Patient Expectations About Palliative Treatment for Symptomatic Spinal Metastases: A Qualitative Study.

OBJECTIVES: Patients with spinal metastases often receive palliative surgery or radiation therapy to maintain or improve health-related quality of life. Patients with unrealistic expectations regarding treatment outcomes have been shown to be less satisfied with their post-treatment health status. This study evaluated expectations of patients with spinal metastases scheduled for surgery and/or radiation therapy. METHODS: Individual semistructured interviews were conducted with patients with symptomatic spinal metastases before and 6 weeks after surgery and/or radiation therapy. Expectations regarding treatment outcomes were discussed before treatment, and level of fulfillment of these pretreatment expectations was discussed after treatment. Interviews were recorded, transcribed and analyzed according to the thematic analysis method to identify themes. RESULTS: Before treatment, patients thought they were not, or minimally, informed about (expected) treatment outcomes, but they felt well informed about treatment procedures and possible complications. Although patients expected pain relief and improvement in daily functioning, they found it difficult to describe any recovery timeline or the impact of these expected improvements on their daily life. Patients generally understood that treatment was not curative, but lacked insight into the impact of treatment on life expectancy given that this was hardly discussed by their surgeon and/or radiation oncologist. Pretreatment expectations regarding pain and daily functioning were only partially met in most patients post-treatment. CONCLUSIONS: Patients thought they were not, or only minimally, informed about expected outcomes after surgery and/or radiation therapy for symptomatic spinal metastases. Improvements in patient-physician communication and counseling could help guide patients toward realistic pretreatment expectations.

Translation and validation of the Dutch Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ2.0) to evaluate health-related quality of life in patients with symptomatic spinal metastases.

BACKGROUND: The primary goal of palliative treatment of spinal metastases is to maintain or improve health-related quality of life (HRQOL). We translated and validated a Dutch version of The Spine Oncology Study Group Outcome Questionnaire (SOSGOQ2.0), a valid and reliable 20-item questionnaire to evaluate HRQOL in patients with spinal metastases. METHODS: After cross-cultural translation and adaptation, the questionnaire was pre-tested in fifteen patients referred for spine surgery and/or radiotherapy. This resulted in a final questionnaire that was sent to patients for assessment of internal consistency, construct (i.e., convergent and divergent) validity, discriminative power and test-retest reliability. RESULTS: Overall, 147 patients (mean age 65.6 years, SD = 10.4) completed the questionnaire after a median time of 45.4 months (IQR = 18.9-72.9) after spine surgery and/or radiotherapy. Internal consistency was good for the Physical function, Pain, and Mental health domains (α = 0.87, 0.86, 0.72), but not for Social function (α = 0.04). Good convergent validity was demonstrated except for Social function (rs = 0.37 95%CI = 0.21-0.51). Discriminative power between patients with ECOG performance scores of 0-1 and 2-4 was found on all domains and Neurological function items. Test-retest reliability was acceptable for Physical function, Pain and Mental health (ICC = 0.89 95%CI = 0.81-0.94, ICC = 0.88 95%CI = 0.78-0.93, ICC = 0.68 95%CI = 0.48-0.81), whereas ICC = 0.45 (95%CI = 0.17-0.66) for Social function was below threshold. After removing item 20 from the Social function domain, internal consistency improved, and convergent validity and test-retest reliability were good. CONCLUSION: The Dutch version of the SOSGOQ2.0 questionnaire is a reliable and valid tool to measure HRQOL in patients with spinal metastases. Item 20 was removed to retain psychometric properties.

Effects of exercise in breast cancer patients: implications of the trials within cohorts (TwiCs) design in the UMBRELLA Fit trial.

