Adipokines including leptin, adiponectin and resistin have been linked to risk of obesity-related cancers potentially through low-grade chronic inflammation pathways. We aimed to assess the role of ...post-diagnosis circulating adipokines on long-term prognosis in a prospective breast cancer cohort. Adipokines were measured in blood collected at baseline shortly after diagnosis (2002-2005) and at follow-up (2009) from 3112 breast cancer patients enrolled in the population-based MARIE study. Half of the patients had measurements at both time-points. All-cause mortality, breast cancer specific mortality and recurrences were ascertained up to June 2015 (11 years median follow-up). Associations with time-varying adipokine concentrations overall and stratified by estrogen and progesterone receptor (ERPR) were evaluated using adjusted proportional hazard regression. At baseline (n = 2700) and follow-up (n = 2027), median concentrations for leptin, adiponectin and resistin were 4.6 and 2.7 ng/ml, 24.4 and 30.0 mg/l, 15.4 and 26.2 ng/ml, respectively. After adjustment, there was no evidence for associations between adipokines and any outcome overall. In ERPR negative tumors, highest vs. lowest quintile of adiponectin was significantly associated with increased breast cancer specific mortality (HR 2.51, 95%CI 1.07-5.92). Overall, post-diagnosis adipokines were not associated with long-term outcomes after breast cancer. In patients with ERPR negative tumors, higher concentrations of adiponectin may be associated with increased breast cancer specific mortality and warrant further investigation.
Breast cancer (BC) survivors often suffer from late and long-term residual symptoms of the disease and its treatment. To date, long-term health-related quality of life (HRQoL) in breast cancer ...survivors has been seldom investigated and rarely compared to unaffected women (controls).
This study aimed to investigate HRQoL over time using patient-reported status before diagnosis, during treatment, 1 year post-surgery, approx. 5 years and ≥10 years post-diagnosis. We also compared survivors' HRQoL with controls' still alive 10 years after recruitment.
Data from the German population-based Mamma Carcinoma Risk Factor Investigation (MARIE) cohort of 1123 BC patients aged 50-74 years at diagnosis (2002-2005) and of 3453 matched controls were used for analysis. HRQoL was assessed with the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30) questionnaire. All analyses were conducted for all ages as well as stratified according to three age groups (≤58 years, 59-64 years, ≥64 years). Differences in survivors' general HRQoL before, during, and after therapy were investigated using a t-test/Wilcoxon signed-rank test. Changes in the HRQoL of survivors stratified by age from FU1 to FU2 were assessed via repeated analysis of variance. The HRQoL of survivors compared to the controls at FU2 was analyzed using an analysis of variance.
Over all ages, the general HRQoL in patients improved in the first 5 years post-diagnosis. In the subsequent years, HRQoL slightly deteriorated but was comparable to that of the controls. Younger survivors mostly improved their HRQoL from the 5 to 10-year follow-up but remained negatively affected for most functioning and symptom scales compared to controls. In older survivors, HRQoL hardly changed over time and detriments were less pronounced compared to controls, except for insomnia.
Restrictions of HRQoL persist for more than 10 years and are most prominent among younger survivors. Researchers and clinicians should be aware of such potential deteriorations and age-dependent differences in order to optimize/adapt long-term cancer survivor care.
ObjectivesAdvanced ovarian cancer is a severe disease with major side effects caused by peritoneal carcinomatosis, ascites and gastrointestinal involvement as well as exhaustive treatment like ...debulking surgery and combination chemotherapy. Two most frequently reported side effects are muscle wasting and malnutrition, leading to frailty, decreased health-related quality of life (HRQoL) and cancer-related fatigue (CRF). As muscle wasting and malnutrition often commence during first-line chemotherapy and develop progressively into a refractory state, an early intervention is warranted. This pilot study aimed to evaluate the safety and acceptance of a combined exercise and nutrition intervention during and after first-line chemotherapy.DesignThe pilot study was conducted as a monocentric 1:1 randomised controlled trial (RCT) with an intervention group (IG) and a control group (CG). Participants were divided by chance into IG or CG. Information on group allocation was conveyed to the study coordinator responsible for making an appointment with the patients for the baseline assessment as well as the physiotherapist and nutritionist responsible for the intervention and outcome assessment in both groups.ParticipantsEligibility criteria included women ≥18 years of age, diagnosed with ovarian cancer, tubal cancer or peritoneal cancer and primary or interval debulking, scheduled but not started adjuvant or neoadjuvant chemotherapy and sufficient German-language skills.InterventionThe IG received a 12-month exercise and nutrition programme, the CG continued to follow usual care.Primary and secondary outcome measuresPrimary outcomes were recruitment rate, adherence to intervention, completion rate and adverse events. In addition, in-person assessments (eg, HRQoL, CRF, muscle quality and function and dietary intake and quality) were conducted at baseline (T0, before chemotherapy), week 9 (T1, mid-chemotherapy), week 19 (T2, after completion of chemotherapy) and after 12 months of intervention (T3).ResultsOf 60 eligible patients, 15 patients signed informed consent (recruitment rate=25.0%) and were randomised into IG (n=8) and CG (n=7). Eleven participants completed the study (completion rate, 73.3%), one patient dropped out due to loss of interest, one due to poor health, one was lost to follow-up and one patient died.ConclusionThe BENITA (Bewegungs- und Ernährungsintervention bei Ovarialkrebs) study demonstrated the safety and acceptance of an exercise and nutrition intervention integrated into first-line therapy and follow-up care of ovarian cancer. A large multicentre RCT is planned to investigate the effectiveness of the intervention on HRQoL, CRF and survival and to establish means of implementation into oncology guidelines and clinic routine.Trial registration numberDRKS00013231.
