chapter 8 - research.vu.nl 8.pdfinterventi ons in which (part of) the weekly exercise sessions were...

General discussion

Chapter 8

Thesis_11-7-2018_Kalter.indd 191 12-7-2018 08:32:57

Chapter 8

192

Current exercise and psychosocial interventi ons are typically off ered to a heterogeneous group of pati ents with cancer and are not targeted to specifi c pati ents. Such a ‘one-size-fi ts all’ approach may explain the modest eff ects of these interventi ons that have been reported. Therefore, these interventi ons should be bett er targeted and tailored to specifi c characteristi cs of pati ents. To be able to shift from this ‘one-size-fi ts-all’ approach to more personalized exercise and psychosocial interventi ons, it is important to identi fy which subgroups of pati ents respond best to these interventi ons. Furthermore, to improve the eff ecti veness of exercise and psychosocial interventi ons on quality of life (QoL) among pati ents with cancer, insights into the working mechanisms of an interventi on are needed. Therefore, this thesis aimed to investi gate the eff ects of exercise and psychosocial interventi ons on QoL in pati ents with cancer during and aft er cancer treatment, and to identi fy demographic, clinical, personal and interventi on-related moderators of these interventi on eff ects. Further, this thesis investi gated some possible mechanisms underlying the eff ects of exercise interventi ons on QoL. Finally, this thesis aimed to build a fl exible data harmonizati on platf orm that facilitates harmonizing raw individual pati ent data (IPD) of original studies for meta-analyses purposes, where such harmonizati on already starts during collecti on of the data from the original studies. The Predicti ng Opti maL Cancer RehabIlitati on and Supporti ve care (POLARIS) study used this platf orm. POLARIS included IPD from 57 randomized controlled trials (RCTs) that evaluated the eff ects of exercise interventi ons and/or psychosocial interventi ons on QoL compared to a wait-list, usual care or att enti on control group in adult pati ents with cancer. Aft er briefl y summarizing and discussing the main fi ndings of this thesis, the methodological considerati ons are discussed. This is followed by implicati ons for clinical practi ce, recommendati ons for future research, and a general conclusion.

Main fi ndingsEff ects and moderators of exercise and psychosocial interventi ons on QoL in pa-ti ents with cancer

The fi rst aim of this thesis was to 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 identi fy moderators of these interventi on eff ects.


General discussion

193

8

The single study described in Chapter 2 suggests that the eff ects of a group-based exercise interventi on on global QoL in pati ents aft er cancer treatment were larger for pati ents who received radiotherapy, and in parti cular, in those who received a combinati on of chemotherapy and radiotherapy, and in pati ents with higher levels of fati gue at baseline (i.e. prior to the exercise interventi on). No moderator eff ects were found for age, sex, educati on level, marital status, employment status, ti me since treatment, presence of comorbidity, self-effi cacy, depression, and anxiety. This study was a fi rst step in identi fying pati ents who may benefi t most from exercise interventi ons to improve QoL [1]. However, single studies are generally not powered to analyze moderators of interventi on eff ects and to conduct subsequent strati fi ed analysis [1]. Therefore, the POLARIS study was launched allowing to set up and conduct meta-analyses of IPD.

Results of the POLARIS IPD meta-analysis of 34 RCTs (n=4,519 pati ents) evaluati ng the eff ects and demographic, clinical, interventi on- and exercise-related moderators of exercise on QoL and physical functi on in pati ents with cancer, demonstrated that exercise interventi ons signifi cantly improved QoL and physical functi on, with small overall eff ects (Chapter 6). These fi ndings are consistent with those reported in previous meta-analyses based on aggregate data [2-4]. Furthermore, the results presented in this thesis showed that the eff ects of exercise interventi ons in which (part of) the weekly exercise sessions were supervised, were twice as large as those of exercise interventi ons in which sessions were unsupervised and conducted at or from home. No signifi cant moderator eff ects were found for age, sex, educati on level, marital status, body mass index, cancer type, the presence of distant metastasis, and type of cancer treatment. Besides, exercise interventi ons during and aft er cancer treatment were found to be equally benefi cial for QoL and physical functi on. Results of earlier RCTs that evaluated whether or not demographic and clinical characteristi cs moderated the exercise interventi on eff ects on QoL and physical functi on were inconsistent [5-9]. Findings from this thesis suggests that targeti ng exercise interventi ons based on these demographic and clinical characteristi cs may not be useful for further improving QoL and physical functi on.

Results of the POLARIS IPD meta-analysis on 22 RCTs with a total sample size of 4,217 pati ents, that investi gated the eff ects of psychosocial interventi ons on QoL showed that these interventi ons have stati sti cally signifi cant but small benefi cial eff ects on QoL, emoti onal functi on, and social functi on, both during and aft er


Chapter 8

194

treatment (Chapter 7). This is consistent with results from previous meta-analyses in this fi eld that used aggregate data [10-22]. Psychotherapy appeared to have larger eff ects compared to coping skills training and providing informati on, but this conclusion was based on two psychotherapy interventi on studies that investi gated interventi ons that specifi cally targeted pati ents with psychological distress. The eff ects of coping skills training were moderated by age, treatment type, and targeted interventi ons (i.e. targeted to pati ents with distress). The eff ects of coping skills training on emoti onal and social functi on were larger among younger pati ents, which may be explained by the higher psychological distress and supporti ve care needs of younger pati ents in physical, informati onal, and emoti onal domains [23, 24]. Consequently, coping skills training may be more eff ecti ve to improve emoti onal functi on and social functi on for this subgroup of pati ents. However, eff ects of coping skills training on emoti onal functi on and social functi on were not moderated by baseline values of emoti onal and social functi on. Further, type of cancer treatment was a signifi cant moderator of the eff ect of coping skills training, such that larger eff ects on QoL and emoti onal functi on were found in pati ents treated with chemotherapy, and larger eff ects on social functi on were found in pati ents with breast cancer that did not receive hormone therapy, and in pati ents who had surgery. The larger eff ects of coping skills training in pati ents treated with chemotherapy may be explained by the systemic eff ect of chemotherapy, that may lead to an increased level of symptoms such as fati gue [25], and emoti onal or cogniti ve problems [26], which are specifi cally targeted by coping skills training. It should be noted, however, that broad categories of treatments were used in this heterogeneous group of pati ents (i.e. previous or current treatment versus no such treatment) and treatment combinati ons may vary. Future studies should therefore examine moderator eff ects of cancer treatment within more homogeneous groups of pati ents. Furthermore, eff ects of coping skills training on QoL were larger in studies that targeted pati ents with distress. It is known that higher levels of distress negati vely aff ect a pati ent’s QoL [27]. Coping skills training may reduce distress and consequently improve a pati ent’s QoL [10]. Pati ents with higher levels of distress at baseline may have more room for reducing their distress, and consequently have larger improvements in QoL. However, eff ects of coping skills training on QoL was not moderated by baseline values of QoL. The eff ects of psychotherapy on emoti onal functi on seems to be moderated by cancer type, with signifi cantly higher eff ects for pati ents with breast and hematological cancer compared to other


General discussion

195

8

cancer types. However, it may be that the moderati ng eff ect of cancer type on the psychotherapy eff ects on QoL was coincidental due to the small sample size of some other cancer types included in the analyses. Therefore, future studies are needed to confi rm whether pati ents with diff erent cancer types indeed respond diff erently to psychosocial interventi ons. Overall, this IPD meta-analysis stresses the need for developing a coping skills training tailored to the specifi c needs of elderly pati ents, and it highlights the importance of targeti ng psychosocial interventi ons to pati ents with distress.

Mechanisms underlying exercise interventi on eff ects on QoL

The second aim of this thesis was to investi gate the mechanisms underlying the eff ects of exercise interventi ons on QoL.

The study described in Chapter 3 found support for the hypothesis that a 12-week resistance and endurance exercise interventi on improved cardiorespiratory fi tness, which is associated with lower physical fati gue and higher global QoL and physical functi on. The mediati ng role of cardiorespiratory fi tness in the exercise interventi on eff ect on physical fati gue and physical functi on emphasizes the importance of improving cardiorespiratory fi tness in pati ents with cancer. The lack of a mediati ng eff ect of improved cardiorespiratory fi tness on general fati gue is in line with previous studies [28, 29]. This may be explained by the fact that general fati gue does not only include physical aspects, but also mental aspects, which are likely to be infl uenced by concepts other than or additi onal to cardiorespiratory fi tness. Furthermore, higher handgrip strength was associated with lower physical fati gue, and bett er lower body muscle functi on was associated with lower general and physical fati gue, which indicate that muscle strength and functi on might be important interventi on targets when aiming to reduce fati gue. However, muscle strength and functi on did not mediate the exercise eff ects on fati gue and physical functi on, because no signifi cant eff ect of the exercise interventi on was found on this outcome. The lack of signifi cant eff ects of exercise on muscle strength and functi on may be related to the choice of instruments used to assess the outcomes, as they may have been less sensiti ve to detect exercise-induced changes [9]. Finally, reducing fati gue was associated with improved global QoL and physical functi on, and exercise appeared to be an eff ecti ve strategy to reduce fati gue.


