTRATION: ClinicalTrials.gov; NCT06307418, registered 12.03.2024 (https://clinicaltrials.gov/search? term=NCT06307418).

Prognostic value of bone marrow and tumor 18 F-FDG uptake on PET/CT in patients with oropharyngeal cancer and the interplay between inflammation and FDG uptake.

AIMS: To examine the prognostic value of F-18 fluorodeoxyglucose (FDG) uptake in the bone marrow (BM) for disease recurrence and survival in patients with oropharyngeal squamous cell carcinoma (OP-SCC). The secondary aims were to evaluate the prognostic value of PET/CT parameters for the primary oropharyngeal tumor and total tumor burden, and to assess the correlation between FDG uptake variables and serum inflammatory markers. METHODS: This was an observational study of 91 patients with OP-SCC who underwent pretreatment FDG-PET/CT. The patients' blood samples were collected before treatment, and treatment was administered with the intention to cure. The median follow-up time was 40 months. The PET parameters measured were SUVmean BM for the assessment of BM FDG uptake, SUVmean , SUVmax , total lesion glycolysis (TLG), and metabolic tumor volume (MTV) for the evaluation of primary oropharyngeal tumor and total tumor burden. Blood samples were analyzed to determine each patient's white cell, red cell, and platelet cell counts, hemoglobin, and C-reactive protein level. In a subgroup of 33 patients, blood serum was analyzed to evaluate the expression of serum immune proteins using a proximity extension assay (Olink Proteomics). RESULTS: The univariate analysis revealed that SUVmean BM and tumor-specific parameters (SUVmax tumor, SUVmean total, SUVmax total, MTVtotal, TLGtotal) were significantly associated with recurrence-free survival (RFS). After adjusting for age, sex, and stage only SUVmean BM remained significantly associated with RFS. Spearman's correlation identified several correlations between PET parameters and inflammatory markers. CONCLUSIONS: Our results show that several FDG-PET/CT parameters may have a prognostic value of treatment outcome in patients with OP-SCC. However, SUVmean BM was the only independent PET parameter that showed a prognostic value for RFS in the study cohort. Moreover, the study findings might suggest an association between systemic inflammation and the metabolic activity in the BM.

Pretreatment fat-free mass index correlates with early death in patients with head and neck squamous cell carcinoma.

BACKGROUND: A significant proportion of patients with head and neck squamous cell carcinoma (HNSCC) are malnourished at diagnosis. In this study, we investigated how pretreatment body mass index (BMI) and fat-free mass index (FFMI) correlate with early death, and whether these measurements are useful markers of prognosis for risk stratification of head and neck cancer patients. METHODS: Patients (n = 404) with newly diagnosed, curable HNSCC and WHO performance status 0-2 were prospectively included and met with a study representative before treatment initiation, as well as up to four follow-up visits. All patients provided an estimate of body weight at 6 months prior to diagnosis. Bioelectrical impedance analysis (BIA) was performed for all patients before treatment initiation. RESULTS: Most patients had oropharyngeal (46%), oral cavity (28%), or laryngeal cancer (12%). Forty-five (11%) patients met the standardized criteria for malnutrition according to the Global Leadership Initiative on Malnutrition (GLIM) at diagnosis. FFMI at diagnosis was lower in patients who died within 6 and 12 months after the start of treatment than in patients who survived these time points (p = 0.035 and p = 0.005, respectively). CONCLUSIONS: In this study, pretreatment FFMI was an independent prognostic factor for death within 6 and 12 months after the start of treatment in patients with HNSCC. Pretreatment BMI was not an independent risk factor for death within 6 and 12 months after treatment termination. Thus, FFMI may be useful for risk stratification of patients with head and neck cancer.

Understanding the challenges and need for support of informal caregivers to individuals with head and neck cancer - A basis for developing internet-based support.

PURPOSE: Being an informal caregiver of an individual with head and neck cancer can be demanding. Still, informal caregivers can provide valuable support to patients throughout the disease trajectory. The aim of this study was to explore informal caregivers' views on their challenges and needs in attaining high preparedness for caregiving. METHODS: Fifteen informal caregivers of individuals with head- and neck cancer participated in a focus group discussion or an individual interview. Thematic analysis utilizing an inductive approach was performed. RESULTS: The results describe the challenges that informal caregivers to individuals with head and neck cancer perceive and their needs for support in preparedness for caregiving. Three main themes were found: Challenges of being an informal caregiver, Transformation in life and Informal caregiver' needs of support and sharing care. CONCLUSION: This study contributes to the understanding of the challenges for informal caregivers to individuals with head and neck cancer in increasing preparedness for caregiving. To improve preparedness for caregiving, informal caregivers need education, information and support regarding physical, psychological and social issues for individuals with head and neck cancer.

