International validation of two EORTC questionnaires for assessment of health-related quality of life for patients with high-grade non-Hodgkin lymphoma (QLQ-NHL-HG29) and low-grade non-Hodgkin lymphoma (QLQ-NHL-LG20).

BACKGROUND: Health-related quality of life (HRQOL) is a critical aspect to consider when making treatment decisions for patients with non-Hodgkin-lymphoma (NHL). This international study by the European Organisation for Research and Treatment of Cancer (EORTC) tested the psychometric properties of two newly developed measures for patients with high-grade (HG)- and low-grade (LG)-NHL: the EORTC QLQ-NHL-HG29 and the EORTC QLQ-NHL-LG20 to supplement the core questionnaire (EORTC QLQ-C30). METHODS: Overall, 768 patients with HG-NHL (N = 423) and LG-NHL (N = 345) from 12 countries completed the QLQ-C30, QLQ-NHL-HG29/QLQ-NHL-LG20 and a debriefing questionnaire at baseline, and a subset at follow-up for either retest (N = 125/124) or responsiveness to change (RCA; N = 98/49). RESULTS: Confirmatory factor analysis showed an acceptable to good fit of the 29 items of the QLQ-NHL-HG29 on its five scales (symptom burden [SB], neuropathy, physical condition/fatigue [PF], emotional impact [EI], and worries about health/functioning [WH]), and of the 20 items of the QLQ-NHL-LG20 on its four scales (SB, PF, EI, and WH). Completion took on average 10 minutes. Test-retest reliability, convergent validity, known-group comparisons, and RCA find satisfactory results of both measures. A total of 31%-78% of patients with HG-NHL and 22%-73% of patients with LG-NHL reported symptoms and/or worries (e.g., tingling in hands/feet, lack of energy, and worries about recurrence). Patients reporting symptoms/worries had substantially lower HRQOL compared to those without. DISCUSSION: The use of the EORTC QLQ-NHL-HG29 and QLQ-NHL-LG20 questionnaires in clinical research and practice will provide clinically relevant data to better inform treatment decision-making. PLAIN LANGUAGE SUMMARY: The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group developed two questionnaires. These questionnaires measure health-related quality of life. The questionnaires are for patients with high-grade or low-grade non-Hodgkin lymphoma. They are called the EORTC QLQ-NHL-HG29 and QLQ-NHL-LG20. The questionnaires are now internationally validated. This study demonstrates that the questionnaires are reliably and valid, which are important aspects of a questionnaire. The questionnaires can now be used in clinical trials and practice. With the information gathered from the questionnaires, patients and clinicians can better evaluate treatments and discuss the best choice for a patient.

Persistent symptoms of fatigue, neuropathy and role-functioning impairment among indolent non-Hodgkin lymphoma survivors: A longitudinal PROFILES registry study.

Little is known about the long-term health-related quality of life (HRQoL) and persistence of symptoms among patients with indolent non-Hodgkin lymphoma (iNHL). This large population-based longitudinal study therefore investigated the long-term HRQoL and persistence of symptoms and identified associated sociodemographic, clinical and psychological factors. Patients diagnosed between 1999 and 2014 and four or more months after diagnosis were invited to participate in a longitudinal survey. Sociodemographic and clinical data were obtained from the Netherlands Cancer Registry. The EORTC QLQ-C30 and CLL-16 were completed by 669 patients (74% response rate). Patients completed on average four questionnaires. Primary treatment was active surveillance (52%), systemic therapy (31%) or radiotherapy (13%). Respectively, 36% reported persistent fatigue, 33% persistent neuropathy and 25% persistent role-functioning impairment. This was 2-3 times higher than in the age- and sex-matched normative population. Up to 10 years after diagnosis, scores remained relatively stable without clinically relevant changes. Comorbidities, psychological distress, shorter time since diagnosis, systemic therapy, younger age, education level and having no partner were associated with worse outcomes (all ps < 0.05). Up to a third of patients with iNHL experience long-term persistent symptoms which do not improve over time. Early recognition of symptoms will help in providing tailored supportive care for those in need.

International validation of the EORTC QLQ-CLL17 questionnaire for assessment of health-related quality of life for patients with chronic lymphocytic leukaemia.