Chapter 8

196

Research into the mechanisms underlying psychosocial interventi on eff ects on QoL were beyond the scope of the current thesis. However, data collected in the POLARIS study will allow to explore which factors may mediate the eff ect of psychosocial interventi ons on QoL.

A fl exible data harmonizati on pla� orm that facilitates harmonizing data during data collecti on

The third aim of this thesis was to build a fl exible data harmonizati on platf orm for use in IPD meta-analyses that facilitates harmonizati on of IPD already during the process of data collecti on. Chapter 5 describes the development and use of this platf orm. This platf orm is the fi rst data harmonizati on platf orm that allows starti ng data harmonizati on already during data collecti on, which is ti me effi cient, especially when the number of studies is large. Furthermore, the data harmonizati on platf orm allows to store, prepare, and harmonize IPD within one transparent platf orm. The harmonizati on process is facilitated by transparent interfaces, which makes the platf orm easy in use. Finally, the data harmonizati on platf orm has the ability to export harmonized IPD and corresponding data dicti onary to the stati sti cal program SPSS [30] for further analysis.

Methodological considerationsWhen interpreti ng the main fi ndings of this thesis, it is important to take into ac-count methodological considerati ons related to stati sti cal power, study design, pri-mary outcome, potenti al sources of bias in IPD meta-analyses, and generalizability. These considerati ons are discussed below.

Stati sti cal power

In Chapter 2, possible moderators of exercise interventi on eff ects on QoL were studied in a single study that evaluated the eff ects of a 12-week group-based exercise program among pati ents with cancer who completed cancer treatment. Although the sample size of this study was relati vely large for an exercise trial in pati ents with


General discussion

197

8

cancer (n= 209), the sample size was small for studying interventi on moderators. In fact, the results of the presented power analyses showed that the sample size should be at least 395 to be able to adequately conduct strati fi ed analyses with a power of 80%. Consequently, the analyses of the moderator eff ects described in this study should be interpreted as exploratory (hypothesis generati ng) analyses [1]. To confi rm fi ndings from single studies or to identi fy new interventi on moderators, a meta-analysis using IPD has been suggested as the preferred method [31, 32]. The large number of raw data points in an IPD meta-analysis facilitates testi ng of interacti ons at the pati ent level, conducti ng subsequent strati fi ed analyses, and standardizing analyti c techniques across the included studies [31, 32]. With over 4,500 pati ents included in the IPD meta-analyses that studied the moderators of exercise on QoL and physical functi on (Chapter 6) and over 4,200 pati ents included in the IPD meta-analyses that studied moderators of psychosocial interventi on on QoL, emoti onal functi on and social functi on (Chapter 7), there was suffi cient power to test potenti al moderators of interventi on eff ects, and conduct subsequent strati fi ed analyses accordingly. To the best of our knowledge, the POLARIS study is currently the largest IPD meta-analysis study in this fi eld of research. However, the search was conducted in September 2012, and, despite maintaining contact with principal investi gators of identi fi ed ongoing trials, not all relevant studies published since September 2012 were included in the POLARIS database as used in the present thesis.

Study design

In Chapter 4, possible physical and psychological mediators of exercise interventi on eff ects on QoL were studied in a single RCT that evaluated the eff ects of a combined resistance and endurance exercise interventi on among pati ents with cancer who had completed treatment with curati ve intent [9, 33]. Although a RCT with pre- and post-interventi on measurements is considered the most rigorous study design to evaluate the eff ecti veness of an interventi on [34], the disadvantage of using this design for mediati on analysis is that inferences about causality between mediators and outcome variables cannot be made because the mediator variables and outcome variables were assessed at the same ti me-points. Preferably, a longitudinal design with multi ple assessment points is needed where the exercise-induced changes in


Chapter 8

198

the mediator can precede the changes in the outcome QoL [5].

On the contrary, RCTs with pre-and post-interventi on measurements are suitable for studying possible moderators of interventi on eff ects. The use of meta-analyses in which IPD of multi ple RCTs are pooled (as used for the studies presented in Chapter 6 and 7) is the best way to study whether the eff ects of an interventi on diff er across subgroups of pati ents, as the large sample sizes provide suffi cient stati sti cal power to detect moderators of interventi on eff ects and conduct subsequent strati fi ed analyses [31, 32].

Primary outcome

The primary outcome of the studies in this thesis was QoL, which is typically assessed with pati ent-reported outcomes (e.g. cancer-specifi c QoL questi onnaires such as the Functi onal Assessment of Cancer Therapy [35] and the European Organizati on for Research and Treatment of Cancer Quality of Life Questi onnaire-Core 30 questi onnaire [36], and the generic QoL questi onnaire Short Form-36 [37]). Although these questi onnaires are well-known, widely used, reliable and valid instruments to measure QoL [35-37], they have limitati ons. QoL may, for instance, be suscepti ble to ‘response shift ’, i.e. a recalibrati on of a parti cipant’s internal standard used to judge one’s current QoL experience [38, 39]. This internal standard of QoL percepti on may change throughout the cancer conti nuum [40]. Therefore, ‘response shift ’ should be taken into account when evaluati ng the exercise and psychosocial interventi on eff ect on QoL in a longitudinal study design.

Potenti al sources of bias in IPD meta-analyses

Despite advantages of IPD meta-analyses, such as the ability to use consistent stati sti cal methods across studies, obtain results for unpublished or poorly reported outcomes, and increase power to detect diff erenti al subgroup eff ects, there may be biases. These biases include publicati on bias and data availability bias (i.e. if the collected studies are a biased subset of all eligible studies [41]), which may hamper the validity of IPD meta-analyses.

Publicati on bias may occur when studies with certain results (e.g. stati sti cally


General discussion

199

8

signifi cant or clinically favorable results) are more likely to be published than other studies [42, 43]. This can generally lead to an overesti mati on of interventi on eff ects [44]. In the POLARIS study that evaluated the eff ects of exercise interventi ons on QoL (Chapter 6) evidence was found for a signifi cant publicati on bias for all eligible RCTs reporti ng on QoL, which overesti mated the interventi on eff ects by 28%. However, the RCTs included in the IPD meta-analysis were a representati ve sample of all published studies. No evidence for publicati on bias was found in the IPD meta-analysis that investi gated the eff ects of psychosocial interventi ons on QoL (Chapter 7).

Data availability bias may occur when investi gators of eligible studies are not willing or able to share the data of their study for an IPD meta-analysis. This situati on leads to a set of available studies that may not refl ect the enti re evidence base [45]. For POLARIS, 49% of the eligible RCTs on exercise and 36% of the eligible RCTs on psychosocial interventi ons were included in the IPD meta-analyses, which may limit the generalizability of the results [46]. However, no signifi cant diff erences in eff ect sizes were found between studies that were included in the IPD meta-analysis and those not included. This indicates that the studies included for both the analyses on exercise interventi ons as well as psychosocial interventi ons were a representati ve sample of the published studies, at least in terms of eff ects found in these studies.

Generalizability

The response rate of each RCT included in the POLARIS study may infl uence the generalizability of our fi ndings. Pati ents who declined parti cipati on in the RCTs may be less interested in or moti vated for exercise and/or psychosocial interventi on [47, 48]. Previous studies that examined diff erences in characteristi cs between pati ents with cancer who parti cipated in exercise trials and those that declined parti cipati on reported no diff erences in exercise levels between parti cipants and non-parti cipants to an exercise trial [49-51]. Diff erences were found in demographic characteristi cs, such that parti cipants were more likely to be younger [49] and to have higher educati on levels [50, 51]. A previous systemati c review that studied diff erences in characteristi cs between pati ents with cancer who parti cipated in psychosocial interventi ons and those that declined parti cipati on showed no diff erences in


Chapter 8

200

demographic (age, sex) and clinical characteristi cs (cancer type) [48]. Besides, most RCTs that examined psychosocial interventi on eff ects included parti cipants that were more likely highly educated, wealthier, and Caucasian pati ents with cancer [52]. Furthermore, the majority of studies evaluati ng the eff ects of exercise and psychosocial interventi ons have been conducted in pati ents with breast cancer or prostate cancer who were treated with curati ve intent [53, 54]. Due to diff erences in disease and treatment trajectories, results may not be generalizable to other (less common) cancer pati ent populati ons, such as pati ents with glioma, esophageal, head and neck and ovarian cancer, and pati ents with metastati c disease.

Clinical implicationsThe results of the POLARIS study showed that exercise interventi ons, and parti cularly those that are (partly) supervised, have signifi cant benefi cial eff ects on QoL and physical functi on in various subgroups of pati ents with cancer with diff erent demographic and clinical characteristi cs, both during and aft er treatment. These fi ndings support and strengthen the evidence base for current nati onal and internati onal exercise recommendati ons that all pati ents with cancer should be physically acti ve during and aft er cancer treatment [54-61]. The results of the POLARIS study also suggest that psychosocial interventi ons are eff ecti ve for improving QoL, emoti onal functi on, and social functi on in pati ents with cancer, both during and post treatment.

