ESMO Expert Consensus Statements on Cancer Survivorship: promoting high-quality survivorship care and research in Europe.

BACKGROUND: The increased number of cancer survivors and the recognition of physical and psychosocial challenges, present from cancer diagnosis through active treatment and beyond, led to the discipline of cancer survivorship. DESIGN AND METHODS: Herein, we reflected on the different components of survivorship care, existing models and priorities, in order to facilitate the promotion of high-quality European survivorship care and research. RESULTS: We identified five main components of survivorship care: (i) physical effects of cancer and chronic medical conditions; (ii) psychological effects of cancer; (iii) social, work and financial effects of cancer; (iv) surveillance for recurrences and second cancers; and (v) cancer prevention and overall health and well-being promotion. Survivorship care can be delivered by structured care models including but not limited to shared models integrating primary care and oncology services. The choice of the care model to be implemented has to be adapted to local realities. High-quality care should be expedited by the generation of: (i) focused and shared European recommendations, (ii) creation of tools to facilitate implementation of coordinated care and (iii) survivorship educational programs for health care teams and patients. The research agenda should be defined with the participation of health care providers, researchers, policy makers, patients and caregivers. The following patient-centered survivorship research areas were highlighted: (i) generation of a big data platform to collect long-term real-world data in survivors and healthy controls to (a) understand the resources, needs and preferences of patients with cancer, and (b) understand biological determinants of survivorship issues, and (ii) develop innovative effective interventions focused on the main components of survivorship care. CONCLUSIONS: The European Society for Medical Oncology (ESMO) can actively contribute in the efforts of the oncology community toward (a) promoting the development of high-quality survivorship care programs, (b) providing educational material and (c) aiding groundbreaking research by reflecting on priorities and by supporting research networking.

Differential impact of endocrine therapy and chemotherapy on quality of life of breast cancer survivors: a prospective patient-reported outcomes analysis.

BACKGROUND: In early breast cancer (BC), there has been a trend to escalate endocrine therapy (ET) and to de-escalate chemotherapy (CT). However, the impact of ET versus CT on the quality of life (QoL) of early BC patients is unknown. Here, we characterize the independent contribution of ET and CT on patient-reported outcomes (PROs) at 2 years after diagnosis. PATIENTS AND METHODS: We prospectively collected PROs in 4262 eligible patients using the European Organization for Research and Treatment of Cancer QLQ-C30/BR23 questionnaires inside CANTO trial (NCT01993498). The primary outcome was the C30 summary score (C30-SumSc) at 2 years after diagnosis. RESULTS: From eligible patients, 37.2% were premenopausal and 62.8% postmenopausal; 81.9% received ET and 52.8% CT. In the overall cohort, QoL worsened by 2 years after diagnosis in multiple functions and symptoms; exceptions included emotional function and future perspective, which improved over time. ET (Pint = 0.004), but not CT (Pint = 0.924), had a persistent negative impact on the C30-SumSc. In addition, ET negatively impacted role and social function, pain, insomnia, systemic therapy side-effects, breast symptoms and further limited emotional function and future perspective recovery. Although CT had no impact on the C30-SumSc at 2-years it was associated with deteriorated physical and cognitive function, dyspnea, financial difficulties, body image and breast symptoms. We found a differential effect of treatment by menopausal status; in premenopausal patients, CT, despite only a non-significant trend for deteriorated C30-SumSc (Pint = 0.100), was more frequently associated with QoL domains deterioration than ET, whereas in postmenopausal patients, ET was more frequently associated with QoL deterioration, namely using the C30-SumSc (Pint = 0.004). CONCLUSION(S): QoL deterioration persisted at 2 years after diagnosis with different trajectories by treatment received. ET, but not CT, had a major detrimental impact on C30-SumSc, especially in postmenopausal women. These findings highlight the need to properly select patients for adjuvant ET escalation.

Cognitive rehabilitation group intervention for breast cancer survivors: results of a randomized clinical trial.

