Mind–body practices for cancer‑related symptoms management: an overview of systematic reviews including one hundred twenty‑nine meta‑analyses

1 MIND-BODY EXERCISES FOR CANCER RELATED SYMPTOMS MANAGEMENT: A SCOPING REVIEW INCLUDING ONE HUNDRED AND TWENTY-NINE META-ANALYZES María Jesús Casuso-Holgado PhD a,b; Alberto Marcos Heredia-Rizo PhD a,b; Paula Gonzalez-Garcia PhD a; María Jesús Muñoz-Fernández PhD b,c*; Javier Martinez-Calderon PhD a,b a Department of Physiotherapy, Faculty of Nursing, Physiotherapy and Podiatry, University of Seville, 41009 Seville, Spain. b Uncertainty, Mindfulness, Self, Spirituality (UMSS) Research Group, University of Seville, Seville, Spain. c Department of Physiotherapy, University School Francisco Maldonado, Avd. de los Cipreses s/n, 41640 Osuna, Spain. *Corresponding author. Department of Physiotherapy, University School Francisco Maldonado, Avd. de los Cipreses s/n, 41640 Osuna, Spain. Tlf.: +34 673481710 Email address: [email protected] Word count: 3247 RUNNING TITLE: Mindful exercises and cancer. Declarations of interest: none. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Availability of data and materials: Not applicable. Competing interests: Not applicable. Funding: Not applicable. Authors' contributions: MJMF is the guarantor and conceived the study. MJCH, MJMF and JMC wrote the first draft of the protocol and manuscript. MJMF, MJCH, and JMC conducted article screening. MJCH, JMC, AMHR, and PGG extracted data. MJCH, JMC, AMHR and PGG assisted in interpreting the data. MJCH and JMC conducted data analysis. All authors contributed importantly to the content and style of the protocol and manuscript. All authors approved the final version. Acknowledgements: Not applicable. 2 ABSTRACT Purpose: Mind-body exercises (e.g yoga, tai chi, qigong) are interesting approaches that combine physical movements, deep breathing, and mental strategies to improve the way people self-care. To summarize the available evidence supported by systematic reviews with meta-analysis on the effectiveness mindful exercises for symptoms management in adults with different cancer diagnoses. Methods: A scoping review was developed. CINHAL, EMBASE, PsycINFO, PubMed, and the Cochrane Plus Library were searched until March 2022. Cancer-related fatigue, pain, psychological factors, and overall quality of life were the outcomes of interest. The AMSTAR 2 tool was used to evaluate the methodological quality of each included review. Citation matrices and the corrected covered area were developed and calculated to explore the potential overlap between reviews. Results: A total of 38 systematic reviews including one hundred and twenty-nine meta-analyzes meeting our selection criteria were included. Some items of the AMSTAR 2 tool were poorly satisfied. The overlap was moderate for the qigong trials and high for both the tai chi trials and the yoga trials. Qigong may be an interesting approach to reduce cancer-related fatigue. Tai chi appears to produce great benefits in reducing anxiety. Yoga has been found to be superior to controls in improving overall quality of life and psychological factors such as anxiety, depression, distress, and stress. Conclusions: Qigong, tai chi, and yoga could be effective approaches to reduce concrete outcomes in people with cancer. Clinical and methodological considerations are discussed. Keywords: cancer; qigong; meta-analysis; systematic review; tai chi; yoga. 3 INTRODUCTION Cancer worldwide affects almost 20 million people every year [1]. Although its survival rates have improved in recent decades particularly when an early diagnosis is possible [1–3], many symptoms remain after interventions, causing chronicity emerge [4,5]. Physical and psychological problems provoke enormous suffering to cancer survivors [6–9], which affects the way they cope with daily activities, social and family relationships, and their own sense of being [10]. Cancer survivorship care plans should aim to include multimodal interventions that focus on improving