PURPOSE: The Trials within Cohorts (TwiCs) design aims to overcome problems faced in conventional RCTs. We evaluated the TwiCs design when estimating the effect of exercise on quality of life (QoL) and fatigue in inactive breast cancer survivors. METHODS: UMBRELLA Fit was conducted within the prospective UMBRELLA breast cancer cohort. Patients provided consent for future randomization at cohort entry. We randomized inactive patients 12-18 months after cohort enrollment. The intervention group (n = 130) was offered a 12-week supervised exercise intervention. The control group (n = 130) was not informed and received usual care. Six-month exercise effects on QoL and fatigue as measured in the cohort were analyzed with intention-to-treat (ITT), instrumental variable (IV), and propensity scores (PS) analyses. RESULTS: Fifty-two percent (n = 68) of inactive patients accepted the intervention. Physical activity increased in patients in the intervention group, but not in the control group. We found no benefit of exercise for dimensions of QoL (ITT difference global QoL: 0.8, 95% CI = - 2.2; 3.8) and fatigue, except for a small beneficial effect on physical fatigue (ITT difference: - 1.1, 95% CI = - 1.8; - 0.3; IV: - 1.9, 95% CI = - 3.3; - 0.5, PS: - 1.2, 95% CI = - 2.3; - 0.2). CONCLUSION: TwiCs gave insight into exercise intervention acceptance: about half of inactive breast cancer survivors accepted the offer and increased physical activity levels. The offer resulted in no improvement on QoL, and a small beneficial effect on physical fatigue. TRIAL REGISTRATION: Netherlands Trial Register (NTR5482/NL.52062.041.15), date of registration: December 07, 2015.

(Ex-)breast cancer patients with (pre-existing) symptoms of anxiety and/or depression experience higher barriers to contact health care providers during the COVID-19 pandemic.

PURPOSE: To identify factors associated with (perceived) access to health care among (ex-)breast cancer patients during the COVID-19 pandemic. METHODS: Cross-sectional study within a large prospective, multicenter cohort of (ex-)breast cancer patients, i.e., UMBRELLA. All participants enrolled in the UMBRELLA cohort between October 2013 and April 2020 were sent a COVID-19-specific survey, including the Hospital Anxiety and Depression Scale (HADS) questionnaire. RESULTS: In total, 1051 (66.0%) participants completed the survey. During COVID-19, 284 (27.0%) participants reported clinically relevant increased levels of anxiety and/or depression, i.e., total HADS score ≥ 12. Participants with anxiety and/or depression reported statistically significant higher barriers to contact their general practitioner (47.5% vs. 25.0%, resp.) and breast cancer physicians (26.8% vs. 11.2%, resp.) compared to participants without these symptoms. In addition, a higher proportion of participants with anxiety and/or depression reported that their current treatment or (after)care was affected by COVID-19 compared to those without these symptoms (32.7% vs. 20.5%, resp.). Factors independently associated with symptoms of anxiety and/or depression during COVID-19 were pre-existent anxiety (OR 6.1, 95% CI 4.1-9.2) or depression (OR 6.0, 95% CI 3.5-10.2). CONCLUSION: During the COVID-19 pandemic, (ex-)breast cancer patients with symptoms of anxiety and/or depression experience higher barriers to contact health care providers. Also, they more often report that their health care was affected by COVID-19. Risk factors for anxiety and/or depression during COVID-19 are pre-existent symptoms of anxiety or depression. Extra attention-including mental health support-is needed for this group.

Expectations of treatment outcomes in patients with spinal metastases; what do we tell our patients? A qualitative study.

BACKGROUND: Realistic pre-treatment expectations are important and have been associated with post-treatment health related quality of life (HRQOL). Patient expectations are greatly influenced by physicians, as they are the primary resource for information. This study aimed to explore the communication practices of physicians regarding treatment outcomes for patients with spinal metastases, and physician experiences with patients' pre-treatment expectations. METHODS: An international qualitative study using semi-structured interviews with physicians routinely involved in treating metastatic spine disease (spine surgeons, radiation and medical oncologists, and rehabilitation specialists) was conducted. Physicians were interviewed about the content and extent of information they provide to patients with spinal metastases regarding treatment options, risks and treatment outcomes. Interviews were transcribed verbatim and analyzed using a thematic coding network. RESULTS: After 22 interviews data saturation occurred. The majority of the physicians indicated that they currently do not establish patients' pre-treatment expectations, despite acknowledging the importance of these expectations. Spine surgeons often believe that patient expectations are disproportionate. Physicians expressed they manage expectations by detailing the most common risks and providing a broad but nonspecific overview of treatment outcomes. While the palliative intent seems clear to the physicians, their perception is that the implications of a palliative treatment remains elusive to most patients. CONCLUSION: This study highlights the current gap in patient-physician communication regarding expectations of treatment outcomes of patients with spinal metastases. These results warrant further research to improve communication practices and determine the effect of patient expectations on patient reported outcomes in this population.

Stereotactic Body and Conventional Radiotherapy for Painful Bone Metastases: A Systematic Review and Meta-Analysis.