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.

Longitudinal Changes in the Fatty Acid Profile in Patients with Head and Neck Cancer: Associations with Treatment and Inflammatory Response.

Studies on fatty acids (FAs) in patients with head and neck cancer (HNC) are limited. We aimed to investigate the longitudinal changes of circulating FAs in patients with HNC and to examine potential correlations of FA changes with treatment. The secondary aims were to investigate correlations of FAs with cytokines and patient-related factors, and if any FAs correlated with disease recurrence or death. A total of 174 patients with HNC were included before treatment and followed-up at three time points after the start of the treatment through blood sampling and body weight measurements. Serum FA profiling was assessed by gas chromatography. The total follow-up time was 3 years. The levels of almost all FAs changed from baseline to 7 weeks. The change in FA 14:0 was associated with treatment and the change in 18:3n-6 was associated with the patients' pre-treatment BMI. FAs 14:0 and 18:0 were correlated with weight changes from baseline to 7 weeks. IL-6 was correlated with three FAs at 7 weeks and with two FAs at 1 year. Patients with higher levels 20:5n-3 at 3 months had a higher risk of all-cause death within 3 years (HR 2.75, 95% CI 1.22-6.21). Treatment, inflammation, and weight loss contributed in a complex manner to the altered FA profile in the studied cohort. The association between IL-6 and FAs in patients with HNC is in line with earlier studies and suggests the opportunity for regulating inflammation in HNC patients through modulation of FAs.

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.

Mapping Health-Related Quality of Life, Anxiety, and Depression in Patients with Head and Neck Cancer Diagnosed with Malnutrition Defined by GLIM.

Patients with cancer deal with problems related to physical, psychological, social, and emotional functions. The aim was to investigate malnutrition defined by the Global Leadership Initiative on Malnutrition (GLIM) criteria in relation to health-related quality of life, anxiety, and depression in patients with head and neck cancer. This was a prospective observational research study with 273 patients followed at the start of treatment, seven weeks, and one year. Data collection included nutritional status and support, and the questionnaires: European Organization for Research and Treatment of Cancer Head and neck cancer module (EORTC QLQ-H&N35) and the Hospital Anxiety and Depression Scale (HADS). Malnutrition was defined using the GLIM criteria. The study showed that patients with malnutrition had significantly greater deterioration in their health-related quality of life at seven weeks. On a group level, health-related quality of life was most severe at this time point and some scores still implied problems at one year. Significantly, more patients reported anxiety at the start of treatment whereas significantly more patients reported depression at seven weeks. Over the trajectory of care, the need for support often varies. Psychosocial support is imperative and at the end of treatment extra focus should be put on nutritional interventions and managing treatment-related symptoms to improve nutritional status and health-related quality of life. In the long-term, head and neck cancer survivors need help to find strategies to cope with the remaining sequel.

Variations in concerns reported on the patient concerns inventory in patients with head and neck cancer from different health settings across the world.

BACKGROUND: The aim was to collate and contrast patient concerns from a range of different head and neck cancer follow-up clinics around the world. Also, we sought to explore the relationship, if any, between responses to the patient concerns inventory (PCI) and overall quality of life (QOL). METHODS: Nineteen units participated with intention of including 100 patients per site as close to a consecutive series as possible in order to minimize selection bias. RESULTS: There were 2136 patients with a median total number of PCI items selected of 5 (2-10). "Fear of the cancer returning" (39%) and "dry mouth" (37%) were most common. Twenty-five percent (524) reported less than good QOL. CONCLUSION: There was considerable variation between units in the number of items selected and in overall QOL, even after allowing for case-mix variables. There was a strong progressive association between the number of PCI items and QOL.

Systemic Inflammatory Reaction in Patients With Head and Neck Cancer-An Explorative Study.

