Strategies to increase survey participation: A randomized controlled study in a population of breast cancer survivors.

BACKGROUND: Data collection by mailing questionnaires to the study population is one of the main research methods in epidemiologic studies. As participation rates are decreasing, easy-to-implement and cost-effective strategies to increase survey participation are needed. In this study, we tested the effect of a pragmatic combination of evidence-based interventions. METHODS: We conducted a two-armed randomized controlled trial, nested in a cohort of breast cancer survivors (n = 1000) in the setting of a health outcomes survey. The intervention arm received a postal pre-notification, a non-monetary incentive (ballpoint with the study logo) and an alternative invitation letter in which several lay-out and textual adjustments were implemented according to behavioural science techniques. The alternative invitation letter also contained a QR-code through which an information video about the study could be accessed. The control arm was invited according to standard practice. Participants had the option to fill-out a questionnaire either on paper or online. A questionnaire with more than 50% of the questions answered classified as participation. RESULTS: Overall participation rate was 62.9%. No significant difference in participation rate was observed between intervention and control arm (64.5% vs 61.3%, Risk Ratio (RR) 1.05, 95% CI [0.96 - 1.16]). Older age at study (>65 vs <51 years), and high socio-economic status (highest vs lowest quartile) were associated with higher participation rates (RR 1.30, 95% CI [1.07 - 1.57] and 1.24, 95% CI [1.09 - 1.42] respectively). In-situ carcinoma compared to invasive cancer and longer interval since treatment were associated with lower participation (RR 0.86, 95% CI [0.74 - 0.99] and RR 0.92, 95% CI [0.87 - 0.99] per 5 year increase, respectively). CONCLUSION: Overall, the combination of four interventions tested in this study did not improve survey participation among breast cancer survivors. The overall participation rate was relatively high, possibly due to the study population of cancer survivors.

The Facilitators and Barriers of the Implementation of a Clinical Decision Support System for Breast Cancer Multidisciplinary Team Meetings-An Interview Study.

BACKGROUND: AI-driven clinical decision support systems (CDSSs) hold promise for multidisciplinary team meetings (MDTMs). This study aimed to uncover the hurdles and aids in implementing CDSSs during breast cancer MDTMs. METHODS: Twenty-four core team members from three hospitals engaged in semi-structured interviews, revealing a collective interest in experiencing CDSS workflows in clinical practice. All interviews were audio recorded, transcribed verbatim and analyzed anonymously. A standardized approach, 'the framework method', was used to create an analytical framework for data analysis, which was performed by two independent researchers. RESULTS: Positive aspects included improved data visualization, time-saving features, automated trial matching, and enhanced documentation transparency. However, challenges emerged, primarily concerning data connectivity, guideline updates, the accuracy of AI-driven suggestions, and the risk of losing human involvement in decision making. Despite the complexities involved in CDSS development and integration, clinicians demonstrated enthusiasm to explore its potential benefits. CONCLUSIONS: Acknowledging the multifaceted nature of this challenge, insights into the barriers and facilitators identified in this study offer a potential roadmap for smoother future implementations. Understanding these factors could pave the way for more effective utilization of CDSSs in breast cancer MDTMs, enhancing patient care through informed decision making.

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.

Surgical outcomes following breast reconstruction in patients with and without a history of chest radiotherapy for Hodgkin lymphoma: a multicentre, matched cohort study.

BACKGROUND: Breast cancer is the most common treatment-related second malignancy among women with previous chest radiotherapy for Hodgkin lymphoma (HL). Little is known about the effects of this kind of radiotherapy on the outcomes of postmastectomy breast reconstruction (BR). This study compared adverse outcomes of BR after HL-related chest radiotherapy to matched controls. METHODS: The authors conducted a retrospective, matched cohort study in two expert cancer centres in the Netherlands. BRs after therapeutic or prophylactic mastectomy in HL survivors who received chest radiotherapy were matched with BRs in nonirradiated patients without HL on age at mastectomy date, date of BR, and type of BR. The primary outcome was complication-related BR failure or conversion and secondary outcomes were complication-related re-operation, capsular contracture, major donor-site complications, and complication-related ICU admission. The authors analyzed all outcomes univariably using Fisher's exact tests and the authors assessed reconstruction failure, complication-related re-operation, and capsular contracture with multivariable Cox regression analysis adjusting for confounding and data clustering. RESULTS: Seventy BRs in 41 patients who received chest radiotherapy for HL were matched to 121 BRs in 110 nonirradiated patients. Reconstruction failure did not differ between HL survivors (12.9%) and controls (12.4%). The comparison groups showed no differences in number of reoperations, major donor-site complications, or capsular contractures. BR in HL survivors more often let to ICU admission due to complications compared with controls ( P =0.048). CONCLUSIONS: We observed no increased risk of adverse outcomes following BR after previous chest radiotherapy for HL. This is important information for counselling these patients and may improve shared decision-making.