Importance: Conventional external beam radiotherapy (cEBRT) and stereotactic body radiotherapy (SBRT) are commonly used treatment options for relieving metastatic bone pain. The effectiveness of SBRT compared with cEBRT in pain relief has been a subject of debate, and conflicting results have been reported. Objective: To compare the effectiveness associated with SBRT vs cEBRT for relieving metastatic bone pain. Data Sources: A structured search was performed in the PubMed, Embase, and Cochrane databases on June 5, 2023. Additionally, results were added from a new randomized clinical trial (RCT) and additional unpublished data from an already published RCT. Study Selection: Comparative studies reporting pain response after SBRT vs cEBRT in patients with painful bone metastases. Data Extraction and Synthesis: Two independent reviewers extracted data from eligible studies. Data were extracted for the intention-to-treat (ITT) and per-protocol (PP) populations. The study is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: Overall and complete pain response at 1, 3, and 6 months after radiotherapy, according to the study's definition. Relative risk ratios (RRs) with 95% CIs were calculated for each study. A random-effects model using a restricted maximum likelihood estimator was applied for meta-analysis. Results: There were 18 studies with 1685 patients included in the systematic review and 8 RCTs with 1090 patients were included in the meta-analysis. In 7 RCTs, overall pain response was defined according to the International Consensus on Palliative Radiotherapy Endpoints in clinical trials (ICPRE). The complete pain response was reported in 6 RCTs, all defined according to the ICPRE. The ITT meta-analyses showed that the overall pain response rates did not differ between cEBRT and SBRT at 1 (RR, 1.14; 95% CI, 0.99-1.30), 3 (RR, 1.19; 95% CI, 0.96-1.47), or 6 (RR, 1.22; 95% CI, 0.96-1.54) months. However, SBRT was associated with a higher complete pain response at 1 (RR, 1.43; 95% CI, 1.02-2.01), 3 (RR, 1.80; 95% CI, 1.16-2.78), and 6 (RR, 2.47; 95% CI, 1.24-4.91) months after radiotherapy. The PP meta-analyses showed comparable results. Conclusions and Relevance: In this systematic review and meta-analysis, patients with painful bone metastases experienced similar overall pain response after SBRT compared with cEBRT. More patients had complete pain alleviation after SBRT, suggesting that selected subgroups will benefit from SBRT.

Competing risk analysis of cardiovascular disease risk in breast cancer patients receiving a radiation boost.

BACKGROUND: Thoracic radiotherapy may damage the myocardium and arteries, increasing cardiovascular disease (CVD) risk. Women with a high local breast cancer (BC) recurrence risk may receive an additional radiation boost to the tumor bed. OBJECTIVE: We aimed to evaluate the CVD risk and specifically ischemic heart disease (IHD) in BC patients treated with a radiation boost, and investigated whether this was modified by age. METHODS: We identified 5260 BC patients receiving radiotherapy between 2005 and 2016 without a history of CVD. Boost data were derived from hospital records and the national cancer registry. Follow-up data on CVD events were obtained from Statistics Netherlands until December 31, 2018. The relation between CVD and boost was evaluated with competing risk survival analysis. RESULTS: 1917 (36.4%) received a boost. Mean follow-up was 80.3 months (SD37.1) and the mean age 57.8 years (SD10.7). Interaction between boost and age was observed for IHD: a boost was significantly associated with IHD incidence in patients younger than 40 years but not in patients over 40 years. The subdistribution hazard ratio (sHR) was calculated for ages from 25 to 75 years, showing a sHR range from 5.1 (95%CI 1.2-22.6) for 25-year old patients to sHR 0.5 (95%CI 0.2-1.02) for 75-year old patients. CONCLUSION: In patients younger than 40, a radiation boost is significantly associated with an increased risk of CVD. In absolute terms, the increased risk was low. In older patients, there was no association between boost and CVD risk, which is likely a reflection of appropriate patient selection.

Introducing the New Patient Expectations in Spine Oncology Questionnaire.