Although the fi ndings presented in this thesis identi fi ed only a few moderators of interventi on eff ects that would enable bett er targeti ng of interventi ons, it is and remains important to target exercise and psychosocial interventi ons to pati ents with cancer most in need for support. Some pati ents may be much bett er able to self-manage the consequences of cancer and its treatment (e.g. physical problems such as lower physical fi tness, and psychological problems such as increased fati gue, anxiety, distress), while other pati ents may have a stronger need for referral to a monodisciplinary healthcare provider (e.g. physiotherapist, psychologist) or to multi disciplinary cancer rehabilitati on [58, 62].

According to internati onal exercise guidelines, pati ents with cancer should avoid inacti vity and be as physically acti ve as abiliti es and conditi ons allow [54]. If


General discussion

201

8

possible, pati ents are recommended to exercise at least 150 minutes per week and include strength training exercises at least two days per week [54]. For pati ents who require supervision or who may need guidance on safe procedures, referral to a physiotherapist or exercise specialist may help [54]. The Dutch evidence-based guideline ‘Medical specialist oncological rehabilitati on’, published in 2017 [58] recommends that pati ents with multi ple related functi onal problems or with serious functi onal disorders with permanent disability should be referred to multi disciplinary cancer rehabilitati on. In the case of a single problem, pati ent should be referred to a monodisciplinary healthcare provider. For example, pati ents with reduced physical functi on or psychological distress may go to a physiotherapist or a psychologist, respecti vely. As recommended by the guideline [58] these interventi ons should opti mally fi t the pati ent’s characteristi cs, health state, needs, preferences, capabiliti es and opportuniti es. It is therefore important to know which existi ng programs works best, and for whom (that is, to identi fy important moderators of interventi on eff ects). This thesis aimed to provide evidence on which moderati ng factors are of importance. Evidence from the studies conducted so far of which data were included in the POLARIS study (i.e. for pati ents with breast or prostate cancer who were treated with curati ve intent), indicates that targeti ng exercise interventi ons based on the studied demographic and clinical characteristi cs may not be useful for further improving QoL and physical functi on (Chapter 6). Therefore, exercise interventi ons can be off ered in routi ne clinical cancer care for various subgroups of pati ents with cancer with diff erent demographic and clinical characteristi cs, both during and aft er treatment. However, more research is needed to obtain insight into (possibly other) factors to improve individual pati ent care.

The Dutch guideline ‘Screening for need psychosocial care’ published in 2017 recommends routi ne screening and referral to specialized psychosocial care based on a pati ents’ level of distress and/or need for care [63]. As recommended by the guideline, routi ne screening for distress is crucial at key points throughout the cancer conti nuum. Pati ents with distress experience lower QoL, have more diffi culty making decisions about treatment, do not comply with treatment protocols, seek medical care more oft en leading to higher costs in health care, and are less sati sfi ed with the medical care they receive [27, 64-66]. When distress is identi fi ed, the guideline recommends that an (specialized) oncology nurse of the treati ng team should take responsibility for coordinati ng proper assessment, referral and follow-up. Referral to psychosocial interventi ons may benefi t from insight into the pati ent’s


Chapter 8

202

characteristi cs, health state, needs, preferences, capabiliti es and opportuniti es.

Based on the evidence from this thesis, targeti ng pati ents by screening for distress (e.g. depression, fati gue, cogniti ve problems, menopausal symptoms) is indeed important and likely results in higher eff ect sizes of psychosocial interventi ons (Chapter 7). In additi on, coping skills training interventi ons may help to improve QoL for younger pati ents and for pati ents treated with chemotherapy. However, this thesis also showed that current coping skills training interventi ons may not address the needs of older pati ents. The supporti ve care needs of elderly pati ents should be identi fi ed and eff ecti ve coping skills training interventi ons targeti ng this populati on should be developed.

Recommendations for future researchTo further improve the eff ecti veness of exercise and psychosocial interventi ons for pati ents with cancer, interventi ons should be targeted to specifi c cancer populati ons with the highest needs, or tailored to specifi c characteristi cs of pati ent groups. This requires more knowledge of (I) the eff ects of exercise and psychosocial interventi ons in less common cancer populati ons, (II) opti mal prescripti ons for exercise and psychosocial interventi on, (III) mediators of exercise and psychosocial interventi on eff ects, (IV) strategies to opti mize adopti on, implementati on and maintenance of exercise and psychosocial care at the pati ent as well as care giver levels, and (V) strategies to opti mize data sharing and secondary analysis of harmonized single studies as a means to understand and predict interventi on eff ects, inform policy makers, and maximize the benefi ts of exercise and psychosocial interventi ons for the individual pati ents with cancer [67-70].

Eff ects of exercise and psychosocial interventi ons in less common cancer populati ons

There is clear evidence that exercise and psychosocial interventi ons improve QoL in pati ents with breast and prostate cancer, and that it should be implemented as part of standard cancer care [3, 4, 10, 17]. However, as this evidence is generally based on breast, prostate, or mixed cancer groups, it is not yet known if similar exercise


General discussion

203

8

and psychosocial interventi ons are feasible among pati ents with less common cancers such as glioma, esophageal, head and neck and ovarian cancer. Pati ents with glioma oft en experience cogniti ve defi cits [71], and may therefore especially benefi t from coping skills training to improve QoL [72]. In additi on to fati gue, and muscle weakness, pati ents with head and neck cancer may experience disti nct side eff ects from the cancer and its treatment, such as a dry mouth or throat, diffi culty swallowing, and shoulder weakness and pain [73, 74], which may hamper parti cipati on in exercise. Informati on on how to manage disease-specifi c exercise barriers during standard cancer care may help these pati ents decreasing their side eff ects [75]. Compared to women with breast cancer, women with ovarian cancer have a disti nct disease and treatment trajectory as ovarian cancer is oft en detected at a more advanced disease stage, has lower survival rates, and treatment oft en includes (interval) debulking surgery and (neo)adjuvant chemotherapy [76]. These pati ents may therefore need exercise and psychosocial interventi ons specifi cally customized their disease and treatment trajectory. By pooling data from similar exercise and psychosocial interventi on studies, benefi ts of these interventi ons in less common cancers may be identi fi ed in larger samples. The POLARIS study that included IPD from multi ple studies had the advantage to conduct IPD meta-analyses in specifi c cancer populati ons, not only from studies among pati ents with more common cancer, but also from studies that included pati ents with mixed cancer groups, including less common cancer populati ons. However, despite the advantage of pooling data from studies with mixed cancer types, allowing to increase the sample size, the sample sizes of these less common cancer types available in the POLARIS database remained small. Therefore, larger multi center RCTs such as the interdisciplinary rehabilitati on interventi on among glioma pati ents [77], the Physical ExeRcise Following Esophageal Cancer Treatment (PERFECT) study in pati ents aft er surgery with curati ve intent [78], and the Physical Acti vity and Dietary interventi on in OVArian cancer (PADOVA) study [79], are needed to confi rm exercise interventi on eff ects on QoL in these less common cancer populati ons, as they may diff er from those with breast and prostate cancer due to diff erences in treatment trajectories. These and other studies conducted in less common cancer types can be included in the POLARIS database for further analyses.


Chapter 8

204

Opti mal prescripti ons for exercise and psychosocial interventi ons

In order to opti mize exercise prescripti ons to improve QoL and physical functi on, more insight into the opti mal exercise-related characteristi cs (i.e. frequency, intensity, type and ti me or durati on of exercise) for pati ents with cancer is required. No diff erences in eff ects between types of exercise were found in this thesis, which is consistent with a previous meta-analysis on aggregate data that contains 32 more studies than our IPD meta-analyses [80]. Larger eff ects of supervised compared to unsupervised exercise interventi ons were found in this thesis and may be explained by a more demanding exercise prescripti on, a higher compliance to the prescribed exercise interventi on, access to bett er equipment with more adjustment and performance feedback, the att enti on and support of the exercise physiologist delivering the interventi on, and possibly social interacti on with other parti cipants [81]. The lack of signifi cant diff erences in exercise eff ects across exercise-related characteristi cs in the current thesis might have resulted from litt le variati on in these characteristi cs across studies that assessed supervised exercise interventi ons, as most of these studies investi gated the eff ect of at least moderate-vigorous-intensity aerobic exercise with or without resistance exercise. However, there is some evidence that the eff ects of exercise vary by exercise frequency, intensity, type and durati on [9, 82, 83]. Previous head-to-head comparisons of exercise-related characteristi cs indicated a dose response eff ect of aerobic exercise on physical functi on but not on QoL during treatment in pati ents with breast cancer [83], larger eff ects of resistance exercise than aerobic exercise compared with usual care on QoL in pati ents with prostate cancer [82], and larger eff ects of high intensity compared to low-moderate intensity exercise post treatment in a populati on with mixed cancer types [9]. Therefore, more adequately powered, high quality RCTs that directly compare exercise-related characteristi cs are warranted to defi ne opti mal exercise prescripti ons on a given outcome, for a given cancer type, and in a parti cular phase of the cancer trajectory (e.g. during treatment, aft er treatment, end of life [84]).

