Dropout from exercise trials among cancer survivors-An individual patient data meta-analysis from the POLARIS study.

INTRODUCTION: The number of randomized controlled trials (RCTs) investigating the effects of exercise among cancer survivors has increased in recent years; however, participants dropping out of the trials are rarely described. The objective of the present study was to assess which combinations of participant and exercise program characteristics were associated with dropout from the exercise arms of RCTs among cancer survivors. METHODS: This study used data collected in the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study, an international database of RCTs investigating the effects of exercise among cancer survivors. Thirty-four exercise trials, with a total of 2467 patients without metastatic disease randomized to an exercise arm were included. Harmonized studies included a pre and a posttest, and participants were classified as dropouts when missing all assessments at the post-intervention test. Subgroups were identified with a conditional inference tree. RESULTS: Overall, 9.6% of the participants dropped out. Five subgroups were identified in the conditional inference tree based on four significant associations with dropout. Most dropout was observed for participants with BMI >28.4 kg/m2 , performing supervised resistance or unsupervised mixed exercise (19.8% dropout) or had low-medium education and performed aerobic or supervised mixed exercise (13.5%). The lowest dropout was found for participants with BMI >28.4 kg/m2 and high education performing aerobic or supervised mixed exercise (5.1%), and participants with BMI ≤28.4 kg/m2 exercising during (5.2%) or post (9.5%) treatment. CONCLUSIONS: There are several systematic differences between cancer survivors completing and dropping out from exercise trials, possibly affecting the external validity of exercise effects.

Effects of physical exercise during adjuvant chemotherapy for breast cancer on long-term tested and perceived cognition: results of a pragmatic follow-up study.

PURPOSE: Cancer-related cognitive impairment (CRCI) following chemotherapy is commonly reported in breast cancer survivors, even years after treatment. Data from preclinical studies suggest that exercise during chemotherapy may prevent or diminish cognitive problems; however, clinical data are scarce. METHODS: This is a pragmatic follow-up study of two original randomized trials, which compares breast cancer patients randomized to exercise during chemotherapy to non-exercise controls 8.5 years post-treatment. Cognitive outcomes include an online neuropsychological test battery and self-reported cognitive complaints. Cognitive performance was compared to normative data and expressed as age-adjusted z-scores. RESULTS: A total of 143 patients participated in the online cognitive testing. Overall, cognitive performance was mildly impaired on some, but not all, cognitive domains, with no significant differences between groups. Clinically relevant cognitive impairment was present in 25% to 40% of all participants, regardless of study group. We observed no statistically significant effect of exercise, or being physically active during chemotherapy, on long-term cognitive performance or self-reported cognition, except for the task reaction time, which favored the control group (ß = -2.04, 95% confidence interval: -38.48; -2.38). We observed no significant association between self-reported higher physical activity levels during chemotherapy or at follow-up and better cognitive outcomes. CONCLUSION: In this pragmatic follow-up study, exercising and being overall more physically active during or after adjuvant chemotherapy for breast cancer was not associated with better tested or self-reported cognitive functioning, on average, 8.5 years after treatment. Future prospective studies are needed to document the complex relationship between exercise and CRCI in cancer survivors.

Perspectives of patients with metastatic breast cancer on physical exercise programs: results from a survey in five European countries.

BACKGROUND: To successfully implement exercise programs for patients with metastatic breast cancer (MBC), services and patient education should consider patients' knowledge, preferences, values, and goals. Hence, gaining insight into their perspectives on exercise and exercise programming is important. METHOD: In this cross-sectional survey, we recruited patients with MBC from the Netherlands, Germany, Poland, Spain, and Sweden. We collected data on patients' knowledge and skills about exercise and outcome expectations. We identified barriers to and facilitators of participation in exercise programs, and patients' preferences for program content and modes of exercise delivery. RESULTS: A total of 420 patients participated in the survey. Respondents were, on average, 56.5 years old (SD 10.8) and 70% had bone metastases. Sixty-eight percent reported sufficient skills to engage in aerobic exercise, but only 35% did so for resistance exercise. Respondents expected exercise to have multiple physical benefits, but a few patients expected exercise to worsen their pain (5%). Not having access to an exercise program for cancer patients (27%), feeling too tired (23%), and/or weak (23%) were the most often reported barriers. Facilitators for exercising regularly were previous positive physical (72%) and emotional (68%) experiences with exercising, and receiving personalized advice from a physiotherapist or sport/fitness instructor (62%). Patients were most interested in walking and preferred exercising at a public gym, although there were differences by country. Fifty-seven percent did not know whether their insurance company reimburses exercise programs and only 9% would be willing to pay more than €50 per month to participate. CONCLUSION: A large percentage of patients with MBC lack the skills to engage in regular exercise as recommended by exercise guidelines for people with cancer. Patients may benefit from personalized advice and appropriate training facilities to overcome barriers. When implementing exercise interventions, attention should be given to reimbursement and the relatively low willingness-to-pay.

