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).

Symptoms and quality of life among men starting treatment for metastatic castration-resistant prostate cancer - a prospective multicenter study.

BACKGROUND: Men with metastatic castration-resistant prostate cancer (mCRPC) have an incurable disease. Along with prolonging life, symptom management is one of the main goals with treatment. This is also important from a palliative care perspective where the life prolonging outcomes should be balanced with quality of life (QoL) in this late phase. It is also essential in symptom management to view different dimensions of symptoms, for example how severe or distressing symptoms are, to support best QoL. Therefore, more knowledge is needed about the symptom experience when these treatments are initiated and thus the aim of this study was to describe different dimensions of symptoms in men with mCRPC starting their first-line of life-prolonging treatment, and to describe the association between symptom burden and QoL. METHODS: Baseline data from a prospective longitudinal study of 143 men with mCRPC starting their first-line life-prolonging treatment were used. Symptoms were measured using the Memorial Symptom Assessment Scale (MSAS) and global QoL was measured by the EORTC QLQ C-30. Data was analyzed using descriptive- and multivariable linear regression analyses. RESULTS: On average, the men had more than 10 symptoms (range 0-31 of 33). 50% or more reported sweats, lack of energy, pain, problems with sexual activity and sexual desire. The symptoms they reported as most severe, or most distressing were not always the ones that were reported as most frequent. There was an association between QoL and physical symptoms, and also between QoL, and analgesic use and prostate-specific antigen (PSA) values. CONCLUSION: Even if some men with mCRPC report many symptoms, the dimensions of severity and distress levels vary, and the most frequent symptoms was not always the most burdensome or distressing. There was an association between high physical symptom burden and QoL, suggesting that it is not the number of symptoms that affects QoL but rather the subjective perceived impact of the physical symptoms experienced. The knowledge of how men with mCRPC experience and perceive their symptoms may help health care professionals in symptom management aiming to improve QoL, which is a cornerstone in integrating early palliative care.

Communication About Complementary and Alternative Medicine When Patients Decline Conventional Cancer Treatment: Patients' and Physicians' Experiences.

BACKGROUND: Complementary and alternative medicine (CAM) is a broad set of nonconventional practices used alongside or instead of conventional treatment: The latter poses obvious risks related to cancer prognosis. Patient-physician dialogue about CAM is crucial for patient safety and mutual trust. Little is known about communication in the rare situations when patients decline recommended cancer treatment and consider using CAM. The objective of this study was to explore patients' and physicians' experiences from situations when patients decline recommended cancer treatment and consider using CAM. MATERIALS AND METHODS: Semi-structured interviews were carried out with 7 CAM-using cancer patients who had declined some or all conventional treatment as well as 10 physicians from oncology and palliative care. Framework analysis was used. RESULTS: Regarding treatment choices, there was a dissonance between physicians' focus on medical reasoning and patients' expression of complex values. Physicians' difficulty in understanding patients' treatment decline was exacerbated when patients considered using CAM, impairing communication even further. Inequalities in roles resulting in power struggles risked pushing both parties toward extreme and inflexible standpoints. Despite these challenges regarding treatment choices and hierarchical roles, both parties considered open and respectful communication as crucial. CONCLUSIONS: This study highlights the difficulty of shared decision-making in practice when patients' and physicians' views on treatment decisions deviate in clinically challenging situations. Our results point to a need to address the complexity of these situations, pay attention to patients' values, and improve knowledge among physicians about CAM.

The Abbey Pain Scale: not sufficiently valid or reliable for assessing pain in patients with advanced cancer.

