The feasibility of a multidimensional intervention in lymphoma survivors with chronic fatigue.

PURPOSE: Chronic fatigue (CF) affects 25-30% of lymphoma survivors, but interventions designed to reduce fatigue are lacking. The main aim of this study was to test the feasibility of a multidimensional intervention study in lymphoma survivors with CF. Secondary aims were to describe individual changes in fatigue, quality of life (QoL) and physical performance from pre (T0) to post (T1) intervention. METHODS: This feasibility study was as a one-armed intervention study performed in 2021. Hodgkin or aggressive non-Hodgkin lymphoma survivors received mailed study information and Chalder Fatigue Questionnaire and were asked to respond if they suffered from fatigue. The 12-week intervention included patient education, physical exercise, a cognitive behavioural therapy (CBT)-based group program and nutritional counselling. Feasibility data included patient recruitment, completion of assessments, adherence to the intervention and patient-reported experience measures. Participants responded to questionnaires and underwent physical tests at T0 and T1. RESULTS: Seven lymphoma survivors with CF were included. Of all assessments, 91% and 83% were completed at T0 and T1, respectively. Adherence to the interventional components varied from 69% to 91%. At T1, all participants rated exercise as useful, of whom five rated the CBT-based program and five rated individual nutritional counselling as useful. Five participants reported improved fatigue, QoL and physical performance. CONCLUSION: Lymphoma survivors with CF participating in a multidimensional intervention designed to reduce the level of fatigue showed high assessment completion rate and intervention adherence rate. Most of the participants evaluated the program as useful and improved their level of fatigue, QoL and physical performance after the intervention. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT04931407. Registered 16. April 2021-Retrospectively registered. https://www. CLINICALTRIALS: gov/ct2/show/NCT04931407.

Work status changes and associated factors in a nationwide sample of Norwegian long-term breast cancer survivors.

PURPOSE: The study aims to describe work status at diagnosis and 8 years post-diagnosis in a nationwide sample of breast cancer survivors (BCSs), and investigate associated and self-reported factors of reduced work status. METHODS: Women aged 20-65 years when diagnosed with stage I-III breast cancer (BC) in 2011 or 2012 were invited to participate in a questionnaire study in 2019 (n = 2803), of whom 49% (n = 1361) responded. For this sub-study, we included 974 BCSs below the legal retirement age in Norway (< 67 years) at survey and with complete work status data. Reduced work status was defined as being in paid work at BC diagnosis and not working at time of survey. Logistic regression analyses were applied to identify factors associated with reduced work status. RESULTS: Of BCSs who were in paid work at diagnosis (n = 845), 63% maintained their work status to 8 years later. Reduced work status was associated with not living with children (OR .44, 95% CI .24-.82), age (OR 1.16, 95% CI 1.11-1.21), chemotherapy (OR 2.83, 95% CI 1.24-6.61), > 2 comorbid conditions (OR 2.27, 95% CI 1.16-4.32), cognitive function (OR .99, 95% CI .98-.99), fatigue (OR 1.02, 95% CI 1.01-1.03), and neuroticism (OR 1.57, 95% CI 1.00-2.46). BC and late effects were reported as reasons for reduced work status and disability. CONCLUSIONS: The majority of BCSs who were in paid work at diagnosis were working 8 years later. IMPLICATIONS FOR CANCER SURVIVORS: Our results suggest a need to focus on fatigue and reduced cognitive function among long-term BCSs, with the ultimate aim of improving work sustainability.

Effects and moderators of exercise on sleep in adults with cancer: Individual patient data and aggregated meta-analyses.