Effects of exercise during chemotherapy for breast cancer on long-term cardiovascular toxicity.

OBJECTIVE: Animal data suggest that exercise during chemotherapy is cardioprotective, but clinical evidence to support this is limited. This study evaluated the effect of exercise during chemotherapy for breast cancer on long-term cardiovascular toxicity. METHODS: This is a follow-up study of two previously performed randomised trials in patients with breast cancer allocated to exercise during chemotherapy or non-exercise controls. Cardiac imaging parameters, including T1 mapping (native T1, extracellular volume fraction (ECV)), left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS), cardiorespiratory fitness, and physical activity levels, were acquired 8.5 years post-treatment. RESULTS: In total, 185 breast cancer survivors were included (mean age 58.9±7.8 years), of whom 99% and 18% were treated with anthracyclines and trastuzumab, respectively. ECV and Native T1 were 25.3%±2.5% and 1026±51 ms in the control group, and 24.6%±2.8% and 1007±44 ms in the exercise group, respectively. LVEF was borderline normal in both groups, with an LVEF<50% prevalence of 22.5% (n=40/178) in all participants. Compared with control, native T1 was statistically significantly lower in the exercise group (ß=-20.16, 95% CI -35.35 to -4.97). We found no effect of exercise on ECV (ß=-0.69, 95% CI -1.62 to 0.25), LVEF (ß=-1.36, 95% CI -3.45 to 0.73) or GLS (ß=0.31, 95% CI -0.76 to 1.37). Higher self-reported physical activity levels during chemotherapy were significantly associated with better native T1 and ECV. CONCLUSIONS: In long-term breast cancer survivors, exercise and being more physically active during chemotherapy were associated with better structural but not functional cardiac parameters. The high prevalence of cardiac dysfunction calls for additional research on cardioprotective measures, including alternative exercise regimens. TRIAL REGISTRATION NUMBER: NTR7247.

Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer (OVHIPEC-1): final survival analysis of a randomised, controlled, phase 3 trial.

BACKGROUND: The OVHIPEC-1 trial previously showed that the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery resulted in improved progression-free and overall survival compared with cytoreductive surgery alone at 4·7 years of follow-up in patients with stage III epithelial ovarian cancer who were ineligible for primary cytoreduction. We report the final survival outcomes after 10 years of follow-up. METHODS: In this open-label, randomised, controlled, phase 3 trial, patients with primary epithelial stage III ovarian cancer were recruited at eight HIPEC centres in the Netherlands and Belgium. Patients were eligible if they were aged 18-76 years, had not progressed during at least three cycles of neoadjuvant carboplatin plus paclitaxel, had a WHO performance status score of 0-2, normal blood counts, and adequate renal function. Patients were randomly assigned (1:1) to undergo interval cytoreductive surgery without HIPEC (surgery group) or with HIPEC (100 mg/m2 cisplatin; surgery-plus-HIPEC group). Randomisation was done centrally by minimisation with a masked web-based allocation procedure at the time of surgery when residual disease smaller than 10 mm diameter was anticipated, and was stratified by institution, previous suboptimal cytoreductive surgery, and number of abdominal regions involved. The primary endpoint was progression-free survival and a secondary endpoint was overall survival, analysed in the intention-to-treat population (ie, all randomly assigned patients). This study is registered with ClinicalTrials.gov, NCT00426257, and is closed. FINDINGS: Between April 1, 2007, and April 30, 2016, 245 patients were enrolled and followed up for a median of 10·1 years (95% CI 8·4-12·9) in the surgery group (n=123) and 10·4 years (95% CI 9·5-13·3) in the surgery-plus-HIPEC group (n=122). Recurrence, progression, or death occurred in 114 (93%) patients in the surgery group (median progression-free survival 10·7 months [95% CI 9·6-12·0]) and 109 (89%) patients in the surgery-plus-HIPEC group (14·3 months [12·0-18·5]; hazard ratio [HR] 0·63 [95% CI 0·48-0·83], stratified log-rank p=0·0008). Death occurred in 108 (88%) patients in the surgery group (median overall survival 33·3 months [95% CI 29·0-39·1]) and 100 (82%) patients in the surgery-plus-HIPEC group (44·9 months [95% CI 38·6-55·1]; HR 0·70 [95% CI 0·53-0·92], stratified log-rank p=0·011). INTERPRETATION: These updated survival results confirm the long-term survival benefit of HIPEC in patients with primary stage III epithelial ovarian cancer undergoing interval cytoreductive surgery. FUNDING: Dutch Cancer Foundation (KWF Kankerbestrijding).