BACKGROUND: Patients with advanced cancer can be unable to verbalize their pain. The Abbey Pain Scale (APS), an observational tool, is used to assess pain in this setting, but has never been psychometrically tested for people with cancer. The aim of this study was to assess the validity, reliability, and the responsiveness of the APS to opioids for patients with advanced cancer in a palliative oncology care setting. MATERIAL AND METHODS: Patients with advanced cancer and poor performance status, drowsiness, unconsciousness, or delirium, were assessed for pain using a Swedish translation of the APS (APS-SE) and, if possible, the Numeric Rating Scale (NRS). The assessments using APS were conducted simultaneously, but independently, by the same raters on two separate occasions, approximately one hour apart. Criterion validity was assessed by comparing the APS and NRS values using Cohen's kappa (κ). Inter-rater reliability was determined using the intraclass correlation coefficient (ICC), internal consistency using Cronbach's α, and responsiveness to opioids using the Wilcoxon signed-rank test. RESULTS: Seventy-two patients were included, of whom n = 45 could rate their pain using the NRS. The APS did not detect any of the n = 22 cases of moderate or severe pain self-reported using the NRS. The APS at first assessment had a κ of 0.08 (CI: -0.06 to 0.22) for criterion validity, an ICC of 0.64 (CI: 0.43-0.78) for inter-rater reliability, and a Cronbach's α of 0.01 for internal consistency. The responsiveness to opioids was z = -2.53 (p = 0.01). CONCLUSION: The APS was responsive to opioids but displayed insufficient validity and reliability and did not detect moderate or severe pain as indicated by the NRS. The study showed a very limited clinical use of the APS in patients with advanced cancer.

The Abbey Pain Scale (APS), an observational pain assessment tool, is used in patients with cancer who cannot verbalize their pain. However, when psychometrically tested, the APS did not display sufficient validity or reliability, so it cannot be recommended for clinical use in patients with advanced cancer.

Physicians' and nurses' experience of using the Abbey Pain Scale (APS) in people with advanced cancer: a qualitative content analysis.

BACKGROUND: The Abbey Pain Scale (APS), an observational scale used to assess pain in people with end-stage dementia, is also widely used in Sweden to assess pain in patients with advanced cancer. It is unclear whether the APS is appropriate in this context. This study aims to explore physicians' and nurses' experiences of using a Swedish translation of the APS (the APS-SE) in people with advanced cancer. METHODS: Conventional qualitative content analysis was used to analyse interviews with physicians (n = 6) and nurses (n = 6) working in oncology and specialised palliative care about their experiences of using the APS-SE. RESULTS: Three categories were created: fills a need, not always on target, and does not fully suit the clinical situation. Participants reported that although the APS-SE provides support in a challenging situation, it sometimes misses the mark: it does not distinguish well between pain and other types of suffering and its pain score tends not to reflect professionals' intuitive perceptions of patients' suffering. Some parts of the APS-SE were not considered useful, and others were perceived as ethically questionable. CONCLUSION: Health professionals greatly need an observational pain assessment tool for people with advanced cancer. The APS-SE is helpful in this context, but participants did not perceive it as ideal. Its problems seem inherent to the original APS rather than related to its translation from English to Swedish. Further research is needed to provide a more suitable pain assessment tool for patients with advanced cancer.

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.

Signs and symptoms in relation to progression, experiences of an uncertain illness situation in men with metastatic castration-resistant prostate cancer-A qualitative study.

OBJECTIVE: Signs and symptoms are important in monitoring prostate cancer, but there is a lack of understanding about the men's interpretation of signs and symptoms in relation to disease progression in advanced phases of the disease. The aim was to illuminate the experience of signs and symptoms in relation to disease progression in men with metastatic castration-resistant prostate cancer (mCRPC). METHOD: Thirty longitudinal interviews were conducted with 11 men undergoing life-prolonging treatment for mCRPC. Conventional content analysis was used. RESULTS: The results illuminate an uncertainty that the men experience when interpreting signs and symptoms. The overarching theme was The experience of an uncertain illness situation within the framework of progression, with four subthemes: Symptoms triggering thoughts about disease progression; Making sense of signs, also in the absence of symptoms; Making sense of symptoms during treatment; Progression triggering thoughts about the remainder of life. CONCLUSION: In the uncertain illness situation, the men strive to make sense of signs and symptoms based on previous experiences and in relation to disease progression. Understanding the men's perspectives on signs and symptoms in this late phase may help health care professionals communicate about disease progression considering the balance between treatment outcome and quality of life.

Need of support perceived by patients primarily curatively treated for breast, colorectal, or prostate cancer and close to discharge from hospital-A qualitative study.