Selecting the most appropriate chronic lymphocytic leukaemia (CLL) treatment is challenging. Patient-reported health-related quality of life (HRQoL) is therefore a critical aspect to consider. This international study by the European Organization for Research and Treatment of Cancer (EORTC) tested the psychometric properties of a newly developed measure for CLL patients: the EORTC QLQ-CLL17 to supplement the core questionnaire (EORTC QLQ-C30). Patients with CLL (n = 341) from 12 countries completed the QLQ-C30, QLQ-CLL17 and a debriefing questionnaire. Sociodemographic and clinical data were recorded from medical records. A high percentage (30%-66%) reported symptoms and/or worries (e.g. aches/pains in muscles, lack of energy and worry/fears about health). Confirmatory factor analysis showed an acceptable to good fit of the 17 items on the three scales (i.e. symptom burden, physical condition/fatigue and worries/fears about health and functioning). Completion took on average 8 min. Test-retest and convergent validity was demonstrated. The QLQ-CLL17 differentiated between patients with an Eastern Cooperative Oncology group (ECOG) performance of 0 versus 1-3 (p's < 0.01 and clinically relevant). The newly developed EORTC QLQ-CLL17 will increase sensitivity of HRQoL assessment in patients with CLL. Implementation of this questionnaire both in clinical research and practice will help to generate unique clinically relevant data to better inform CLL treatment decision-making.

Quality of Life Is Associated With Survival in Patients With Gastric Cancer: Results From the Randomized CRITICS Trial.

BACKGROUND: The evaluation of health-related quality of life (HRQoL) in clinical trials has become increasingly important because it addresses the impact of treatment from the patient's perspective. The primary aim of this study was to investigate the effect of postoperative chemotherapy and chemoradiotherapy (CRT) after neoadjuvant chemotherapy and surgery with extended (D2) lymphadenectomy on HRQoL in the CRITICS trial. Second, we investigated the potential prognostic value of pretreatment HRQoL on event-free survival (EFS) and overall survival (OS). PATIENTS AND METHODS: Patients in the CRITICS trial were asked to complete HRQoL questionnaires (EORTC Quality-of-Life Questionnaire-Core 30 and Quality-of-Life Questionnaire gastric cancer-specific module) at baseline, after preoperative chemotherapy, after surgery, after postoperative chemotherapy or CRT, and at 12 months follow-up. Patients with at least 1 evaluable questionnaire (645 of 788 randomized patients) were included in the HRQoL analyses. The predefined endpoints included dysphagia, pain, physical functioning, fatigue, and Quality-of-Life Questionnaire-Core 30 summary score. Linear mixed modeling was used to assess differences over time and at each time point. Associations of baseline HRQoL with EFS and OS were investigated using multivariate Cox proportional hazards analyses. RESULTS: At completion of postoperative chemo(radio)therapy, the chemotherapy group had significantly better physical functioning (P=.02; Cohen's effect size = 0.42) and less dysphagia (P=.01; Cohen's effect size = 0.38) compared with the CRT group. At baseline, worse social functioning (hazard ratio [HR], 2.20; 95% CI, 1.36-3.55; P=.001), nausea (HR, 1.89; 95% CI, 1.39-2.56; P<.001), worse WHO performance status (HR, 1.55; 95% CI, 1.13-2.13; P=.007), and histologic subtype (diffuse vs intestinal: HR, 1.94; 95% CI, 1.42-2.67; P<.001; mixed vs intestinal: HR, 2.35; 95% CI, 1.35-4.12; P=.003) were significantly associated with worse EFS and OS. CONCLUSIONS: In the CRITICS trial, the chemotherapy group had significantly better physical functioning and less dysphagia after postoperative treatment. HRQoL scales at baseline were significantly associated with EFS and OS.

Assessing measurement invariance in the EORTC QLQ-C30.