Health-related quality of life (HRQOL) has become increasingly important for breast cancer survivors, but clinically relevant declines often persist for many years after treatment. This study aimed ...to investigate whether social relationships can mitigate or prevent this decline in HRQOL.
Data were used from the German population-based Mamma Carcinoma Risk Factor Investigation (MARIE) cohort of 2022 breast cancer cases with follow-up information for more than 15 years after diagnosis. Correlations between social integration, social support, and global health status (GHS) as an overall measure of HRQOL were analyzed, and linear regression analysis was performed with structural equation modeling.
The majority of participants reported high levels of social integration and social support and moderate levels of GHS. Social integration 5 years after diagnosis was associated with GHS 5 years after diagnosis (β = 1.12; 95% CI, 0.25-1.99), but no longitudinal effects were found. Social support 5 years after diagnosis was associated with better GHS 5 years (β = 0.42; 95% CI, 0.36-0.48) and 10 years after diagnosis (β = 0.12; 95% CI, 0.02-0.22), whereas social support 10 years after diagnosis was associated with GHS 10 years (β = 0.29; 95% CI, 0.20-0.39) and 15 years after diagnosis (β = 0.10; 95% CI, 0.01-0.21).
These results confirm that social relationships positively influence HRQOL in long-term breast cancer survivors and that their association should receive more attention clinically and beyond routine care.
Cancer‐related fatigue is a frequent, burdensome and often insufficiently treated symptom. A more targeted treatment of fatigue is urgently needed. Therefore, we examined biomarkers and clinical ...factors to identify fatigue subtypes with potentially different pathophysiologies. The study population comprised disease‐free breast cancer survivors of a German population‐based case‐control study who were re‐assessed on average 6 (FU1, n = 1871) and 11 years (FU2, n = 1295) after diagnosis. At FU1 and FU2, we assessed fatigue with the 20‐item multidimensional Fatigue Assessment Questionnaire and further factors by structured telephone‐interviews. Serum samples collected at FU1 were analyzed for IL‐1ß, IL‐2, IL‐4, IL‐6, IL‐10, TNF‐a, GM‐CSF, IL‐5, VEGF‐A, SAA, CRP, VCAM‐1, ICAM‐1, leptin, adiponectin and resistin. Exploratory cluster analyses among survivors with fatigue at FU1 and no history of depression yielded three clusters (CL1, CL2 and CL3). CL1 (n = 195) on average had high levels of TNF‐α, IL1‐β, IL‐6, resistin, VEGF‐A and GM‐CSF, and showed high BMI and pain levels. Fatigue in CL1 manifested rather in physical dimensions. Contrarily, CL2 (n = 78) was characterized by high leptin level and had highest cognitive fatigue. CL3 (n = 318) did not show any prominent characteristics. Fatigued survivors with a history of depression (n = 214) had significantly higher physical, emotional and cognitive fatigue and showed significantly less amelioration of fatigue from FU1 to FU2 than survivors without depression. In conclusion, from the broad phenotype “cancer‐related fatigue” we were able to delineate subgroups characterized by biomarkers or history of depression. Future investigations may take these subtypes into account, ultimately enabling a better targeted therapy of fatigue.
What's new?
Fatigue associated with cancer frequently persists years after treatment, often with consequences for quality of life. Moreover, fatigue is commonly treated in an undifferentiated manner, owing to a lack of knowledge of possible fatigue subtypes and related markers. Here, the authors investigated the possibility of delineating fatigue subtypes according to biomarkers and psychological factors. Analyses reveal the existence of three fatigue subgroups: one distinguished by history of depression, another by high levels of inflammatory markers, and the third by high leptin levels. Consideration of potential fatigue subtypes could enable the development of targeted and more effective treatment options.
Data on the treatment-supporting effect of modifiable lifestyle factors such as nutrition and physical activity on survival or quality of life (QoL) are scarce in patients with ovarian cancer. ...Despite a strong rationale for evaluating the effect of a multimodal intervention and multiple studies targeting other cancer sites, randomized controlled trials (RCTs) on the effects of a combined nutrition and exercise intervention on survival and QoL in ovarian cancer patients are rare. No study has investigated the impact of an early intervention during first-line chemotherapy.
