Jacobien Marije Kieffer

ObjectiveRisk-reducing salpingo-oophorectomy (RRSO) is advised before 40-45 years of age for BRCA1/2 mutation carriers. This study describes the effect of RRSO on lipid determinants, hemoglobin A1c (HbA1c) and C-reactive protein (CRP).MethodsA total of 142 women with increased risk of ovarian cancer were included, 92 premenopausal and 50 postmenopausal. Serum levels of low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol and total cholesterol, triglycerides, HbA1c and CRP were determined at three points in time: before (T0) and 6 weeks (T1) and 7 months (T2) following RRSO. The Hot Flush Rating Scale was administered at the same time points.ResultsIn premenopausal women, levels of HDL-cholesterol, the cholesterol ratio and HBA1c increased significantly over time, although still staying within the reference range. In this group, hot flushes increased over time (p < 0.001). In postmenopausal women, no significant changes were observed following RRSO. At T2, serum LDL-cholesterol, triglycerides, HbA1c and CRP were significantly lower in premenopausal women compared to postmenopausal women, whereas HDL was increased.ConclusionsSeven months after RRSO, the lipid profile in premenopausal women had changed, although still staying within the reference range. For postmenopausal women, we did not observe any significant changes. Our results do not suggest a worsening of cardiovascular risk within 7 months of RRSO.

Background: There has been a cultural shift toward patient engagement in health, with a growing demand from patients to access their results. Objective: The Lymphoma Intervention (LIVE) trial is conducted to examine the impact of return of individual patient-reported outcome (PRO) results and a web-based self-management intervention on psychological distress, self-management, satisfaction with information, and health care use in a population-based setting. Methods: Return of PRO results included comparison with age- and sex-matched peers and was built into the Patient-Reported Outcomes Following Initial Treatment and Long-Term Evaluation of Survivorship registry. The self-management intervention is an adaptation of a fully automated evidence-based intervention for breast cancer survivors. Patients with lymphoma who completed the web-based questionnaire were equally randomized to care as usual, return of PRO results, and return of PRO results plus self-management intervention. Patients completed questionnaires 9 to 18 months after diagnosis (T0; n=227), 4 months (T1; n=190), 12 months (T2; n=170), and 24 months (T3; n=98). Results: Of all invited patients, 51.1% (456/892) responded and web-based participants (n=227) were randomly assigned to care as usual (n=76), return of PRO results (n=74), or return of PRO results and access to Living with lymphoma (n=77). Return of PRO results was viewed by 76.7% (115/150) of those with access. No statistically significant differences were observed for psychological distress, self-management, satisfaction with information provision, and health care use between patients who received PRO results and those who did not (P>.05). Use of the self-management intervention was low (2/76, 3%), and an effect could therefore not be determined. Conclusions: Return of individual PRO results seems to meet patients’ wishes but had no beneficial effects on patient outcome. No negative effects were found when individual PRO results were disclosed, and the return of individual PRO results can therefore be safely implemented in daily clinical practice. Trial Registration: Netherlands Trial Register NTR5953; https://www.trialregister.nl/trial/5790 International Registered Report Identifier (IRRID): RR2-10.1186/s13063-017-1943-2

Purpose: To evaluate the short- and long-term effects of light therapy on fatigue (primary outcome) and sleep quality, depression, anxiety, quality of life, and circadian rhythms (secondary outcomes) in survivors of (non-)Hodgkin lymphoma presenting with chronic cancer-related fatigue. Methods: We randomly assigned 166 survivors (mean survival 13 years) to a bright white light intervention (BWL) or dim white light comparison (DWL) group. Measurements were completed at baseline (T0), post-intervention (T1), at three (T2), and nine (T3) months follow-up. A mixed-effect modeling approach was used to compare linear and non-linear effects of time between groups. Results: There were no significant differences between BWL and DWL in the reduction in fatigue over time. Both BWL and DWL significantly (p < 0.001) improved fatigue levels during the intervention followed by a slight reduction in this effect during follow-up (ES_T0-T1 = −0.71; ES_T1-T3 = 0.15). Similar results were found for depression, sleep quality, and some aspects of quality of life. Light therapy had no effect on circadian rhythms. Conclusions: BWL was not superior in reducing fatigue compared to DWL in HL and DLBCL survivors. Remarkably, the total sample showed clinically relevant and persistent improvements on fatigue not commonly seen in longitudinal observational studies in these survivors.