biopsychosocial well-being and self-care skills [11–13]. Mindful exercises are an interesting approach to achieve it. These exercises combine physical movements, deep breathing, and mental strategies (e.g., meditation) to improve motivation [14], selfmanagement [15], self-states (e.g. self-efficacy) [16], and spiritual well-being [17]. Qigong, tai chi, and yoga are the most common mindful exercises in health research. These approaches have shown positive effects on brain health [18,19] in different populations and greater benefits in managing chronic symptoms [20–23]. Systematic reviews have been published evaluating whether these interventions are effective to improve outcomes in people with cancer [24–29]. However, no specific scoping or umbrella reviews have been conducted on this topic. This type of reviews present attractive content to summarize large amounts of evidence [30]. This design helps to achieve higher-level synthesis and recognize potential uncertainties, biases, and knowledge gaps [30]. This review aims to synthesize the available evidence on the effectiveness of qigong, tai chi, and yoga on cancer-related fatigue, pain, psychological factors, and overall quality of life in people with different cancer diagnoses. 4 METHODS This umbrella review followed the Preferred Reporting Items for Overviews of Systematic Reviews (PRIO- harms) [31]. The review protocol was prospectively registered on the Open Science Framework (OSF) registries (https://doi.org/10.17605/OSF.IO/9HUCR). Protocol Deviations Some information that was published in our review protocol was not included in this umbrella review: mean age and sex distribution. Consensus in the review selection process was only discussed with one researcher. Data Sources and Search Strategy One researcher (MJMF) searched the following electronic databases from inception until March 15, 2022: CINHAL, EMBASE, PsycINFO, PubMed, and the Cochrane Plus Library. Medical Subject Headings (MeSH) terms related to the intervention (e.g., qigong, tai chi, yoga) and condition (e.g., cancer, neoplasm) were combined to develop a comprehensive search strategy for each database. Another researcher (MJCH) manually checked the reference lists of similar overviews after our review selection process was completed. The detailed strategy search is found in Supplementary File A. Eligibility Criteria The PICO framework (Population, Intervention, Comparison, Outcome) [32] was followed to develop our eligibility criteria: Inclusion criteria Systematic reviews [33] written in English or Spanish with meta-analysis of at least two randomized controlled trials (RCTs) including: (P): Adults with any cancer diagnosis at any stage of treatment or disease. (I): Any qigong, tai chi, or yoga style. (C): There are no restrictions with respect to the control group. (O): Cancer-related fatigue, pain, psychological factors (e.g., anxiety), and overall quality of life. Only publications in peer review journals were included. Ethnicity, gender, or setting restrictions were not imposed. Exclusion Criteria Systematic reviews where their meta-analyzes did not separately evaluate qigong, tai chi, or yoga from other interventions (e.g., other types of exercises); cancer from other chronic disease; or randomized from 5 nonrandomized trials. Meta-analyzes based on indirect comparisons (network meta-analysis) were also excluded. Review Selection Duplicates were removed using the Mendeley desktop citation management software v1.19.8 and manually checked (MJCH). All records were screened by the same researcher based on title/abstract. Subsequently, the full texts of those studies that were potentially eligible or with unavailable abstracts were revised following our eligibility criteria. Consensus was reached with JMC, when necessary. Data extraction The following information was extracted from each review: first author and year of publication, implemented risk of bias tools, availability or not of the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach [34], RCTs