OBJECTIVES: To evaluate the effects of exercise interventions on sleep disturbances and sleep quality in patients with mixed cancer diagnoses, and identify demographic, clinical, and intervention-related moderators of these effects. METHODS: Individual patient data (IPD) and aggregated meta-analyses of randomized controlled trials (RCTs). Using data from the Predicting OptimaL cAncer RehabIlitation and Supportive care project, IPD of 2173 adults (mean age = 54.8) with cancer from 17 RCTs were analyzed. A complementary systematic search was conducted (until November 2018) to study the overall effects and test the representativeness of analyzed IPD. Effect sizes of exercise effects on self-reported sleep outcomes were calculated for all included RCTs. Linear mixed-effect models were used to evaluate the effects of exercise on post-intervention outcome values, adjusting for baseline values. Moderator effects were studied by testing interactions for demographic, clinical and intervention-related characteristics. RESULTS: For all 27 eligible RCTs from the updated search, exercise interventions significantly decreased sleep disturbances in adults with cancer (g = -0.09, 95% CI [-0.16; -0.02]). No significant effect was obtained for sleep quality. RCTs included in IPD analyses constituted a representative sample of the published literature. The intervention effects on sleep disturbances were not significantly moderated by any demographic, clinical, or intervention-related factor, nor by sleep disturbances. CONCLUSIONS: This meta-analysis provides some evidence that, compared to control conditions, exercise interventions may improve sleep disturbances, but not sleep quality, in cancer patients, although this effect is of a small magnitude. Among the investigated variables, none was found to significantly moderate the effect of exercise interventions on sleep disturbances.

The effect of strength training on muscle cellular stress in prostate cancer patients on ADT.

BACKGROUND: Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with several side effects, including loss of muscle mass. Muscle atrophy is associated with reduced mitochondrial function and increased muscle cellular stress that may be counteracted by strength training. Thus, the aim of this study was to investigate the effect of strength training on mitochondrial proteins and indicators of muscle cellular stress in PCa patients on ADT. METHODS: Men diagnosed with locally advanced PCa receiving ADT were randomised to a strength training group (STG) (n=16) or a control group (CG) (n=15) for 16 weeks. Muscle biopsies were collected pre- and post-intervention from the vastus lateralis muscle, and analysed for mitochondrial proteins (citrate synthase, cytochrome c oxidase subunit IV (COXIV), HSP60) and indicators of muscle cellular stress (heat shock protein (HSP) 70, alpha B-crystallin, HSP27, free ubiquitin, and total ubiquitinated proteins) using Western blot and ELISA. RESULTS: No significant intervention effects were observed in any of the mitochondrial proteins or indicators of muscle cellular stress. However, within-group analysis revealed that the level of HSP70 was reduced in the STG and a tendency towards a reduction in citrate synthase levels was observed in the CG. Levels of total ubiquitinated proteins were unchanged in both groups. CONCLUSION: Although reduced HSP70 levels indicated reduced muscle cellular stress in the STG, the lack of an intervention effect precluded any clear conclusions.

Effects of strength training on muscle cellular outcomes in prostate cancer patients on androgen deprivation therapy.

Androgen deprivation therapy (ADT) improves life expectancy in prostate cancer (PCa) patients, but is associated with adverse effects on muscle mass. Here, we investigated the effects of strength training during ADT on muscle fiber cross-sectional area (CSA) and regulators of muscle mass. PCa patients on ADT were randomized to 16 weeks of strength training (STG) (n = 12) or a control group (CG; n = 11). Muscle biopsies were obtained from m. vastus lateralis and analyzed by immunohistochemistry and western blot. Muscle fiber CSA increased with strength training (898 µm(2) , P = 0.04), with the only significant increase observed in type II fibers (1076 µm(2) , P = 0.03). There was a trend toward a difference in mean change between groups myonuclei number (0.33 nuclei/fiber, P = 0.06), with the only significant increase observed in type I fibers, which decreased the myonuclear domain size of type I fibers (P = 0.05). Satellite cell numbers and the content of androgen receptor and myostatin remained unchanged. Sixteen weeks of strength training during ADT increased type II fiber CSA and reduced myonuclear domain in type I fibers in PCa patients. The increased number of satellite cells normally seen following strength training was not observed.