The Areola study: design and rationale of a cohort study on long-term health outcomes in women with implant-based breast reconstructions.

BACKGROUND: Implant-based breast reconstructions contribute considerably to the quality of life of breast cancer patients. A knowledge gap exists concerning the potential role of silicone breast implants in the development of so-called "breast implant illness" (BII) and autoimmune diseases in breast cancer survivors with implant-based reconstructions. BII is a constellation of non-specific symptoms reported by a small group of women with silicone breast implants. METHODS: The Areola study is a multicenter retrospective cohort study with prospective follow-up aiming to assess the risk of BII and autoimmune diseases in female breast cancer survivors with and without silicone breast implants. In this report, we set out the rationale, study design, and methodology of this cohort study. The cohort consists of breast cancer survivors who received surgical treatment with implant-based reconstruction in six major hospitals across the Netherlands in the period between 2000 and 2015. As a comparison group, a frequency-matched sample of breast cancer survivors without breast implants will be selected. An additional group of women who received breast augmentation surgery in the same years will be selected to compare their characteristics and health outcomes with those of breast cancer patients with implants. All women who are still alive will be invited to complete a web-based questionnaire covering health-related topics. The entire cohort including deceased women will be linked to population-based databases of Statistics Netherlands. These include a registry of hospital diagnostic codes, a medicines prescription registry, and a cause-of-death registry, through which diagnoses of autoimmune diseases will be identified. Outcomes of interest are the prevalence and incidence of BII and autoimmune diseases. In addition, risk factors for the development of BII and autoimmune disorders will be assessed among women with implants. DISCUSSION: The Areola study will contribute to the availability of reliable information on the risks of BII and autoimmune diseases in Dutch breast cancer survivors with silicone breast implants. This will inform breast cancer survivors and aid future breast cancer patients and their treating physicians to make informed decisions about reconstructive strategies after mastectomy. REGISTRATION: This study is registered at ClinicalTrials.gov on June 2, 2022 (NCT05400954).

Mapping Current Organizational Structure and Improvement Points of Breast Cancer Multidisciplinary Team Meetings - An Interview Study.

Purpose: The aim of the study was to map current organization, and document potential improvement points of breast cancer multidisciplinary team meetings (MDTMs), in order to support the optimization of the present breast cancer MDTM organization. Methods: From January 2019 to February 2021, 24 core team members of the breast cancer multidisciplinary team (MDT) in three hospitals were interviewed. Semi-structured interviews were performed based on an interview guide. All interviews were recorded and transcribed verbatim. Deductive coding was performed on the transcripts by two independent researchers. The codes were organized in categories and themes. Results: In total 24 healthcare professionals; surgeons, medical oncologists, radiotherapists, pathologists, radiologists, and specialized nurses, from three different hospitals were interviewed. According to the participants, improving efficiency before and during MDTMs is possible by ensuring proper preparation of attendees, implementing more structure during discussions, improving access to and availability of patient data and optimizing general meeting discipline. Conclusion: Preparation, structure, data availability and meeting discipline were highlighted as essential factors for efficient breast cancer MDTM improvement. These topics seem to be applicable to other types of oncology MDTMs as well. Improving MDTM efficiency on the long term ensures high-quality discussions for all breast cancer patients.

Challenges in breast cancer genetic testing. A call for novel forms of multidisciplinary care and long-term evaluation.

Current methods of next generation sequencing may simultaneously detect multiple germline breast cancer susceptibility variants. However, it is a challenge to maximize the clinical benefit of genetic analysis for patients and family members while minimizing potentially harmful effects. Relevant issues include criteria for referral, the choice of gene panel, handling of variants of unknown significance, cancer risk counselling in clinical context including family history data, risks of tumours other than breast cancer, handling of potential germline findings revealed by tumour testing and the clinical management of gene variant carriers, including surveillance, targeted therapy, radiotherapy and risk-reducing surgery. We outline current challenges in the field of breast cancer genetics and call for novel forms of multidisciplinary care and long-term evaluation.