AIM: To describe perceived needs of support among patients close to discharge from the hospital and at the end of primary curative radiotherapy for breast, colorectal or prostate cancer. BACKGROUND: Few studies have specifically explored patients' early support needs when ending primary curative treatment. DESIGN: Qualitative interview study design. METHODS: A purposive sample of 27 participants with breast, colorectal or prostate cancer aged 33-88 years. The interviews were analysed by qualitative content analysis. Reporting followed the COREQ guidelines. RESULTS: Personal support to reach a sense of control and Social support for personal growth were two main themes, highlighting that people required adapted support from health care since needs of support could change over time. This support from health care was also relying on that trust-based relationships were developed. Through mutuality with others and engagement in meaningful activities people became enabled and felt further supported. Personal support from health care seems specifically important for the patients' feelings of control and could be a facilitator for patients to identify further support for personal growth in how to manage, on the one hand, illness and insecurity, and on the other, their well-being and everyday life with cancer. CONCLUSION: To empower patients who are ending primary treatment and being close to discharge from hospital, healthcare professionals should recognise patients' shifting needs and adapt the support. Adapted support is significant for patients' sense of safety. Biomedical information is not sufficient to fully support patients. RELEVANCE TO CLINICAL PRACTICE: Offering easy access to supportive care when primary treatment is finished could diminish people's stress, insecurity and avoidable use of healthcare services. Even after discharge, nurses preferably should adapt and offer support tailored to patients' needs. Such support may improve patients' sense of control and safety, trust in health care, feelings of community and encourage personal growth.

Identification of early symptoms and changes in QoL and functioning among men with primary localized prostate cancer who later develop metastases: A matched, prospective study.

OBJECTIVE: To identify early symptoms and changes in QoL among men with primary localized prostate cancer (PC) who later develop metastases. METHODS: From an ongoing prospective study of 3.885 men with localized PC, primarily treated with radiotherapy (RT), a subsample of men developing metastatic PC (mPC) following the first year after the start of RT and that had died during the follow-up (mPC group, n = 107) were matched against men who did not develop metastases (non-mPC group, n = 214). Data were collected using the EORTC QLQ-C30 and PCSS instruments. Non-parametric tests were performed for comparisons at baseline, end of RT, 3 months, and 1, 2, 3, and 5 years after RT. RESULTS: The final sample consists of 317 men (mPC n = 106; non-mPC n = 211) who had completed at least one questionnaire. Initially, symptom levels were generally low and QoL and functioning high in both groups. An increasing difference between the groups was found, where the mPC group gradually deteriorated from the 2-year follow-up. Significant differences were found for several outcomes at 3 and 5 years. In a sensitivity analysis, where metastatic patients were removed from the time-point of verified metastases, most differences did not remain significant. Significant deterioration over time was seen within both groups for some outcomes. SIGNIFICANCE OF RESULTS: The results indicate that unmet supportive needs occur over time among these men. Worsening QoL or functioning and symptoms may be difficult to recognize when the development is gradual over several years, and with various access to systematic follow-up in late phases. This highlights the need for continuous monitoring of PC patients to detect needs for supportive interventions early and throughout the disease course, also among those with non-metastatic disease who have undergone curatively intended treatment.

Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer (HYPO-RT-PC): patient-reported quality-of-life outcomes of a randomised, controlled, non-inferiority, phase 3 trial.