that we selected in our umbrella from the included reviews, the number and diagnoses of participants, experimental and control groups, main findings (effects sizes). We tried to extract the information from meta-analyzes based on their overall effects. When a review did not report an overall effect or this did not satisfy our inclusion criteria, we decided to extract the information from subgroup analysis in the following order: time-point effects, health conditions, type of experimental group, type of control group. Methodological quality Two researchers (PGG, AMHR) independently used the AMSTAR-2 tool [35] to evaluate the methodological quality of the included reviews. This instrument is composed of 16 items that are rated as 'yes', 'no' or 'partial yes'. In this umbrella review, an overall confidence score was not built following the recommendations of the tool developers [35]. We considered the potential impact of an inadequate score of each item, particularly for those labeled as critical domains (items 2, 4, 7, 9, 11, 13, 15) [35]. Disagreements were resolved by consensus. Data Synthesis The available evidence was narratively synthesized according to the type of experimental group (qigong, tai chi, or yoga) and the outcomes of interest (cancer-related fatigue, pain, psychological factors, and overall quality of life). We also organized this information into three different data synthesis tables. Citation matrices were developed to calculate the “Corrected Covered Area” (CCA) [36] that is needed to detect the presence of potential overlap between the included reviews. The overlap can be slight (CCA<6%), moderate (6-10%), high (11-15%), and very high (CCA>15%) [36]. Finally, a co-occurrence analysis and 6 bibliometric mapping were performed with the software VOS Viewer v. 1.6.18 (www.vosviewer.com/), using the keywords reported by the included reviews through a complete counting method. This analysis aimed to identify the most relevant terms in all reviews. RESULTS The electronic databases retrieved 1,266 references. A total of 1,078 titles and abstracts were checked after removing duplicates. Finally, 124 full texts were evaluated, including 38 systematic reviews including one hundred and twenty-nine meta-analyses of our interest (Figure 1). The reasons for exclusion in the last screening process (n = 86) are listed Supplementary File B. Some meta-analyses were not included in our umbrella review. Supplementary file C lists the reason to exclude from this umbrella review some potential meta-analyzes that were performed in the included reviews. A total of six additional reviews were found during the manual search. Any of them met our inclusion criteria (Figure 1). A total of 134 original trials were retrieved from included reviews without double counting. Breast cancer was the most common diagnosis in all reviews. Yoga was often evaluated in the included reviews. The included reviews often used the Cochrane Risk of Bias Tool [37] to assess the risk of bias of their included trials. The GRADE approach was only applied for 18.42% of the included reviews to judge the overall certainty of the evidence. Co-occurrence Analysis The network and density visualizations found that some keywords were interrelated. The most common words were breast cancer, depression, fatigue, meta-analysis, qigong, quality of life, systematic review, tai chi, and yoga (Figures 2 and 3). Overlapping Included reviews returned 378 original trials. Of these, there were 134 trials without double counting. The overlap was moderate for the qigong trials (CCA = 9 %), high for both, the tai chi trials (CCA = 11%) and the yoga trials (CCA = 12%). Supplementary files D-F show all the citations matrices and the CCA calculations. AMSTAR 2 Rating The AMSTAR 2 tool found some concerns about the review protocol, how the review authors decided to include a determined research design, and the lack of information related to the excluded studies in the last 7 screening. Furthermore, information associated with the sources