Post-operative re-irradiation with hyperthermia in locoregional breast cancer recurrence: Temperature matters.

PURPOSE: To investigate the impact of hyperthermia thermal dose (TD) on locoregional control (LRC), overall survival (OS) and toxicity in locoregional recurrent breast cancer patients treated with postoperative re-irradiation and hyperthermia. METHODS: In this retrospective study, 112 women with resected locoregional recurrent breast cancer treated in 2010-2017 with postoperative re-irradiation 8frx4Gy (n = 34) or 23frx2Gy (n = 78), combined with 4-5 weekly hyperthermia sessions guided by invasive thermometry, were subdivided into 'low' (n = 56) and 'high' TD (n = 56) groups by the best session with highest median cumulative equivalent minutes at 43 °C (Best CEM43T50) < 7.2 min and ≥7.2 min, respectively. Actuarial LRC, OS and late toxicity incidence were analyzed. Backward multivariable Cox regression and inverse probability weighting (IPW) analysis were performed. RESULTS: TD subgroups showed no significant differences in patient/treatment characteristics. Median follow-up was 43 months (range 1-107 months). High vs. low TD was associated with LRC (p = 0.0013), but not with OS (p = 0.29) or late toxicity (p = 0.58). Three-year LRC was 74.0% vs. 92.3% in the low and high TD group, respectively (p = 0.008). After three years, 25.0% and 0.9% of the patients had late toxicity grade 3 and 4, respectively. Multivariable analysis showed that distant metastasis (HR 17.6; 95%CI 5.2-60.2), lymph node involvement (HR 2.9; 95%CI 1.2-7.2), recurrence site (chest wall vs. breast; HR 4.6; 95%CI 1.8-11.6) and TD (low vs. high; HR 4.1; 95%CI 1.4-11.5) were associated with LRC. TD was associated with LRC in IPW analysis (p = 0.0018). CONCLUSIONS: High thermal dose (best CEM43T50 ≥ 7.2 min) was associated with significantly higher LRC for patients with locoregional recurrent breast cancer treated with postoperative re-irradiation and hyperthermia, without augmenting toxicity.

Development of a patient decision aid for patients with breast cancer who consider immediate breast reconstruction after mastectomy.

PURPOSE: The aim of this study was to develop a patient decision aid (pDA) that could support patients with breast cancer (BC) in making an informed decision about breast reconstruction (BR) after mastectomy. METHODS: The development included four stages: (i) Establishment of a multidisciplinary team; (ii) Needs assessment consisting of semi-structured interviews in patients and a survey among healthcare professionals (HCPs); (iii) Creation of content, design and technical system; and (iv) Acceptability and usability testing using a think-aloud approach in patients and interviews among HCPs and representatives of the Dutch Breast Cancer Patient Organization. RESULTS: From the needs assessment, three themes were identified: Challenging period to make a decision, Diverse motivations for a personal decision and Information needed to make a decision about BR. HCPs valued the development of a pDA, especially to prepare patients for consultation. The pDA that was developed contained three parts: first, a consultation sheet for oncological breast surgeons to introduce the choice; second, an online tool including an overview of reconstructive options, the pros and cons of each option, information on the consequences of each option for daily life, exercises to clarify personal values and patient stories; and third, a summary sheet with patients' values, preferences and questions to help inform and guide the discussion between the patient and her plastic surgeon. The pDA was perceived to be informative, helpful and easy to use by patients and HCPs. CONCLUSION: Consistent with information needs, a pDA was developed to support patients with BC who consider immediate BR in making an informed decision together with their plastic surgeon. PATIENT OR PUBLIC CONTRIBUTION: Patients participated in the needs assessment and in acceptability and usability testing.

Characteristics of Participants and Nonparticipants in a Blended Internet-Based Physical Activity Trial for Breast and Prostate Cancer Survivors: Cross-sectional Study.