BACKGROUND: The HYPO-RT-PC trial compared conventionally fractionated radiotherapy with ultra-hypofractionated radiotherapy in patients with localised prostate cancer. Ultra-hypofractionation was non-inferior to conventional fractionation regarding 5-year failure-free survival and toxicity. We aimed to assess whether patient-reported quality of life (QOL) differs between conventional fractionation and ultra-hypofractionation up to 6 years after treatment in the HYPO-RT-PC trial. METHODS: HYPO-RT-PC is a multicentre, open-label, randomised, controlled, non-inferiority, phase 3 trial done in 12 centres (seven university hospitals and five county hospitals) in Sweden and Denmark. Inclusion criteria were histologically verified intermediate-to-high-risk prostate cancer (defined as T1c-T3a with one or two of the following risk factors: stage T3a; Gleason score ≥7; and prostate-specific antigen 10-20 ng/mL with no evidence of lymph node involvement or distant metastases), age up to 75 years, and WHO performance status 0-2. Participants were randomly assigned (1:1) to conventional fractionation (78·0 Gy in 39 fractions, 5 days per week for 8 weeks) or ultra-hypofractionation (42·7 Gy in seven fractions, 3 days per week for 2·5 weeks) via a minimisation algorithm with stratification by trial centre, T-stage, Gleason score, and prostate-specific antigen. QOL was measured using the validated Prostate Cancer Symptom Scale (PCSS) and European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) at baseline, the end of radiotherapy, months 3, 6, 12, and 24 after radiotherapy, every other year thereafter up to 10 years, and at 15 years. The primary endpoint (failure-free survival) has been reported elsewhere. Here we report QOL, a secondary endpoint analysed in the per-protocol population, up to 6 years after radiotherapy. The HYPO-RT-PC trial is registered with the ISRCTN registry, ISRCTN45905321. FINDINGS: Between July 1, 2005, and Nov 4, 2015, 1200 patients were enrolled and 1180 were randomly assigned (conventional fractionation n=591, ultra-hypofractionation n=589); 1165 patients (conventional fractionation n=582, ultra-hypofractionation n=583) were included in this QOL analysis. 158 (71%) of 223 patients in the conventional fractionation group and 146 (66%) of 220 in the ultra-hypofractionation group completed questionnaires at 6 years. The median follow-up was 48 months (IQR 25-72). In seven of ten bowel symptoms or problems the proportion of patients with clinically relevant deteriorations at the end of radiotherapy was significantly higher in the ultra-hypofractionation group than in the conventional fractionation group (stool frequency [p<0·0001], rush to toilet [p=0·0013], flatulence [p=0·0013], bowel cramp [p<0·0001], mucus [p=0·0014], blood in stool [p<0·0001], and limitation in daily activity [p=0·0014]). There were no statistically significant differences in the proportions of patients with clinically relevant acute urinary symptoms or problems (total 14 items) and sexual functioning between the two treatment groups at end of radiotherapy. Thereafter, there were no clinically relevant differences in urinary, bowel, or sexual functioning between the groups. At the 6-year follow-up there was no difference in the incidence of clinically relevant deterioration between the groups for overall urinary bother (43 [33%] of 132 for conventional fractionation vs 33 [28%] of 120 for ultra-hypofractionation; mean difference 5·1% [95% CI -4·4 to 14·6]; p=0·38), overall bowel bother (43 [33%] of 129 vs 34 [28%] of 123; 5·7% [-3·8 to 15·2]; p=0·33), overall sexual bother (75 [60%] of 126 vs 59 [50%] of 117; 9·1% [-1·4 to 19·6]; p=0·15), or global health/QOL (56 [42%] of 134 vs 46 [37%] of 125; 5·0% [-5·0 to 15·0]; p=0·41). INTERPRETATION: Although acute toxicity was higher for ultra-hypofractionation than conventional fractionation, this long-term patient-reported QOL analysis shows that ultra-hypofractionation was as well tolerated as conventional fractionation up to 6 years after completion of treatment. These findings support the use of ultra-hypofractionation radiotherapy for intermediate-to-high-risk prostate cancer. FUNDING: The Nordic Cancer Union, the Swedish Cancer Society, and the Swedish Research Council.

Clinical characteristics and factors associated with COVID-19-related death and morbidity among hospitalized patients with cancer: a Swedish cohort study.

INTRODUCTION: Cancer patients are considered to have a higher risk of dying and developing severe Coronavirus Disease 2019 (COVID-19). To date, there are few studies including co-morbidities and sociodemographic factors when investigating the outcome of COVID-19 in a cohort of cancer patients. In this study, we analyzed cancer patients that have been hospitalized due to COVID-19 during the first wave of the pandemic in Sweden to investigate the impact of COVID-19 on mortality and morbidity. PATIENTS AND METHODS: We retrospectively collected data on all patients with cancer that were hospitalized due to COVID-19-related symptoms at Uppsala University Hospital and Karolinska University Hospital between 1 March and 31 August 2020. The primary endpoint was COVID-19-related death and the secondary endpoint was to describe COVID-19 severity, defined as symptom severity (grades 0-4) and length of stay (LOS) at the university hospitals. RESULTS: In total, 193 patients were included among which 31% died due to COVID-19 and 8% died of other causes. In a multivariable analysis, older age >70 (OR 3.6; 95% CI [1.8-7.3], p < 0.001) and male gender (OR 2.8 [1.4-5.8], p = 0.005) were factors associated with higher likelihood of COVID-19-related death. Several comorbidities ≥2 (OR 5.4 [2.0-14.3], p = 0.001) was independently associated with COVID-19 severity. Treatment with chemotherapy within 90 days prior to COVID-19 diagnosis were not associated with COVID-19-related death or severity. CONCLUSION: Factors associated with higher likelihood of COVID-19-related death were older age and male gender. More severe COVID-19 symptoms were seen in patients with multiple comorbidities. We did not see any associations between COVID-19-related death or severity and recent treatment including chemotherapy. In summary, this supports a thorough assessment regarding potential risks with COVID-19 infection in patients with cancer, with a combination of individual risk factors in addition to cancer treatments.