of funding was often unavailable for those clinical trials that were included in each review (Supplementary G). Qigong for Cancer Nine reviews [24,25,38–44] evaluated the effects of qigong on cancer (Table 1). Qigong and Cancer-related fatigue Qigong was often more effective than controls in improving cancer-related fatigue [25,38–40]. Only one review explored a specific cancer diagnosis, breast cancer [24], concluding that qigong was not more beneficial than controls. Mixed results were found in one review when findings were evaluated by subgroups of time-point effects [41]. Qigong and Anxiety Mixed cancer diagnoses were explored in four reviews [24,39,40,42]. No differences were often observed between groups [39,40,42]. Qigong and Depression Mixed cancer diagnoses were analyzed in five reviews [24,39–42]. Most reviews found no differences between groups [39–42]. Qigong and Stress Qigong was not better than controls in decreasing stress between mixed cancer diagnoses [40]. Qigong and Overall quality of life Two reviews showed positive effects of qigong on improving overall quality of life, including mixed cancer diagnoses [25,39]. However, qigong was not superior to controls in most reviews [40,42–44]. Tai Chi for Cancer Twelve reviews [26,27,42,43,45–52] analyzed the effects of tai chi on cancer (Table 2). Tai chi and Cancer-related fatigue Inconclusive findings were found. Three reviews concluded that tai chi was superior to controls in reducing cancer-related fatigue [42,47,48], while two reviews found no differences between groups [26,49]. A review observed the presence of mixed results when the findings were analyzed by subgroups of time-point effects [27]. Tai chi and Cancer-related pain 8 A review showed that tai chi was not superior to controls in decreasing pain in people with breast cancer [50]. Another review found mixed results when the findings were evaluated by subgroups of time-point effects in the same clinical condition [48]. Tai chi and Anxiety Tai chi was more beneficial than controls in reducing anxiety in people with breast cancer [48,51]. Tai chi and Depression Tai chi was more effective than controls in decreasing depression in people with mixed cancer diagnoses [52], but this effect was not maintained in reviews that specifically evaluated breast cancer participants [49,51]. Tai chi and Overall quality of life The effects of tai chi on overall quality of life were inconclusive. Three reviews showed positive effects in favor of tai chi [45,48,49], while four reviews found that this intervention was not superior to controls [43,46,50,52]. Yoga for Cancer Twenty-two reviews [28,29,42,44,45,53–69] analyzed the effects of yoga on cancer (Table 3). Yoga and Cancer-related fatigue Inconsistent results were found. Seven reviews showed positive effects in favor of yoga to reduce fatigue [28,53,65–69], while no differences were found between groups in seven reviews [42,44,54–58]. Two reviews observed mixed results when the findings were analyzed by subgroups of the type of control group or time-point effects [59,60]. Yoga and Cancer-related pain The effects of yoga on pain were inconsistent in people with breast cancer. One review found that yoga was superior to controls in reducing pain severity [66], but no differences between groups were observed in another review [56]. Yoga and Anxiety Most reviews showed that yoga was more effective than controls in reducing anxiety [29,42,53,56,57,61,66,69]. Only one review found no differences between groups [58]. Two reviews found mixed results when the results were assessed by subgroups of the type of control group or time-point effects [59,62]. Yoga and Depression 9 Yoga produced more benefits than controls in decreasing depression in most reviews [28,29,42,53,56,57,62,66,69]. Three reviews found no differences between groups [58,63,68]. Mixed results were observed when the analysis was performed by subgroups of the type of control group or timepoint effects [59,61]. Yoga and Distress Three reviews found positive