The effectiveness of sarcopenia interventions for cancer patients receiving chemotherapy: A systematic review and meta-analysis

Abstract

Background:

Among people with cancer undergoing chemotherapy, generalized loss of muscle mass, termed secondary sarcopenia, is associated with treatment toxicities and physical disability.

Objective:

This systematic review and meta-analysis aimed to provide an overview of current interventions for sarcopenia in cancer patients receiving chemotherapy and to assess potentially effective interventions.

Methods:

We searched PubMed, Scopus, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) Plus, and Embase for primary original research of exercise and nutrition interventions for sarcopenia published in English. The review used PRISMA guidelines. Standardized mean difference and 95% confidence interval (CI) were calculated as effect measures by applying the random effects model.

Results:

The six included studies showed a trend toward significantly increasing skeletal muscle mass after intervention (mean difference = 0.168, 95% CI −0.015–0.352, P = 0.072), with no significant changes in lean body mass loss after intervention (mean difference = −0.014, 95% CI −1.291–1.264, P = 0.983). Resistance exercise and combined exercise and nutrition intervention were more effective at preserving or increasing muscle mass.

Conclusions:

Early implementation of a resistance exercise intervention or a combined exercise and nutrition intervention is a promising strategy for avoiding muscle mass loss during chemotherapy. Additional evidence-based assessments of interventions for secondary sarcopenia are needed to identify the most effective approach.

Implications for Practice:

In clinical practice, oncology nurses should frequently assess cancer patients’ muscle mass, and when warranted, should implement the most feasible early sarcopenia intervention to minimize adverse outcomes of this condition.

Secondary sarcopenia has been receiving increased attention in oncology research and clinical settings.¹ While primary sarcopenia is typically associated with aging, secondary sarcopenia is described as generalized loss of muscle mass related to diseases such as cancer and may have minimal involvement of muscle function.^2,3 Recent data shows that preserving muscle significantly predicts lower treatment toxicities and complications during adjuvant chemotherapy.^4,5 In addition, low muscle mass negatively affects cancer-related symptoms, infection rates, lengths of hospitalization, and mortality risk.^6–9 Decreased muscle mass may increase vulnerability to malnutrition, endocrine changes, muscle disuse, and low-grade systemic inflammation,¹⁰ as well as reduce quality of life for people with cancer.⁷ One review study found that prevalence of low muscle mass in people with cancer ranged from 5% to 89%.¹⁰ Thus, loss of muscle mass represents a major oncological issue.

Various assessment methods exist for sarcopenia. One of the most commonly used methods defines sarcopenia as skeletal muscle mass index (SMI) of less than 52.4 cm²/m² for males and less than 38.5 cm²/m² for females.¹¹ Low SMI has been found to predict dose-limiting toxicities, an important consideration in clinical care in curative settings.^12–18 Given the critical nature and negative impacts of loss of muscle mass in cancer care, preservation of muscle mass through optimally effective interventions would be a powerful means of reducing chemotherapy toxicities and cancer-related complications and improving health and quality of life.

Exercise and nutrition interventions have been investigated as strategies for maintaining and increasing muscle mass and improving physical function in curative settings. For example, one study reported that an exercise and nutritional support intervention, which consisted of resistance training, walking, and recommended total daily intake of calories, protein, and oral supplementation, was associated with clinically relevant improvements in skeletal muscle mass and physical function and increased gait speed after the intervention.¹⁹ Resistance exercise in particular is known to be a promising strategy for improving muscle strength, body composition, and physical function, as well as quality of life, during and after cancer treatment.²⁰ For instance, a multicenter randomized controlled trial involving 242 breast cancer patients receiving adjuvant chemotherapy found that resistance exercise was related to significant improvement of lean body mass, muscle strength, and chemotherapy completion rate.²¹

Given that the prevalence of malnutrition among people undergoing cancer treatment is approximately 39%,²² nutritional intervention is also an important strategy for preserving muscle mass during cancer treatment. Cotogni et al. emphasized that malnutrition could be a predictor of physical performance status and quality of life among those receiving chemoradiotherapy and that health care providers need to be aware of the necessity for timely nutritional therapy.²³ Researchers have also called for greater evidence to support the effectiveness of nutrition interventions. Jang et al. noted that the efficacy of exercise and nutrition interventions for preserving skeletal muscle mass during chemotherapy requires further substantiation.²⁴ Therefore, although exercise and nutrition interventions may be advantageous for maintaining muscle mass and decreasing adverse treatment effects, a comprehensive examination of the evidence for their benefits in curative cancer treatment settings is needed.

The lack of standardized evidence of the effectiveness of interventions focusing on mitigating secondary sarcopenia is a current challenge in oncology. In fact, no standardized interventions have been recognized as effective in addressing muscle wasting.²⁵ In addition, few systematic reviews or meta-analyses have examined exercise and nutrition interventions for addressing sarcopenia in cancer patients or evaluated how such interventions might improve patient outcomes in curative settings. This study (a) provides an overview of the current interventions for preserving muscle mass or mitigating muscle mass loss in cancer patients receiving chemotherapy through a systematic review of the literature and (b) assesses potentially effective interventions by means of a meta-analysis.