BACKGROUND AND OBJECTIVES: It has been hypothesized that a discrepancy between pretreatment expectations and perceived outcomes is a significant source of patient dissatisfaction. Currently, there is lack in understanding and tools to assess patient expectations regarding the outcomes of treatment for spinal metastases. The objective of this study was therefore to develop a patient expectations questionnaire regarding the outcomes after surgery and/or radiotherapy for spinal metastases. METHODS: A multiphase international qualitative study was conducted. Phase 1 of the study included semistructured interviews with patients and relatives to understand their expectations of the outcomes of treatment. In addition, physicians were interviewed about their communication practices with patients regarding treatment and expected outcomes. In phase 2, items were developed based on the results of the interviews in phase 1. In phase 3, patients were interviewed to validate the content and language of the questionnaire. Selection of the final items was based on feedback from patients regarding content, language, and relevance. RESULTS: In phase 1, 24 patients and 22 physicians were included. A total of 34 items were developed for the preliminary questionnaire. After phase 3, a total of 22 items were retained for the final version of the questionnaire. The questionnaire is divided into 3 sections: (1) patient expectations regarding treatment outcomes, (2) prognosis, and (3) consultation with the physician. The items cover expectations related to pain, analgesia requirements, daily and physical function, overall quality of life, life expectancy, and information provided by the physician. CONCLUSION: The new Patient Expectations in Spine Oncology questionnaire was developed to evaluate patient expectations regarding the outcomes after treatment for spinal metastases. The Patient Expectations in Spine Oncology questionnaire will allow physicians to systematically assess patient expectations of planned treatment and thus help guide patients toward realistic expectations of treatment outcome.

Most patients reported positively or neutrally of having served as controls in the trials within cohorts design.

OBJECTIVES: To evaluate patients' experience of having served as controls without a notification at the time of randomization in the context of the trial within cohorts (TwiCs) design. METHODS: Patients were asked for their opinion on having served as controls in TwiCs, before and after having been provided the trial results. Patients had provided broad consent to randomization at cohort entry and had served as controls in one of two TwiCs (an exercise program after breast cancer treatment or radiotherapy dose-escalation for rectal cancer). RESULTS: Two to 6 years after cohort entry, 15% (n = 16) of all patients remembered having provided broad consent to randomization. Before disclosure of trial results, 47% (n = 52) of patients thought positively, 45% (n = 50) neutrally, and 2% (n = 2) negatively of having served as controls in one of the two trials. Seventeen percent (n = 18) of patients were positive, 65% (n = 71) neutral, and 11% (n = 12) negative about not having been notified when serving as controls. The survey results were comparable after disclosure of trial results. CONCLUSIONS: These results support the use of the TwiCs design with the staged-informed consent procedure. Keeping patients engaged and aware of the consents provided might further improve patients' experience of serving as controls in TwiCs.

AI-Based Radiation Dose Quantification for Estimation of Heart Disease Risk in Breast Cancer Survivors After Radiation Therapy.

PURPOSE: To investigate whether the dose planned for cardiac structures is associated with the risk of heart disease (HD) in patients with breast cancer treated with radiation therapy, and whether this association is modified by the presence of coronary artery calcification (CAC). METHODS AND MATERIALS: Radiation therapy planning computed tomographic (CT) scans and corresponding dose distribution maps of 5561 patients were collected, 5300 patients remained after the exclusion of ineligible patients and duplicates; 1899 patients received their CT scan before 2011, allowing long follow-up. CAC was detected automatically. Using an artificial intelligence-based method, the cardiac structures (heart, cardiac chambers, large arteries, 3 main coronary arteries) were segmented. The planned radiation dose to each structure separately and to the whole heart were determined. Patients were assigned to a low-, medium-, or high-dose group based on the dose to the respective heart structure. Information on HD hospitalization and mortality was obtained for each patient. The association of planned radiation dose to cardiac structures with risk of HD was investigated in patients with and without CAC using Cox proportional hazard analysis in the long follow-up population. Tests for interaction were performed. RESULTS: After a median follow-up of 96.0 months (interquartile range, 84.2-110.4 months) in the long follow-up group, 135 patients were hospitalized for HD or died of HD. If the dose to a structure increased 1 Gy, the relative HD risk increased by 3% to 11%. The absolute increase in HD risk was substantially higher in patients with CAC (event-ratelow-dose = 14-15 vs event-ratehigh-dose = 15-34 per 1000 person-years) than in patients without CAC (event-ratelow-dose = 6-8 vs event-ratehigh-dose = 5-17 per 1000 person-years). No interaction between CAC and radiation dose was found. CONCLUSIONS: Radiation exposure of cardiac structures is associated with increased risk of HD. Automatic segmentation of cardiac structures enables spatially localized dose estimation, which can aid in the prevention of radiation therapy-induced cardiac damage. This could be especially valuable in patients with breast cancer and CAC.