PURPOSE: We conducted a randomized clinical trial evaluating the efficacy of a cognitive rehabilitation (CR) intervention compared with a wait list (WL) control condition on cognitive complaints, neuropsychological and brain functioning in breast cancer survivors (BCS). METHODS: The small group intervention of five sessions included psychoeducation and cognitive exercises. ELIGIBILITY: Disease-free BCS with cognitive complaints, diagnosed with stage I, II or III breast cancer, completed primary treatment 18 months to 5 years earlier. Neurocognitive test data and cognitive complaints on the Patient's Assessment of Own Functioning Inventory (PAOFI) were assessed at baseline (T1), immediately post-intervention (T2), and 2 months later (T3). A subgroup of participants underwent resting state quantitative electroencephalography (qEEG) at all three assessment time points. RESULTS: Forty-eight participants [mean age (SD) 53.8 (8.2)] completed T1 assessments, and 29 participants had analyzable qEEG data. The CR group improved significantly over time compared with the WL group on PAOFI total and memory scores (both p = .01) and on Rey Auditory Verbal Learning Test (RAVLT) total (trials I-V) (p = .02) and RAVLT delayed recall (p = .007) scores. On qEEG, the CR group showed a significant decrease in delta 'slow wave' power (p = .02) and an increase in the frontal distribution of alpha power (p = .04) from T1 to T2. CONCLUSIONS: BCS in the CR group showed immediate and sustained improvements in self-reported cognitive complaints and memory functioning on neurocognitive testing. Results of the qEEG substudy provide some support for neurophysiological changes underlying the intervention. Copyright © 2015 John Wiley & Sons, Ltd.

The association between pro-inflammatory cytokines, regional cerebral metabolism, and cognitive complaints following adjuvant chemotherapy for breast cancer.

To examine relationships following adjuvant chemotherapy between circulating pro-inflammatory cytokines, regional cerebral metabolism, and cognitive complaints in early stage breast cancer patients. 33 breast cancer patients who had completed initial treatment (surgery, ± radiation, 23 chemotherapy, 10 no chemotherapy) obtained resting (18)F-FDG PET/CT brain imaging at baseline and 1 year later. Pro-inflammatory cytokine markers (IL-1ra, sTNF-RII, CRP, and IL-6) and cognitive complaints were also assessed at both time points. At baseline, consistent correlations were seen between the left medial frontal and right inferior lateral anterior temporal cortices and inflammatory markers within the chemotherapy group, and not in the no chemotherapy group. After 1 year, correlations persisted in the medial frontal cortex and the temporal cortex, the latter shifting superiorly. Both of these regional correlations demonstrated the highest levels of significance when looking across the 1 year time frame (IL-1ra: peak voxel p < 0.0005; cluster size p < 0.0005, p = 0.001 after correction (medial prefrontal), p < 0.0005; cluster size p = 0.001, p = 0.029 corr. (anterior temporal), sTNF-RII: p < 0.0005; cluster size p = 0.001, p = 0.040 corr. (medial prefrontal)). Positive correlations were also seen within the chemotherapy group between baseline memory complaints and the medial frontal (p < 0.0005; cluster size p < 0.0005, p < 0.0005 corr.) and anterior temporal (p < 0.0005; cluster size p < 0.0005, p = 0.002 corr.) cortices at baseline and 1 year later. Metabolism in the medial prefrontal cortex and anterior temporal cortex was found to correlate with both memory complaints and cytokine marker levels in chemotherapy patients.

1st International consensus guidelines for advanced breast cancer (ABC 1).

The 1st international Consensus Conference for Advanced Breast Cancer (ABC 1) took place on November 2011, in Lisbon. Consensus guidelines for the management of this disease were developed. This manuscript summarizes these international consensus guidelines.

Complementary and alternative therapies among very long-term breast cancer survivors.

Breast cancer patients may have different complementary and alternative medicine (CAM) usage rates and may turn to CAM for different reasons than healthy adults. CAM has mostly been studied in recently diagnosed women; no studies have included survivors 10 years post-diagnosis. We examined very long-term breast cancer survivors to determine whether CAM users had dissimilar patterns of association with survivorship factors. Interviews of 374 breast cancer case patients from a population-based case-control breast cancer study of young women from Los Angeles County, California, during the 1980s occurred at follow-up; 371 patients with complete information were included. CAM represented 28 herbal remedies. Quality-of-life originated from the Medical Outcomes Study Short Form 36 questionnaire (SF-36). Higher rates of CAM (59%) usage occurred compared to nationwide estimates. CAM users resembled non-users on follow-up age, exercise, original disease, treatment, smoking, body-mass index, alcohol, and fear of recurrence. CAM users had a higher prevalence of medical co-morbidities (P = 0.0005), and scored significantly lower on the SF-36 emotional well-being subscale than non-CAM users (P = 0.01). CAM users and non-users did not differ on the SF-36 physical sub-scale. Very long-term breast cancer survivors who use CAM may have poorer emotional functioning and more medical problems than non-users.