Many non-central nervous system (CNS) cancer survivors experience cognitive symptoms, which may affect their self-perceived work ability. Little is known about trajectories of self-perceived cognitive functioning in cancer survivors in the period after work disability assessment. Therefore, we evaluated: (1) trajectories of self-reported cognitive functioning, in cancer survivors with work capacity, (2) differences in trajectories of self-reported cognitive functioning between three work disability groups, and (3) explanatory factors of trajectories of self-reported cognitive functioning. Participants (n = 206) were assessed on self-reported cognitive functioning at three time points between two and four years after first day of sick leave. A statistically significant improvement in cognitive functioning was found in the total group (β = 4.62, SE = 0.91, p < 0.001). When comparing cancer survivors in different work disability groups, similar trajectories of cognitive functioning were observed. Fatigue was the only factor found to be associated with the reported trajectory (β = −0.23, SE = 0.086, p = 0.08). Self-perceived cognitive functioning scores remained considerably lower than the mean score of the general Dutch population, indicating that cognitive symptoms are a persistent problem in sick-listed cancer survivors and that evidence-based treatment options are warranted.

BACKGROUND There has been a cultural shift toward patient engagement in health, with a growing demand from patients to access their results. OBJECTIVE The Lymphoma Intervention (LIVE) trial is conducted to examine the impact of return of individual patient-reported outcome (PRO) results and a web-based self-management intervention on psychological distress, self-management, satisfaction with information, and health care use in a population-based setting. METHODS Return of PRO results included comparison with age- and sex-matched peers and was built into the Patient-Reported Outcomes Following Initial Treatment and Long-Term Evaluation of Survivorship registry. The self-management intervention is an adaptation of a fully automated evidence-based intervention for breast cancer survivors. Patients with lymphoma who completed the web-based questionnaire were equally randomized to care as usual, return of PRO results, and return of PRO results plus self-management intervention. Patients completed questionnaires 9 to 18 months after diagnosis (T0; n=227), 4 months (T1; n=190), 12 months (T2; n=170), and 24 months (T3; n=98). RESULTS Of all invited patients, 51.1% (456/892) responded and web-based participants (n=227) were randomly assigned to care as usual (n=76), return of PRO results (n=74), or return of PRO results and access to Living with lymphoma (n=77). Return of PRO results was viewed by 76.7% (115/150) of those with access. No statistically significant differences were observed for psychological distress, self-management, satisfaction with information provision, and health care use between patients who received PRO results and those who did not (P>.05). Use of the self-management intervention was low (2/76, 3%), and an effect could therefore not be determined. CONCLUSIONS Return of individual PRO results seems to meet patients’ wishes but had no beneficial effects on patient outcome. No negative effects were found when individual PRO results were disclosed, and the return of individual PRO results can therefore be safely implemented in daily clinical practice. CLINICALTRIAL Netherlands Trial Register NTR5953; https://www.trialregister.nl/trial/5790 INTERNATIONAL REGISTERED REPORT RR2-10.1186/s13063-017-1943-2