The estimand framework had implications in time to patient-reported outcomes deterioration analyses in cancer clinical trials.

OBJECTIVES: To apply the estimand framework in time to deterioration (TTD) analysis of patient-reported outcomes (PROs), and identify the appropriate statistical methods to deal with intercurrent event (IEs) such as death. STUDY DESIGN AND SETTING: Data from phase II randomized trial were used. We estimated TTD using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 questionnaire with death as the IE, by applying Kaplan-Meier (K.M.) estimator and Cox proportional hazards (PH) model. The Fine-Gray approach was explored, accounting for death as a competing risk. The estimands targeted by the aforementioned methods were defined. RESULTS: We analyzed the data of 64 patients with available questionnaires at baseline. The most notable differences in TTD estimates were observed for deterioration in physical functioning: the hazard ratios were 0.44 [95% CI 0.22-0.90] and 0.62 [95% CI 0.36-1.07] by either ignoring death (31 events) or considering it as deterioration (58 events), respectively (Cox-PH model). When considering death as a competing event (Fine-Gray model), the sub-HRs was 0.51 [95% CI 0.26-1.01]. CONCLUSION: Depending on the proportion and distribution of deaths occurring before deterioration between arms, the Fine-Gray competing risks model should be considered rather than KM estimator and Cox PH model to reflect the patient's experience of the disease and treatment burden.

Quality of life after patient-initiated vs physician-initiated response to symptom monitoring: the SYMPRO-Lung trial.

BACKGROUND: Previous studies using patient-reported outcomes measures (PROMs) to monitor symptoms during and after (lung) cancer treatment used alerts that were sent to the health-care provider, although an approach in which patients receive alerts could be more clinically feasible. The primary aim of this study was to compare the effect of weekly PROM symptom monitoring via a reactive approach (patient receives alert) or active approach (health-care provider receives alert) with care as usual on health-related quality of life (HRQOL) at 15 weeks after start of treatment in lung cancer patients. METHODS: The SYMPRO-Lung trial is a multicenter randomized controlled trial using a stepped wedge design. Stage I-IV lung cancer patients in the reactive and active groups reported PROM symptoms weekly, which were linked to a common alerting algorithm. HRQOL was measured by the EORTC QLQ-C30 at baseline and after 15 weeks. Linear regression analyses and effect size estimates were used to assess mean QOL-C30 change scores between groups, accounting for confounding. RESULTS: A total of 515 patients were included (160 active group, 89 reactive group, 266 control group). No differences in HRQOL were observed between the reactive and active group (summary score: unstandardized beta [B] = 0.51, 95% confidence interval [CI] = -3.22 to 4.24, Cohen d effect size [ES] = 0.06; physical functioning: B = 0.25, 95% CI = -5.15 to 4.64, ES = 0.02). The combined intervention groups had statistically and clinically significantly better mean change scores on the summary score (B = 4.85, 95% CI = 1.96 to 7.73, ES = 0.57) and physical functioning (B = 7.00, 95% CI = 2.90 to 11.09, ES = 0.71) compared with the control group. CONCLUSIONS: Weekly PRO symptom monitoring statistically and clinically significantly improves HRQOL in lung cancer patients. The logistically less intensive, reactive approach may be a better fit for implementation.

Moderators of exercise effects on self-reported cognitive functioning in cancer survivors: an individual participant data meta-analysis.