Bone mineral density and adjuvant therapy in breast cancer survivors.

Compared to mean values from a US database, premenopausal breast cancer survivors (BCS) had significantly higher whole body bone mineral density (BMD) compared to age and ethnicity matched referents; higher whole body BMD was present in all premenopausal BCS, including those who received chemotherapy, tamoxifen+chemotherapy, or no adjuvant therapy. Postmenopausal BCS who had received no adjuvant therapy also had higher whole body BMD compared to similarly aged women. In contrast, hip and lumbar spine BMD values in BCS were similar to those of the population-based database.

Quality of life in diverse groups of midlife women: assessing the influence of menopause, health status and psychosocial and demographic factors.

This paper examines whether menopausal status is associated with global quality of life (QOL) among women aged 40-55 and whether this association varies by race/ethnicity. We further examine the contributions of other health-related and psychosocial factors to QOL and whether these associations vary by racial/ethnic group. Analyses are based on 13,874 women who participated in the multi-ethnic, multi-race study of mid-aged women called the Study of Women's Health Across the Nation (SWAN). Study participants completed a 15-min telephone or in-person interview that contained questions on a variety of health-related topics. Items of interest for these analyses include global QOL, menstrual history (to assess menopausal status), sociodemographics, health status, lifestyle, and psychosocial variables. Results showed that in unadjusted analyses, early perimenopausal women reported lower QOL compared with premenopausal women, but menopausal status was no longer associated with QOL when analyses were adjusted for other variables. In multivariable models, being married and having low levels of perceived stress were associated with better QOL across all racial/ethnic groups. While there were many consistencies across racial/ethnic groups, we also found that the nature of the associations between QOL and education, marital status, perceived stress and social support varied across racial/ethnic groups.

Why and how to study the fate of cancer survivors: observations from the clinic and the research laboratory.

This paper provides a rationale for the importance of studying health outcomes in cancer survivors, including their growing numbers, the need for detailed information on the short and long-term effects of treatment, and the interactions of cancer with other comorbid conditions. However, there are a number of challenges associated with this research. Identification and recruitment of cancer survivors is not always easy, and linking their current health status to details of medical treatment is important, but not always feasible. National surveys and databases are a potential source of information on survivors, but may not provide sufficient details for this type of research. Strategies need to be developed to plan for long-term outcome studies in cancer patients from the very beginning of treatment to obtain the most comprehensive data on the outcomes of survivors.

Quality of life in advanced non-small-cell lung cancer: results of a Southwest Oncology Group randomized trial.

PURPOSE: The main purpose of this paper is to present the results of a randomized trial comparing the effects of two chemotherapy regimens on the Quality of life (QOL) of patients with advanced non-small-cell lung cancer (NSCLC). Trials in advanced stage disease represent an important treatment context for QOL assessment. A second purpose of this paper is to examine methods for handling the level of missing data commonly observed in the advanced stage disease context. METHODS: Patients were randomized to receive cisplatin plus vinorelbine or carboplatin plus paclitaxel. The QOL of 222 patients was assessed with the Functional Assessment of Cancer Therapy-Lung (FACT-L) prior to randomization; follow-up assessments occurred at 13 and 25 weeks. Three methods were used to analyze the QOL data: (1) cross-sectional analysis of four patient categories (improved, stable, missing, and declined) based on changes in the FACT-L score, (2) a mixed linear model, and (3) a pattern mixture model. The longitudinal analyses addressed two potential data biases. RESULTS: Questionnaire submission rates were 91% at baseline, 68% at 13 weeks, and 47% at 25 weeks. The cross-sectional and mixed linear model analyses did not show significant differences by treatment arm in patient-reported QOL. The pattern mixture model analysis, more appropriate given non-ignorable missing data, also found no statistically significant effect of treatment on patient QOL. CONCLUSION: We present a sensitivity analysis approach with multiple methods for analyzing treatment effects on patient QOL in the presence of substantial, non-ignorable missing data in an advanced stage disease clinical trial. We conclude that the two treatment arms did not differ statistically in their effects on patient QOL over a 25-week treatment period.

Tamoxifen and depression: more evidence from the National Surgical Adjuvant Breast and Bowel Project's Breast Cancer Prevention (P-1) Randomized Study.