Factors associated with healthcare utilisation during first year after cancer diagnose-a population-based study.

BACKGROUND: Improved cancer treatments and models of care (such as early palliative care) has developed during recent years. Aspects of healthcare utilisation-unplanned care have been used for evaluation of coordination and quality. The aim was to explore factors associated with cancer healthcare utilisation, during the first year after a cancer diagnosis. METHODS: Population-based registry and patient-reported data, (The European Organisation of Research and Treatment of Cancer (EORTC), QLQ- C30 questionnaire and study-specific questions) were collected. Descriptive statistics and multivariate regression models were performed. RESULTS: The sample consists of 1718 patients (haematological, gynaecological, upper gastrointestinal and head and neck cancers). Living alone were associated with unplanned hospital admissions (OR 1.35; 95% CI [1.15, 1.59], p < 0.001). Patients with specialised palliative home care had a higher likelihood of unplanned hospital admissions, (OR 4.35; 95% CI [3.22-5.91], p < 0.001) and re-admissions within 30 days, (OR, 5.8; 95% CI [4.12-8.19], p < 0.001). CONCLUSIONS: Sociodemographic and clinical factors, such as living alone and disease stage, is associated with healthcare utilisation. Patients with specialised palliative home care report lower levels of HRQoL and higher levels of unplanned care, and our findings stresses the importance of a holistic view when planning care.

Development and initial psychometric evaluation of a radiotherapy-related symptom assessment tool, based on data from patients with brain tumours undergoing proton beam therapy.

BACKGROUND: Currently, no available tool easily and effectively measures both the frequency, intensity and distress of symptoms among patients receiving radiotherapy. A core symptom set (fatigue, insomnia, pain, appetite loss, cognitive problems, anxiety, nausea, depression, constipation, diarrhoea and skin reaction) has been identified and assessed across oncology research to better understand the pattern of symptoms and treatment side effects. AIM: The aim was to develop a tool measuring the multiple-symptom experience in patients undergoing radiotherapy and evaluate its psychometric properties (validity, reliability and responsiveness). DESIGN: This study has a prospective, longitudinal and quantitative design. METHODS: We developed a patient-reported outcome questionnaire, the Radiotherapy-Related Symptoms Assessment Scale to assess the frequency, intensity and distress associated with symptoms. Patients (n = 175) with brain tumours undergoing proton beam therapy completed the Radiotherapy-Related Symptoms Assessment Scale and the health-related quality of life questionnaire (EORTC QLQ-C30) during treatment. We assessed the validity, reliability and responsiveness of the Radiotherapy-Related Symptoms Assessment Scale and evaluated the validity against QLQ-C30. RESULTS: There were significant questionnaire-questionnaire correlations regarding selected items, primarily fatigue, insomnia and pain, indicating satisfactory criterion-related validity. The Radiotherapy-Related Symptoms Assessment Scale had fair to good retest reliability. CONCLUSION: The Radiotherapy-Related Symptoms Assessment Scale is a valid instrument for assessing symptom intensity and distress in patients with brain tumour undergoing PBT, with psychometric properties within the expected range. The Radiotherapy-Related Symptoms Assessment Scale provides nurses with substantial information on symptom experience but requires little effort from the patient. Additional studies are required to further assess the psychometric properties in patients with different cancer diagnoses receiving conventional radiotherapy.

Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial.