BACKGROUND: As the number of cancer survivors is increasing, it is important to be able to offer exercise and physical activity (PA)-promoting interventions that are both effective and reasonably accessible. Internet-based interventions are typically less expensive and more accessible alternatives to on-site supervised interventions. Currently, little is known about the characteristics of nonparticipants in PA promotion trials in the cancer survivorship setting, both in general and specifically in trials using internet-supported interventions. OBJECTIVE: This study aims to gain insight into the characteristics associated with nonparticipation in a blended internet-based supported intervention trial to promote PA. METHODS: Breast and prostate cancer survivors, 3-36 months after primary curative treatment, were invited to participate in the PABLO trial; this trial compared an internet-based intervention to enhance PA levels, with or without additional support from a physical therapist, to usual care. Participants and nonparticipants were asked to complete a comprehensive questionnaire assessing sociodemographics, fatigue, and health-related quality of life. Baseline data for participants and nonparticipants were compared using the independent Student t test and chi-square test. RESULTS: The inclusion rate in the trial was 11.03% (137/1242). Of the nonparticipants, 13.95% (154/1104) completed the questionnaire. Participants were more highly educated (P=.04), had a paid job less often (P=.03), and were on sick leave more often (P=.03). They reported less PA per week, both moderate (P=.03) and vigorous (P<.01), before diagnosis and during leisure time (P<.01, effect size [ES]=0.44). They reported a significantly lower stage of change (P≤.01), lower self-efficacy (P<.01, ES=0.61), perceived barriers to PA (P<.01, ES=0.54), and more general fatigue (P<.01, ES=0.60). Participants reported lower health-related quality of life for most domains (ES ranging from 0.34 for mental health to 0.48 for social functioning). No significant differences were found for other sociodemographics, mood state, or attitudes toward or perceived social support for PA. CONCLUSIONS: The participants who self-selected for trial participation reported lower PA levels before diagnosis and a stronger need for support compared with nonparticipants. The trial thus included those patients who might benefit the most from internet-based supportive PA interventions. TRIAL REGISTRATION: Netherlands trial register NTR6911; https://www.trialregister.nl/trial/6733.

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.

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.

Measuring decline in white matter integrity after systemic treatment for breast cancer: omitting skeletonization enhances sensitivity.

Chemotherapy for non-central nervous system cancers is associated with abnormalities in brain structure and function. Diffusion tensor imaging (DTI) allows for studying in vivo microstructural changes in brain white matter. Tract-based spatial statistics (TBSS) is a widely used processing pipeline in which DTI data are typically normalized to a generic DTI template and then 'skeletonized' to compensate for misregistration effects. However, this approach greatly reduces the overall white matter volume that is subjected to statistical analysis, leading to information loss. Here, we present a re-analysis of longitudinal data previously analyzed with standard TBSS (Menning et al., BIB 2018, 324-334). For our current approach, we constructed a pipeline with an optimized registration method in Advanced Normalization Tools (ANTs) where DTI data are registered to a study-specific, high-resolution T1 template and the skeletonization step is omitted. In a head to head comparison, we show that with our novel approach breast cancer survivors who had received chemotherapy plus or minus endocrine therapy (BC + SYST, n = 26) showed a global decline in overall FA that was not present in breast cancer survivors who did not receive systemic therapy (BC-SYST, n = 23) or women without a cancer diagnosis (no cancer controls, NC, n = 30). With the standard TBSS approach we did not find any group differences. Moreover, voxel-based analysis for our novel pipeline showed a widespread decline in FA in the BC + SYST compared to the NC group. Interestingly, the BC-SYST group also showed a decline in FA compared to the NC group, although in much less voxels. These results were not found with the standard TBSS approach. We demonstrate that a modified processing pipeline makes DTI data more sensitive to detecting changes in white matter integrity in non-CNS cancer patients after treatment, particularly chemotherapy.

Surgical Complications of Skin-Sparing Mastectomy and Immediate Implant-Based Breast Reconstruction in Women Concurrently Treated With Adjuvant Chemotherapy for Breast Cancer.