PURPOSE: This individual participant data meta-analysis (IPD-MA) assesses exercise effects on self-reported cognitive functioning (CF) and investigates whether effects differ by patient-, intervention-, and exercise-related characteristics. METHODS: IPD from 16 exercise RCTs, including 1987 patients across multiple types of non-metastatic cancer, was pooled. A one-stage IPD-MA using linear mixed-effect models was performed to assess exercise effects on self-reported CF (z-score) and to identify whether the effect was moderated by sociodemographic, clinical, intervention- and exercise-related characteristics, or fatigue, depression, anxiety, and self-reported CF levels at start of the intervention (i.e., baseline). Models were adjusted for baseline CF and included a random intercept at study level to account for clustering of patients within studies. A sensitivity analysis was performed in patients who reported cognitive problems at baseline. RESULTS: Minimal significant beneficial exercise effects on self-reported CF (ß=-0.09 [-0.16; -0.02]) were observed, with slightly larger effects when the intervention was delivered post-treatment (n=745, ß=-0.13 [-0.24; -0.02]), and no significant effect during cancer treatment (n=1,162, ß=-0.08 [-0.18; 0.02]). Larger effects were observed in interventions of 12 weeks or shorter (ß=-0.14 [-0.25; -0.04]) or 24 weeks or longer (ß=-0.18 [-0.32; -0.02]), whereas no effects were observed in interventions of 12-24 weeks (ß=0.01 [-0.13; 0.15]). Exercise interventions were most beneficial when provided to patients without anxiety symptoms (ß=-0.10 [-0.19; -0.02]) or after completion of treatment in patients with cognitive problems (ß=-0.19 [-0.31; -0.06]). No other significant moderators were identified. CONCLUSIONS: This cross-cancer IPD meta-analysis observed small beneficial exercise effects on self-reported CF when the intervention was delivered post-treatment, especially in patients who reported cognitive problems at baseline. IMPLICATIONS FOR CANCER SURVIVORS: This study provides some evidence to support the prescription of exercise to improve cognitive functioning. Sufficiently powered trials are warranted to make more definitive recommendations and include these in the exercise guidelines for cancer survivors.

Emotionally focused couple therapy in cancer survivor couples with marital and sexual problems: a replicated single-case experimental design.

Objective: The current research examined the effect of Emotionally Focused Couples Therapy (EFCT) on perceived intimacy, affect, and dyadic connection in cancer survivor couples with relationship challenges. Method: In this longitudinal replicated single-case study, positive and negative affect, intimacy, partner responsiveness, and expression of attachment-based emotional needs were reported every 3 days before and during treatment. Thirteen couples, with one partner having survived colorectal cancer or breast cancer, participated for the full duration of the study. Statistical analysis of the data was performed using randomization tests, piecewise regression, and multilevel analyses. Results: Adherence to the therapeutic protocol was tested and found adequate. Compared with baseline, significant positive effects on affect variables were found during the therapeutic process. Positive affect increased and negative affect decreased. Partner responsiveness, perceived intimacy, and the expression of attachment-based emotional needs improved, but only in the later phase of treatment. Results at the group level were statistically significant, whereas effects at the individual level were not. Discussion: This study found positive group-level effects of EFCT on affect and dyadic outcome measures in cancer survivors. The positive results warrant further research, including randomized clinical trials, to replicate these effects of EFCT in cancer survivor couples experiencing marital and sexual problems.

A Bayesian-adaptive decision-theoretic approach can reduce the sample sizes for multiarm exercise oncology trials.

OBJECTIVES: Adaptive designs may reduce trial sample sizes and costs. This study illustrates a Bayesian-adaptive decision-theoretic design applied to a multiarm exercise oncology trial. STUDY DESIGN AND SETTING: In the Physical exercise during Adjuvant Chemotherapy Effectiveness Study (PACES) trial, 230 breast cancer patients receiving chemotherapy were randomized to supervised resistance and aerobic exercise (OnTrack), home-based physical activity (OncoMove) or usual care (UC). Data were reanalyzed as an adaptive trial using both Bayesian decision-theoretic and a frequentist group-sequential approach incorporating interim analyses after every 36 patients. Endpoint was chemotherapy treatment modifications (any vs. none). Bayesian analyses were performed for different continuation thresholds and settings with and without arm dropping and both in a 'pick-the-winner' and a 'pick-all-treatments-superior-to-control' setting. RESULTS: Treatment modifications occurred in 34% of patients in UC and OncoMove vs. 12% in OnTrack (P = 0.002). Using a Bayesian-adaptive decision-theoretic design, OnTrack was identified as most effective after 72 patients in the 'pick-the-winner' setting and after 72-180 patients in the 'pick-all-treatments-superior-to-control' setting. In a frequentist setting, the trial would have been stopped after 180 patients, and the proportion of patients with treatment modifications was significantly lower for OnTrack than UC. CONCLUSION: A Bayesian-adaptive decision-theoretic approach substantially reduced the sample size required for this three-arm exercise trial, especially in the 'pick-the-winner' setting.