Quality of Life After Stereotactic Body Radiation Therapy Versus Conventional Radiation Therapy in Patients With Bone Metastases.

PURPOSE: Painful bone metastases hamper quality of life (QoL). The aim of this prespecified secondary analysis of the PRESENT trial was to compare change in global QoL, physical functioning, emotional functioning, functional interference, and psychosocial aspects after conventional radiation therapy (cRT) versus stereotactic body RT (SBRT). METHODS AND MATERIALS: A total of 110 patients were enrolled in the phase 2 randomized controlled VERTICAL trial (NCT02364115) following the "trials within cohorts" design and randomized 1:1 to cRT or SBRT. Patient-reported global QoL, physical functioning, emotional functioning, functional interference, and psychosocial aspects were assessed by the European Organization for Research and Treatment of Cancer QoL Questionnaire (QLQ) Core 15 Palliative Care and QLQ Bone Metastases 22 modules. Changes in QoL domains over time were compared between patients treated with cRT and SBRT using intention-to-treat (ITT) and per-protocol (PP) linear mixed model analysis adjusting for baseline scores. Proportions of patients in the cRT versus SBRT arm reporting a clinically relevant change in QoL within 3 months were compared using a χ2 test. RESULTS: QoL scores had improved over time and were comparable between groups for all domains in both the ITT and PP analyses, except for functional interference and psychological aspects in the ITT. Functional interference scores had improved more after 12 weeks in the cRT arm than in the SBRT arm (25.5 vs 14.1 points, respectively; effect size [ES] = 0.49, P = .04). Psychosocial aspects scores had improved more after 8 weeks in the cRT arm than in the SBRT arm (12.2 vs 7.3; ES = 0.56, P = .04). No clinically relevant differences between groups at 12 weeks in terms of global QoL, physical functioning, emotional functioning, functional interference, and psychosocial aspects were observed. CONCLUSIONS: Palliative RT improves QoL. Both SBRT and cRT have a comparable effect on patient-reported QoL outcomes in patients with painful bone metastases. Functional interference and psychological aspects scores improved more in patients treated with cRT versus patients offered SBRT.

Coronary artery calcifications on breast cancer radiotherapy planning CT scans and cardiovascular risk: What do patients want to know?

BACKGROUND: Coronary artery calcifications (CAC) is a strong predictor of cardiovascular disease (CVD), which can be automatically quantified on routine breast radiotherapy planning computed tomography (CT) scans. Around 8% of patients have (very) high CAC scores and corresponding increased risks of CVD. AIM: This study explores whether, how, and under what conditions women with breast cancer want to be informed about their CAC-based CVD risk. METHODS: A cross-sectional survey study was conducted in a random sample of UMBRELLA, a prospective breast cancer cohort. Participants (n = 79) filled out a questionnaire about their knowledge on the CVD risk following breast cancer, their interest in being informed about their CVD risk based on CAC score, and preferences on how they would want to receive this information. RESULTS: Most participants (66%) were not aware that the presence of CAC indicates an increased CVD risk. Participants indicated that they were not or only slightly aware of the risk of treatment-induced cardiotoxicity (48%), and that the risk of cardiotoxicity was higher in patients with pre-existing CVD risk factors (82%). The vast majority (90%) indicated that they want to be informed about in increased CAC-based CVD risk. CONCLUSIONS: The majority of patients with breast cancer wants to be informed about their CAC-based CVD risk. With the majority of patients with breast cancer undergoing radiotherapy, and with low cost and automated options for accurate CAC measurement in planning CT scans, it is important to develop strategies to manage patients with an increased CAC-based risk of CVD.

Pain Response After Stereotactic Body Radiation Therapy Versus Conventional Radiation Therapy in Patients With Bone Metastases-A Phase 2 Randomized Controlled Trial Within a Prospective Cohort.