In order to opti mize the eff ects of psychosocial interventi ons, insight into the interventi on-related characteristi cs such as delivery format (e.g. individual, group or couple therapy), method (e.g. face-to-face, telephone, or web-based), profession (e.g. psychologist versus nurse) and techniques, (e.g. behavioral acti vati on, cogniti ve restructuring, problem-solving, relaxati on training,) for pati ents with


General discussion

205

8

cancer is required [85]. A previous RCT in pati ents with advanced cancer and their caregivers that investi gated the opti mal dose of a psychosocial interventi on, found no diff erences in eff ects on QoL, emoti onal functi on and social functi on between a brief psychosocial program (that consisted of three contacts) and an extensive psychosocial program (that consisted of six contacts) [86]. However, the RCT also suggest that the opti mal interventi on dose may depend on which outcome is targeted for change. In additi on, a previous RCT that examined the effi cacy of Internet-based cogniti ve behavioral therapy for severe fati gue in pati ents with breast cancer [87], found that the eff ecti veness on severe fati gue was not signifi cantly diff erent from face-to-face cogniti ve behavioral therapy [88, 89]. More head-to-head comparisons of psychosocial interventi on-related characteristi cs and techniques are needed to personalize psychosocial interventi ons on a given outcome.

Mediators of exercise and psychosocial interventi on eff ects

To improve the eff ecti veness of exercise and psychosocial interventi ons on QoL, it is important to gain more knowledge oft he working mechanisms of an interventi on (i.e. interventi on mediators) [1, 90, 91]. Insight into mediators of exercise and psychosocial interventi ons is important for identi fying and subsequently targeti ng criti cal interventi on components to improve eff ecti veness and effi ciency and to reduce the costs [92, 93]. Although the current thesis showed that cardiorespiratory fi tness is an important interventi on target when aiming to reduce fati gue and improve physical functi on, and that muscle strength and functi on might be important interventi on targets when aiming to reduce fati gue (Chapter 3), other psychosocial factors, such as reduced sleep quality, mastery and self-effi cacy may also mediate the eff ect of exercise on fati gue [94, 95]. In additi on, exercise interventi ons are specially focused on physical dimensions of QoL, whereas QoL also comprises emoti onal and social functi on [96]. Consequently, only improving or maintaining components of physical fi tness (which exercise interventi ons generally aim for [94]) might not be suffi cient and concepts other than or additi onal to physical fi tness (such as emoti onal and social functi on) should be taken into account when aiming to improve QoL. In contrast, psychosocial interventi ons that aim to improve distress (e.g. depression, fati gue, cogniti ve problems, menopausal symptoms) showed benefi cial eff ects on QoL, suggesti ng a role for improving emoti onal and social


Chapter 8

206

domains of QoL.

In additi on to psychosocial mediators, biological factors may mediate the eff ect of exercise on fati gue and QoL [97]. The associati on between elevated concentrati ons of C-reacti ve protein [98] and pro-infl ammatory cytokines [99, 100] and cancer-related fati gue has been suggested in earlier studies. Exercise may lower these concentrati ons [101-104], and thereby reducing fati gue, and improve QoL. Future studies among pati ents with cancer should further explore anti -infl ammatory eff ects of exercise and their mediati ng role on reducing fati gue and improve QoL, and focus how exercise can improve clinical outcomes such as tumour growth and (disease-free) survival as this would likely help adopti ng exercise as standard clinical practi ce [105].

Opti mizing adopti on, implementati on and suffi cient maintenance of exercise and psychosocial care

The RE-AIM (reach, effi cacy, adopti on, implementati on, maintenance) framework sensibly argues that true (populati on) eff ecti veness of interventi ons is dependent on the effi cacy as well as on how many pati ents adhere to the interventi on program [106, 107]. To improve the eff ecti veness of the interventi on, it is therefore essenti al to improve the adherence of these exercise and psychosocial interventi ons. Regarding exercise interventi ons, the associati on between several demographic (smoking, alcohol consumpti on), clinical (obesity) and psychosocial factors (self-effi cacy, psychological distress), and exercise adherence has been suggested in earlier studies [50, 108]. However, more research is needed whether other factors such as social and environmental factors and the role of cancer treatment may play a role [50, 108]. Furthermore, as health behavior change theory-based interventi ons have shown to be more eff ecti ve in changing behavior than non-theory based interventi ons [109], incorporati on of these theories may further assist with adopti on and maintenance of exercise and psychosocial interventi ons [50, 110]. Health behavior change theories may especially inform how the pati ents’ personal moti vati on and abiliti es can be strengthened for parti cipati on in interventi on programs [111, 112]. This is needed as 32-65% of eligible pati ents do not parti cipate in exercise or psychosocial interventi ons in the studies conducted to date [50, 83, 86, 113, 114]. Previous studies suggested that exercise parti cipati on


General discussion

207

8

may improve when exercise interventi ons are focused on intrinsic moti vati on, social support, self-effi cacy, perceived benefi ts (in the long term), and perceived barriers [49, 50, 115, 116]. In order to improve the opportuniti es for parti cipati on in exercise and psychosocial interventi ons, interventi ons should be off ered in a convenient manner to pati ents with cancer and supported by well-informed and trained health professionals.

Furthermore, for opti mal implementati on of exercise and psychosocial interventi ons in cancer care it is important to get insight in the cost-eff ecti veness of these interventi ons. Given the shortage of healthcare resources and the increasingly ti ght funding of healthcare systems, it is vital that exercise and psychosocial interventi ons be evaluated not only in terms of effi cacy in symptom reducti on and improving QoL (which evidence has been shown in the current thesis), but in economic terms as well [117]. Earlier studies suggest that off ering exercise and psychosocial interventi on to pati ents with cancer can be cost-eff ecti ve [9, 116, 118-121]. However, as studies diff ered regarding types of exercise and psychosocial care and pati ent populati ons, future studies should provide more clear informati on as to which types of exercise and psychosocial inventi ons are most likely to be cost-eff ecti ve and for whom.

Opti mal data sharing

The POLARIS database has been developed in which IPD from – so far – 57 RCTs are harmonized to conduct IPD meta-analyses to evaluate the eff ects of exercise and psychosocial interventi ons on QoL in pati ents with cancer, and to identi fy moderators of interventi on eff ects. Furthermore, this collecti on of datasets allows studying the eff ects and moderators of exercise and psychosocial interventi ons on other relevant outcomes than QoL including fati gue, sleep, and distress [122]. However, gathering IPD from principal investi gators from the original study showed to be a ti mely endeavor. Delays occurred when these principal investi gators did not respond to initi al requests, or did not have the ti me to prepare their data for data sharing, or when legal issues needed to be resolved before data could be shared [123]. Of all 136 identi fi ed RCTs for POLARIS, IPD was not available for 45 RCTs, principal investi gators of 27 RCTs did not respond to our request aft er a number of att empts, and principal investi gators from another 7 RCTs had no approval from


Chapter 8

208

their insti tute/university to share their IPD. Consequently, at the ti me of analyses, IPD had been obtained from 57 RCTs (42% or the total number of RCTs identi fi ed at the ti me), which is lower than the mean of 64% of all eligible studies that researchers usually obtain for IPD meta-analysis [124]. These results show that there is an urgent need to facilitate the data stewardship (i.e. a collecti on of data management methods covering acquisiti on, storage, aggregati on, and de-identi fi cati on, and procedures for IPD release and use [125]) supporti ng the reuse of IPD from exercise and psychosocial interventi ons among pati ents with cancer. To facilitate good data stewardship and to promote open science, a broad community of internati onal stakeholders have developed the Findable, Accessible, Interoperable, Reusable (FAIR) Data principles [126]. When publishing data, authors should comply to these principles when maximizing the reusability of their datasets. The FAIR Data principles fi rst posit that each study should be registered or indexed in a searchable resource, so that they can be located (‘Findable’). For POLARIS, we identi fi ed eligible RCTs via systemati c searches in four electronic databases (PubMed, EMBASE, PsycINFO, and CINAHL), reference checking of systemati c reviews, meta-analyses, and personal communicati on with collaborators, colleagues, and other experts in the fi eld. Principal investi gators from eligible RCTs were invited to join the POLARIS consorti um and share their IPD. Second, the FAIR data principles recommends that each study should provide and thus make available relevant metadata from these datasets to interested researchers, for instance, on the types of variables, age groups under study, study design, measurement instruments used, ti me frame (‘Accessible’). For POLARIS, principal investi gators that expressed interest in data sharing were asked to fi ll in a data request form where questi ons needed to be answered on their metadata (e.g. study design, contact details principal investi gator(s)), and which IPD they want to share. Third, according to FAIR the IPD should be ‘Interoperable’ and thus use a consistent data format and classifi cati on for knowledge representati on. The datasets from the individual studies included in POLARIS were imported in a data harmonizati on platf orm (Chapter 5) where they were re-coded according to standardized protocols and harmonized. Finally, IPD should be ‘Reusable’, that is, made available to other researchers [126]. For POLARIS, the harmonized datasets were, and are, used to study the eff ects and moderators of exercise and psychosocial interventi ons on QoL, fati gue, sleep, and distress, and are made available to other researchers [122]. Thus, the POLARIS study showed that it is possible to successfully undertake IPD meta-analyses to evaluate the eff ects of exercise and psychosocial


General discussion

209

8

interventi ons on QoL in pati ents with cancer, and to identi fy moderators of interventi on eff ects. However, the reusability of datasets was limited to the 42% of all identi fi ed datasets to which access was granted. Therefore, diff erent approaches should be investi gated in the future how to encourage principal investi gators to share their dataset for IPD meta-analysis. Principal investi gators should publish an open and freely accessible study protocol for easily retrieving metadata from their study such as types of variables, age groups under study, study design, measurement instruments used, and ti me frame. Besides, principal investi gators should be clear which IPD will be made (openly) available for interested researchers, legal and ethical issues should be resolved, and IPD should be clearly stored aft er fi nalizing their study. The POLARIS study applies to these FAIR data principles, as publicati ons from the POLARIS study can be fi nd through search approaches (‘Findability’). It is possible to retrieve the metadata from these datasets on the types of variables, age groups under study, study design, measurement instruments used, and ti me frame (‘Accessibility’). The IPD available in the POLARIS study use a consistent data format and classifi cati on for knowledge representati on (‘Interoperable’), and IPD are made available to other researchers (‘Reusability’). Complying to the FAIR principles will help the reusability of relevant IPD. This will help future research to understand and predict interventi on eff ects, inform policy makers, and maximize the benefi ts of exercise and psychosocial interventi ons for the individual pati ents with cancer.