BACKGROUND: Concerns have been raised that tamoxifen may be associated with depression. To investigate this question, we examined the psychological effects of tamoxifen treatment for breast cancer prevention on women at different levels of risk for clinical depression who were enrolled in the National Surgical Adjuvant Breast and Bowel Project's Breast Cancer Prevention (P-1) Study. METHODS: A total of 11 064 women were randomly assigned to receive for 5 years daily doses of 20 mg of tamoxifen or placebo in the P-1 study, a multicenter, double-blind, placebo-controlled chemoprevention trial. Each woman was prospectively assessed for depression risk on the basis of medical history items collected at the baseline examination and placed in a high-, medium-, or low-risk group. Every 6 months, for a total of 36 months, the participants were assessed for depressive symptoms by completing the Center for Epidemiological Studies-Depression (CES-D) questionnaire. Scores of 16 or higher were indicative of an episode of affective distress. Differences between the risk groups and treatment arms were analyzed by logistic regression. All statistical tests were two-sided. RESULTS: Women in the higher risk depression groups were more likely to score 16 or higher on the CES-D (percent follow-up examinations with a score of > or = 16: high-risk group = 35.7%, with 95% confidence interval [CI] = 32.5% to 38.9%; medium-risk group = 19.2%, with 95% CI = 18.1% to 20.3%; and low-risk group = 8.7%, with 95% CI = 8.3 to 9.1%) and to have these scores more frequently and for longer periods than women in the lower risk groups. Within each depression risk group, there was no difference in the proportion of women scoring 16 or higher by treatment assignment (tamoxifen versus placebo) (odds ratio = 0.98; 95% CI = 0.93 to 1.02). A post-hoc analysis indicated that the lack of a tamoxifen effect was not a result of differential missing data. CONCLUSIONS: Physicians need not be overly concerned that treatment with tamoxifen will increase the risk for or exacerbate existing depression in women. Nevertheless, physicians should continue to screen for and treat or refer potential cases of depression encountered in routine clinical practice.

Ductal lavage for detection of cellular atypia in women at high risk for breast cancer.

BACKGROUND: Breast cancer originates in breast epithelium and is associated with progressive molecular and morphologic changes. Women with atypical breast ductal epithelial cells have an increased relative risk of breast cancer. In this study, ductal lavage, a new procedure for collecting ductal cells with a microcatheter, was compared with nipple aspiration with regard to safety, tolerability, and the ability to detect abnormal breast epithelial cells. METHODS: Women at high risk for breast cancer who had nonsuspicious mammograms and clinical breast examinations underwent nipple aspiration followed by lavage of fluid-yielding ducts. All statistical tests were two-sided. RESULTS: The 507 women enrolled included 291 (57%) with a history of breast cancer and 199 (39%) with a 5-year Gail risk for breast cancer of 1.7% or more. Nipple aspirate fluid (NAF) samples were evaluated cytologically for 417 women, and ductal lavage samples were evaluated for 383 women. Adequate samples for diagnosis were collected from 111 (27%) and 299 (78%) women, respectively. A median of 13,500 epithelial cells per duct (range, 43-492,000 cells) was collected by ductal lavage compared with a median of 120 epithelial cells per breast (range, 10-74,300) collected by nipple aspiration. For ductal lavage, 92 (24%) subjects had abnormal cells that were mildly (17%) or markedly (6%) atypical or malignant (<1%). For NAF, corresponding percentages were 6%, 3%, and fewer than 1%. Ductal lavage detected abnormal intraductal breast cells 3.2 times more often than nipple aspiration (79 versus 25 breasts; McNemar's test, P<.001). No serious procedure-related adverse events were reported. CONCLUSIONS: Large numbers of ductal cells can be collected by ductal lavage to detect atypical cellular changes within the breast. Ductal lavage is a safe and well-tolerated procedure and is a more sensitive method of detecting cellular atypia than nipple aspiration.

Making effective use of tumor registries for cancer survivorship research.