PURPOSE: Pain response after conventional external beam radiation therapy (cRT) in patients with painful bone metastases is observed in 60% to 70% of patients. The aim of the VERTICAL trial was to investigate whether stereotactic body radiation therapy (SBRT) improves pain response. METHODS AND MATERIALS: This single-center, phase 2, randomized controlled trial was conducted within the PRESENT cohort, which consists of patients referred for radiation therapy of bone metastases to our tertiary center. Cohort participants with painful bone metastases who gave broad informed consent for randomization were randomly assigned to cRT or SBRT. Only patients in the intervention arm received information about the trial and were offered SBRT (1 × 18 Gy, 3 × 10 Gy, or 5 × 7 Gy), which they could accept or refuse. Patients who refused SBRT underwent standard cRT (1 × 8 Gy, 5 × 4 Gy, or 10 × 3 Gy). Patients in the control arm were not informed. Primary endpoint was pain response at 3 months after radiation therapy. Secondary outcomes were pain response at any point within 3 months, mean pain scores, and toxicity. Data were analyzed intention to treat (ITT) and per protocol (PP). This trial was registered with Clinicaltrials.gov, NCT02364115. RESULTS: Between January 29, 2015, and March 20, 2019, 110 patients were randomized. ITT analysis included 44 patients in the cRT arm and 45 patients in the SBRT arm. In the intervention arm, 12 patients (27%) declined SBRT, and 7 patients (16%) were unable to complete the SBRT treatment. In ITT, 14 of 44 patients (32%; 95% confidence interval [CI], 18%-45%) in the control arm and 18 of 45 patients (40%; 95% CI, 26%-54%) in the SBRT arm reported a pain response at 3 months (P = .42). In PP, these proportions were 14 of 44 (32%; 95% CI, 18%-45%) and 12 of 23 patients (46%; 95% CI, 27%-66%), respectively (P = .55). In ITT, a pain response within 3 months was reported by 30 of 44 control patients (82%; 95% CI, 68%-90%) and 38 of 45 patients (84%; 95% CI, 71%-92%) in the SBRT arm (P = .12). In PP, these proportions were 36 of 44 (82%; 95% CI, 68%-90%) and 26 of 27 patients (96%; 95% CI; 81%-100%), respectively (P = .12). No grade 3 or 4 toxicity was observed in either arm. CONCLUSIONS: SBRT did not significantly improve pain response in patients with painful bone metastases. One in 4 patients preferred to undergo cRT over SBRT, and 1 in 5 patients starting SBRT was unable to complete this treatment. Because of this selective dropout, which can be attributed to the character of the intervention, the trial was underpowered to detect the prespecified difference in pain response.

Oncology patients were found to understand and accept the Trials within Cohorts design.

BACKGROUND AND OBJECTIVE: The Trials within Cohorts design aims to reduce recruitment difficulties and disappointment bias in pragmatic trials. On cohort enrollment, broad informed consent for randomization is asked, after which cohort participants can be randomized to interventions or serve as controls without further notification. We evaluated patients' recollection, understanding, and acceptance of broad consent in a clinical oncology setting. METHODS: We surveyed 610 patients with cancer participating in ongoing TwiCs; 482 patients (79%) responded, of which 312 patients shortly after cohort enrollment, 108 patients after randomization to an intervention (12-18 months after cohort enrollment), and a random sample of 62 cohort participants who had not been selected for interventions (1-6 months after cohort enrollment). RESULTS: Shortly after providing cohort consent, 76% of patients (238/312) adequately remembered whether they had given broad consent for randomization. Of patients randomly offered interventions, 76% (82/108) remembered giving broad consent for randomization; 41% (44/108) understood they were randomly selected, 44% (48/108) were not interested in selection procedures, and 10% (11/108) did not understand selection was random. Among patients not selected for interventions, 42% (26/62) understood selection was random; 89% felt neutral regarding the scenario of "not being selected for an intervention while your data were being used in comparison with patients receiving interventions," 10% felt reassured (6/62) and 2% scared/insecure (2/62). CONCLUSION: Patients adequately remember giving broad consent for randomization shortly after cohort enrollment and after being offered an intervention, but recollection is lower in those never selected for interventions. Patients are acceptant of serving as control without further notifications.

Identification of Risk of Cardiovascular Disease by Automatic Quantification of Coronary Artery Calcifications on Radiotherapy Planning CT Scans in Patients With Breast Cancer.