ConclusionThis thesis has the following conclusions. First, the eff ects of a group-based exercise interventi on on global QoL were larger in pati ents who received radiotherapy, and parti cular those who received a combinati on of chemotherapy and radiotherapy, and in pati ents with higher levels of fati gue at baseline (i.e. prior to the exercise interventi on). Second, the current thesis showed that exercise, and parti cular those with a supervised component, has small but signifi cant benefi cial eff ects in improving QoL and physical functi on across subgroups of pati ents with cancer with diff erent demographic and clinical characteristi cs, both during and aft er treatment. Third, psychosocial interventi ons signifi cantly improved QoL, emoti onal functi on and social functi on, but overall eff ects were small. Signifi cant diff erences in eff ects of diff erent types of psychosocial interventi ons were found, with largest eff ects of


Chapter 8

210

psychotherapy compared to coping skills training and informati on provision. The eff ects of coping skills training were moderated by age, treatment type, and targeted interventi ons. Eff ects of psychotherapy on emoti onal functi on may be moderated by cancer type, but these analyses were based on two RCTs with small sample sizes of some cancer types. Fourth, benefi cial eff ects of exercise on global QoL and physical functi on in pati ents with cancer were mediated by increased cardiorespiratory fi tness, and subsequent reducti ons in fati gue. Finally, IPD meta-analyses benefi ts from a fl exible data harmonizati on platf orm that facilitates harmonizing data during data collecti on, especially when the number of studies and variables is large.

In conclusion, the results of the current thesis showed that exercise and psychosocial interventi ons have signifi cant benefi cial eff ects on QoL. However, the eff ects diff ered by several demographic, clinical, personal, and interventi on-related characteristi cs. More research is needed how to fully implement these interventi ons into clinical oncology practi ce and to make exercise and psychosocial interventi ons an essenti al component of cancer care that opti mally fi t the pati ent’s characteristi cs, health state, needs, preferences, capabiliti es and opportuniti es.


General discussion

211

8

References1. Kraemer HC, Wilson GT, Fairburn CG, Agras WS: Mediators and moderators of treatment

eff ects in randomized clinical trials. Arch Gen Psychiatry 2002, 59(10):877-883.

2. Speck RM, Courneya KS, Masse LC, Duval S, Schmitz KH: An update of controlled physical

acti vity trials in cancer survivors: a systemati c review and meta-analysis. Journal of cancer

survivorship : research and practi ce 2010, 4(2):87-100.

3. Mishra SI, Scherer RW, Geigle PM, Berlanstein DR, Topaloglu O, Gotay CC, Snyder C:

Exercise interventi ons on health-related quality of life for cancer survivors. Cochrane

Database Syst Rev 2012, 8(8):CD007566.

4. Mishra SI, Scherer RW, Snyder C, Geigle PM, Berlanstein DR, Topaloglu O: Exercise

interventi ons on health-related quality of life for people with cancer during acti ve

treatment. Cochrane Database Syst Rev 2012(8):CD008465.

5. Buff art LM, Newton RU, Chinapaw MJ, Taaff e DR, Spry NA, Denham JW, Joseph DJ, Lamb

DS, Brug J, Galvao DA: The eff ect, moderators, and mediators of resistance and aerobic

exercise on health-related quality of life in older long-term survivors of prostate cancer.

Cancer 2015, 121(16):2821-2830.

6. Courneya KS, McKenzie DC, Mackey JR, Gelmon K, Reid RD, Friedenreich CM, Ladha AB,

Proulx C, Vallance JK, Lane K et al: Moderators of the eff ects of exercise training in breast

cancer pati ents receiving chemotherapy: a randomized controlled trial. Cancer 2008,

112(8):1845-1853.

7. Courneya KS, Sellar CM, Stevinson C, McNeely ML, Friedenreich CM, Peddle CJ, Basi S, Chua

N, Tankel K, Mazurek A et al: Moderator eff ects in a randomized controlled trial of exercise

training in lymphoma pati ents. Cancer Epidemiol Biomarkers Prev 2009, 18(10):2600-2607.

8. Kalter J, Buff art LM, Korstjens I, van Weert E, Brug J, Verdonck-de Leeuw IM, Mesters I, van

den Borne B, Hoekstra-Weebers JE, Ros WJ et al: Moderators of the eff ects of group-based

physical exercise on cancer survivors’ quality of life. Support Care Cancer 2015, 23(9):2623-

2631.


Chapter 8

212

9. Kampshoff CS, Chinapaw MJ, Brug J, Twisk JW, Schep G, Nijziel MR, van Mechelen W,

Buff art LM: Randomized controlled trial of the eff ects of high intensity and low-to-

moderate intensity exercise on physical fi tness and fati gue in cancer survivors: results of

the Resistance and Endurance exercise Aft er ChemoTherapy (REACT) study. BMC Med

2015, 13:275.

10. Faller H, Schuler M, Richard M, Heckl U, Weis J, Kuff ner R: Eff ects of psycho-oncologic

interventi ons on emoti onal distress and quality of life in adult pati ents with cancer:

systemati c review and meta-analysis. J Clin Oncol 2013, 31(6):782-793.

11. Tamagawa R, Garland S, Vaska M, Carlson LE: Who benefi ts from psychosocial interventi ons

in oncology? A systemati c review of psychological moderators of treatment outcome.

Journal of behavioral medicine 2012, 35(6):658-673.

12. Galway K, Black A, Cantwell M, Cardwell CR, Mills M, Donnelly M: Psychosocial

interventi ons to improve quality of life and emoti onal wellbeing for recently diagnosed

cancer pati ents. Cochrane Database Syst Rev 2012, 11:CD007064.

13. Semple C, Parahoo K, Norman A, McCaughan E, Humphris G, Mills M: Psychosocial

interventi ons for pati ents with head and neck cancer. Cochrane Database Syst Rev 2013,

7(7):CD009441.

14. Linden W, Girgis A: Psychological treatment outcomes for cancer pati ents: what do meta-

analyses tell us about distress reducti on? Psychooncology 2012, 21(4):343-350.

15. Heron-Speirs HA, Baken DM, Harvey ST: Moderators of psycho-oncology therapy

eff ecti veness: Meta-analysis of socio-demographic and medical pati ent characteristi cs.

Clinical Psychology: Science and Practi ce 2012, 19(4):402-416.

16. Heron-Speirs HA, Harvey ST, Baken DM: Moderators of psycho-oncology therapy

eff ecti veness: meta-analysis of therapy characteristi cs. Journal of psychosocial oncology

2013, 31(6):617-641.

17. Parahoo K, McDonough S, McCaughan E, Noyes J, Semple C, Halstead EJ, Neuberger MM,

Dahm P: Psychosocial interventi ons for men with prostate cancer: a Cochrane systemati c

review. BJU Int 2015, 116(2):174-183.


General discussion

213

8

18. Matsuda A, Yamaoka K, Tango T, Matsuda T, Nishimoto H: Eff ecti veness of

psychoeducati onal support on quality of life in early-stage breast cancer pati ents: a

systemati c review and meta-analysis of randomized controlled trials. Qual Life Res 2014,

23(1):21-30.

19. Jassim GA, Whitf ord DL, Hickey A, Carter B: Psychological interventi ons for women with

non-metastati c breast cancer. Cochrane Database Syst Rev 2015, 5(5):CD008729.

20. Osborn RL, Demoncada AC, Feuerstein M: Psychosocial interventi ons for depression,

anxiety, and quality of life in cancer survivors: meta-analyses. Internati onal journal of

psychiatry in medicine 2006, 36(1):13-34.

21. Rehse B, Pukrop R: Eff ects of psychosocial interventi ons on quality of life in adult cancer

pati ents: meta analysis of 37 published controlled outcome studies. Pati ent educati on and

counseling 2003, 50(2):179-186.

22. Zimmermann T, Heinrichs N, Baucom DH: “Does one size fi t all?” moderators in

psychosocial interventi ons for breast cancer pati ents: a meta-analysis. Annals of behavioral

medicine : a publicati on of the Society of Behavioral Medicine 2007, 34(3):225-239.

23. Puts MT, Papoutsis A, Springall E, Tourangeau AE: A systemati c review of unmet needs of

newly diagnosed older cancer pati ents undergoing acti ve cancer treatment. Support Care

Cancer 2012, 20(7):1377-1394.

