Exercise and psychosocial interventions to improve quality of life in patients with
cancer
Kalter, J.
2018
document version
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citation for published version (APA)
Kalter, J. (2018). Exercise and psychosocial interventions to improve quality of life in patients with cancer:
Secondary and individual patient data analyses evaluating intervention moderators and mediators.
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Cancer, treatment, and treatment-related symptoms
Cancer counts for 14 million new cases worldwide every year, and the number of new cases is expected to rise by 70% over the next two decades due to aging and growth of the populati on [1]. Lung, prostate and colorectal cancer are the most commonly diagnosed types of cancer among men worldwide, accounti ng for 17%, 15% and 10% of the total cancer diagnosis, respecti vely. Breast (25%), colorectal (9%) and lung cancer (9%) are the most commonly diagnosed cancers among women worldwide [1]. In the Netherlands, the number of people diagnosed with cancer increased from 64,604 in 1995 to 105,844 in 2015 [2], and it is expected that the number of pati ents with cancer will increase up to 666,000 in 2020 [3]. The most prevalent cancer types in the Netherlands are breast, skin, and prostate cancer, representi ng 56% of all new cases [2].
In the last decades, cancer survival rates have increased substanti ally, but diff ers greatly between cancer types. In the Netherlands, the overall 5-year cancer survival rate has increased from 47% in 1989-1993 to 64% in 2011-2015 [2]. These improvements in survival rates are caused by advances in early cancer detecti on (i.e. diagnosis and screening) and more eff ecti ve treatments [4]. Advances in radiati on, chemotherapy, immunotherapy, and targeted treatments have improved survival, especially for cancer of the breast, prostate, lung, liver, melanoma, and colon or rectum [5, 6]. The type of treatment(s) used depends on the locati on and size of the tumor, the presence of metastases, and the general health status of the pati ent [1].
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functi on [17] and fi tness [18], and poorer survival [15]. Furthermore, depression and anxiety disorder, as measured by a diagnosti c interview is prevalent in 14% and 10% of pati ents with cancer during treatment, respecti vely [19, 20]. Prevalence of symptoms of depression and anxiety (based on pati ent reported outcome measures) is esti mated to be much higher (27% [20] and 26% [21], respecti vely). In pati ents with cancer who were at least 2 years aft er diagnosis, the prevalence of depression and anxiety disorder is esti mated to be 8% and 18%, respecti vely [22]. These physical and psychosocial problems are associated with reduced health-related quality of life (QoL) [23, 24]. QoL is a subjecti ve multi dimensional health outcome, encompassing physical, emoti onal and social functi oning, symptom burden and perceived health status [25, 26]. With the increasing number of pati ents with cancer in the coming decades, the demand for developing interventi on strategies that not only focus on treati ng the cancer itself, but also on preventi ng or reducing physical problems, and maintaining or improving QoL will rise as well [27-33].
Exercise and psychosocial interventi ons
Previous studies showed that physical acti vity (i.e. any bodily movement that results in energy expenditure [34]), exercise (i.e. a form of physical acti vity that is planned, structured and repeti ti ve and aims to improve fi tness, performance or health [34]) and/or psychosocial interventi ons improve physical and/or psychosocial functi on and QoL in pati ents with cancer [27-33]. It is hypothesized that physical inacti vity induces muscle catabolism and causes further detraining, which may result in a self-perpetuati ng detraining state with easily induced cancer-related fati gue [24, 35]. Physical acti vity and exercise may interfer this self-perpetuati ng cycle by improved physical fi tness, and consequently reduced cancer-related fati gue and improved QoL [24, 35]. Furthermore, psychosocial interventi ons may help to reduce psychological distress, depression, anxiety, and fati gue, and to reduce sleep problems, and subsequently improve the pati ent’s QoL [30-33].
for pati ents with cancer can be categorized into diff erent types. Cunningham’s hierarchic classifi cati on disti nguishes fi ve types of heterogeneti c psychosocial interventi ons based on the degree of psychological change the diff erent interventi ons seek to promote in pati ents with cancer: (I) informati on provision, i.e. interventi ons aimed at increasing the pati ent’s knowledge of cancer, its treatments, side eff ects and consequences; (II) support, i.e. interventi ons intended to help pati ents to cope with the implicati ons of cancer and its treatment, e.g. express associated emoti ons, diminish a sense of isolati on, identi fy unmet needs, take some control over events, deal with family members and health care personnel and accept losses and changed roles; (III) coping skills training, i.e. interventi ons targeted at att aining new cogniti ve-behavioral skills such as relaxati on, mental imaging, thought and aff ect management and acti vity planning; (IV) psychotherapy, i.e. interventi ons delivered by a well-trained professional that aim to achieve a more fundamental psychological change to increase self-understanding via, for example, psychodynamic therapy and supporti ve-therapeuti c approaches; and (V) spiritual or existenti al therapy, i.e. interventi ons promoti ng experienti al awareness of a transcendent order or power, some sense of belonging to a meaningful universe including mediati on and prayer (where meaningful to the pati ent), appropriate reading, discussion and refl ecti on around spiritual topics [37]. In additi on, psychosocial interventi ons may exist in diff erent durati ons, formats (e.g. individual, group, or couple therapy), methods (e.g. face-to-face, telephone, or web-based), and can be delivered by diff erent professions (e.g. psychologist or nurse) and at diff erent moments (e.g. during or aft er primary cancer treatment).
