Internet-based cognitive rehabilitation for working cancer survivors: results of a multicenter randomized controlled trial.

BACKGROUND: Cognitive problems contribute to decline in work performance. We evaluated (1) the effectiveness of basic self-management and extensive therapist-guided online cognitive rehabilitation on attainment of individually predetermined work-related goals among occupationally active cancer survivors, and (2) whether effectiveness of the programs differed for survivors with and without formal cognitive impairment. METHODS: In a 3-arm randomized controlled trial (NCT03900806), 279 non-central nervous system cancer survivors with cognitive complaints were assigned to the basic program (n = 93), the extensive program (n = 93), or a waiting-list control group (n = 93). Participants completed measurements pre-randomization (T0), 12 weeks post-randomization upon program completion (T1), and 26 weeks post-randomization (T2). Mixed-effects modeling was used to compare intervention groups with the control group on goal attainment, and on self-perceived cognitive problems, work ability, and health-related quality of life. RESULTS: Participants in the extensive program achieved their predetermined goals better than those in the control group, at short- and long-term follow-up (effect size [ES] = .49; P < .001; ES = .34; P = .014). They also had fewer recovery needs after work (ES = -.21; P = .011), more vitality (ES = .20; P = .018), and better physical role functioning (ES = .0.43 P = .015) than controls. At long-term follow-up, this finding persisted for physical role functioning (ES = .42; P = .034). The basic program elicited a small positive nonsignificant short-term (not long-term) effect on goal attainment for those with adequate adherence (ES = .28, P = .053). Effectiveness of the programs did not differ for patients with or without cognitive impairment. CONCLUSIONS: Internet-based therapist-guided extensive cognitive rehabilitation improves work-related goal attainment. Considering the prevalence of cognitive problems in survivors, it is desirable to implement this program.

Efficacy of a decision aid in breast cancer patients considering immediate reconstruction: results of a randomized controlled trial.

PURPOSE: Breast cancer patients face complex decisions about immediate breast reconstruction (BR) after mastectomy. We evaluated the efficacy of an online decision aid in improving the decision-making process, decision quality and health outcomes in breast cancer patients considering immediate BR. METHODS: In a multicenter randomized controlled trial, patients were allocated to either the intervention group receiving care-as-usual (CAU) with access to an online decision aid, or the control group receiving CAU with an information leaflet. The primary outcome was decisional conflict. Secondary outcomes assessed the process of decision making (e.g. preparation for decision making, satisfaction with information), decision quality (decision regret, knowledge) and health outcomes (e.g. satisfaction with BR outcomes, body image). Patients completed questionnaires at baseline (T0), 1 week after consultation with a plastic surgeon (T1), 3 months (T2), and 12 months post-surgery (T3). RESULTS: We included 250 patients. Decisional conflict decreased over time in both groups, with no between group differences. Intervention participants felt better prepared for decision making than controls (P = .002). At T2, 87% of intervention participants were (very) satisfied with the information about BR, compared to 73% of control participants (P = .011). No significant between group differences were observed in any other outcome. CONCLUSION: Our online decision aid was as effective in reducing decisional conflict as an information leaflet about immediate BR after mastectomy. However, the decision aid substantially improved the decision-making process by better preparing breast cancer patients for decisions about immediate BR.

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.

Effects of tamoxifen and exemestane on cognitive function in postmenopausal patients with breast cancer.

BACKGROUND: Cognitive effects of tamoxifen have been described. We augment data from a previous short-term (ST) follow-up study with long-term (LT) data to evaluate ST and LT cognitive effects of tamoxifen followed by exemestane and exemestane in breast cancer patients. METHODS: Patients from the Tamoxifen and Exemestane Adjuvant Multinational trial received 5 years exemestane (exemestane group, n = 114) or 2.5 years tamoxifen followed by 2.5 years exemestane (sequential group, n = 92). Neuropsychological performance was assessed pre-endocrine therapy, after 1 year (ST follow-up) and at 5 years (LT follow-up). A control group of healthy participants (n = 120) were assessed with parallel intervals. With random effects modeling we evaluated cognitive changes from baseline to ST and LT follow-up. Statistical tests were 2-sided. RESULTS: After controlling for age, intelligence quotient, attrition, menopausal symptoms, anxiety and/or depression, and/or fatigue, the sequential group showed ST and LT decline compared with control participants on verbal memory (effect size [ES] = 0.26, P = .01; ES = 0.34, P = .003) and executive function (ES = 0.27, P = .007; ES = 0.38, P = .002). Compared with the exemestane group, the sequential group demonstrated ST decline on information processing speed (ES = 0.33, P = .01) and executive function (ES = 0.32, P = .01) and LT decline on verbal memory (ES = 0.33, P = .02). The exemestane group showed no cognitive decline compared with control participants. CONCLUSION: Cognitive adverse effects of tamoxifen alone and after switching to exemestane were observed, suggestive of a carryover effect of tamoxifen. Our results underline the need for well-controlled, prospective trials studying cognitive effects of endocrine therapy.