effects in favor of yoga in decreasing distress [57,62,69]. Specifically, a review concluded that yoga was not superior to controls in people with breast cancer [58]. Another review showed mixed results when the findings were evaluated by subgroups of time-point effects [61]. Yoga and Stress Yoga was superior to controls in reducing stress in three reviews [57,62,66]. No differences between groups were found in one review [42]. A review showed mixed results when the analyzes were carried out by subgroup of time-point effects [61]. Yoga and Overall quality of life Seven reviews showed that yoga is superior to controls in improving overall quality of life [45,53,56,58,61,64,69], while no differences between groups were found in four reviews [28,42,44,57]. Mixed results were found when the findings were evaluated by subgroups of the type of control group or time-point effects [59,60]. DISCUSSION This umbrella review provided an overview of the effectiveness of qigong, tai chi, and yoga in modulating cancer-related fatigue, pain, psychological factors, and overall quality of life in adults with any type of cancer. Thirty-eight systematic reviews including one hundred and twenty-nine meta-analyzes were evaluated. In general, qigong, tai chi, and yoga were found to be beneficial in improving most of the outcomes of interest. Mostly, qigong was more effective than controls in reducing cancer-related fatigue in different types of cancer (e.g., breast, prostate, or colorectal). Tai chi could be more beneficial than controls in reducing anxiety in women with breast cancer. Yoga was shown to be superior to controls to improve overall quality of life and reduce negative psychological factors such as anxiety, depression, distress, and stress in people with different cancer diagnoses (e.g., breast, prostate, or lymphoma). Previous overviews have focused their efforts on exploring breast cancer [20,70–74]. This umbrella review supports previous findings that were observed for tai chi in reducing cancer-related fatigue [71] and for the 16 30. Ioannidis J. Next-generation systematic reviews: prospective meta-analysis, individual-level data, networks and umbrella reviews. Vol. 51, British journal of sports medicine. England; 2017. p. 1456–8. 31. Bougioukas KI, Liakos A, Tsapas A, Ntzani E, Haidich AB. Preferred reporting items for overviews of systematic reviews including harms checklist: a pilot tool to be used for balanced reporting of benefits and harms. 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Similarities, reliability and gaps in assessing the quality of conduct of systematic reviews using AMSTAR-2 and ROBIS: systematic survey of nutrition reviews. BMC Med Res Methodol. 2021 Nov;21(1):261. 22 23 Footnotes Contributorship: MJMF is the guarantor and conceived the study. MJCH, MJMF and JMC wrote the first draft of the protocol and manuscript. MJMF, MJCH, and JMC conducted article screening. MJCH, JMC, AMHR, and PGG extracted data. MJCH, JMC, AMHR and PGG assisted in interpreting the data. MJCH and JMC conducted data analysis. All authors contributed importantly to the content and style of the protocol and manuscript. All authors approved the final version. Acknowledgements: Not applicable. Funding: Not applicable. Competing interests: None declared. Provenance and peer review: Not commissioned; externally peer review. Supplemental material: This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise. 24 25 Figure 2. Network Visualization Cancer 32 Table 2. Included reviews: Tai Chi. Study and year Tools for quality assessment RCTs included in this umbrella Participants Interventions Effect sizes Cai et al. 2022 [51] GRADE Unavailable Risk of bias tool for individual trials The Cochrane risk of bias tool 5 586 with breast cancer diagnosis Experimental Mixed Tai Chi styles (e.g., Chen or Yang) Control Mixed controls (e.g., exercise or usual care) Ø Depression (SMD 95%CI): cancer subgroup -0.63 (-1.42 to 0.16) p = 0.12; I2 = 92% Ø Anxiety (SMD 95%CI): cancer subgroup -0.69 (-1.22 