PERSPECTIVEs on supervised exercise programs in people with metastatic breast cancer- a qualitative study in four European countries.

PURPOSE: Supervised exercise is a potentially promising supportive care intervention for people with metastatic breast cancer (MBC), but research on the patients' perspective is limited. The aim of the current focus group study was to gain an in-depth understanding of MBC patients' perceived barriers, facilitators, and preferences for supervised exercise programs. METHODS: Eleven online focus groups with, in total, 44 MBC patients were conducted in four European countries (Germany, Poland, Spain, Sweden). Main topics of the semi-structured discussions covered attitudes towards participation in supervised exercise programs, perceived facilitators, experienced barriers, and exercise preferences. Interviews were transcribed verbatim, translated into English, and coded based on a preliminary coding framework, supplemented by themes emerging during the sessions. The codes were subsequently examined for interrelations and re-organized into overarching clusters. RESULTS: Participants had positive attitudes towards exercise, but experienced physical limitations and insecurities that inhibited their participation. They expressed a strong desire for exercise tailored to their needs, and supervision by an exercise professional. Participants also highlighted the social nature of group training as an important facilitator. They had no clear preference for exercise type, but rather favored a mixture of different activities. Flexible training modules were considered helpful to increase exercise program adherence. CONCLUSIONS: MBC patients were generally interested in supervised exercise programs. They preferred group exercise that facilitates social interaction, but also expressed a need for individualized exercise programs. This suggests the relevance to develop flexible exercise programs that are adjusted to the individual's needs, abilities, and preferences.

Dutch prostate cancer patients' views about exercise and experience with exercise advice: a national survey.

PURPOSE: To support the development and implementation of exercise programming for people with prostate cancer (PC), we investigated their views on exercise. METHODS: Online survey with open recruitment. We collected data on clinical and sociodemographic variables, experiences with exercise advice, outcome expectations, and preferences. We explored determinants of (1) having been counselled about exercise and (2) preferring supervised exercise. RESULTS: The survey was completed by 171 patients (mean age = 70 years, SD = 6.5) from all PC treatment pathways. Sixty-three percent of the respondents reported never having been informed about the potential benefits of exercise. Forty-nine percent preferred exercise to be supervised. Respondents generally reported a positive attitude towards exercise. Seventy-four percent indicated barriers to exercising, including fatigue and lack of access to specific programmes. Outcome expectations were generally positive but moderately strong. Receiving hormonal therapy and younger age were significantly associated with having received exercise advice. Being insured and having higher fatigue levels contributed significantly to the preference for supervised exercise. CONCLUSION: Dutch people with PC report receiving insufficient effective exercise counselling. Yet, they are open to exercise and expect exercise to improve their health, although they experience various barriers that limit their ability to exercise. IMPLICATIONS FOR CANCER SURVIVORS: The moderate outcome expectations for exercise of people with PC and their limited recall of exercise counselling highlight the need for better integration of exercise in clinical pathways. The lack of access to specific programming limits the use of evidence-based exercise programmes for people with PC.

Differences in Quality of Life between German and Dutch Patients with Prostate Cancer Treated with Robot-assisted Radical Prostatectomy: Implications for International Multicenter Randomized Controlled Trials.