To evaluate the study design, feasibility, safety, and acceptance of combined nutrition and exercise in patients diagnosed with ovarian cancer during and after first-line chemotherapy.
Physical exercise and a cancer-specific nutrition intervention after ovarian cancer diagnosis is feasible, accepted, and safe for patients receiving first-line chemotherapy.
A 1:1 RCT with an intervention group and a control group. The intervention group receives an exercise and nutrition program whereas the control group continues to follow the usual care.
Inclusion: women ≥18 years of age; women diagnosed with ovarian cancer, tubal cancer, or peritoneal cancer and primary or interval debulking surgery. Exclusion: Eastern Cooperative Oncology Group (ECOG) status of 2 or worse.
Recruitment rate, completion rate, side effects, and adherence.
n=30 patients (15 per arm) will be recruited.
Accrual completion is planned for the end of 2019. Results will be presented in the months following study completion 1 year after recruitment has been finalised.
The pilot phase was approved by the ethics committee of the Medical Faculty of Hamburg on December 13, 2017 (PV5456). The study was registered on September 9, 2018 at the German Study Registry for Clinical Studies (DRKS00013231).
In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since ...HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859-1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482-1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.
Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new ...insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies similar to 7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.
IntroductionChronic diseases in older adults are one of the major epidemiological challenges of current times and leading cause of disability, poor quality of life, high healthcare costs and death. ...Self-management of chronic diseases is essential to improve health behaviours and health outcomes. Technology-assisted interventions have shown to improve self-management of chronic diseases. Virtual avatars can be a key factor for the acceptance of these technologies. Addison Care is a home-based telecare solution equipped with a virtual avatar named Addison, connecting older persons with their caregivers via an easy-to-use technology. A central advantage is that Addison Care provides access to self-management support for an up-to-now highly under-represented population—older persons with chronic disease(s), which enables them to profit from e-health in everyday life.Methods and analysisA pragmatic, non-randomised, one-arm pilot study applying an embedded mixed-methods approach will be conducted to examine user experience, usability and user engagement of the virtual avatar Addison. Participants will be at least 65 years and will be recruited between September 2022 and November 2022 from hospitals during the discharge process to home care. Standardised instruments, such as the User Experience Questionnaire, System Usability Scale, Instrumental Activities of Daily Living scale, Short-Form-8-Questionnaire, UCLA Loneliness Scale, Geriatric Depression Scale, Stendal Adherence with Medication Score and Self-Efficacy for Managing Chronic Diseases Scale, as well as survey-based assessments, semistructured interviews and think-aloud protocols, will be used. The study seeks to enrol 20 patients that meet the criteria.Ethics and disseminationThe study protocol has been approved by the ethic committee of the German Society for Nursing Science (21-037). The results are intended to be published in peer-reviewed journals and disseminated through conference papers.Trial registration numberDRKS00025992.
Mandibular condylar fractures represent 25%-35% of all mandibular fractures. Despite profound research, there is still a controverse debate about treating these fractures conservatively or by open ...reduction and internal fixation (ORIF). The aim of this study is to analyse the outcome after open and closed treatment of extracapsular mandibular condyle fractures regarding general characteristics, post-treatment malocclusion, facial nerve palsy (FNP), maximum mouth opening (MMO) and parotid complications.
A retrospective cohort of 377 fractures (350 open, 27 closed treatment) was reviewed by reference to clinical and radiological pre- and postoperative documentation. Follow-up period was 12 months. Pearsons' chi-square-test, correlations, Kruskal-Wallis test and t-test were carried out for statistical analysis.
The dominant type of fracture was type II in Spiessl and Schroll classification (50.1%). In the open treated fractures, the most common approach was retromandibular transparotid (91.7%). Post-treatment malocclusion occurred in 18.0% and was significantly increased in bilateral fractures (p = .039), in luxation fractures (p = .016) and in patients with full dentition (p = .004). After open reduction and internal fixation (ORIF), temporary FNP was documented in 7.1% whereas a permanent paresis occurred in 1.7%. FNP was significantly associated with high fractures (p = .001), comminution (p = .028) and increased duration of surgery (p = .040). Parotid complications were significantly associated with revision surgery (p = .009). Post-treatment reduction of MMO mainly occurred in female patients (p < .001) as well as in patients with bilateral fractures (p < .001), high fractures (p = .030) and concomitant mandibular (p = .001) and midfacial fractures (p = .009).
Malocclusion seems to be the most frequent long-term complication after open reduction and osteosynthesis of extracapsular mandibular condyle fractures. We suggest ORIF by a transparotid approach to be an appropriate treatment with a low complication rate regarding especially FNP for extracapsular fractures of the mandibular condyle.
PDF