to -0.17) p = 0.009; I2 = 72% Chen et al. 2016 [52] GRADE Unavailable Risk of bias tool for individual trials The PEDro scale 4 279 with mixed cancer diagnoses (e.g., breast) Experimental Mixed Tai Chi styles (e.g., Yang) Control Mixed controls (e.g., education or spiritual growth) Ø General quality of life (SMD 95%CI): cancer subgroup -0.17 (-0.82 to 0.49) p = 0.62; I2 = 48% Ø Depression (SMD 95%CI): cancer subgroup -0.97 (-1.90 to -0.05) p = 0.04; I2 = 51% Duan et al. 2020 [42] GRADE Unavailable 3 222 with mixed cancer diagnoses (e.g., lung or prostate) Experimental (Tai Chi style unspecified) Ø Fatigue (SMD 95%CI): Tai Chi subgroup -0.95 (-1.48 to -0.43) p = 0.0004; I2 = 69% 33 Risk of bias tool for individual trials Based on the Cochrane Handbook Control Mixed controls (e.g., exercise or usual care) Lee et al. 2010 [46] GRADE Unavailable Risk of bias tool for individual trials Based on the Cochrane Handbook 2 50 with breast cancer diagnosis Experimental Mixed Tai Chi styles (e.g., Yang) Control Mixed controls (e.g., spiritual growth or supportive therapy) Ø General quality of life overall effect (SMD 95%CI) 0.45 (-0.25 to 1.14) p = 0.21; I2 = 0% Liu et al. 2020 [49] GRADE Unavailable Risk of bias tool for individual trials The PEDro scale 5 490 with breast cancer diagnosis Experimental Mixed Tai Chi styles (e.g., Chuan or Yang) Control Mixed controls (e.g., supportive therapy or usual care) Ø Fatigue (MD 95%CI): three months -0.46 (-1.09 to 0.17) p = 0.15; I2 = 0% Ø Fatigue (MD 95%CI): six months -0.16 (-0.98 to 0.67) p = 0.71; I2 = 0% Ø Depression (SMD 95%CI): three months 0.22 (-0.05 to 0.49) p = 0.12; I2 = 0% Ø Depression (SMD 95%CI): six months 0.16 (-0.15 to 0.47) p = 0.30; I2 = 0% Ø General quality of life (SMD 95%CI): three months 34 0.32 (0.07 to 0.56) p = 0.01; I2 = 67% Luo et al. 2020 [48] GRADE Available Risk of bias tool for individual trials The Cochrane risk of bias tool 10 736 with breast cancer diagnosis Experimental Mixed Tai Chi styles (e.g., Chuan or Yang) Control Mixed controls (e.g., supportive therapy or usual care) Ø Fatigue overall effect (SMD 95%CI) -1.11 (-1.53 to -0.69) p < 0.00001; I2 = 30% Ø Anxiety (MD 95%CI): 12 weeks -4.90 (-7.83 to -1.98) p = 0.001; I2 = 84% Ø Anxiety (MD 95%CI): 25 weeks -4.25 (-5.87 to -2.63) p < 0.00001; I2 = 0% Ø Pain (SMD 95%CI): three weeks 0.25 (-0.02 to 0.51) p = 0.07; I2 = 0% Ø Pain (SMD 95%CI): 12 weeks 0.30 (0.08 to 0.51) p = 0.007; I2 = 0% Ø General quality of life overall effect (SMD 95%CI) 0.37 (0.15 to 0.59) p = 0.001; I2 = 0% Ni et al. 2019 [26] GRADE Available 3 117 with mixed cancer diagnoses (e.g., breast or lung) Experimental Mixed Tai Chi styles Ø Fatigue overall effect (SMD 95%CI) -0.04 (-0.30 to 0.22) p = 0.76; I2 = 80% 35 Risk of bias tool for individual trials Based on the Cochrane Handbook (e.g., Yang) Control Mixed controls (e.g., sham Qigong or usual care) Pan et al. 2015 [50] GRADE Unavailable Risk of bias tool for individual trials Based on the Cochrane Handbook 5 196 with breast cancer diagnosis Experimental Mixed Tai Chi styles (e.g., Yang) Control Mixed controls (e.g., health education or usual care) Ø Pain overall effect (SMD 95%CI) -0.11 (-0.41 to 0.18) p = 0.78; I2 = 0% Ø General quality of life overall effect (SMD 95%CI) -0.12 (-0.59 to 0.35) p = 0.61; I2 = 53.7% Song et al. 2018 [27] * GRADE Unavailable Risk of bias tool for individual trials The Cochrane risk of bias tool 6 373 with mixed cancer diagnoses (e.g., breast or lung) Experimental (Tai Chi style unspecified) Control Mixed controls (e.g., exercise or health education) Ø Fatigue (SMD 95%CI): short term effects -0.54 (-0.75 to -0.33) p < 0.0001; I2 = 32% Ø Fatigue (SMD 95%CI): long term effects 0.23 (-0.61 to 1.08) p = 0.59; I2 = 89% Ø General quality of life (SMD 95%CI): Tai Chi subgroup 36 Tao et al. 2016 [43] GRADE Unavailable Risk of bias tool for individual trials Based on the Cochrane Handbook 3 162 with breast cancer diagnosis Experimental (Tai Chi style unspecified) Control Mixed controls (e.g., psychosocial therapy