Background: Most breast cancer patients undergoing mastectomy are candidates for breast reconstruction. Deciding about breast reconstruction is complex and the preference-sensitive nature of this decision requires an approach of shared decision making between patient and doctor. Women considering breast reconstruction have expressed a need for decision support. We developed an online patient decision aid (pDA) to support decision making in women considering immediate breast reconstruction. The primary aim of this study is to assess the impact of the pDA in reducing decisional conflict, and more generally, on the decision-making process and the decision quality. Additionally, we will investigate the pDA's impact on health outcomes, explore predictors, and assess its cost-effectiveness. Methods: A multicenter, two-armed randomized controlled trial (1:1) will be conducted. Women with breast cancer or ductal carcinoma in situ who will undergo a mastectomy and are eligible for immediate breast reconstruction will be invited to participate. The intervention group will receive access to the online pDA, whereas the control group will receive a widely available free information leaflet on breast reconstruction. Participants will complete online questionnaires at: baseline (TO), 1 week after consultation with a plastic surgeon (T1), and 3 (T2) and 12 months (T3) after surgery. The primary outcome is decisional conflict. Secondary outcomes include other measures reflecting the decision-making process and decision quality (e.g., decision regret), patient-reported health outcomes (e.g., satisfaction with the breasts) and costs. Discussion: This study will provide evidence about the impact of an online pDA for women who will undergo mastectomy and are deciding about breast reconstruction. It will contribute to the knowledge on how to optimally support women in making this difficult decision.

Objectives: The aim of this study was to investigate whether serum anti-Müllerian hormone (AMH) predicts symptom burden after risk-reducing salpingo-oophorectomy (RRSO) in order to individualize counseling. Methods: Patient-reported menopausal symptoms, sexual functioning, and psychological distress (depression and anxiety) were assessed 1 day before (T0) and 6 weeks (T1) and 7 months (T2) after RRSO. AMH was assessed before RRSO. Multivariable regression analysis was used to investigate the association between AMH and short-term and long-term change in symptom burden following RRSO. Results: Ninety-one premenopausal women at high risk of ovarian cancer were included. Presurgical AMH was not related significantly to change in symptoms post RRSO. As a secondary outcome we found that regular menses before RRSO was associated specifically with long-term increase in hot flushes (sr = 0.40, p = 0.001; total R² = 0.171) and depression (sr = 0.29, p = 0.012; total R² = 0.132). Earlier receipt of chemotherapy was associated with long-term improvement in sexual functioning (sr = 0.24, p = 0.041; total R² = 0.348). Conclusion: In this cohort, AMH was not a significant predictor of change in symptoms following RRSO. Regular menses prior to RRSO and earlier receipt of chemotherapy were significantly, but relatively weakly, associated with changes in outcomes 6 weeks and/or 7 months after RRSO.

Cancer related fatigue (CRF) is one of the most prevalent and distressing long-term complaints reported by (non-) Hodgkin survivors. To date there has been no standard treatment for CRF in this population. A novel and promising approach to treat CRF is exposure to bright white light therapy. Yet, large scale randomized controlled trials testing its efficacy in these patients and research on potential mechanisms is lacking. The objective of the current study is to investigate the efficacy of light therapy as a treatment for CRF and to explore potential mechanisms. In a multicenter, randomized controlled trial we are evaluating the efficacy of two intensities of light therapy in reducing CRF complaints and restrictions caused by CRF in survivors of Hodgkin lymphoma or diffuse large B-cell lymphoma. Secondary outcomes include sleep quality, depression, anxiety, quality of life, cognitive complaints, cancer worries, fatigue catastrophizing, self-efficacy to handle fatigue, biological circadian rhythms of melatonin, cortisol and activity, and biomarkers of inflammation. We will recruit 128 survivors, with fatigue complaints, from academic and general hospitals. Survivors are randomized to either an intervention (exposure to bright white light) or a comparison group (exposure to dim white light). The longitudinal design includes four measurement points at baseline (T0), post-intervention at 3.5 weeks (T1), 3 months post-intervention (T2) and 9 months post-intervention (T3). Each measurement point includes self-reported questionnaires and actigraphy (10 days). T0 and T1 measurements also include collection of blood and saliva samples. Light therapy has the potential to be an effective treatment for CRF in cancer survivors. This study will provide insights on its efficacy and potential mechanisms. If proven to be effective, light therapy will provide an easy to deliver, low-cost and low-burden intervention, introducing a new era in the treatment of CRF. The study is registered at ClinicalTrials.gov on August 8th 2017( NCT03242902 ).