Aim: To assess the longitudinal pattern of pro-inflammatory cytokines and growth factors in serum up to 1 year following treatment for head and neck cancer. Materials and Methods: Patients with newly diagnosed, curable head and neck cancer were included (n = 30). The most common subsite was oropharynx (n = 13) followed by oral cavity (n = 9). Blood was drawn from all patients at regular intervals (before treatment, 7 weeks after the start of the treatment, and at 3 months and 1 year after termination of treatment) and analyzed for cytokines (Il-1ß, Il-2, Il-4, Il-5, Il-6, Il-8, Il-10, GM-CSF, TNF-α, and IFN-γ) and growth factors (G-CSF, FGF-2, EGF, and VEGF). Results: The time point of the peak level of pro-inflammatory cytokines was 7 weeks after start of treatment which corresponded for the majority of patients with termination of radiotherapy or chemoradiotherapy. Patients undergoing chemoradiotherapy exhibited a significant increase of IL-1ß, IL-6, and IL-10 at 7 weeks as compared to pre-treatment levels. At 1 year after termination of treatment four patients experienced recurrence of disease while 26 patients were considered disease-free. The patients with recurrence had significantly higher levels of IL-1ß, IL-6, IL-8, and IL-10 at 7 weeks after the start of treatment than patients without recurrence. Correlated with T stadium patients with T3-T4 had higher levels of IL-1ß and IL-8 than patients with T1-T2 7 weeks after the start of treatment. Conclusions: The observed immune response in this explorative study demonstrates that chemoradiotherapy may induce not only a local treatment effect on the immune system but also effects far outside the irradiated field. The result of the study indicates that analysis of a pro-inflammatory panel of cytokines in serum at 7 weeks after the start of treatment could be of prognostic value in patients with head and neck cancer. Further study of a larger cohort could help identify patients at larger risk for recurrent disease with measurements of pro-inflammatory cytokines under and after treatment.

Trismus in patients with head and neck cancer and 5-year overall survival.

BACKGROUND: Trismus is a common complication of radiotherapy for head and neck cancer but its impact on survival is unknown. AIMS/OBJECTIVES: This prospective study evaluates the incidence of trismus in patients with head and neck cancer receiving radiotherapy and the impact of trismus on 5-year overall survival. MATERIAL AND METHODS: Two hundred forty-four patients with head and neck cancer were included. All patients received instructions on jaw exercises and were evaluated before initiation of radiotherapy and at 2, 6, and 12 months after termination of radiotherapy. RESULTS: One year after treatment 25% had a reduced maximum interincisal opening (MIO) of 13 mm or more as compared to the pretreatment MIO. Trismus was most prevalent in patients with oral and oropharyngeal cancer. A trend towards worse 5-year overall survival was seen among patients with trismus. CONCLUSIONS: The trismus rate was approximately 30% at 12 months. Jaw exercises should primarily be offered to patients with oral and oropharyngeal cancer who are most likely to benefit. Further studies are required to investigate the effect of trismus on survival. SIGNIFICANCE: This study identifies patients likely to benefit from jaw exercises and provides basis for further research on trismus and survival.

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.

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.

Head and neck cancer patients' perceptions of quality of life and how it is affected by the disease and enteral tube feeding during treatment.

AIM: To explore individual quality of life in patients with head and neck cancer from diagnosis up to 3 months after termination of radiotherapy. RESEARCH QUESTIONS: 1) Which areas in life are important to quality of life, and which are influenced by the disease and by having oral or enteral nutrition; and 2) Which areas in life are influenced by having a nasogastric feeding tube (NGT) or a percutaneous endoscopic gastrostomy (PEG) tube? MATERIAL AND METHODS: Data were collected in 36 patients. Semi-structured interviews were conducted using an extended version of the Schedule for the Evaluation of Individual Quality of Life (SEIQoL) and analysed with content analysis. RESULTS: Negative and positive experiences of quality of life in general were about relation to family, own health, and leisure activities. Negative impacts on physical, psychological, existential and social problems, but also positive experiences are described by the patients related to the disease. More than half expressed eating-related problems. Enteral nutrition entailed negative and positive experiences, and no greater variations were described by the patients with NGT or PEG tube. Overall, there were interindividual variations. CONCLUSIONS: The patients' perception of general or disease-related quality of life was not affected by whether they had enteral nutrition or not. From the patients' perspective neither of the two feeding tubes (NGT or PEG) was clearly in favour. We suggest that more studies are needed on how the choice of enteral feeding tube can be evidence-based, and incorporating the patients' perspective.