BACKGROUND: Hypofractionated radiotherapy for prostate cancer has gained increased attention due to its proposed high radiation-fraction sensitivity. Recent reports from studies comparing moderately hypofractionated and conventionally fractionated radiotherapy support the clinical use of moderate hypofractionation. To date, there are no published randomised studies on ultra-hypofractionated radiotherapy. Here, we report the outcomes of the Scandinavian HYPO-RT-PC phase 3 trial with the aim to show non-inferiority of ultra-hypofractionation compared with conventional fractionation. METHODS: In this open-label, randomised, phase 3 non-inferiority trial done in 12 centres in Sweden and Denmark, we recruited men up to 75 years of age with intermediate-to-high-risk prostate cancer and a WHO performance status between 0 and 2. Patients were randomly assigned to ultra-hypofractionation (42·7 Gy in seven fractions, 3 days per week for 2·5 weeks) or conventional fractionated radiotherapy (78·0 Gy in 39 fractions, 5 days per week for 8 weeks). No androgen deprivation therapy was allowed. The primary endpoint was time to biochemical or clinical failure, analysed in the per-protocol population. The prespecified non-inferiority margin was 4% at 5 years, corresponding to a critical hazard ratio (HR) limit of 1·338. Physician-recorded toxicity was measured according to the Radiation Therapy Oncology Group (RTOG) morbidity scale and patient-reported outcome measurements with the Prostate Cancer Symptom Scale (PCSS) questionnaire. This trial is registered with the ISRCTN registry, number ISRCTN45905321. FINDINGS: Between July 1, 2005, and Nov 4, 2015, 1200 patients were randomly assigned to conventional fractionation (n=602) or ultra-hypofractionation (n=598), of whom 1180 (591 conventional fractionation and 589 ultra-hypofractionation) constituted the per-protocol population. 1054 (89%) participants were intermediate risk and 126 (11%) were high risk. Median follow-up time was 5·0 years (IQR 3·1-7·0). The estimated failure-free survival at 5 years was 84% (95% CI 80-87) in both treatment groups, with an adjusted HR of 1·002 (95% CI 0·758-1·325; log-rank p=0·99). There was weak evidence of an increased frequency of acute physician-reported RTOG grade 2 or worse urinary toxicity in the ultra-hypofractionation group at end of radiotherapy (158 [28%] of 569 patients vs 132 [23%] of 578 patients; p=0·057). There were no significant differences in grade 2 or worse urinary or bowel late toxicity between the two treatment groups at any point after radiotherapy, except for an increase in urinary toxicity in the ultra-hypofractionation group compared to the conventional fractionation group at 1-year follow-up (32 [6%] of 528 patients vs 13 [2%] of 529 patients; (p=0·0037). We observed no differences between groups in frequencies at 5 years of RTOG grade 2 or worse urinary toxicity (11 [5%] of 243 patients for the ultra-hypofractionation group vs 12 [5%] of 249 for the conventional fractionation group; p=1·00) and bowel toxicity (three [1%] of 244 patients vs nine [4%] of 249 patients; p=0·14). Patient-reported outcomes revealed significantly higher levels of acute urinary and bowel symptoms in the ultra-hypofractionation group compared with the conventional fractionation group but no significant increases in late symptoms were found, except for increased urinary symptoms at 1-year follow-up, consistent with the physician-evaluated toxicity. INTERPRETATION: Ultra-hypofractionated radiotherapy is non-inferior to conventionally fractionated radiotherapy for intermediate-to-high risk prostate cancer regarding failure-free survival. Early side-effects are more pronounced with ultra-hypofractionation compared with conventional fractionation whereas late toxicity is similar in both treatment groups. The results support the use of ultra-hypofractionation for radiotherapy of prostate cancer. FUNDING: The Nordic Cancer Union, the Swedish Cancer Society, and the Swedish Research Council.

Exploring the effects of deep brain stimulation and vision on tremor in Parkinson's disease - benefits from objective methods.

BACKGROUND: Tremor is a cardinal symptom of Parkinson's disease (PD) that may cause severe disability. As such, objective methods to determine the exact characteristics of the tremor may improve the evaluation of therapy. This methodology study aims to validate the utility of two objective technical methods of recording Parkinsonian tremor and evaluate their ability to determine the effects of Deep Brain Stimulation (DBS) of the subthalamic nucleus and of vision. METHODS: We studied 10 patients with idiopathic PD, who were responsive to L-Dopa and had more than 1 year use of bilateral subthalamic nucleus stimulation. The patients did not have to display visible tremor to be included in the study. Tremor was recorded with two objective methods, a force platform and a 3 dimensional (3D) motion capture system that tracked movements in four key proximal sections of the body (knee, hip, shoulder and head). They were assessed after an overnight withdrawal of anti-PD medications with DBS ON and OFF and with eyes open and closed during unperturbed and perturbed stance with randomized calf vibration, using a randomized test order design. RESULTS: Tremor was detected with the Unified Parkinson's Disease Rating Scale (UPDRS) in 6 of 10 patients but only distally (hands and feet) with DBS OFF. With the force platform and the 3D motion capture system, tremor was detected in 6 of 10 and 7 of 10 patients respectively, mostly in DBS OFF but also with DBS ON in some patients. The 3D motion capture system revealed that more than one body section was usually affected by tremor and that the tremor amplitude was non-uniform, but the frequency almost identical, across sites. DBS reduced tremor amplitude non-uniformly across the body. Visual input mostly reduced tremor amplitude with DBS ON. CONCLUSIONS: Technical recording methods offer objective and sensitive detection of tremor that provide detailed characteristics such as peak amplitude, frequency and distribution pattern, and thus, provide information that can guide the optimization of treatments. Both methods detected the effects of DBS and visual input but the 3D motion system was more versatile in that it could detail the presence and properties of tremor at individual body sections.