Phase III study of the European Organisation for Research and Treatment of Cancer Quality of Life cancer survivorship core questionnaire.

PURPOSE: The purpose of this study is to develop a European Organisation for Research and Treatment of Cancer Quality of Life Group (EORTC QLG) questionnaire that captures the full range of physical, mental, and social health-related quality of life (HRQOL) issues relevant to disease-free cancer survivors. In this phase III study, we pretested the provisional core questionnaire (QLQ-SURV111) and aimed to identify essential and optional scales. METHODS: We pretested the QLQ-SURV111 in 492 cancer survivors from 17 countries with one of 11 cancer diagnoses. We applied the EORTC QLG decision rules and employed factor analysis and item response theory (IRT) analysis to assess and, where necessary, modify the hypothesized questionnaire scales. We calculated correlations between the survivorship scales and the QLQ-C30 summary score and carried out a Delphi survey among healthcare professionals, patient representatives, and cancer researchers to distinguish between essential and optional scales. RESULTS: Fifty-four percent of the sample was male, mean age was 60 years, and, on average, time since completion of treatment was 3.8 years. Eleven items were excluded, resulting in the QLQ-SURV100, with 12 functional and 9 symptom scales, a symptom checklist, 4 single items, and 10 conditional items. The essential survivorship scales consist of 73 items. CONCLUSIONS: The QLQ-SURV100 has been developed to assess comprehensively the HRQOL of disease-free cancer survivors. It includes essential and optional scales and will be validated further in an international phase IV study. IMPLICATIONS FOR CANCER SURVIVORS: The availability of this questionnaire will facilitate a standardized and robust assessment of the HRQOL of disease-free cancer survivors.

The Effects of Being Informed About Chemotherapy-Related Cognitive Symptoms With And Without Self-Affirmation on Perceived Cognitive Symptoms of Breast Cancer Patients: A Randomized Prospective, Longitudinal Study.

BACKGROUND: Informing patients about chemotherapy-related cognitive symptoms (CRCS) may increase perceived cognitive symptoms. This longitudinal randomized study evaluated this Adverse Information Effect (AIE) in breast cancer patients and examined whether self-affirmation (SA) can reduce AIEs (ClinicalTrials.gov identifier: NCT04813965). PATIENTS AND METHODS: Before (neo) adjuvant chemotherapy, 160 newly diagnosed breast cancer patients were randomly allocated to receive: standard information on side-effects (control), standard information with additional information about CRCS (information), or standard and additional information with a subsequent self-affirmative text (information+SA). Online-questionnaires assessed the perceived frequency (MOS-cog) and severity (MDASI-cog) of cognitive symptoms before chemotherapy (baseline, T0), and 2.5-months (T1) and 6.5-months (T2) post-chemotherapy. Higher scores indicate less frequent, and more severe symptoms, respectively. Baseline-to-follow-up analyses using a mixed-effects modeling approach compared groups over time. RESULTS: At T0-T2, 148, 140 and 133 patients responded, respectively (attrition rates: 8%, 5%, 5%). Frequency (ES = -0.36, P =.003) and severity (ES = 0.54, P <.001) of symptoms worsened from baseline to T1, without differences between groups. At T2, symptom frequency remained stable for informed (ES=-0.3, P =.021) and self-affirmed (ES=-0.3, P =.019) patients, but returned to baseline levels for controls. At T2, symptom severity remained increased for informed patients (ES = 0.3, P =.006), but normalized for self-affirmed patients (ES = 0.2, P =.178) and controls. CONCLUSION: No AIEs occurred until T2. The initial overall increase in perceived cognitive symptoms recovered at T2 for controls, but not for patients who received additional information about CRCS. Self-affirmation attenuated these longer-term AIEs for the perceived severity but not the frequency of symptoms.

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.

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.

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.

Light Therapy for Cancer-Related Fatigue in (Non-)Hodgkin Lymphoma Survivors: Results of a Randomized Controlled Trial.

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 (EST0-T1 = -0.71; EST1-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.

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).

Brain White Matter Microstructure as a Risk Factor for Cognitive Decline After Chemotherapy for Breast Cancer.