or usual care) -0.01 (-0.90 to 0.89) p = 0.99; I2 = 79% Xiang et al. 2017 [47] GRADE Available Risk of bias tool for individual trials The Cochrane risk of bias tool 3 221 with mixed cancer diagnoses (e.g., breast or lung) Experimental Mixed Tai Chi styles (e.g., Yang) Control Mixed controls (e.g., exercise or usual care) Ø Fatigue (SMD 95%CI): cancer subgroup -0.37 (-0.64 to -0.10) p = 0.006; I2 = 0% Zeng et al. 2014 b [45] GRADE Unavailable Risk of bias tool for individual trials The Cochrane risk of bias tool 2 50 with breast cancer diagnosis Experimental Unspecified Tai Chi styles Control Support therapy with or without exercise Ø General quality of life (SMD 95%CI): Tai Chi subgroup 1.97 (0.31 to 3.64) p = 0.02; I2 = 76% 37 Note: CI = confidence interval; GRADE = grading of recommendations, assessment, development, and evaluation; MD = mean difference; OR = odds ratio; RCT = randomized controlled trials; SMD = standardized mean difference. * See the original systematic review to understand how the authors classified outcomes by short-, medium-, or long-term effects. 38 Table 3. Included reviews: Yoga. Study and year Tools for quality assessment RCTs included in this umbrella Participants Interventions Effect sizes Armer et al. 2020 [28] GRADE Unavailable Risk of bias tool for individual trials A quality score was developed 29 1,828 with mixed cancer diagnoses (e.g., breast or prostate) Experimental Mixed Yoga styles (e.g., Hatha or Iyengar) Control Mixed controls (e.g., health education or waitlist) Ø Fatigue overall effect (Hedge’s g 95%CI): 0.45 (0.09 to 0.82) p = 0.013; I2 = 90.87% Ø Depression overall effect (Hedge’s g 95%CI): 0.72 (0.20 to 1.24) p = 0.007; I2 = 89.82% Ø General quality of life overall effect (Hedge’s g 95%CI): 1.08 (-1.92 to 4.07) p = 0.48; I2 = 99.75% Buffart et al. 2012 [69] GRADE Unavailable Risk of bias tool for individual trials A Delphi list 13 728 with mixed cancer diagnoses (e.g., breast or lymphoma) Experimental Mixed Yoga styles (e.g., Iyengar or Tibetan) Control Mixed controls (e.g., supportive therapy or waitlist) Ø Fatigue overall effect (SMD 95%CI): -0.51 (-0.79 to -0.22) p = 0.001; I2 = 43.52% Ø Depression overall effect (SMD 95%CI): -1.47 (-2.42 to -0.53) p = 0.002; I2 = 93.29% Ø Anxiety overall effect (SMD 95%CI): -1.25 (-1.93 to -0.56) p < 0.001; I2 = 91.45% Ø Distress overall effect (SMD 95%CI): -0.95 (-1.49 to -0.49) p < 0.001; I2 = 80.79% Ø General quality of life overall effect (SMD 95%CI): 39 0.88 (0.25 to 1.50) p = 0.006; I2 = 86.49% Cramer et al. 2012 [61] * GRADE Unavailable Risk of bias tool for individual trials The Cochrane risk of bias tool 9 669 with breast cancer diagnosis Experimental Mixed Yoga styles (e.g., Iyengar or Viniyoga) Control Mixed controls (e.g., supportive therapy or waitlist) Ø Depression (SMD 95%CI): short term effects -1.59 (-2.68 to -0.51) p = 0.004; I2 = 94% Ø Depression (SMD 95%CI): long term effects -0.36 (-0.80 to 0.07) p = 0.10; I2 = 4% Ø Anxiety (SMD 95%CI): short term effects -1.51 (-2.47 to -0.55) p = 0.002; I2 = 94% Ø Distress (SMD 95%CI): short term effects -0.86 (-1.50 to -0.22) p = 0.008; I2 = 88% Ø Distress (SMD 95%CI): long term effects -1.73 (-4.02 to 0.56) p = 0.14; I2 = 96% Ø Perceived stress (SMD 95%CI): short term effects -1.14 (-2.16 to -0.12) p = 0.03; I2 = 88% Ø Perceived stress (SMD 95%CI): long term effects -1.76 (-5.08 to 1.56) p = 0.30; I2 = 96% Ø General quality of life (SMD 95%CI): short term effects 0.62 (0.04 to 1.21) p = 0.04; I2 = 79% 40 Cramer et al. 2017 [59] * GRADE Available Risk of bias tool for individual trials The Cochrane risk of bias tool 21 1,775 with breast cancer diagnosis Experimental Mixed Yoga styles (e.g., Hatha or Iyengar) Control Mixed controls (e.g., supportive therapy or waitlist) Ø Fatigue (SMD 95%CI): short term effects (no treatment controls) -0.48 (-0.75 to -0.2) p = 0; I2 = 72.08% Ø Fatigue (SMD 95%CI): short term effects (psychological therapy controls) -0.9 (-1.31 to -0.5) p < 0.0001; I2 = 0% Ø Fatigue (SMD 95%CI): short term effects (exercise controls) -0.21 (-0.66 to 0.25) p = 0.37; I2 = 64.42% Ø Fatigue (SMD 95%CI): medium term effects (no treatment controls) -0.04 (-0.36 to 0.29) p = 0.82; I2 = 0% Ø Depression (SMD 95%CI): short term effects (no treatment controls) -0.13 (-0.31 to 0.05) p = 0.15; I2 = 0% Ø Depression (SMD 95%CI): short term effects (psychological therapy controls) -2.29 (-3.97 to -0.61) p = 0.01; I2 = 95.95% Ø Anxiety (SMD 95%CI): short term effects (no treatment controls) -0.53 (-1.1 to 0.04) p = 0.07; I2 = 82.92% 41 Ø Anxiety (SMD 95%CI): short term effects (psychological therapy controls) -2.21 (-3.9 to -0.52) p = 0.01; I2 = 95.27% Ø General quality of life (SMD 95%CI): short term effects (no treatment controls) 0.22 (0.04 to 0.4) p = 0.02; I2 = 18.68% Ø General quality of life (SMD 95%CI): short term effects (psychological therapy controls) 0.81 (-0.5 to 2.12) p = 0.23; I2 = 92.84% Ø General quality of life (SMD 95%CI): short term effects (exercise controls) -0.04 (-0.3 to 0.23) p = 0.79; I2 = 5.91% Ø General quality of life (SMD 95%CI): medium term effects (no treatment controls) 0.1 (-0.23 to 0.42) p = 0.56; I2 = 0% Dong et al. 2019 [65] GRADE Unavailable Risk of bias tool for individual trials 17 1,162 with breast cancer diagnosis Experimental Mixed Ypga styles (e.g., Hatha or Iyengar) Control Ø Fatigue overall score (SMD 95%CI): -0.31 (-0.52 to -0.10) p = 0.003; I2 = 81% 48 The Jadad scale Yi et al. 2021 [53] * GRADE Unavailable Risk of bias tool for individual trials The Cochrane risk of bias tool 7 693 with breast cancer diagnosis Experimental Mixed Yoga styles (e.g., Dru or Tibetan) Controls (unspecified) Ø Fatigue (SMD 95%CI): short term effects -0.62 (-1.17 to -0.07) p = 0.03; I2 = 86% Ø Depression overall effect (SMD 95%CI) -0.56 (-1.05 to -0.07) p = 0.03; I2 = 84% Ø Anxiety overall effect (SMD 95%CI) -0.50 (-0.70 to -0.31) p < 0.00001; I2 = 46% Ø General quality of life overall effect (MD 95%CI) 12.14 (8.88 to 15.40) p < 0.00001; I2 = 29% Zeng et al. 2014 b [45] GRADE Unavailable Risk of bias tool for individual trials The Cochrane risk of bias tool 2 172 with breast cancer diagnosis Experimental Unspecified Yoga styles Control Waitlist Ø General quality of life (SMD 95%CI): Yoga subgroup 0.42 (0.09 to 0.75) p = 0.01; I2 = 0% GRADE 6 Experimental Ø Fatigue overall effect (SMD 95%CI) 49 Zhang et al. 2012 [58] Unavailable Risk of bias tool for individual trials Based on the Cochrane Handbook 382 with breast cancer diagnosis Mixed Yoga styles (e.g., Hatha or Iyengar) Control Mixed controls (e.g., no intervention or waitlist) 0.11 (-0.12 to 0.35) p = 0.35; I2 = 0% Ø Depression overall effect (MD 95%CI) -4.12 (-13.05 to 4.81) p = 0.37; I2 = 59% Ø Anxiety overall effect (SMD 95%CI) -0.24 (-0.54 to 0.06) p = 0.11; I2 = 0% Ø Distress overall effect (SMD 95%CI) -3.05 (-8.63 to 2.53) p = 0.28; I2 = 98% Ø General quality of life overall effect (SMD 95%CI) 0.27 (0.02 to 0.52) p = 0.03; I2 = 0% Zuo et al. 2016 [62] * GRADE Unavailable Risk of bias tool for individual trials The Cochrane risk of bias tool 17 1,552 with breast cancer diagnosis Experimental Unspecified Yoga styles Control Mixed controls (e.g., health education or waitlist) Ø Anxiety (SMD 95%CI): immediate effects -0.42 (-0.57 to -0.26) p < 0.00001; I2 = 36% Ø Anxiety (SMD 95%CI): 3 months effects -0.16 (-0.55 to 0.23) p = 0.43; I2 = 0% Ø Depression (SMD 95%CI): immediate effects -0.77 (-0.89 to -0.65) p < 0.00001; I2 = 40% Ø Depression (SMD 95%CI): 3 months effects 50 -0.38 (-0.63 to -0.12) p = 0.004; I2 = 0% Ø Distress (SMD 95%CI): immediate effects -0.60 (-0.78 to -0.42) p < 0.00001; I2 = 12% Ø Perceived stress (SMD 95%CI): unspecified period effects -0.82 (-1.12 to -0.52) p < 0.00001; I2 = 36% Note: CI = confidence interval; GRADE = grading of recommendations, assessment, development, and evaluation; MD = mean difference; RCT = randomized controlled trials; SMD = standardized mean difference. * See the original systematic review to understand how the authors classified outcomes by short-, medium-, or long-term effects.