IMPORTANCE: Cardiovascular disease (CVD) is common in patients treated for breast cancer, especially in patients treated with systemic treatment and radiotherapy and in those with preexisting CVD risk factors. Coronary artery calcium (CAC), a strong independent CVD risk factor, can be automatically quantified on radiotherapy planning computed tomography (CT) scans and may help identify patients at increased CVD risk. OBJECTIVE: To evaluate the association of CAC with CVD and coronary artery disease (CAD) in patients with breast cancer. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter cohort study of 15 915 patients with breast cancer receiving radiotherapy between 2005 and 2016 who were followed until December 31, 2018, age, calendar year, and treatment-adjusted Cox proportional hazard models were used to evaluate the association of CAC with CVD and CAD. EXPOSURES: Overall CAC scores were automatically extracted from planning CT scans using a deep learning algorithm. Patients were classified into Agatston risk categories (0, 1-10, 11-100, 101-399, >400 units). MAIN OUTCOMES AND MEASURES: Occurrence of fatal and nonfatal CVD and CAD were obtained from national registries. RESULTS: Of the 15 915 participants included in this study, the mean (SD) age at CT scan was 59.0 (11.2; range, 22-95) years, and 15 879 (99.8%) were women. Seventy percent (n = 11 179) had no CAC. Coronary artery calcium scores of 1 to 10, 11 to 100, 101 to 400, and greater than 400 were present in 10.0% (n = 1584), 11.5% (n = 1825), 5.2% (n = 830), and 3.1% (n = 497) respectively. After a median follow-up of 51.2 months, CVD risks increased from 5.2% in patients with no CAC to 28.2% in patients with CAC scores higher than 400. After adjustment, CVD risk increased with higher CAC score (hazard ratio [HR]CAC = 1-10 = 1.1; 95% CI, 0.9-1.4; HRCAC = 11-100 = 1.8; 95% CI, 1.5-2.1; HRCAC = 101-400 = 2.1; 95% CI, 1.7-2.6; and HRCAC>400 = 3.4; 95% CI, 2.8-4.2). Coronary artery calcium was particularly strongly associated with CAD (HRCAC>400 = 7.8; 95% CI, 5.5-11.2). The association between CAC and CVD was strongest in patients treated with anthracyclines (HRCAC>400 = 5.8; 95% CI, 3.0-11.4) and patients who received a radiation boost (HRCAC>400 = 6.1; 95% CI, 3.8-9.7). CONCLUSIONS AND RELEVANCE: This cohort study found that coronary artery calcium on breast cancer radiotherapy planning CT scan results was associated with CVD, especially CAD. Automated CAC scoring on radiotherapy planning CT scans may be used as a fast and low-cost tool to identify patients with breast cancer at increased risk of CVD, allowing implementing CVD risk-mitigating strategies with the aim to reduce the risk of CVD burden after breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03206333.

Breast Cancer Survivors' Experiences With an Activity Tracker Integrated Into a Supervised Exercise Program: Qualitative Study.

BACKGROUND: There is growing evidence that physical activity is related to a better prognosis after a breast cancer diagnosis, whereas sedentary behavior is associated with worse outcomes. It is therefore important to stimulate physical activity and reduce sedentary time among patients with breast cancer. Activity trackers offer a new opportunity for interventions directed at stimulating physical activity behavior change. OBJECTIVE: This study aimed to explore the experience of patients with breast cancer who used an activity tracker in addition to a supervised exercise intervention in the randomized UMBRELLA Fit trial. METHODS: A total of 10 patients with breast cancer who completed cancer treatment participated in semistructured in-depth interviews about their experience with and suggestions for improvements for the Jawbone UP2 activity tracker. RESULTS: The activity tracker motivated women to be physically active and created more awareness of their (sedentary) lifestyles. The women indicated that the automatically generated advice (received via the Jawbone UP app) lacked individualization and was not applicable to their personal situations (ie, having been treated for cancer). Furthermore, women felt that the daily step goal was one-dimensional, and they preferred to incorporate other physical activity goals. The activity tracker's inability to measure strength exercises was a noted shortcoming. Finally, women valued personal feedback about the activity tracker from the physiotherapist. CONCLUSIONS: Wearing an activity tracker raised lifestyle awareness in patients with breast cancer. The women also reported additional needs not addressed by the system. Potential improvements include a more realistic total daily physical activity representation, personalized advice, and personalized goals.

The Trials within Cohorts design faced methodological advantages and disadvantages in the exercise oncology setting.