PURPOSE: We aimed to investigate measurement invariance (MI) in the European Organisation for research and treatment of cancer quality of life questionnaire core 30 (EORTC QLQ-C30) in a heterogeneous sample of patients with cancer. METHODS: Data from 12 studies within the PROFILES registry were used for secondary analyses (n = 7007). We tested MI by successive restrictions on thresholds, loadings, and intercepts across subgroups based on primary cancer sites, age, sex, time since diagnosis, and life stage, using multigroup confirmatory factor analysis (MGCFA) for ordered categorical measures. We also evaluated the impact of potentially miss-specified parameter equality across groups on latent factor means by releasing threshold and loading equality constraints for each item at a time. RESULTS: Results showed that the highest level of MI (invariance of thresholds, loadings, and intercepts) was found across groups based on time since diagnosis and life stage and to a lesser extent across groups based on sex, age, and primary tumor site. On item level, however, changes in the item's associated factor means were relatively small and in most cases canceled each other out to some extent. CONCLUSIONS: Given only a few instances of non-invariance in our study, there is reason to be confident that valid conclusions can be drawn from between-group comparisons of QLQ-C30 latent means as operationalized in our study. Nonetheless, further research into MI between other subgroups for the QLQ-C30 (i.e., treatment effects and ethnicity) is warranted. We stress the importance of including MI evaluations in the development and validation of measurement instruments.

Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer.

BACKGROUND: Treatment of newly diagnosed advanced-stage ovarian cancer typically involves cytoreductive surgery and systemic chemotherapy. We conducted a trial to investigate whether the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery would improve outcomes among patients who were receiving neoadjuvant chemotherapy for stage III epithelial ovarian cancer. METHODS: In a multicenter, open-label, phase 3 trial, we randomly assigned 245 patients who had at least stable disease after three cycles of carboplatin (area under the curve of 5 to 6 mg per milliliter per minute) and paclitaxel (175 mg per square meter of body-surface area) to undergo interval cytoreductive surgery either with or without administration of HIPEC with cisplatin (100 mg per square meter). Randomization was performed at the time of surgery in cases in which surgery that would result in no visible disease (complete cytoreduction) or surgery after which one or more residual tumors measuring 10 mm or less in diameter remain (optimal cytoreduction) was deemed to be feasible. Three additional cycles of carboplatin and paclitaxel were administered postoperatively. The primary end point was recurrence-free survival. Overall survival and the side-effect profile were key secondary end points. RESULTS: In the intention-to-treat analysis, events of disease recurrence or death occurred in 110 of the 123 patients (89%) who underwent cytoreductive surgery without HIPEC (surgery group) and in 99 of the 122 patients (81%) who underwent cytoreductive surgery with HIPEC (surgery-plus-HIPEC group) (hazard ratio for disease recurrence or death, 0.66; 95% confidence interval [CI], 0.50 to 0.87; P=0.003). The median recurrence-free survival was 10.7 months in the surgery group and 14.2 months in the surgery-plus-HIPEC group. At a median follow-up of 4.7 years, 76 patients (62%) in the surgery group and 61 patients (50%) in the surgery-plus-HIPEC group had died (hazard ratio, 0.67; 95% CI, 0.48 to 0.94; P=0.02). The median overall survival was 33.9 months in the surgery group and 45.7 months in the surgery-plus-HIPEC group. The percentage of patients who had adverse events of grade 3 or 4 was similar in the two groups (25% in the surgery group and 27% in the surgery-plus-HIPEC group, P=0.76). CONCLUSIONS: Among patients with stage III epithelial ovarian cancer, the addition of HIPEC to interval cytoreductive surgery resulted in longer recurrence-free survival and overall survival than surgery alone and did not result in higher rates of side effects. (Funded by the Dutch Cancer Society; ClinicalTrials.gov number, NCT00426257 ; EudraCT number, 2006-003466-34 .).

Supporting participation in paid work of cancer survivors and their partners in the Netherlands: protocol of the SusTained Employability in cancer Patients and their partnerS (STEPS) multi-centre randomized controlled trial and cohort study.