BACKGROUND AND AIM: To date, studies on adjuvant chemotherapy as a risk factor for the surgical outcome of combined mastectomy and breast reconstruction were hampered by the inclusion of mixed reconstructive cohorts of both delayed and immediate timing and of both autologous and implant-based techniques. Consequently, there is a paucity of data on the impact of adjuvant chemotherapy on surgical complication rates after combined skin-sparing mastectomy and immediate implant-based breast reconstruction. METHODOLOGY: We compared the postoperative complications that occurred within 16 weeks after this combined procedure in 131 women (139 breasts) treated with adjuvant chemotherapy with those in a control group of 491 women (517 breasts) not receiving any adjuvant therapy within 16 weeks. RESULTS: In line with the clinically indicated selection of women to undergo adjuvant chemotherapy, the interventional group differed significantly from the control group in 7 of the 12 patient- and procedure-related characteristics. The prevalence of minor complications (13.7% and 12.4%, respectively, P = 0.68) and major complications (31.7% and 29.4%, respectively, P = 0.60) did not differ significantly between the interventional group and the controls. The fraction of breasts that needed unscheduled surgery (0.29 and 0.24, respectively, P = 0.20), the fraction of total number of interventions (0.34 and 0.33, respectively, P = 0.24), and the fraction of implants lost (0.72 and 0.67, respectively, P = 0.86) did not differ significantly between both groups. The onset of chemotherapy, furthermore, seemed not to influence the occurrence or severity of complications. CONCLUSIONS: Like other women who have to undergo mastectomy, women who need to undergo adjuvant chemotherapy can potentially benefit from combined skin-sparing mastectomy and immediate implant-based breast reconstruction.

Prediction of contralateral breast cancer: external validation of risk calculators in 20 international cohorts.

BACKGROUND: Three tools are currently available to predict the risk of contralateral breast cancer (CBC). We aimed to compare the performance of the Manchester formula, CBCrisk, and PredictCBC in patients with invasive breast cancer (BC). METHODS: We analyzed data of 132,756 patients (4682 CBC) from 20 international studies with a median follow-up of 8.8 years. Prediction performance included discrimination, quantified as a time-dependent Area-Under-the-Curve (AUC) at 5 and 10 years after diagnosis of primary BC, and calibration, quantified as the expected-observed (E/O) ratio at 5 and 10 years and the calibration slope. RESULTS: The AUC at 10 years was: 0.58 (95% confidence intervals [CI] 0.57-0.59) for CBCrisk; 0.60 (95% CI 0.59-0.61) for the Manchester formula; 0.63 (95% CI 0.59-0.66) and 0.59 (95% CI 0.56-0.62) for PredictCBC-1A (for settings where BRCA1/2 mutation status is available) and PredictCBC-1B (for the general population), respectively. The E/O at 10 years: 0.82 (95% CI 0.51-1.32) for CBCrisk; 1.53 (95% CI 0.63-3.73) for the Manchester formula; 1.28 (95% CI 0.63-2.58) for PredictCBC-1A and 1.35 (95% CI 0.65-2.77) for PredictCBC-1B. The calibration slope was 1.26 (95% CI 1.01-1.50) for CBCrisk; 0.90 (95% CI 0.79-1.02) for PredictCBC-1A; 0.81 (95% CI 0.63-0.99) for PredictCBC-1B, and 0.39 (95% CI 0.34-0.43) for the Manchester formula. CONCLUSIONS: Current CBC risk prediction tools provide only moderate discrimination and the Manchester formula was poorly calibrated. Better predictors and re-calibration are needed to improve CBC prediction and to identify low- and high-CBC risk patients for clinical decision-making.

Moderators of the effect of psychosocial interventions on fatigue in women with breast cancer and men with prostate cancer: Individual patient data meta-analyses.

OBJECTIVE: Psychosocial interventions can reduce cancer-related fatigue effectively. However, it is still unclear if intervention effects differ across subgroups of patients. These meta-analyses aimed at evaluating moderator effects of (a) sociodemographic characteristics, (b) clinical characteristics, (c) baseline levels of fatigue and other symptoms, and (d) intervention-related characteristics on the effect of psychosocial interventions on cancer-related fatigue in patients with non-metastatic breast and prostate cancer. METHODS: Data were retrieved from the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) consortium. Potential moderators were studied with meta-analyses of pooled individual patient data from 14 randomized controlled trials through linear mixed-effects models with interaction tests. The analyses were conducted separately in patients with breast (n = 1091) and prostate cancer (n = 1008). RESULTS: Statistically significant, small overall effects of psychosocial interventions on fatigue were found (breast cancer: ß = -0.19 [95% confidence interval (95%CI) = -0.30; -0.08]; prostate cancer: ß = -0.11 [95%CI = -0.21; -0.00]). In both patient groups, intervention effects did not differ significantly by sociodemographic or clinical characteristics, nor by baseline levels of fatigue or pain. For intervention-related moderators (only tested among women with breast cancer), statistically significant larger effects were found for cognitive behavioral therapy as intervention strategy (ß = -0.27 [95%CI = -0.40; -0.15]), fatigue-specific interventions (ß = -0.48 [95%CI = -0.79; -0.18]), and interventions that only targeted patients with clinically relevant fatigue (ß = -0.85 [95%CI = -1.40; -0.30]). CONCLUSIONS: Our findings did not provide evidence that any selected demographic or clinical characteristic, or baseline levels of fatigue or pain, moderated effects of psychosocial interventions on fatigue. A specific focus on decreasing fatigue seems beneficial for patients with breast cancer with clinically relevant fatigue.