24. Sanson-Fisher R, Girgis A, Boyes A, Bonevski B, Burton L, Cook P: The unmet supporti ve

care needs of pati ents with cancer. Supporti ve Care Review Group. Cancer 2000, 88(1):226-

237.

25. Koornstra RH, Peters M, Donofrio S, van den Borne B, de Jong FA: Management of fati gue

in pati ents with cancer -- a practi cal overview. Cancer Treat Rev 2014, 40(6):791-799.

26. Vardy J, Rourke S, Tannock IF: Evaluati on of cogniti ve functi on associated with

chemotherapy: a review of published studies and recommendati ons for future research. J

Clin Oncol 2007, 25(17):2455-2463.

27. Skarstein J, Aass N, Fossa SD, Skovlund E, Dahl AA: Anxiety and depression in cancer

pati ents: relati on between the Hospital Anxiety and Depression Scale and the European

Organizati on for Research and Treatment of Cancer Core Quality of Life Questi onnaire. J

Psychosom Res 2000, 49(1):27-34.


Chapter 8

214

28. Buff art LM, Galvao DA, Chinapaw MJ, Brug J, Taaff e DR, Spry N, Joseph D, Newton RU:

Mediators of the resistance and aerobic exercise interventi on eff ect on physical and

general health in men undergoing androgen deprivati on therapy for prostate cancer.

Cancer 2014, 120(2):294-301.

29. Rogers LQ, Hopkins-Price P, Vicari S, Pamenter R, Courneya KS, Markwell S, Verhulst S,

Hoelzer K, Naritoku C, Jones L et al: A randomized trial to increase physical acti vity in breast

cancer survivors. Med Sci Sports Exerc 2009, 41(4):935-946.

30. SPSS® [htt p://www.ibm.com/analyti cs/us/en/technology/spss/]

31. Riley RD, Lambert PC, Abo-Zaid G: Meta-analysis of individual parti cipant data: rati onale,

conduct, and reporti ng. Bmj 2010, 340:c221.

32. Tierney JF, Vale C, Riley R, Smith CT, Stewart L, Clarke M, Rovers M: Individual Parti cipant

Data (IPD) Meta-analyses of Randomised Controlled Trials: Guidance on Their Use. PLoS

medicine 2015, 12(7):e1001855.

33. Kampshoff CS, Buff art LM, Schep G, van Mechelen W, Brug J, Chinapaw MJ: Design of the

Resistance and Endurance exercise Aft er ChemoTherapy (REACT) study: a randomized

controlled trial to evaluate the eff ecti veness and cost-eff ecti veness of exercise

interventi ons aft er chemotherapy on physical fi tness and fati gue. Bmc Cancer 2010,

10:658.

34. Akobeng AK: Understanding randomised controlled trials. Arch Dis Child 2005, 90(8):840-

844.

35. Cella DF, Tulsky DS, Gray G, Sarafi an B, Linn E, Bonomi A, Silberman M, Yellen SB, Winicour

P, Brannon J et al: The Functi onal Assessment of Cancer Therapy scale: development and

validati on of the general measure. J Clin Oncol 1993, 11(3):570-579.

36. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H,

Fleishman SB, Dehaes JCJM et al: The European-Organizati on-for-Research-and-Treatment-

of-Cancer Qlq-C30 - a Quality-of-Life Instrument for Use in Internati onal Clinical-Trials in

Oncology. Journal of the Nati onal Cancer Insti tute 1993, 85(5):365-376.

37. Ware JE, Jr., Sherbourne CD: The MOS 36-item short-form health survey (SF-36). I.

Conceptual framework and item selecti on. Medical care 1992, 30(6):473-483.


General discussion

215

8

38. Gerlich C, Schuler M, Jelitt e M, Neuderth S, Flentje M, Graefen M, Kruger A, Mehnert A,

Faller H: Prostate cancer pati ents’ quality of life assessments across the primary treatment

trajectory: ‘True’ change or response shift ? Acta Oncol 2016, 55(7):814-820.

39. Anota A, Bascoul-Mollevi C, Conroy T, Guillemin F, Velten M, Jolly D, Mercier M, Causeret

S, Cuisenier J, Graesslin O et al: Item response theory and factor analysis as a mean to

characterize occurrence of response shift in a longitudinal quality of life study in breast

cancer pati ents. Health Qual Life Outcomes 2014, 12:32.

40. Sprangers MA, Schwartz CE: Integrati ng response shift into health-related quality of life

research: a theoreti cal model. Soc Sci Med 1999, 48(11):1507-1515.

41. Riley RD: Commentary: like it and lump it? Meta-analysis using individual parti cipant data.

Int J Epidemiol 2010, 39(5):1359-1361.

42. Sutt on AJ, Duval SJ, Tweedie RL, Abrams KR, Jones DR: Empirical assessment of eff ect of

publicati on bias on meta-analyses. Bmj 2000, 320(7249):1574-1577.

43. Sterne JA, Egger M, Smith GD: Systemati c reviews in health care: Investi gati ng and dealing

with publicati on and other biases in meta-analysis. Bmj 2001, 323(7304):101-105.

44. Rosenthal R: The File Drawer Problem and Tolerance for Null Results. Psychological Bulleti n

1979, 86(3):638-641.

45. Ahmed I, Sutt on AJ, Riley RD: Assessment of publicati on bias, selecti on bias, and

unavailable data in meta-analyses using individual parti cipant data: a database survey. Bmj

2012, 344:d7762.

46. Thorlund K, Imberger G, Walsh M, Chu R, Gluud C, Wett erslev J, Guyatt G, Devereaux PJ,

Thabane L: The number of pati ents and events required to limit the risk of overesti mati on

of interventi on eff ects in meta-analysis--a simulati on study. PLoS One 2011, 6(10):e25491.

47. Courneya KS: Effi cacy, eff ecti veness, and behavior change trials in exercise research. Int J

Behav Nutr Phys Act 2010, 7:81.

48. Wakefi eld CE, Fardell JE, Doolan EL, Aaronson NK, Jacobsen PB, Cohn RJ, King M:

Parti cipati on in psychosocial oncology and quality-of-life research: a systemati c review. The

Lancet Oncology 2017, 18(3):e153-e165.


Chapter 8

216

49. Gollhofer SM, Wiskemann J, Schmidt ME, Klassen O, Ulrich CM, Oelmann J, Hof H, Pott hoff

K, Steindorf K: Factors infl uencing parti cipati on in a randomized controlled resistance

exercise interventi on study in breast cancer pati ents during radiotherapy. Bmc Cancer

2015, 15:186.

50. Kampshoff CS, van Mechelen W, Schep G, Nijziel MR, Witlox L, Bosman L, Chinapaw MJ,

Brug J, Buff art LM: Parti cipati on in and adherence to physical exercise aft er completi on of

primary cancer treatment. Int J Behav Nutr Phys Act 2016, 13(1):100.

51. van Waart H, van Harten WH, Buff art LM, Sonke GS, Stuiver MM, Aaronson NK: Why do

pati ents choose (not) to parti cipate in an exercise trial during adjuvant chemotherapy for

breast cancer? Psychooncology 2015.

52. Aaronson NK, Matti oli V, Minton O, Weis J, Johansen C, Dalton SO, Verdonck-de Leeuw IM,

Stein KD, Alfano CM, Mehnert A et al: Beyond treatment - Psychosocial and behavioural

issues in cancer survivorship research and practi ce. EJC Suppl 2014, 12(1):54-64.

53. Buff art LM, Galvao DA, Brug J, Chinapaw MJ, Newton RU: Evidence-based physical acti vity

guidelines for cancer survivors: current guidelines, knowledge gaps and future research

directi ons. Cancer Treat Rev 2014, 40(2):327-340.

54. Schmitz KH, Courneya KS, Matt hews C, Demark-Wahnefried W, Galvao DA, Pinto BM, Irwin

ML, Wolin KY, Segal RJ, Lucia A et al: American College of Sports Medicine roundtable on

exercise guidelines for cancer survivors. Med Sci Sports Exerc 2010, 42(7):1409-1426.

55. Brown JK, Byers T, Doyle C, Coumeya KS, Demark-Wahnefried W, Kushi LH, McTieman

A, Rock CL, Aziz N, Bloch AS et al: Nutriti on and physical acti vity during and aft er cancer

treatment: an American Cancer Society guide for informed choices. CA Cancer J Clin 2003,

53(5):268-291.

56. Doyle C, Kushi LH, Byers T, Courneya KS, Demark-Wahnefried W, Grant B, McTiernan A,

Rock CL, Thompson C, Gansler T et al: Nutriti on and physical acti vity during and aft er

cancer treatment: an American Cancer Society guide for informed choices. CA Cancer J Clin

2006, 56(6):323-353.

57. Hayes SC, Spence RR, Galvao DA, Newton RU: Australian Associati on for Exercise and Sport

Science positi on stand: opti mising cancer outcomes through exercise. J Sci Med Sport

2009, 12(4):428-434.


General discussion

217

8

58. Nederlandse Vereniging van Revalidati eartsen: Concept richtlijn Medisch Specialisti sche

Revalidati e bij Oncoloie (2.0). Evidence-based guideline. 2017.