BACKGROUND: As a local treatment for prostate cancer (PCa), robot-assisted radical prostatectomy (RARP) may have a quality of life (QoL) benefit over open surgery. Recent analyses revealed substantial between-country differences in the function and symptom scale scores for the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), which is typically used to assess patient-reported QoL. Such differences could have implications for multinational studies in PCa. OBJECTIVE: To examine whether nationality is significantly associated with patient-reported QoL. DESIGN, SETTING, AND PARTICIPANTS: The study cohort comprised Dutch and German patients with PCa treated with RARP in a single high-volume prostate center from 2006 to 2018. Analyses were restricted to patients who were preoperatively continent with at least one follow-up time point. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: QoL was measured in terms of the global Quality of Life (QL) scale score and the overall summary score for the EORTC QLQ-C30. Linear mixed models for repeated-measures multivariable analyses (MVAs) were used to examine the association between nationality and both the global QL score and the summary score. MVAs were further adjusted for QLQ-C30 baseline values, age, Charlson comorbidity index, preoperative prostate-specific antigen, surgical expertise, pathological tumor and nodal stage, Gleason grade, degree of nerve-sparing, surgical margin status, 30-d Clavien-Dindo grade complications, urinary continence recovery, and biochemical recurrence/postoperative radiotherapy. RESULTS AND LIMITATIONS: For Dutch (n = 1938) versus German (n = 6410) men, the mean baseline scores were 82.8 versus 71.9 for the global QL scale score and 93.4 versus 89.7 for the QLQ-C30 summary score. Urinary continence recovery (QL: +8.9, 95% confidence interval [CI] 8.1-9.8; p < 0001) and Dutch nationality (QL: +6.9, 95% CI 6.1-7.6; p < 0001) were the strongest positive contributors to the global QL and summary scores, respectively. The main limitation is the retrospective study design. In addition, our Dutch cohort may not be representative of the general Dutch population and reporting bias cannot be ruled out. CONCLUSIONS: Our findings provide observational evidence under specific conditions involving the same setting for patients of two different nationalities suggesting that cross-national patient-reported QoL differences appear to be real and may need to be taken into consideration in multinational studies. PATIENT SUMMARY: We observed differences in the quality-of-life scores reported by Dutch and German patients with prostate cancer after they underwent robot-assisted removal of the prostate. These findings should be taken into consideration in cross-national studies.

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.

Sexual functioning more than 15 years after premenopausal risk-reducing salpingo-oophorectomy.

BACKGROUND: Women with a BRCA1/2 pathogenic variant are advised to undergo premenopausal risk-reducing salpingo-oophorectomy after completion of childbearing, to reduce their risk of ovarian cancer. Several studies reported less sexual pleasure 1 to 3 years after a premenopausal oophorectomy. However, the long-term effects of premenopausal oophorectomy on sexual functioning are unknown. OBJECTIVE: This study aimed to study long-term sexual functioning in women at increased familial risk of breast or ovarian cancer who underwent a risk-reducing salpingo-oophorectomy either before the age of 46 years (premenopausal group) or after the age of 54 years (postmenopausal group). Subgroup analyses were performed in the premenopausal group, comparing early (before the age of 41 years) and later (at ages 41-45 years) premenopausal risk-reducing salpingo-oophorectomy. STUDY DESIGN: Between 2018 and 2021, 817 women with a high familial risk of breast or ovarian cancer from an ongoing cohort study were invited to participate in our study. Because of a large difference in age in the study between the premenopausal and postmenopausal salpingo-oophorectomy groups, we restricted the comparison of sexual functioning between the groups to 368 women who were 60 to 70 years old at completion of the questionnaire (226 in the premenopausal group and 142 in the postmenopausal group). In 496 women with a premenopausal risk-reducing salpingo-oophorectomy, we compared the sexual functioning between women in the early premenopausal group (n=151) and women in the later premenopausal group (n=345). Differences between groups were analyzed using multiple regression analyses, adjusting for current age, breast cancer history, use of hormone replacement therapy, body mass index, chronic medication use (yes or no), and body image. RESULTS: Mean times since risk-reducing salpingo-oophorectomy were 20.6 years in the premenopausal group and 10.6 years in the postmenopausal group (P<.001). The mean age at questionnaire completion was 62.7 years in the premenopausal group, compared with 67.0 years in the postmenopausal group (P<.001). Compared with 48.9% of women in the postmenopausal group, 47.4% of women in the premenopausal group were still sexually active (P=.80). Current sexual pleasure scores were the same for women in the premenopausal group and women in the postmenopausal group (mean pleasure score, 8.6; P=.99). However, women in the premenopausal group more often reported substantial discomfort than women in the postmenopausal group (35.6% vs 20.9%; P=.04). After adjusting for confounders, premenopausal risk-reducing salpingo-oophorectomy was associated with substantially more discomfort during sexual intercourse than postmenopausal risk-reducing salpingo-oophorectomy (odds ratio, 3.1; 95% confidence interval, 1.04-9.4). Moreover, after premenopausal risk-reducing salpingo-oophorectomy, more severe complaints of vaginal dryness were observed (odds ratio, 2.6; 95% confidence interval, 1.4-4.7). Women with a risk-reducing salpingo-oophorectomy before the age of 41 years reported similar pleasure and discomfort scores as women with a risk-reducing salpingo-oophorectomy between ages 41 and 45 years. CONCLUSION: More than 15 years after premenopausal risk-reducing salpingo-oophorectomy, the proportion of sexually active women was comparable with the proportion of sexually active women with a postmenopausal risk-reducing salpingo-oophorectomy. However, after a premenopausal risk-reducing salpingo-oophorectomy, women experienced more vaginal dryness and more often had substantial sexual discomfort during sexual intercourse. This did not lead to less pleasure with sexual activity.