BACKGROUND: Many cancer survivors experience physical and/or psychosocial problems affecting return to work (RTW) and work retention. Current interventions on RTW lack evidence regarding effectiveness, while interventions for work retention are missing. Partners of cancer survivors may also experience work- and health-related outcomes; yet, these consequences are not well understood. Here, the protocol of the STEPS study is described. The study aims are to: 1) evaluate the (cost-)effectiveness of a rehabilitation program for RTW and work retention in cancer survivors, and 2) assess health- and work-related outcomes among cancer survivors' partners. METHODS: In a multicentre Randomized Controlled Trial (RCT), 236 working-age cancer survivors with an employment contract will be randomly allocated to a usual care group or an intervention group receiving a multidisciplinary rehabilitation program, combining occupational therapy facilitating work retention (e.g., energy management and self-efficacy training) and reintegration consultation addressing work-related issues (e.g., RTW planning and discussing workplace or task modifications with the supervisor). Alongside the RCT, a prospective cohort study will be conducted among cancer survivors' partners (n = 267). Participants in the RCT and cohort study will be asked to complete questionnaires at baseline, and after six and 12 months, assessing work- and health-related outcomes. Generalized estimating equations will be used to assess intervention's effectiveness, compared to usual care, regarding primary (i.e., working hours per week) and secondary outcomes. Also economic and process evaluations will be performed. For the cohort study, logistic or linear regression modelling will be applied assessing work- and health-related outcomes (primary outcome: working hours) of cancer survivors' partners, and what factors predict these outcomes. RESULTS: The study is planned to start in September 2021; results are expected in 2023. CONCLUSION: Compared to usual care, the STEPS intervention is hypothesized to be (cost-)effective and the intervention could be a valuable addition to standard care helping cancer survivors to sustain employment. Further, it is expected that living with a cancer survivor has a substantial impact on work and health of partners, while specific groups of partners that are at particular risk for this impact are likely to be identified. TRIAL REGISTRATION: Dutch Trial Register ( NTR;NL9094 ; 15-12-2020).

Web-Based Return of Individual Patient-Reported Outcome Results Among Patients With Lymphoma: Randomized Controlled Trial.

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.

The EORTC QLQ-C30 Summary Score as Prognostic Factor for Survival of Patients with Cancer in the "Real-World": Results from the Population-Based PROFILES Registry.

BACKGROUND: Health-related quality of life (HRQoL) has been shown to be a prognostic factor for cancer survival in randomized clinical trials and observational "real-world" cohort studies; however, it remains unclear which HRQoL domains are the best prognosticators. The primary aims of this population-based, observational study were to (a) investigate the association between the novel European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 (QLQ-C30) summary score and all-cause mortality, adjusting for the more traditional sociodemographic and clinical prognostic factors; and (b) compare the prognostic value of the QLQ-C30 summary score with the global quality of life (QoL) and physical functioning scales of the QLQ-C30. MATERIALS AND METHODS: Between 2008 and 2015, patients with cancer (12 tumor types) were invited to participate in PROFILES disease-specific registry studies (response rate, 69%). In this secondary analysis of 6,895 patients, multivariate Cox proportional hazard regression models were used to investigate the association between the QLQ-C30 scores and all-cause mortality. RESULTS: In the overall Cox regression model including sociodemographic and clinical variables, the QLQ-C30 summary score was associated significantly with all-cause mortality (hazard ratio [HR], 0.77; 99% confidence interval [CI], 0.71-0.82). In stratified analyses, significant associations between the summary score and all-cause mortality were observed for colon, rectal, and prostate cancer, non-Hodgkin lymphoma, chronic lymphocytic leukemia, and multiple myeloma. The QLQ-C30 summary score had a stronger association with all-cause mortality than the global QoL scale (HR, 0.82; 99% CI, 0.77-0.86) or the physical functioning scale (HR, 0.81; 95% CI, 0.77-0.85). CONCLUSION: In a real-world setting, the QLQ-C30 summary score has a strong prognostic value for overall survival for a number of populations of patients with cancer above and beyond that provided by clinical and sociodemographic variables. The QLQ-C30 summary score appears to have more prognostic value than the global QoL, physical functioning, or any other scale within the QLQ-C30. IMPLICATIONS FOR PRACTICE: The finding that health-related quality of life provides distinct prognostic information beyond known sociodemographic and clinical measures, not only around cancer diagnosis (baseline) but also at follow-up, has implications for clinical practice. Implementation of cancer survivorship monitoring systems for ongoing surveillance may improve post-treatment rehabilitation that leads to better outcomes.

International validation of the EORTC CAT Core: a new adaptive instrument for measuring core quality of life domains in cancer.