Evaluation of quality of care in relation to health-related quality of life of patients diagnosed with brain tumor: a novel clinic for proton beam therapy.

PURPOSE: Patients with brain tumors constitute a vulnerable group, and it is important that they receive the highest quality of care (QoC). The study aim was to describe the perceptions of QoC and its association with health-related quality of life in brain tumor patients undergoing proton beam therapy in a newly established clinic. METHOD: Data were collected at the start of treatment and after 3 and 6 weeks. Adult patients (≥ 18 years old) with brain tumors (n = 186) completed two self-administered questionnaires: a modified Quality from the Patients' Perspective, which measures perceived reality and subjective importance of care, and the EORTC QLQ-C30. Data were analyzed using parametric and non-parametric statistical tests. RESULTS: The perceived QoC was highest for treatment information and lowest for dietician and smoking information, whereas interaction with doctors and nurses was rated as the most important aspect of quality of care. Subjective importance ratings were significantly higher than perceived reality ratings for 60% of items. A better global health was moderately correlated with a higher perceived support for fatigue. CONCLUSIONS: A need for quality improvement was identified for several aspects of patient care. Greater symptom distress during the treatment period led to greater perceived importance of symptom support. Ensuring QoC is complex and collaboration with other health care professionals is essential. RELEVANCE TO CLINICAL PRACTICE: The clinic could improve QoC regarding information about possible symptoms, adjust care according to patient perceptions of importance, and involve patients in care decisions.

Prostate-specific antigen (PSA) and distress: - a cross-sectional nationwide survey in men with prostate cancer in Sweden.

BACKGROUND: The prostate-specific antigen (PSA) -value is often used during the prostate cancer trajectory as a marker of progression or response to treatment. Concerns about PSA-values are often expressed by patients in clinical situations. Today there is a lack of larger studies that have investigated the association between PSA-value and distress. The aim was to investigate the association between PSA-values and distress adjusted for sociodemographic factors, hormonal therapy and quality of life (QoL), among men with prostate cancer. METHODS: In this cross-sectional survey of 3165 men with prostate cancer, members of the Swedish Prostate Cancer Federation, answered questions about sociodemographic factors, PSA, distress, QoL and treatments. Descriptive statistics, and bivariate and multivariable analyses were performed. The result was presented based on four PSA-value groups: 0-19, 20-99, 100-999, and ≥ 1000 ng/ml. RESULTS: Of the men, 53% experienced distress. An association between distress and PSA-values was found where higher PSA-values were associated with higher OR:s for experiencing distress in the different PSA-groups: 0-19 ng/ml (ref 1), 20-99 ng/ml (OR 1.25, 95% CI 1.01-1.55), 100-999 ng/ml (OR 1.47, 95% CI 1.12-1.94), ≥1000 ng/ml (OR 1.77, 95% CI 1.11-2.85). These associations were adjusted for sociodemographic factors and hormonal therapy. In the multivariable analyses, beside PSA-values, higher levels of distress were associated with being without partner or hormonal therapy. When adding QoL in the multivariable analysis, the association between PSA and distress did not remain significant. CONCLUSION: These results indicate that the PSA-values are associated with distress, especially for those with higher values. However, to be able to support these men, continued research is needed to gain more knowledge about the mechanisms behind the association between emotional distress and PSA-values.

Different Visual Weighting due to Fast or Slow Vestibular Deafferentation: Before and after Schwannoma Surgery.