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.

Prediction and clinical utility of a contralateral breast cancer risk model.

BACKGROUND: Breast cancer survivors are at risk for contralateral breast cancer (CBC), with the consequent burden of further treatment and potentially less favorable prognosis. We aimed to develop and validate a CBC risk prediction model and evaluate its applicability for clinical decision-making. METHODS: We included data of 132,756 invasive non-metastatic breast cancer patients from 20 studies with 4682 CBC events and a median follow-up of 8.8 years. We developed a multivariable Fine and Gray prediction model (PredictCBC-1A) including patient, primary tumor, and treatment characteristics and BRCA1/2 germline mutation status, accounting for the competing risks of death and distant metastasis. We also developed a model without BRCA1/2 mutation status (PredictCBC-1B) since this information was available for only 6% of patients and is routinely unavailable in the general breast cancer population. Prediction performance was evaluated using calibration and discrimination, calculated by a time-dependent area under the curve (AUC) at 5 and 10 years after diagnosis of primary breast cancer, and an internal-external cross-validation procedure. Decision curve analysis was performed to evaluate the net benefit of the model to quantify clinical utility. RESULTS: In the multivariable model, BRCA1/2 germline mutation status, family history, and systemic adjuvant treatment showed the strongest associations with CBC risk. The AUC of PredictCBC-1A was 0.63 (95% prediction interval (PI) at 5 years, 0.52-0.74; at 10 years, 0.53-0.72). Calibration-in-the-large was -0.13 (95% PI: -1.62-1.37), and the calibration slope was 0.90 (95% PI: 0.73-1.08). The AUC of Predict-1B at 10 years was 0.59 (95% PI: 0.52-0.66); calibration was slightly lower. Decision curve analysis for preventive contralateral mastectomy showed potential clinical utility of PredictCBC-1A between thresholds of 4-10% 10-year CBC risk for BRCA1/2 mutation carriers and non-carriers. CONCLUSIONS: We developed a reasonably calibrated model to predict the risk of CBC in women of European-descent; however, prediction accuracy was moderate. Our model shows potential for improved risk counseling, but decision-making regarding contralateral preventive mastectomy, especially in the general breast cancer population where limited information of the mutation status in BRCA1/2 is available, remains challenging.

Cost-utility, cost-effectiveness, and budget impact of Internet-based cognitive behavioral therapy for breast cancer survivors with treatment-induced menopausal symptoms.

PURPOSE: Internet-based cognitive behavioral therapy (iCBT), with and without therapist support, is effective in reducing treatment-induced menopausal symptoms and perceived impact of hot flushes and night sweats (HF/NS) in breast cancer survivors. The aim of the current study was to evaluate the cost-utility, cost-effectiveness, and budget impact of both iCBT formats compared to a waiting list control group from the Dutch healthcare perspective. METHODS: A Markov model was constructed with a 5-year time horizon. Costs and health outcomes were measured alongside a randomized controlled clinical trial and included quality-adjusted life years (QALYs), overall levels of menopausal symptoms, and perceived impact of HF/NS. Uncertainty was examined using probabilistic and deterministic sensitivity analyses, together with a scenario analysis incorporating a different perspective. RESULTS: iCBT was slightly more expensive than the waiting list control, but also more effective, resulting in incremental cost-utility ratios of €23,331/QALY and €11,277/QALY for the guided and self-managed formats, respectively. A significant reduction in overall levels of menopausal symptoms or perceived impact of HF/NS resulted in incremental costs between €1460 and €1525 for the guided and €500-€753 for the self-managed format. The estimated annual budget impact for the Netherlands was €192,990 for the guided and €74,592 for the self-managed format. CONCLUSION: Based on the current trial data, the results indicate that both guided and self-managed iCBT are cost-effective with a willingness-to-pay threshold of well below €30,000/QALY. Additionally, self-managed iCBT is the most cost-effective strategy and has a lower impact on healthcare budgets.

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 ).