BACKGROUND: The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group (QLG) has developed computerised adaptive tests (CATs) for the 14 functional and symptom domains of the EORTC QLQ-C30 quality of life questionnaire. This is expected to optimise measurement precision, relevance to patients and flexibility. Here, we present the first international validation of the EORTC CAT Core. METHODS: A heterogeneous sample of 699 cancer patients scheduled for chemotherapy and/or radiotherapy was recruited across seven European countries. The EORTC CAT Core and all QLQ-C30 items were administered to participants before and after initiating treatment. Correlations between CAT and QLQ-C30 scores and floor/ceiling effects were calculated. Using several grouping variables, relative validity (cross-sectional known groups difference), responsiveness (changes over time) and relative sample size requirements of the CAT compared to the QLQ-C30 were estimated. RESULTS: Correlations of the CAT and QLQ-C30 ranged from 0.81 to 0.93 across domains. The mean relative reduction in floor and ceiling effects using the CAT was 42% (range 3-99%). Analyses of known groups validity and responsiveness indicated that, across domains, mean sample size requirements for the CAT were 72% and 70%, respectively, of those using the QLQ-C30. CONCLUSIONS: The EORTC CAT Core measures the same domains as the QLQ-C30 with reduced floor/ceiling effects. The CAT generally facilitated the use of smaller samples (about 30% smaller on average) without loss of power compared to the QLQ-C30. Based on this study, the EORTC QLG will release the EORTC CAT Core for general use.

Validation of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 Summary Score in Patients With Hematologic Malignancies.

OBJECTIVES: We investigated the validity of the recently developed European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) summary score in patients with hematologic malignancies. Specifically, we evaluated the adequacy of a single-factor measurement model for the QLQ-C30, and its known-groups validity and responsiveness to change over time. METHODS: We used confirmatory factor analysis to test the single-factor model of the QLQ-C30, using baseline QLQ-C30 data (N = 2134). The QLQ-C30 summary score was compared to the original QLQ-C30 scales using general (age, sex, Eastern Cooperative Oncology Group performance status, comorbidity) and disease-specific (red blood cell transfusion dependency) groups. Repeated measurements allowed us to investigate responsiveness to change in a subgroup of patients with acute myeloid leukemia. RESULTS: The single-factor model of the QLQ-C30 exhibited adequate fit in patients with hematologic malignancies. Known-group comparisons generally supported the construct validity of the summary score when using more general grouping variables (sociodemographics, broad clinical parameters). Nevertheless, when groups were formed on the basis of disease-specific variables (eg, transfusion dependency), the summary score performed less well the some of the original, separate scales of the QLQ-C30. CONCLUSION: Our findings provide support for the validity of the single-factor model of the EORTC QLQ-C30 in patients with hematologic malignancies. Specifically, the results suggest that the summary score can be used as an endpoint in this population when symptom- or other health domain-specific hypotheses are not available.

Sexual Functioning and Relationship Satisfaction of Partners of Breast Cancer Survivors Who Receive Internet-Based Sex Therapy.

As part of a larger, randomized controlled trial, we evaluated longitudinally the sexual functioning and relationship satisfaction of 69 partners of breast cancer (BC) survivors who received Internet-based cognitive behavioral therapy (CBT) for sexual dysfunction. The findings suggest that Internet-based CBT positively affects the partners' immediate post-CBT and longer-term overall sexual satisfaction, sexual intimacy, and sexual relationship satisfaction. No sustained changes in other areas of sexual functioning were observed. Our CBT program was focused primarily on the sexual health of the BC survivors. We recommend that future programs include more psychoeducational and behavioral elements targeted at the partners.

The impact of an online patient decision aid for women with breast cancer considering immediate breast reconstruction: study protocol of a multicenter randomized controlled trial.

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 (T0), 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. TRIAL REGISTRATION: This study is retrospectively registered at ClinicalTrials.gov ( NCT03791138 ).

Light therapy as a treatment of cancer-related fatigue in (non-)Hodgkin lymphoma survivors (SPARKLE trial): study protocol of a multicenter randomized controlled trial.

BACKGROUND: 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. METHODS/DESIGN: 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. DISCUSSION: 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. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov on August 8th 2017( NCT03242902 ).

A cross-cultural convergent parallel mixed methods study of what makes a cancer-related symptom or functional health problem clinically important.