BACKGROUND: The growing number of cancer survivors has created an increased need for survivorship research; however, the identification and recruitment of cancer survivors present some challenges. This report describes how two hospital cancer registries were used to recruit a large sample of breast cancer survivors (BCS) for a study examining the late reproductive effects of breast cancer treatments. Limitations and opportunities associated with this type of recruitment strategy are described, and the overall success of recruitment using this approach is presented. METHODS: Tumor registries from a comprehensive cancer center and a community hospital were used to identify BCS who met the study screening criteria. Invitations and response forms were mailed to all potentially eligible women, and those who did not respond by mail also were contacted by telephone. Women who indicated interest and met the study requirements were asked to give written consent, were enrolled in the study, and were sent a self-report questionnaire. RESULTS: Seventy percent of the eligible women (n = 733 women) responded to the mailing. Seventy-seven percent of the 512 respondents indicated a willingness to participate and were sent a questionnaire. Of these, 78% (n = 368 women) completed questionnaires. BCS recruited from the cancer center registry were more likely than those from the community hospital registry to respond to the invitation form (P = 0.033) and were more likely to return a completed questionnaire (P = 0.001). However, the community hospital provided access to a more ethnically diverse sample of survivors. CONCLUSIONS: The two participating cancer registries were an excellent source for identifying a large sample of long-term BCS, and the different types of registries provided greater sample size and diversity. Although there are some limitations to this approach, including nonresponse of a significant number of BCS, tumor registries represent an important resource for the rapid identification of cancer survivors for research studies. Findings from this study suggest several enhancements for future studies that may increase the yield from registry recruitment.

Psychologic distress and natural menopause: a multiethnic community study.

OBJECTIVES: This study examined the association between psychologic distress and natural menopause in a community sample of African American, White, Chinese, Hispanic, and Japanese women participating in a national women's health study. METHODS: A cohort of 16,065 women aged 40 to 55 years provided information on menstrual regularity in the previous year, psychosocial factors, health, and somatic-psychologic symptoms. Psychologic distress was defined as feeling tense, depressed, and irritable in the previous 2 weeks. RESULTS: Rates of psychologic distress were highest in early perimenopause (28.9%) and lowest in premenopause (20.9%) and postmenopause (22%). In comparison with premenopausal women, early perimenopausal women were at a greater risk of distress, with and without adjustment for vasomotor and sleep symptoms and covariates. Odds of distress were significantly higher for Whites than for the other racial/ethnic groups. CONCLUSIONS: Psychologic distress is associated with irregular menses in midlife. It is important to determine whether distress is linked to alterations in hormone levels and to what extent a mood-hormone relationship may be influenced by socioeconomic and cultural factors.

Menopause and breast cancer: symptoms, late effects, and their management.

Menopause and breast cancer are common independent health events, and coincide in some women. This article will describe what is known about the impact of menopause on breast cancer survivors, focusing on short-term symptoms and other late effects. Common menopausal syndromes in breast cancer survivors will be examined, with suggestions for their management. Strategies for prevention of the late effects of menopause in breast cancer survivors will be considered. Semin Oncol 28:274-283.

The role of hormones in breast carcinogenesis: issues of relevance to female childhood cancer survivors.

Breast cancer is the most common cancer among women in Western industrialized countries, and is an important potential second cancer to consider in young women who are survivors of childhood or adolescent cancers. This paper reviews the relationship between hormones and breast biology, cancer treatment factors that may increase or reduce the risk of breast cancer in female survivors of childhood cancer, the treatment of ovarian failure in these survivors, and the potential for preventive strategies in this population. The expanding numbers of female childhood cancer survivors increase the need for health care providers to understand the late health effects of treatments on reproductive health and breast cancer risk.

Quality of life in patients with heart failure: do gender differences exist?

OBJECTIVE: The purpose of this study was to evaluate gender differences in quality of life (QOL) in a large sample of age-matched and ejection fraction (EF)-matched patients with heart failure. DESIGN: Matched comparisons of secondary data were used. SETTING: The setting consisted of multicenter Studies of Left Ventricular Dysfunction trials. SAMPLE: The sample included 1382 patients (691 men and 691 women) who were age-matched and EF-matched. OUTCOME MEASURES: Global QOL and the QOL dimensions of physical function, emotional distress, social health, and general health were measured using the Ladder of Life, items from the Profile of Mood States Inventory, the Functional Status Questionnaire, the beta-Blocker Heart Attack Trial instrument, and an item from the RAND Medical Outcomes Study instrument. RESULTS: Women had significantly worse general life satisfaction, physical function, and social and general health scores than men. There were no significant differences found between gender groups for current life situation or emotional distress. After controlling for New York Heart Association classification, women still had significantly worse ratings for intermediate activities of daily living (a sub-dimension of physical functioning) and social activity. CONCLUSIONS: Despite controlling for age, EF, and New York Heart Association classification, women had worse QOL ratings than did men for intermediate activities of daily living and social activity. Research should focus on identifying why differences exist and developing measures to improve QOL, particularly physical functioning, in women with heart failure.