Background: Feedback postural control depends upon information from somatosensation, vision, and the vestibular system that are weighted depending on their relative importance within the central nervous system. Following loss of any sensory component, the weighting changes, e.g., when suffering a vestibular loss, the most common notion is that patients become more dependent on visual cues for maintaining postural control. Dizziness and disequilibrium are common after surgery in schwannoma patients, which could be due to interpretation of the remaining sensory systems involved in feedback-dependent postural control and spatial orientation. Objective: To compare visual dependency in spatial orientation and postural control in patients suffering from unilateral vestibular loss within different time frames. Methods: Patients scheduled for schwannoma surgery: group 1 (n = 27) with no vestibular function prior to surgery (lost through years), group 2 (n = 12) with remaining vestibular function at the time of surgery (fast deafferentation), and group 3 (n = 18) with remaining function that was lost through gentamicin installations in the middle ear (slow deafferentation). All patients performed vibratory posturography and rod and frame investigation before surgery and 6 months after surgery. Results: Postural control improved after surgery in patients that suffered a slow deafferentation (groups 1 and 3) (p < 0.001). Patients that suffered fast loss of remaining vestibular function (group 2) became less visual field dependent after surgery (p ≤ 0.035) and were less able to maintain stability compared with group 1 (p = 0.010) and group 3 (p = 0.010). Conclusions: The nature and time course of vestibular deafferentation influence the weighting of remaining sensory systems in order to maintain postural control and spatial orientation.

Prognosis is similar for patients who undergo primary PCI during regular-hours and off-hours: A report from SCAAR.

BACKGROUND: Timely percutaneous coronary intervention (PCI) improves prognosis in ST-elevation myocardial infarction (STEMI). However, recent reports indicate that patients with STEMI who present during non-regular working hours (off-hours) have a worse prognosis. The aim of this study was to compare outcome between patients with STEMI who underwent primary PCI during off-hours and regular hours. METHODS: We retrieved data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) for all patients who underwent primary PCI in Region Västra Götaland due to STEMI between January 2004 and May 2013. We modeled unadjusted and adjusted Cox proportional-hazards regression and logistic regression models for the outcomes death, cardiogenic shock, stent thrombosis and in-stent restenosis. A propensity score-adjusted Cox proportional-hazards model, which adjusted for traditional cardiovascular risk factors was predefined as the primary statistical model. Death at any time during the study period was pre-specified as primary end-point. RESULTS: During the study period 4.611 (65%) patients underwent primary PCI due to STEMI during off-hours and 2,525 (35%) during regular hours. The risk of dying was similar among the groups for the primary endpoint death at any time during the study period (HR 1.00, 95% CI 0.89-1.12, P = 0.991) and for secondary end-point death within 30 days (HR 1.03; 95% CI 0.85-1.25, P = 0.735). The risks of developing cardiogenic shock, stent thrombosis, or in-stent restenosis were similar between the groups. CONCLUSIONS: In our region, short- and long-term prognosis for patients with STEMI who undergo primary PCI is similar for patients presenting during off-hours and regular hours.

Quality of life in men with metastatic prostate cancer in their final years before death - a retrospective analysis of prospective data.

BACKGROUND: Quality of Life (QoL) is the most important outcome for patients in palliative care along with symptom alleviation. Metastatic prostate cancer (mPC) is a life-threatening illness, and hence, a palliative care approach may be beneficial to this group. Over time, new life-prolonging treatments have been developed for men with mPC, but the possibility to prolong life should also be balanced against the men's QoL, particularly because there are side effects involved with these treatments. The aim of this study was to evaluate QoL, functioning and symptoms in men with mPC during their final years before death. METHODS: This is a retrospective analysis of data from a long-term prospective study of men (n = 3885) with prostate cancer from two regions in Sweden. Validated questionnaires asking about participants' QoL, functioning and symptoms were used to collect data. From the overall study, 190 men with mPC were identified. They were stratified into three groups, depending on the amount of time that had passed between the last questionnaire and their death; < 6 months, 6-18 months and > 18 months before death. RESULTS: Men with mPC generally rated their QoL poorly compared to established clinically significant threshold values. The group of men that were < 6 months before death rated their QoL, functioning and several symptoms significantly worse than the two other groups. Men that died after the year 2006 reported lower QoL and functioning and more pain and fatigue than those who died before 2006. CONCLUSION: The results in this study indicate that men with mPC have unmet needs with regards to QoL and symptoms. A palliative care approach, alongside possible life-prolonging treatments, that focuses on QoL and symptom relief, may serve as an important frame to give the best support to these men in their final years of life.