OBJECTIVE: In this study, we investigated what makes a symptom or functional impairment clinically important, that is, relevant for a patient to discuss with a health care professional (HCP). This is the first part of a European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group project focusing on the development of thresholds for clinical importance for the EORTC QLQ-C30 questionnaire and its corresponding computer-adaptive version. METHODS: We conducted interviews with cancer patients and HCPs in 6 European countries. Participants were asked to name aspects of a symptom or problem that make it clinically important and to provide importance ratings for a predefined set of aspects (eg, need for help and limitations of daily functioning). RESULTS: We conducted interviews with 83 cancer patients (mean age, 60.3 y; 50.6% men) and 67 HCPs. Participants related clinical importance to limitations of everyday life (patients, 65.1%; HCPs, 77.6%), the emotional impact of a symptom/problem (patients, 53.0%; HCPs, 64.2%), and duration/frequency (patients, 51.8%; HCPs, 49.3%). In the patient sample, importance ratings were highest for worries by partner or family, limitations in everyday life, and need for help from the medical staff. Health care professionals rated limitations in everyday life and need for help from the medical staff to be most important. CONCLUSIONS: Limitations in everyday life, need for (medical) help, and emotional impact on the patient or family/partner were found to be relevant aspects of clinical importance. Based on these findings, we will define anchor items for the development of thresholds for clinical importance for the EORTC measures in a Europe-wide field study.

Internet-Based Cognitive Behavioral Therapy Realizes Long-Term Improvement in the Sexual Functioning and Body Image of Breast Cancer Survivors.

The study aim was to evaluate the long-term efficacy of Internet-based cognitive behavioral therapy (CBT) for sexual dysfunctions in 84 breast cancer survivors. The positive effects of the intervention on overall sexual functioning, sexual desire, sexual arousal, vaginal lubrication, discomfort during sex, sexual distress, and body image observed immediately posttreatment were maintained at three- and nine-month follow-ups. Although sexual pleasure decreased during follow-up, it did not return to baseline levels. Our findings provide evidence that Internet-based CBT has a sustained, positive effect on sexual functioning and body image of breast cancer survivors with a sexual dysfunction.

Sustained employability and health-related quality of life in cancer survivors up to four years after diagnosis.

BACKGROUND: Most cancer survivors are able to return to work at some point after diagnosis. However, literature on sustained employability and health-related quality of life (HRQoL) is limited. Therefore, the aims of this study were to explore the influence of change in employment status on HRQoL in cancer survivors long term after diagnosis, and to identify predictors of work continuation in occupationally active survivors. MATERIAL AND METHODS: We used prospective data (T0 = two years after diagnosis, T1 = one-year follow-up, and T2 = two-year follow-up) from a cohort of cancer survivors that had an employment contract and were of working age at T0 (N = 252, 69.8% female). Groups were formed on the basis of change in employment status: 'continuously not working' (19.8%), 'positive change in employment status' (5.6%), 'negative change in employment status' (14.7%), and 'continuously working' (59.9%). ANCOVA was used to explore the relationship between change in employment status and HRQoL at T1. Generalized estimating equations (GEE) were used to identify predictors of work continuation (at T1 and T2) in survivors that were occupationally active at T0 (N = 212). RESULTS: 'Continuously working' survivors scored significantly better on the EORTC QLQ-C30 scales: role functioning, fatigue, pain, constipation, global health/QoL and the Summary score, than 'continuously not working' survivors, and better on physical, role and emotional functioning, fatigue, financial impact, global health/QoL and the Summary score than survivors with a 'negative change in employment status' (effect size range = 0.49-0.74). In occupationally active survivors, a high score on current work ability was associated with work continuation one year later [odds ratio (OR) 1.46; 95% CI 1.11-1.92]. CONCLUSION: Cancer survivors 'continuously working' function better and have a better health and QoL than those who are not able to work. However, in occupationally active cancer survivors, one should monitor those with low self-perceived work ability, because they have an increased risk to discontinue their work.

International evaluation of the psychometrics of health-related quality of life questionnaires for use among long-term survivors of testicular and prostate cancer.