Content validity of the EORTC quality of life questionnaire QLQ-C30 for use in cancer.

AIM: The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) is among the most widely used patient-reported outcome measures in cancer research and practice. It was developed prior to guidance that content should be established directly from patients to confirm it measures concepts of interest and is appropriate and comprehensive for the intended population. This study evaluated the content validity of the QLQ-C30 for use with cancer patients. METHODS: Adults undergoing cancer treatment in Europe and the USA participated in open-ended concept elicitation interviews regarding their functional health, symptoms, side-effects and impacts on health-related quality of life. Thematic analysis was conducted, and similarities across cancer types, disease stages and countries or languages were explored. RESULTS: Interviews with 113 patients with cancer (85 European, 28 USA) including breast, lung, prostate, colorectal and other cancers were conducted between 2016 and 2020. Conceptual saturation was achieved. The most frequently reported concepts were included in the QLQ-C30 conceptual framework. QLQ-C30 items were widely understood across language versions and were relevant to patients across cancer types and disease stages. While several new concepts were elicited such as difficulty climbing steps or stairs, weight loss, skin problems and numbness, many were not widely experienced and/or could be considered sub-concepts of existing concepts. CONCLUSIONS: The QLQ-C30 demonstrates good evidence of content validity for the assessment of functional health, symptom burden and health-related quality of life in patients with localised-to-advanced cancer.

Quality of early prostate cancer follow-up care from the patients' perspective.

PURPOSE: To develop optimal cancer survivorship care programs, this study assessed the quality of prostate cancer follow-up care as experienced by patients shortly after completion of primary treatment. METHODS: We surveyed 402 patients with localized prostate cancer participating in a randomized controlled trial comparing specialist versus primary care-based follow-up. For the current study, we used patient-reported data at the time of the first follow-up visit at the hospital, prior to randomization. We assessed patients' ratings of the quality of follow-up care using the Assessment of Patient Experiences of Cancer Care survey. This survey includes 13 scales about different aspects of care and an overall rating of care. Multivariable linear regression analysis was used to identify factors associated with perceived follow-up quality. RESULTS: Patients reported positive experiences at first follow-up for 9 of 13 scales, with mean (M) scores ranging from 79 to 97 (on a 0-100 response scale). Patients reported most frequently (over 70%) suboptimal care regarding symptom management (84%; M = 44, SD = 37), health promotion (75%; M = 45, SD = 39), and physician's knowledge about patients' life (84%; M = 65, SD = 23). Overall, patients' lower quality of follow-up ratings were associated with younger age, higher education level, having more than one comorbid condition, having undergone primary surgery, and experiencing significant symptoms. CONCLUSION: Patients with prostate cancer are generally positive about their initial, hospital-based follow-up care. However, efforts should be made to improve symptom management, health promotion, and physician's knowledge about patients' life. These findings point to areas where prostate cancer follow-up care can be improved.

Design of a multinational randomized controlled trial to assess the effects of structured and individualized exercise in patients with metastatic breast cancer on fatigue and quality of life: the EFFECT study.