PURPOSE: Cognitive decline is frequently observed after chemotherapy. As chemotherapy is associated with changes in brain white matter microstructure, we investigated whether white matter microstructure before chemotherapy is a risk factor for cognitive decline after chemotherapy. METHODS: Neuropsychologic tests were administered before and 6 months (n = 49), 2 years (n = 32), and 3 years (n = 32) after chemotherapy in patients with breast cancer receiving anthracycline-based chemotherapy (BC + CT group), at matched intervals to patients with BC who did not receive systemic therapy (BC - CT group: n = 39, 23, and 19, respectively) and to no-cancer controls (NC group: n = 37, 29, and 28, respectively). Using multivariate normative comparison, we evaluated to what extent the cognitive profiles of patients deviated from those of controls. Fractional anisotropy (FA), derived from magnetic resonance diffusion tensor imaging, was used to measure white matter microstructure before treatment. FA was evaluated as a risk factor for cognitive decline, in addition to baseline age, fatigue, cognitive complaints, and premorbid intelligence quotient. We subsequently ran voxel-wise diffusion tensor imaging analyses to investigate white matter microstructure in specific nerve tracts. RESULTS: Low FA independently predicted cognitive decline early (6 months, P = .013) and late (3 years, P < .001) after chemotherapy. FA did not predict cognitive decline in the BC - CT and NC groups. Voxel-wise analysis indicated involvement of white matter tracts essential for cognitive functioning. CONCLUSION: Low FA may reflect low white matter reserve. This may be a risk factor for cognitive decline after chemotherapy for BC. If validated in future trials, identification of patients with low white matter reserve could improve patient care, for example, by facilitating targeted, early interventions or even by influencing choices of patients and doctors for receiving chemotherapy.

Trajectories of Cognitive Symptoms in Sick-Listed Cancer 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 (ß = 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 (ß = -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.

A questionable factor structure of the multidimensional fatigue inventory in the general Dutch population.

OBJECTIVE: One of the most commonly used tools to measure fatigue is the Multidimensional Fatigue Inventory (MFI). Studies into the scale structure of the MFI show discrepant findings. The objective of this study was to investigate the scale structure of the MFI in the general Dutch population. STUDY DESIGN AND SETTING: Using data from a Dutch probability-based internet panel (n = 2512), the original 5-factor model, a 4-factor, and a 5- and 4-bifactor model of the MFI were tested with confirmatory factor analyses. Additional models were investigated using exploratory factor analysis. RESULTS: Results neither confirmed a 5-factor (RMSEA = 0.120, CFI = 0.933, TLI = 0.920) nor a 4-factor model (RMSEA = 0.122, CFI = 0.928, TLI = 0.917). The two bi-factor models also showed a poor fit (bi-4-factor: RMSEA = 0.151, CFI = 0.895, TLI = 0.873; bi-5-factor: RMSEA = 0.153, CFI = 0.894, TLI = 0.871). Exploratory factor analysis did not support an alternative model, but seemed to show robustness in the loading of the original general fatigue items. CONCLUSION: Our results did not provide empirical support for a four or five (bi-)factor structure of the MFI, nor for an alternative model. The most reliable scale of the MFI seems to be the general fatigue scale that could be used as a general indicator of fatigue.

Decisional conflict in breast cancer patients considering immediate breast reconstruction.

BACKGROUND: Breast cancer (BC) patients who are treated with mastectomy are frequently offered immediate breast reconstruction. This study aimed to assess decisional conflict in patients considering immediate breast reconstruction, and to identify factors associated with clinically significant decisional conflict (CSDC). METHODS: Baseline data of a multicenter randomized controlled trial evaluating the impact of an online decision aid for BC patients considering immediate breast reconstruction after mastectomy were analyzed. Participants completed questionnaires assessing sociodemographic and clinical characteristics, decisional conflict and other patient-reported outcomes related to decision-making such as breast reconstruction preference, knowledge, information resources used, preferred involvement in decision-making, information coping style, and anxiety. Multivariable logistic regression analysis was performed to identify factors associated with CSDC (score > 37.5 on decisional conflict). RESULTS: Of the 250 participants, 68% experienced CSDC. Patients with a slight preference for breast reconstruction (odds ratio (OR) = 6.19, p < .01), with no preference for or against breast reconstruction (OR = 11.84, p < .01), and with a strong preference for no breast reconstruction (OR = 5.20, p < .05) were more likely to experience CSDC than patients with a strong preference for breast reconstruction. Furthermore, patients with more anxiety were more likely to experience CSDC (OR = 1.03, p = .01). CONCLUSION: A majority of BC patients who consider immediate breast reconstruction after mastectomy experience clinically significant decisional conflict. The findings emphasize the need for decision support, especially for patients who do not have a strong preference for breast reconstruction.

Time to health-related quality of life improvement analysis was developed to enhance evaluation of modern anticancer therapies.