59. Rock CL, Doyle C, Demark-Wahnefried W, Meyerhardt J, Courneya KS, Schwartz AL,

Bandera EV, Hamilton KK, Grant B, McCullough M et al: Nutriti on and physical acti vity

guidelines for cancer survivors. CA Cancer J Clin 2012, 62(4):243-274.

60. Van den Berg JP, Velthuis MJ, Gijssen BCM, Lindeman E, van der Pol MA, Hillen HFP:

Richtlijn ‘Oncologische revalidati e’ [Guideline cancer rehabilitati on]. Ned Tijdschr Geneeskd

2011:155.

61. Campbell A, Stevinson C, Crank H: The BASES Expert Statement on exercise and cancer

survivorship. J Sports Sci 2012, 30(9):949-952.

62. Strategic presentati on on cancer rehabilitati on [htt ps://www.

cancer.dk/dyn/resources/File/fi le/1/1561/1385430087/

strategicpresentati ononcancerrehabilitati onthedanishcancersociety.pdf]

63. Screening for need psychosocial care [Dutch: Detecteren behoeft e psychosociale zorg]

[htt p://www.oncoline.nl/detecteren-behoeft e-psychosociale-zorg]

64. Clinical Practi ce Guidelines in Oncology: Distress Management Version 3 [htt p://www.nccn.

org/professionals/physician_gls/f_guidelines.asp]

65. Kennard BD, Stewart SM, Olvera R, Bawdon RE, hAilin AO, Lewis CP, Winick NJ:

Nonadherence in adolescent oncology pati ents: Preliminary data on psychological risk

factors and relati onships to outcome. J Clin Psychol Med S 2004, 11(1):31-39.

66. Von Essen L, Larsson G, Oberg K, Sjoden PO: ‘Sati sfacti on with care’: associati ons with

health-related quality of life and psychosocial functi on among Swedish pati ents with

endocrine gastrointesti nal tumours. Eur J Cancer Care (Engl) 2002, 11(2):91-99.

67. Doiron D, Burton P, Marcon Y, Gaye A, Wolff enbutt el BHR, Perola M, Stolk RP, Foco L,

Minelli C, Waldenberger M et al: Data harmonizati on and federated analysis of populati on-

based studies: the BioSHaRE project. Emerg Themes Epidemiol 2013, 10(1):12.

68. Pisani E, AbouZahr C: Sharing health data: good intenti ons are not enough. Bull World

Health Organ 2010, 88(6):462-466.


Chapter 8

218

69. Schofi eld PN, Eppig J, Huala E, de Angelis MH, Harvey M, Davidson D, Weaver T, Brown

S, Smedley D, Rosenthal N et al: Research funding. Sustaining the data and bioresource

commons. Science 2010, 330(6004):592-593.

70. Piwowar HA, Becich MJ, Bilofsky H, Crowley RS, ca BIGDS, Intellectual Capital W: Towards a

data sharing culture: recommendati ons for leadership from academic health centers. PLoS

medicine 2008, 5(9):e183.

71. Taphoorn MJ, Klein M: Cogniti ve defi cits in adult pati ents with brain tumours. Lancet

Neurol 2004, 3(3):159-168.

72. van der Linden SD, Sitskoorn MM, Rutt en GM, Gehring K: Feasibility of the evidence-based

cogniti ve telerehabilitati on program Remind for pati ents with primary brain tumors. J

Neurooncol 2018.

73. Lokker ME, Off erman MP, van der Velden LA, de Boer MF, Pruyn JF, Teunissen SC:

Symptoms of pati ents with incurable head and neck cancer: prevalence and impact on

daily functi oning. Head Neck 2013, 35(6):868-876.

74. Haisfi eld-Wolfe ME, McGuire DB, Soeken K, Geiger-Brown J, De Forge B, Suntharalingam

M: Prevalence and correlates of symptoms and uncertainty in illness among head and neck

cancer pati ents receiving defi niti ve radiati on with or without chemotherapy. Support Care

Cancer 2012, 20(8):1885-1893.

75. Midgley AW, Lowe D, Levy AR, Mepani V, Rogers SN: Exercise program design

considerati ons for head and neck cancer survivors. Eur Arch Otorhinolaryngol 2018,

275(1):169-179.

76. Hennessy BT, Coleman RL, Markman M: Ovarian cancer. Lancet 2009, 374(9698):1371-

1382.

77. Hansen A, Rosenbek Minet LK, Sogaard K, Jarden JO: The eff ect of an interdisciplinary

rehabilitati on interventi on comparing HRQoL, symptom burden and physical functi on

among pati ents with primary glioma: an RCT study protocol. BMJ open 2014,

4(10):e005490.


General discussion

219

8

78. van Vulpen JK, Siersema PD, van Hillegersberg R, Nieuwenhuijzen GAP, Kouwenhoven EA,

Groenendijk RPR, van der Peet DL, Hazebroek EJ, Rosman C, Schippers CCG et al: Physical

ExeRcise Following Esophageal Cancer Treatment (PERFECT) study: design of a randomized

controlled trial. Bmc Cancer 2017, 17(1):552.

79. Nederlands Trial Register: Identi fi er NTR6300, Physical Acti vity and Dietary interventi on

in OVArian cancer (PADOVA) [htt p://www.trialregister.nl/trialreg/admin/rctview.

asp?TC=6300]

80. Sweegers MG, Altenburg TM, Chinapaw MJ, Kalter J, Verdonck-de Leeuw IM, Courneya KS,

Newton RU, Aaronson NK, Jacobsen PB, Brug J et al: Which exercise prescripti ons improve

quality of life and physical functi on in pati ents with cancer during and following treatment?

A systemati c review and meta-analysis of randomised controlled trials. Br J Sports Med

2017.

81. Knols R, Aaronson NK, Uebelhart D, Fransen J, Aufdemkampe G: Physical exercise in cancer

pati ents during and aft er medical treatment: a systemati c review of randomized and

controlled clinical trials. J Clin Oncol 2005, 23(16):3830-3842.

82. Segal RJ, Reid RD, Courneya KS, Sigal RJ, Kenny GP, Prud’Homme DG, Malone SC, Wells

GA, Scott CG, Slovinec D’Angelo ME: Randomized controlled trial of resistance or aerobic

exercise in men receiving radiati on therapy for prostate cancer. J Clin Oncol 2009,

27(3):344-351.

83. Courneya KS, McKenzie DC, Mackey JR, Gelmon K, Friedenreich CM, Yasui Y, Reid RD,

Cook D, Jespersen D, Proulx C et al: Eff ects of exercise dose and type during breast cancer

chemotherapy: multi center randomized trial. J Natl Cancer Inst 2013, 105(23):1821-1832.

84. Courneya KS: Physical acti vity in cancer survivors: a fi eld in moti on. Psychooncology 2009,

18(4):337-342.

85. Tatrow K, Montgomery GH: Cogniti ve behavioral therapy techniques for distress and pain

in breast cancer pati ents: a meta-analysis. Journal of behavioral medicine 2006, 29(1):17-

27.

86. Northouse LL, Mood DW, Schafenacker A, Kalemkerian G, Zalupski M, LoRusso P, Hayes

DF, Hussain M, Ruckdeschel J, Fendrick AM et al: Randomized clinical trial of a brief and

extensive dyadic interventi on for advanced cancer pati ents and their family caregivers.

Psychooncology 2013, 22(3):555-563.


Chapter 8

220

87. Abrahams HJG, Gielissen MFM, Donders RRT, Goedendorp MM, van der Wouw AJ,

Verhagen C, Knoop H: The effi cacy of Internet-based cogniti ve behavioral therapy for

severely fati gued survivors of breast cancer compared with care as usual: A randomized

controlled trial. Cancer 2017, 123(19):3825-3834.

88. Gielissen MF, Verhagen S, Witjes F, Bleijenberg G: Eff ects of cogniti ve behavior therapy in

severely fati gued disease-free cancer pati ents compared with pati ents waiti ng for cogniti ve

behavior therapy: a randomized controlled trial. Journal of clinical oncology : offi cial

journal of the American Society of Clinical Oncology 2006, 24(30):4882-4887.

89. Prinsen H, Bleijenberg G, Heijmen L, Zwarts MJ, Leer JW, Heerschap A, Hopman MT, van

Laarhoven HW: The role of physical acti vity and physical fi tness in postcancer fati gue: a

randomized controlled trial. Support Care Cancer 2013, 21(8):2279-2288.

90. Hafeman DM, Schwartz S: Opening the Black Box: a moti vati on for the assessment of

mediati on. Int J Epidemiol 2009, 38(3):838-845.

91. MacKinnon DP, Luecken LJ: How and for whom? Mediati on and moderati on in health

psychology. Health psychology : offi cial journal of the Division of Health Psychology,

American Psychological Associati on 2008, 27(2S):S99-S100.

92. Cerin E, Mackinnon DP: A commentary on current practi ce in mediati ng variable analyses

in behavioural nutriti on and physical acti vity. Public Health Nutr 2009, 12(8):1182-1188.

93. MacKinnon DP, Luecken LJ: Stati sti cal analysis for identi fying mediati ng variables in public

health denti stry interventi ons. J Public Health Dent 2011, 71 Suppl 1:S37-46.