Sexual and contraceptive behavior among female university students in Sweden - repeated surveys over a 25-year period.

OBJECTIVE: To study female students' sexual and contraceptive behavior and compare these results with earlier surveys. DESIGN: Comparative, repeated cross-sectional surveys, started in 1989 and repeated every fifth year. SETTING: Contraceptive counseling delivered at a Student Health Center in Sweden. POPULATION: Female university students (n = 359). METHODS: Multiple-choice waiting-room questionnaire. MAIN OUTCOME MEASURES: Sexual and contraceptive behavior. RESULTS: In 1989, age at first intercourse was 17.6 years vs. 16.7 years in 2014, number of lifetime sexual partners was 4.0 vs. 12.1 in 2014, and number of sexual partners during the previous 12 months was 1.0 vs. 2.8 in 2014. Condom use during first intercourse with the latest partner decreased from 49% to 41% (n = 172 in 2009 vs. n = 148 in 2014: p < 0.001), and experience of anal sex increased from 39% to 46% (n = 136 in 2009 vs. n = 165 in 2014: p = 0.038), and 25% (n = 41 in 2014) always used a condom during anal sex. A total of 70% (n = 251) made use of pornography, and 48% (n = 121) considered their sexual behavior affected by pornography. Eighty-nine percent (n = 291) wanted two to three children and 9% (n = 33) had thought about freezing eggs for the future. The female students' knowledge about increasing age being correlated with decreased fertility varied. CONCLUSIONS: Sexual behavior among female university students has gradually changed during the last 25 years and behavior appears more risky today. As this may have consequences on future reproductive health, it is vital to inform women about consistent and correct condom use and about the limitations of the fertile window.

Nutritional surveillance and weight loss in head and neck cancer patients.

PURPOSE: This retrospective single-institution cohort study aims to evaluate if therapeutic approach, tumour site, tumour stage, BMI, gender, age and civil status predict body weight loss and to establish the association between weight loss on postoperative infections and mortality. METHODS: Consecutive patients with head and neck cancer were seen for nutritional control at a nurse-led outpatient clinic and followed-up for 2 years after radiotherapy. Demographic, disease-specific and nutrition data were collected from case records. The primary outcome measure was maximum body weight loss during the whole study period. RESULTS: The nadir of body weight loss was observed 6 months after radiotherapy. In total, 92 patients of 157 (59%) with no evidence of residual tumour after treatment received enteral nutrition. The mean maximum weight loss for patients receiving enteral nutrition and per oral feeding was 13% and 6%, respectively (p < 0.001). Using multivariate analysis, tumour stage (p < 0.001) was the only independent factor of maximum weight loss. Weight loss was not significantly related to risk for postoperative infection. CONCLUSIONS: Weight loss is frequently noted among head and neck cancer patients during and after treatment. Weight loss was not found to be associated with postoperative infections and mortality. Nutritional surveillance is important in all patients, but special attention should be given to those on enteral nutrition and those with more advanced disease.

Explorative study on the predictive value of systematic inflammatory and metabolic markers on weight loss in head and neck cancer patients undergoing radiotherapy.

PURPOSE: This study aimed to explore the predictive value of systematic inflammatory and metabolic markers in head and neck (H&N) cancer patients during radiotherapy (RT). METHODS: Twenty-seven patients were evaluated. The protocol included serial blood tests [highly sensitive C-reactive protein (hsCRP), albumin, insulin-like growth factor 1 (IGF-1), IGF binding protein 1 (IGFBP-1) and ghrelin], measurements of body weight and assessment of oral mucositis. RESULTS: The mean nadir of weight loss was observed at the end of RT. At the time of diagnosis, mean hsCRP was 5.2 ± 1.0 mg/L. HsCRP significantly increased during RT and decreased during the post-RT period. Mean maximum hsCRP was 35.8 ± 8.5 mg/L, with seven patients reaching >40 mg/L. A numerical decrease of albumin (by 18.2%) and only small changes in IGF-1, IGFBP-1 and ghrelin levels were observed. None of the metabolic parameters was significantly associated with weight loss. CONCLUSIONS: HsCRP increased in response to RT for H&N cancer as a sign of irradiation-induced inflammation. Weight loss was not preceded by changes of the metabolic parameters, indicating that assessment of the blood markers used in this study is of little value. Regular body weight measurement and assessment of oral mucositis are feasible, cheap and important procedures to control the metabolic homeostasis during RT.