OBJECTIVES: Major advances have recently been made in the treatments of cancer, which now also have the potential to improve patients' health-related quality of life (HRQOL). We propose the time to HRQOL improvement (TTI) and the time to sustained HRQOL improvement (TTSI) as potentially important cancer outcomes to be used in longitudinal HRQOL analyses. STUDY DESIGN AND SETTING: As proof of principle, we defined TTI and TTSI, using the Fine-Gray model to include competing risks in estimates, in a case study in real life of a cohort of newly diagnosed patients with cancer receiving a targeted therapy. HRQOL was evaluated before and during therapy with six assessments over a 24-month period, using the well-validated European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. RESULTS: For each assessed HRQOL domain, we assessed TTI and TTSI and estimated the cumulative incidence of patients' clinically meaningful improvements, also accounting for the occurrence of competing events. CONCLUSION: TTI and TTSI are potentially important outcomes in the era of modern anticancer therapies. The analysis of TTI and TTSI by competing risks approach will further add to the statistical methods that can be used to inform on the impact of cancer therapies on patients' HRQOL.

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.

Patient-reported Outcomes Following Treatment of Localised Prostate Cancer and Their Association with Regret About Treatment Choices.

BACKGROUND: Well-documented reports of patients' experiences with different treatments are important for helping localised prostate cancer (LPC) patients choose among the available treatment options. OBJECTIVE: To document differences in patient-reported outcomes (PROs) following radical prostatectomy (RP), external beam radiotherapy (EBRT), brachytherapy (BT), and active surveillance (AS), and to evaluate how these PROs and other factors are associated with treatment decision regret. DESIGN, SETTING, AND PARTICIPANTS: A prospective, observational, multicentre study of men diagnosed with LPC (stage cT1-2) during 2014-2016. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients completed validated PRO measures (Quality of Life Questionnaire Core 30 [QLQ-C30], Quality of Life Questionnaire prostate cancer-specific module [QLQ-PR25], Decision Regret Scale, and the Memorial Anxiety Scale for Prostate Cancer) before treatment and at 3, 6, and 12mo after treatment. Mixed-effect models were used to describe different PRO patterns. RESULTS AND LIMITATIONS: The analytic cohort included 434 men (AS=32%; RP=45%; EBRT=12%; BT=10%). Follow-up response rates were above 90%. At 1-yr follow-up, (1) men who had received RP reported significantly (p<0.01) more urinary incontinence, sexual dysfunction, hormonal/masculinity-related symptoms, and less emotional distress; (2) those having received EBRT reported more sexual dysfunction, hormonal/masculinity-related symptoms, and physical distress; and (3) those having received BT reported more urinary obstruction and irritation symptoms, compared with patients under AS. Irrespective of the treatment modality, 23% of the patients reported clinically relevant treatment regret (99% confidence interval, 17-28%). Multivariate correlates of decision regret were hormonal/masculinity-related symptoms, educational level, and positive surgical margins. CONCLUSIONS: Post-treatment physical and psychosocial functioning was significantly associated with specific treatment modalities and pretreatment functioning. Regret was relatively frequently reported by patients who experienced unwanted physical, psychosocial, and oncological outcomes. Greater efforts should be made to understand whether carefully educating patients about the possible consequences and effectiveness of treatments may help limit the feeling of treatment regret. PATIENT SUMMARY: In men with localised prostate cancer, regret about the treatment choice was more common among those who experienced more treatment-related symptoms during the year after treatment.

Internet-based cognitive behavioral therapy aimed at alleviating treatment-induced menopausal symptoms in breast cancer survivors: Moderators and mediators of treatment effects.

OBJECTIVES: Results from our recently conducted randomized controlled trial (RCT) indicated that Internet-based cognitive behavioral therapy (iCBT), with or without therapist support, is effective in reducing the perceived impact of hot flushes and night sweats (HF/NS) and overall levels of menopausal symptoms in breast cancer survivors with treatment-induced menopausal symptoms. STUDY DESIGN: We used data of 235 women and compared the iCBT groups combined (n = 156) with the control group (n = 79). Bootstrapped multiple regression analyses with interaction terms (group x potential moderator) or indirect effects (mediation pathway) were conducted. MAIN OUTCOME MEASURES: Reductions in perceived impact of HF/NS and overall levels of menopausal symptoms. RESULTS: Women with lower levels of education benefited most from the iCBT. Age, time since diagnosis, current endocrine treatment, oophorectomy, frequency of HF/NS, and psychological distress did not moderate the treatment effects. Factors that mediated treatment effects were the development of healthier beliefs about experiencing hot flushes in a social context, about the impact of night sweats on sleep and daily functioning, and about the ability to control and cope with hot flushes. The acquisition of behavioral coping strategies and decreased psychological distress did not mediate treatment effects. CONCLUSION: The results suggest that women with lower levels of education may benefit most from the current iCBT program, with or without therapist support. The development of healthier HF/NS beliefs contribute significantly to the observed positive effect of iCBT on the burden of menopausal symptoms. CLINICAL TRIAL INFORMATION: NCT02672189.