Opti mizing QoL with exercise and psychosocial interventi ons
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contribute to more eff ecti ve interventi on programs [39]. It is therefore important to identi fy subgroups of pati ents that respond best to the interventi on, by conducti ng moderati on analysis [38]. Moderators are variables that aff ect the directi on and/or strength of the relati on between the interventi on and outcome [40, 41]. This will inform clinical practi ce such that some interventi ons may only be used for a parti cular subgroup of pati ents with cancer, ensuring opti mal use of limited resources [42].
Few previous studies have found that demographic, clinical and personal factors may moderate the eff ects of exercise and psychosocial interventi ons on QoL [43-47]. However, as these single studies have insuffi cient power to conduct strati fi ed analyses by the moderator subgroup, the moderator eff ects found in previous single studies should be interpreted as exploratory analyses [38]. Thus, to study the moderators of exercise and psychosocial interventi ons on QoL, and to conduct subsequently strati fi ed analyses by the moderator subgroup, a study with a much larger sample size is needed [38].
To further improve the eff ecti veness of exercise and psychosocial inter-venti ons on QoL among pati ents with cancer, insights in the working mechanisms of an interventi on (i.e. insight into the mediators of the eff ect of an interventi on) are needed [38, 48, 49]. Interventi on mediators are intermediate variables that explain how or why an interventi on infl uences an outcome [38].
Predicti ng Opti maL Cancer RehabIlitati on and Supporti ve care
(POLARIS) study
Meta-analyses that synthesize results of diff erent individual studies inform health professionals about the best available treatment and are an integral part of evidence based medicine [55, 56]. An important aspect of a meta-analysis is the ability to explore whether interventi on eff ects vary or are moderated by study characteristi cs (e.g. type or durati on of interventi on) [57]. Subgroup analyses or meta-regression, in which the change in overall interventi on eff ect in relati on to study-level characteristi cs is investi gated, are used to compare interventi on eff ects across diff erent modes of interventi on or across diff erent pati ent populati ons [57]. Summary data can be used to investi gate these sorts of study-level interacti ons. However, to investi gate interacti ons between the interventi on and pati ent-level characteristi cs (e.g. age or stage of cancer), a meta-regression relies on summary data, such as the mean age of the pati ents [56, 57]. In contrast, a meta-analysis that uses individual pati ent data (IPD) is not limited to using summary data. It obtains and harmonize the raw IPD from multi ple related studies [56], and has the advantage to test interacti ons between interventi ons and pati ent-level characteristi cs using the large number of raw data points, conducti ng subsequent strati fi ed analyses, and standardized analyti c techniques across the included studies [58, 59]. IPD meta-analysis is therefore considered the ‘gold-standard’ to evaluate moderators of interventi on eff ects with suffi cient power [56, 60, 61], and it will help to ensure that clinical practi ce and research is informed by robust evidence about the eff ect of interventi ons [57].
To study moderator eff ects of exercise and psychosocial interventi ons on QoL, the Predicti ng Opti maL Cancer RehabIlitati on and Supporti ve care (POLARIS) study has been set up. For POLARIS, an internati onal consorti um and a database of IPD from multi ple randomized controlled trials was created to (I) conduct an IPD meta-analysis to evaluate the eff ects of exercise and psychosocial interventi ons on the QoL in pati ents with cancer compared to a wait-list, usual care or att enti on control group, and to (II) identi fy demographic, clinical and personal characteristi cs, and interventi on-related characteristi cs that moderate the eff ects of exercise and psychosocial interventi ons on QoL.
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single studies. Harmonizing IPD from single studies is a ti mely endeavor, parti cularly when many eligible studies are available [62]. Diffi culti es may arise with harmonizing IPD as diff erent studies oft en use diff erent coding schemes or constructs [63]. A platf orm that enables harmonizing as soon as IPD from the fi rst studies has been received is more ti me-effi cient, especially when the number of variables and datasets are large. Thus, a fl exible data harmonizati on platf orm that enables harmonizing data during data collecti on is therefore useful. To our knowledge, a platf orm allowing this fl exible approach has not yet been developed.
Aims and outline of this thesis
This thesis aims to (I) investi gate the eff ects of exercise and psychosocial interventi ons on QoL in pati ents with cancer during and aft er treatment and to assess the possible moderators of these interventi on eff ects; (II) investi gate the mechanisms of exercise interventi ons on QoL; and (III) build a fl exible data harmonizati on platf orm that facilitates harmonizing data starti ng already during data collecti on.
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