94. Rogers LQ, Vicari S, Trammell R, Hopkins-Price P, Fogleman A, Spenner A, Rao K, Courneya

KS, Hoelzer KS, Robbs R et al: Biobehavioral factors mediate exercise eff ects on fati gue in

breast cancer survivors. Med Sci Sports Exerc 2014, 46(6):1077-1088.

95. Buff art LM, Ros WJ, Chinapaw MJ, Brug J, Knol DL, Korstjens I, van Weert E, Mesters I, van

den Borne B, Hoekstra-Weebers JE et al: Mediators of physical exercise for improvement in

cancer survivors’ quality of life. Psychooncology 2014, 23(3):330-338.

96. The World Health Organizati on Quality of Life Assessment (WHOQOL): development and

general psychometric properti es. Soc Sci Med 1998, 46(12):1569-1585.


General discussion

221

8

97. Schmidt ME, Semik J, Habermann N, Wiskemann J, Ulrich CM, Steindorf K: Cancer-related

fati gue shows a stable associati on with diurnal corti sol dysregulati on in breast cancer

pati ents. Brain Behav Immun 2016, 52:98-105.

98. Wratt en C, Kilmurray J, Nash S, Seldon M, Hamilton CS, O’Brien PC, Denham JW: Fati gue

during breast radiotherapy and its relati onship to biological factors. Int J Radiat Oncol Biol

Phys 2004, 59(1):160-167.

99. Bower JE: Cancer-related fati gue: links with infl ammati on in cancer pati ents and survivors.

Brain Behav Immun 2007, 21(7):863-871.

100. Schubert C, Hong S, Natarajan L, Mills PJ, Dimsdale JE: The associati on between fati gue and

infl ammatory marker levels in cancer pati ents: a quanti tati ve review. Brain Behav Immun

2007, 21(4):413-427.

101. Fairey AS, Courneya KS, Field CJ, Bell GJ, Jones LW, Marti n BS, Mackey JR: Eff ect of exercise

training on C-reacti ve protein in postmenopausal breast cancer survivors: a randomized

controlled trial. Brain Behav Immun 2005, 19(5):381-388.

102. Jones LW, Eves ND, Peddle CJ, Courneya KS, Haykowsky M, Kumar V, Winton TW, Reiman T:

Eff ects of presurgical exercise training on systemic infl ammatory markers among pati ents

with malignant lung lesions. Appl Physiol Nutr Metab 2009, 34(2):197-202.

103. Galvao DA, Taaff e DR, Spry N, Joseph D, Newton RU: Combined resistance and aerobic

exercise program reverses muscle loss in men undergoing androgen suppression therapy

for prostate cancer without bone metastases: a randomized controlled trial. J Clin Oncol

2010, 28(2):340-347.

104. Seruga B, Zhang H, Bernstein LJ, Tannock IF: Cytokines and their relati onship to the

symptoms and outcome of cancer. Nat Rev Cancer 2008, 8(11):887-899.

105. Courneya KS: Exercise guidelines for cancer survivors: are fi tness and quality-of-life benefi ts

enough to change practi ce? Curr Oncol 2017, 24(1):8-9.

106. Glasgow RE, Klesges LM, Dzewaltowski DA, Bull SS, Estabrooks P: The future of health

behavior change research: what is needed to improve translati on of research into health

promoti on practi ce? Annals of behavioral medicine : a publicati on of the Society of

Behavioral Medicine 2004, 27(1):3-12.


Chapter 8

222

107. Glasgow RE, Vogt TM, Boles SM: Evaluati ng the public health impact of health promoti on

interventi ons: the RE-AIM framework. Am J Public Health 1999, 89(9):1322-1327.

108. Kampshoff CS, Jansen F, van Mechelen W, May AM, Brug J, Chinapaw MJ, Buff art LM:

Determinants of exercise adherence and maintenance among cancer survivors: a

systemati c review. Int J Behav Nutr Phys Act 2014, 11:80.

109. Glanz K, Bishop DB: The role of behavioral science theory in development and

implementati on of public health interventi ons. Annu Rev Public Health 2010, 31:399-418.

110. Stacey FG, James EL, Chapman K, Courneya KS, Lubans DR: A systemati c review and meta-

analysis of social cogniti ve theory-based physical acti vity and/or nutriti on behavior change

interventi ons for cancer survivors. Journal of cancer survivorship : research and practi ce

2015, 9(2):305-338.

111. Abraham C, Michie S: A taxonomy of behavior change techniques used in interventi ons.

Health psychology : offi cial journal of the Division of Health Psychology, American

Psychological Associati on 2008, 27(3):379-387.

112. Michie S, Ashford S, Sniehott a FF, Dombrowski SU, Bishop A, French DP: A refi ned

taxonomy of behaviour change techniques to help people change their physical acti vity

and healthy eati ng behaviours: the CALO-RE taxonomy. Psychol Health 2011, 26(11):1479-

1498.

113. van Waart H, Stuiver MM, van Harten WH, Geleijn E, Kieff er JM, Buff art LM, de Maaker-

Berkhof M, Boven E, Schrama J, Geenen MM et al: Eff ect of Low-Intensity Physical Acti vity

and Moderate- to High-Intensity Physical Exercise During Adjuvant Chemotherapy on

Physical Fitness, Fati gue, and Chemotherapy Completi on Rates: Results of the PACES

Randomized Clinical Trial. J Clin Oncol 2015, 33(17):1918-1927.

114. Braamse AM, van Meijel B, Visser OJ, Boenink AD, Cuijpers P, Eelti nk CE, Hoogendoorn AW,

van Marwijk Kooy M, van Oppen P, Huijgens PC et al: A randomized clinical trial on the

eff ecti veness of an interventi on to treat psychological distress and improve quality of life

aft er autologous stem cell transplantati on. Annals of hematology 2016, 95(1):105-114.

115. van Waart H, van Harten WH, Buff art LM, Sonke GS, Stuiver MM, Aaronson NK: Why do

pati ents choose (not) to parti cipate in an exercise trial during adjuvant chemotherapy for

breast cancer? Psychooncology 2016, 25(8):964-970.


General discussion

223

8

116. Kampshoff CS, Van Dongen JM, Van Mechelen W, schep G, Vreugdenhil A, Twisk JWR,

Bosmans JE, Brug J, Chinapaw MJM, Buff art LM: Long-term eff ecti veness and cost-

eff ecti veness of high versus low-to-moderate intensity resistance and endurance exercise

among cancer survivors. 2018.

117. Carlson LE, Bultz BD: Effi cacy and medical cost off set of psychosocial interventi ons in

cancer care: making the case for economic analyses. Psychooncology 2004, 13(12):837-

849; discussion 850-836.

118. Jansen F, van Zwieten V, Coupe VM, Leemans CR, Verdonck-de Leeuw IM: A Review on

Cost-Eff ecti veness and Cost-Uti lity of Psychosocial Care in Cancer Pati ents. Asia-Pacifi c

journal of oncology nursing 2016, 3(2):125-136.

119. Dieng M, Cust AE, Kasparian NA, Mann GJ, Morton RL: Economic evaluati ons of

psychosocial interventi ons in cancer: a systemati c review. Psychooncology 2016,

25(12):1380-1392.

120. May AM, Bosch MJ, Velthuis MJ, van der Wall E, Steins Bisschop CN, Los M, Erdkamp F,

Bloemendal HJ, de Roos MA, Verhaar M et al: Cost-eff ecti veness analysis of an 18-week

exercise programme for pati ents with breast and colon cancer undergoing adjuvant

chemotherapy: the randomised PACT study. BMJ open 2017, 7(3):e012187.

121. Mewes JC, Steuten LM, Ijzerman MJ, van Harten WH: Eff ecti veness of multi dimensional

cancer survivor rehabilitati on and cost-eff ecti veness of cancer rehabilitati on in general: a

systemati c review. The oncologist 2012, 17(12):1581-1593.

122. Predicti ng Opti maL cAncer RehabIlitati on and Supporti ve care (POLARIS) study [htt p://

www.polaris-study.org/]

123. Griffi th LE, Shannon HS, Wells RP, Walter SD, Cole DC, Cote P, Frank J, Hogg-Johnson S,

Langlois LE: Individual parti cipant data meta-analysis of mechanical workplace risk factors

and low back pain. Am J Public Health 2012, 102(2):309-318.

124. Riley RD, Simmonds MC, Look MP: Evidence synthesis combining individual pati ent data

and aggregate data: a systemati c review identi fi ed current practi ce and possible methods.

Journal of clinical epidemiology 2007, 60(5):431-439.

125. Diamond CC, Mostashari F, Shirky C: Collecti ng and sharing data for populati on health: a

new paradigm. Health Aff (Millwood) 2009, 28(2):454-466.


Chapter 8

224

126. Wilkinson MD, Dumonti er M, Aalbersberg IJ, Appleton G, Axton M, Baak A, Blomberg N,

Boiten JW, da Silva Santos LB, Bourne PE et al: The FAIR Guiding Principles for scienti fi c

data management and stewardship. Sci Data 2016, 3:160018.


chapter 8 - research.vu.nl 8.pdfinterventi ons in which (part of) the weekly exercise sessions were...

Documents