BACKGROUND: Many patients with metastatic breast cancer experience cancer- and treatment-related side effects that impair activities of daily living and negatively affect the quality of life. There is a need for interventions that improve quality of life by alleviating fatigue and other side effects during palliative cancer treatment. Beneficial effects of exercise have been observed in the curative setting, but, to date, comparable evidence in patients with metastatic breast cancer is lacking. The aim of this study is to assess the effects of a structured and individualized 9-month exercise intervention in patients with metastatic breast cancer on quality of life, fatigue, and other cancer- and treatment-related side effects. METHODS: The EFFECT study is a multinational, randomized controlled trial including 350 patients with metastatic breast cancer. Participants are randomly allocated (1:1) to an exercise or control group. The exercise group participates in a 9-month multimodal exercise program, starting with a 6-month period where participants exercise twice a week under the supervision of an exercise professional. After completing this 6-month period, one supervised session is replaced by one unsupervised session for 3 months. In addition, participants are instructed to be physically active for ≥30 min/day on all remaining days of the week, while being supported by an activity tracker and exercise app. Participants allocated to the control group receive standard medical care, general written physical activity advice, and an activity tracker, but no structured exercise program. The primary outcomes are quality of life (EORTC QLQ-C30, summary score) and fatigue (EORTC QLQ-FA12), assessed at baseline, 3, 6 (primary endpoint), and 9 months post-baseline. Secondary outcomes include physical fitness, physical performance, physical activity, anxiety, depression, pain, sleep problems, anthropometric data, body composition, and blood markers. Exploratory outcomes include quality of working life, muscle thickness, urinary incontinence, disease progression, and survival. Additionally, the cost-effectiveness of the exercise program is assessed. Adherence and safety are monitored throughout the intervention period. DISCUSSION: This large randomized controlled trial will provide evidence regarding the (cost-) effectiveness of exercise during treatment of metastatic breast cancer. If proven (cost-)effective, exercise should be offered to patients with metastatic breast cancer as part of standard care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04120298 . Registered on October 9, 2019.

Physical Activity and Cardiac Function in Long-Term Breast Cancer Survivors: A Cross-Sectional Study.

Background: Higher levels of physical activity are associated with a lower risk of cardiovascular disease in the general population. Whether the same holds for women who underwent treatment for breast cancer is unclear. Objectives: The aim of this study was to evaluate the association between physical activity in a typical week in the past 12 months and cardiac dysfunction in breast cancer survivors. Methods: We used data from a cohort of breast cancer survivors who were treated at ages 40 to 50 years (N = 559). The association between physical activity and global longitudinal strain (GLS) and left ventricular ejection fraction (LVEF) was evaluated using both linear and modified Poisson regression analyses adjusted for relevant confounders. Results: In total, 559 breast cancer survivors were included, with median age of 55.5 years and a median time since treatment of 10.2 years. GLS was less favorable in inactive survivors (-17.1%) than in moderately inactive (-18.4%), moderately active (-18.2%), and active survivors (-18.5%), with an adjusted significant difference for active versus inactive survivors (ß = -1.31; 95% CI: -2.55 to -0.06)). Moderately active (n = 57/130) and active survivors (n = 87/124) had significantly lower risks of abnormal GLS (defined as >-18%) compared with inactive survivors (n = 17/26) (RR: 0.65 [95% CI: 0.45-0.94] and RR: 0.61 [95% CI: 0.43-0.87], respectively). LVEF, in normal ranges in all activity categories, was not associated with physical activity. Conclusions: In long-term breast cancer survivors, higher physical activity levels were associated with improved GLS but not LVEF, with the relatively largest benefit for doing any activity versus none. This finding suggests that increasing physical activity may contribute to cardiovascular health benefits, especially in inactive survivors.

Specialist versus Primary Care Prostate Cancer Follow-Up: A Process Evaluation of a Randomized Controlled Trial.

Background: A randomized controlled trial (RCT) is currently comparing the effectiveness of specialist- versus primary care-based prostate cancer follow-up. This process evaluation assesses the reach and identified constructs for the implementation of primary care-based follow-up. Methods: A mixed-methods approach is used to assess the reach and the implementation through the Consolidated Framework for Implementation Research. We use quantitative data to evaluate the reach of the RCT and qualitative data (interviews) to indicate the perspectives of patients (n = 15), general practitioners (GPs) (n = 10), and specialists (n = 8). Thematic analysis is used to analyze the interview transcripts. Results: In total, we reached 402 (67%) patients from 12 hospitals and randomized them to specialist- (n = 201) or to primary care-based (n = 201) follow-up. From the interviews, we identify several advantages of primary care- versus specialist-based follow-up: it is closer to home, more accessible, and the relationship is more personal. Nevertheless, participants also identified challenges: guidelines should be implemented, communication and collaboration between primary and secondary care should be improved, quality indicators should be collected, and GPs should be compensated. Conclusion: Within an RCT context, 402 (67%) patients and their GPs were willing to receive/provide primary care-based follow-up. If the RCT shows that primary care is equally as effective as specialist-based follow-up, the challenges identified in this study need to be addressed to enable a smooth transition of prostate cancer follow-up to primary care.