Interest and preferences for exercise counselling and programming among Norwegian cancer survivors.

To be able to make suitable exercise intervention programmes for cancer survivors, we need more information about exercise preferences. The primary aim of the study was to investigate the interest and preferences for exercise among Norwegian cancer survivors. A secondary aim was to identify demographic and medical characteristics associated with interest in exercise counselling. A questionnaire was completed by 1284 cancer survivors. Overall, 76% of participants were interested or maybe interested in receiving exercise counselling at some point during their cancer experience. Logistic regression analyses indicated that the interest in exercise counselling in men was associated with younger age, presence of comorbidity and having received chemotherapy. In women, the interest was associated with younger age, higher education and change in physical activity level. The participants preferred face-to-face exercise counselling with an exercise specialist from a cancer centre, at a hospital, immediately after treatment. Most cancer survivors were interested in an exercise programme, walking as activity, at moderate intensity and they wanted to start immediately after treatment. The knowledge from this study can contribute to make suitable physical rehabilitation available to cancer patients in the future.

Radiotherapy reduces sialorrhea in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. Sialorrhea is a frequent problem in ALS patients with bulbar symptoms, because of progressive weakness of oral, lingual and pharyngeal muscles. This prospective study aimed to investigate the putative effect of palliative single-dose radiotherapy on problematic sialorrhea in patients with ALS. Twenty patients with ALS and problematic drooling were included; 14 were given radiotherapy with a single fraction of 7.5 Grey (Gy). Five patients were treated with botulinum toxin A (BTX-A) injections (20 U) into the parotid glands; two of these were later given radiotherapy. Symptom assessment, clinical examination and measurements of salivary flow (ml/min) were performed before and after treatment (1-2 weeks, 3 months). Salivary secretion was significantly reduced after radiation treatment, with a mean reduction of 60% (1 week) and 51% (2 weeks). Three months post-treatment, 21% reduction of the salivary secretion was observed compared with salivation before treatment. Mean salivary flow was not reduced after BTX-A treatment in five patients. No serious side-effects were observed with either of the two treatment modalities. Single-dose radiotherapy (7.5 Gy) significantly reduces sialorrhea and is an effective and safe palliative treatment in patients with ALS.

Cardiorespiratory fitness in relation to self-reported physical function in cancer patients after chemotherapy.

AIM: The aim of this study was to estimate the association between objective cardiorespiratory fitness (CRF) and subjective self-reported physical function, taking into account the influence of mental distress. We hypothesized an association between these parameters, since they might be thought to measure parts of the same phenomenon. METHODS: Approximately 1 month after discontinuation of all primary treatment, 90 cancer patients aged 18-50 years treated with chemotherapy were surveyed. CRF was determined by the Astrand-Ryhming indirect cycle ergometer test, which indicate peak VO2 in mL x kg(-1) x min(-1) (predicted VO2max). Self-reported physical function was assessed by The European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). The relation between VO2max and self-reported physical function was estimated by multiple linear regression. Mental distress (assessed by The Hospital Anxiety and Depression scale), age, gender, body mass index (BMI), time from treatment to physical test and diagnoses were included as potential confounders. RESULTS: There was no association between predicted VO2max and self-reported physical function. Mental distress was negatively associated with self-reported physical function (P<0.001), but is not associated with predicted VO2max. CONCLUSIONS: The results suggest that predicted VO2max does not reflect self-reported physical function and vice versa in cancer patients after chemotherapy. If information about cardiac and/or pulmonary status is required, direct or indirect measures of VO2max should be used.

The level of physical activity in long-term survivors of testicular cancer.