OBJECTIVES: The Trials within Cohorts (TwiCs) design is an alternative for pragmatic randomized controlled trials (RCTs) and might overcome disadvantages such as difficult recruitment, dropout after randomization to control, and contamination. We investigated the applicability of the TwiCs design in an exercise oncology study regarding the recruitment process, representativeness of the study sample, contamination, participation, and dropout. METHODS: The Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaLuAtion (UMBRELLA) Fit TwiCs evaluates an exercise intervention in inactive breast cancer patients. Eligible patients participating in the prospective UMBRELLA were identified and randomized. Patients randomized to the intervention (n = 130) were offered the intervention, whereas controls (n = 130) were not informed. RESULTS: Fifty-two percent (n = 68) accepted the intervention. Because this rate was lower than expected, a larger sample size was required than initially estimated (n = 166). However, recruitment of 260 patients was still completed by one researcher within 30 months. Unselective eligibility screening and randomization before invitation improved representativeness. Disadvantage of the design might be inclusion of ineligible patients when cohort information is limited. Furthermore, the design faced higher noncompliance in the intervention group, but prevention of contamination. CONCLUSION: The TwiCs design improved logistics in recruitment and prevented contamination, but noncompliance due to refusal of the intervention was higher compared with conventional pragmatic exercise oncology RCTs, which may dilute the estimated intervention effect.

The Effect of Physical Activity Interventions Comprising Wearables and Smartphone Applications on Physical Activity: a Systematic Review and Meta-analysis.

BACKGROUND: Worldwide physical activity levels of adults are declining, which is associated with increased chronic disease risk. Wearables and smartphone applications offer new opportunities to change physical activity behaviour. This systematic review summarizes the evidence regarding the effect of wearables and smartphone applications on promoting physical activity. METHODS: PubMed, EMBASE and Cochrane databases were searched for RCTs, published since January 2008, on wearables and smartphone applications to promote physical activity. Studies were excluded when the study population consisted of children or adolescents, the intervention did not promote physical activity or comprised a minor part of the intervention, or the intervention was Internet-based and not accessible by smartphone. Risk of bias was assessed by the Cochrane collaboration tool. The primary outcome was changed in physical activity level. Meta-analyses were performed to assess the pooled effect on (moderate-to-vigorous) physical activity in minutes per day and daily step count. RESULTS: Eighteen RCTs were included. Use of wearables and smartphone applications led to a small to moderate increase in physical activity in minutes per day (SMD = 0.43, 95% CI = 0.03 to 0.82; I2 = 85%) and a moderate increase in daily step count (SMD = 0.51, 95% CI = 0.12 to 0.91; I2 = 90%). When removing studies with an unclear or high risk of bias, intervention effects improved and statistical heterogeneity was removed. CONCLUSIONS: This meta-analysis showed a small to moderate effect of physical activity interventions comprising wearables and smartphone applications on physical activity. Hence, wearables and smartphone applications are likely to bring new opportunities in delivering tailored interventions to increase levels of physical activity.

The effects of exercise on the quality of life of patients with breast cancer (the UMBRELLA Fit study): study protocol for a randomized controlled trial.

BACKGROUND: Meta-analyses of randomized controlled trials (RCTs) have shown that exercise has beneficial effects on quality of life (QoL) in patients with breast cancer. However, these effects were often small. Blinding in an exercise trial is not possible, which has the possible disadvantage of difficult accrual, drop-out after randomization to control and contamination between study groups (controls adopting the behaviour of the intervention group). The cohort multiple randomized controlled trial (cmRCT) is an alternative for conventional RCTs and has the potential to overcome these disadvantages. METHODS: This cmRCT will be performed within the Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaLuAtion (UMBRELLA). Patients with breast cancer who visit the radiotherapy department of the University Medical Center Utrecht are asked to participate in UMBRELLA. Patients give consent for collection of medical information, providing patient-reported outcomes through regular questionnaires and randomization into future intervention studies. Patients who fulfill the UMBRELLA Fit study eligibility criteria (12 to 18 months post inclusion in UMBRELLA, low physical activity level) will be randomly allocated to the intervention or control group (1:1 ratio). Patients randomized to the intervention group will be offered a 12-week exercise programme. The control group will not be informed. Regular cohort measurements will be used for outcome assessment. Feasiblity (including participation, contamination, generalizability and retention) of the cmRCT design and effects of the intervention on QoL will be evaluated. DISCUSSION: We will examine the feasibility of the cmRCT design in exercise-oncology research and compare this with conventional RCTs. Furthermore, the effectiveness of an exercise intervention on the QoL of patients with breast cancer in the short term (6 months) and long term (24 months) will be studied. TRIAL REGISTRATION: Netherlands Trial Register, NTR5482/NL.52062.041.15 . Retrospectively registered on 7 December 2015.