BACKGROUND: Understanding of the physical, functional and psychosocial health problems and needs of cancer survivors requires cross-national and cross-cultural standardization of health-related quality of life (HRQoL) questionnaires that capture the full range of issues relevant to cancer survivors. To our knowledge, only one study has investigated in a comprehensive way whether a questionnaire used to evaluate HRQoL in cancer patients under active treatment is also reliable and valid when used among (long-term) cancer survivors. In this study we evaluated, in an international context, the psychometrics of HRQoL questionnaires for use among long-term, disease-free, survivors of testicular and prostate cancer. METHODS: In this cross-sectional study, we recruited long-term survivors of testicular and prostate cancer from Northern and Southern Europe and from the United Kingdom who had participated in two phase III EORTC clinical trials. Participants completed the SF-36 Health Survey, the EORTC QLQ-C30 questionnaire, the QLQ-PR25 (for prostate cancer) or the QLQ-TC26 (for testicular cancer) questionnaires, and the Impact of Cancer questionnaire. Testicular cancer survivors also completed subscales from the Nordic Questionnaire for Monitoring the Age Diverse Workforce. RESULTS: Two hundred forty-two men (66% response rate) were recruited into the study. The average time since treatment was more than 10 years. Overall, there were few missing questionnaire data, although scales related to sexuality, satisfaction with care and relationship concerns of men without partners were missing in more than 10% of cases. Debriefing showed that in general the questionnaires were accepted well. Many of the survivors scored at the upper extremes of the questionnaires, resulting in floor and ceiling effects in 64% of the scales. All of the questionnaires investigated met the threshold of 0.70 for group level reliability, with the exception of the QLQ-TC26 (mean reliability .64) and the QLQ-PR25 (mean reliability .69). The questionnaires were able to discriminate clearly between patients with and without comorbid conditions. CONCLUSIONS: The currently available HRQoL questionnaires exhibit acceptable psychometric properties and were well received by patients, but additional efforts are needed to ensure that the full range of survivor-specific issues is assessed.

Evaluation of the psychometric properties of the EORTC chemotherapy-induced peripheral neuropathy questionnaire (QLQ-CIPN20).

PURPOSE: To investigate the scale structure and psychometrics of the EORTC chemotherapy-induced peripheral neuropathy module (QLQ-CIPN20). METHODS: Using confirmatory factor analyses (CFA), we tested two hypothesized scale structure models of the QLQ-CIPN20 in 473 patients with non-small cell lung cancer, 281 patients with heterogeneous cancer diagnoses, and 500 patients with colorectal cancer. We also modeled the two hypothesized models as bi-factor models. These included a general factor, in addition to the specific domain factors. Additional models were investigated with exploratory factor analysis (EFA). Known groups validity was evaluated where justified. RESULTS: CFA could not confirm the two hypothesized models (Model 1: CFI < 0.926; TLI < 0.914; RMSEA > 0.077 and Model 2: CFI < 0.906; TLI < 0.887; RMSEA > 0.105) in any of the three samples. Including a general factor to these two hypothesized models to produce a bi-factor model also did not yield satisfactory results. Using EFA, we identified four different factor structures in the three samples that were unstable due to cross loadings of the items. When scoring the QLQ-CIPN20 as a simple, additive checklist evidence was found for known groups validity in the first two samples based on Common Toxicity Criteria (CTC-AE), and in the third sample based on exposure to CIPN-inducing chemotherapy. CONCLUSIONS: Neither CFA nor EFA yielded support for a stable subscale structure for the QLQ-CIPN20. Scoring the questionnaire as a simple additive checklist results in acceptable validity.

Does rapid genetic counseling and testing in newly diagnosed breast cancer patients cause additional psychosocial distress? results from a randomized clinical trial.

PURPOSE: Female breast cancer patients carrying a BRCA1/2 mutation have an increased risk of second primary breast cancer. Rapid genetic counseling and testing (RGCT) before surgery may influence choice of primary surgical treatment. In this article, we report on the psychosocial impact of RGCT. METHODS: Newly diagnosed breast cancer patients at risk for carrying a BRCA1/2 mutation were randomized to an intervention group (offer of RGCT) or a usual care control group (ratio 2:1). Psychosocial impact and quality of life were assessed with the Impact of Events Scale, Hospital Anxiety and Depression Scale, Cancer Worry Scale, and the EORTC QLQ-C30 and QLQ-BR23. Assessments took place at study entry and at 6- and 12-month follow-up visits. RESULTS: Between 2008 and 2010, 265 patients were recruited into the study. Completeness of follow-up data was more than 90%. Of the 178 women in the intervention group, 177 had genetic counseling, of whom 71 (40%) had rapid DNA testing and 59 (33%) received test results before surgery. Intention-to-treat and per-protocol analyses showed no statistically significant differences between groups over time in any of the psychosocial outcomes. CONCLUSIONS: In this study, RGCT in newly diagnosed breast cancer patients did not have any measurable adverse psychosocial effects.