The aim of this study was to estimate the level of physical activity (LPA) in a large cohort of testicular cancer survivors (TCSs) and compare these results with observations from men in the same age range in the general population (GenPop). We also wanted to identify parameters that influenced physical activity. The study populations consisted of 1276 TCSs treated with surgery, radiotherapy or chemotherapy with or without surgery (mean observation time was 12 years), and 20391 male inhabitants from a Norwegian county (GenPop). All completed a question investigating two sub-levels of physical activity. The logistic regression analysis adjusting for different covariates, showed significantly more physically active men among the TCSs compared with the GenPop (43 versus 37%) (adjusted odds ratio (aOR)=1.32 (95% Confidence Interval (CI) 1.10-1.58)). The results indicate that the experience of testicular cancer increases rather than reduces the LPA in TCSs, independent of treatment given.

Interactions of human blood platelets with three circulating plasma fibrinogens of different molecular weights.

The ability of three naturally occurring human fibrinogen species, HMW, LMW and LMW', to support ADP-induced platelet aggregation was investigated and compared to their ability to bind to gel-filtered platelets. Whereas HMW had intact subunit chains, LMW and LMW' had defined lesions in the C-terminal part of one (LMW) or both (LMW') of the A alpha-chains. The ADP-induced aggregation of gel-filtered platelets in the presence of LMW was about 75 per cent of that obtained with HMW (0.2 mumol/l of fibrinogen and 10 mumol/l of ADP). A mixture of equal amounts of LMW and LMW' showed around 50% decrease in aggregation. Compared to these difference in aggregation co-factor function, direct binding to gel-filtered platelets was less affected by the A alpha-chain degradation. However, a difference between LMW, LMW' and HMW binding was significant when the fibrinogens labelled with two different isotopes of iodine were present simultaneously. These results demonstrate that naturally occurring plasma fibrinogens differ in their interactions with platelets. As the HMW/LMW ratio changes during the acute phase, this may be of physiological significance.

Competitions between fibrinogen with its degradation products for interactions with the platelet-fibrinogen receptor.

Direct binding of 125-I-labelled plasmic and CNBr-derived fibrin (ogen) fragments (pre-X, X, Y, D, Degta, Efg, E1, N-DSK, N-dsk) to gel-filtered platelets was compared to their ability to support or inhibit ADP-induced aggregation, and to compete with fibrinogen for binding to ADP-stimulated platelets. Pre-X was the only fragment that supported aggregation. All fragments tested except for E derived from fibrinogen (Efg) and Degta bound specifically to the platelets and inhibited ADP-induced aggregation in the presence of fibrinogen. Competitive binding studies with fibrinogen and fragments labelled with different isotopes of iodine, or inhibition of binding of labelled fibrinogen with unlabelled fragments showed that all of the fragments except Efg and Degta were able to compete with fibrinogen for binding. When simultaneous binding of N-dsk and fibrinogen was studied, an increased binding of both ligands was observed probably due to complex formation. The results fully agree with previous findings of binding to immunoprecipitated glycoprotein IIb-IIIa after crossed immunoelectrophoresis. We conclude that the fibrinogen molecule contains at least six sequences responsible for platelet interaction, two in the E domain and two in each of the C-terminal parts of the fibrinogen molecule.

Increased binding to ADP-stimulated platelets and aggregation effect of the dysfibrinogen Oslo I as compared with normal fibrinogen.

Interactions of the dysfibrinogen Oslo I with platelets were investigated. This fibrinogen is a B beta-chain variant with faster than normal fibrin monomer polymerization. Fibrinogen Oslo I acted more efficiently in ADP-induced platelet aggregation, and bound to gel-filtered platelets with a higher affinity constant than did normal fibrinogen. At all concentrations more fibrinogen molecules became bound per platelet with the dysfibrinogen than with normal fibrinogen, both when the fibrinogens were tested separately or as a mixture using 125I or 131I to label the two types. At high concentrations this was probably due to ligand polymerization of the dysfibrinogen. These observations indicate that the increased cofactor function in platelet aggregation may be related to the increased affinity of the dysfibrinogen for the platelets.