Methods

Data sources and search strategy

This systematic review and meta-analysis was carried out in accordance with the Cochrane Handbook for Systematic Reviews of Interventions²⁶ and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed a comprehensive search for relevant publications using MEDLINE via PubMed, Scopus, CINAHL Plus with Full Text (Cumulative Index of Nursing and Allied Health Literature), and Embase. These databases employ different Medical Subject Heading (MeSH) terms, so we consulted with a research librarian and expert researchers about selecting MeSH terms and keywords likely to generate the most productive search results. The resulting general search terms were low muscle mass (or sarcopenia or skeletal muscle mass or muscular atrophy) AND exercise (or physical activity or diet or nutrition intervention) AND neoplasms (or cancer or oncology) AND chemotherapy. Figure 1 illustrates the results of the search strategy employed. With the search limited to published English-language articles, 396 studies were retrieved from the four databases. Two reviewers independently examined the studies’ titles and abstracts and then reviewed the full text of each relevant article. Following final selection of the studies to be included, the two reviewers evaluated the studies’ quality and extracted appropriate data.

Figure. 1. PRISMA flow diagram used in the identification and selection of studies.

Abbreviations: PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Study selection and inclusion criteria

The study eligibility criteria were as follows: (a) primary original research published in a peer-reviewed journal; (b) study sample consisting of cancer patients undergoing chemotherapy; (c) study including an exercise and/or nutrition intervention; and (d) English-language article published before the search date of October 2019. We excluded studies that (a) did not include an exercise and/or nutrition intervention focusing on cancer and low muscle mass; (b) were animal studies; (c) did not report original primary research (such as review papers); (d) focused on pharmacological or molecular studies; (e) focused on body weight, body fat, performance status, or physical function; (f) did not report values of change in skeletal muscle mass or lean body mass, and only showed figures or coefficient values; (g) focused on cancer survivors who had already completed cancer treatment; (h) only explained study protocols and did not report findings; or (i) focused on hormone therapy such as androgen therapy.

Study quality assessments of individual studies

We evaluated study quality using tools from the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH).²⁷ After considering the various study designs included in our review, we used three NIH quality assessment tools: Quality Assessment of Controlled Intervention Studies, Quality Assessment of Case-Control Studies, and Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group. Two independent reviewers carefully examined each included study for quality. NIH’s study quality assessment guidelines rate studies as good, fair, or poor. A rating of good quality indicates that a low risk of bias exists and that the study can be considered valid; a rating of fair quality indicates that the study may be susceptible to some bias; and a rating of poor quality indicates a high risk of bias. The two independent reviewers selected yes, no, or not applicable/not reported for each item of the quality assessment tool being applied. Quality assessment discrepancies were resolved by means of discussions among the authors.

Data extraction and analysis

For each of the included studies, we collected data on the sample and its characteristics, the intervention type and duration, and the measurements of muscle mass (primary outcome). To allow comparisons of study outcomes, effect sizes and 95% confidence intervals (CIs) were calculated using Stata. The heterogeneity of effect sizes was assessed using the I² statistic (the ratio of interstudy variance) and Cochran’s Q statistics. If an I² value exceeded 50% and the P value of x² was below 0.1, we concluded that there was substantial heterogeneity, based on the criteria suggested in the Cochrane Handbook for Systematic Reviews of Interventions.²⁶ To estimate mean intervention-related differences for parallel group analysis, we used the muscle mass change values reported across the studies. We then used a random effects model to estimate overall intervention effects. Between-study heterogeneity was assessed by visually inspecting forest plots generated from study data.

Given the various definitions and body composition measurement methods used to evaluate secondary sarcopenia across the studies, we measured the effectiveness of each sarcopenia intervention through changes in skeletal muscle mass and/or lean body mass before and after the intervention using the index of muscle mass change (e.g., SMI or lean body mass) that was measured and reported in each article. To identify intervention-specific differences in muscle mass change, we applied a subgroup meta-analysis to explore the heterogeneity of the studies. Meta-analysis of even a small number of studies can generate meaningful findings and achieve strong statistical power.²⁸

To identify potential publication bias with regard to estimates of intervention effects for individual studies against the measure of each study’s effect size,²⁶ a funnel plot analysis was completed. The funnel plots provided a scatter plot of the intervention effects of the included studies. We applied two funnel plots for effects of sarcopenia interventions on skeletal muscle mass and lean body mass changes during cancer treatment. An asymmetric pattern indicates high risk of publication bias, whereas a symmetric pattern indicates low risk.

Results

Characteristics of included studies

Of the 396 studies retrieved and evaluated, six peer-reviewed journal articles that focused on exercise and/or nutrition interventions for sarcopenia were selected for analysis (Figure 1). The Table summarizes the six studies reviewed. Four cancer types were involved: breast cancer was the most common (n = 3, 50%), while gastric cancer, cervical cancer, and combined advanced pancreatic and non-small cell lung cancer were each represented in a single study. Participants’ mean age was 53.44 years, and the intervention times varied from 3 weeks to 6 months. Four studies had combined exercise and nutrition interventions, one study focused only on exercise, and one focused only on nutritional supplementation. Three of the studies were randomized controlled trials, two were case-control designs, and one was a prospective single-arm study. Following the study quality assessments, using the NIH tools, we rated five studies (83.3%) as good.^{19, 30–33} One study (16.7%)—the Denmark et al. study²⁹ —did not provide an explanation to fully justify the sample size and research approach and was assessed as being of fair quality rather than good.

Table.

Summary of Reviewed Articles (N = 6)

Author (Year) / Country	Cancer type / Ethnicity (n)	Sample / Group(s) (n)	Study design	Intervention types	Body composition measure / Additional measures	Body composition mean (SD or SE) before intervention	Body composition mean (SD or SE) after intervention / (Target duration)
Demark-Wahnefried et al29 (2002) US	Breast cancer US White (9)	T: 45 Groups: 1) E (9) 2) C (36)	Case control	1) E: clinically based exercise program promoting strength training (lower extremities 2–3 days per week), aerobic activity (15–60 minutes 3–5 days per week), and healthful diet (low fat, calcium adequate, high vegetable and fruit) 2) C: No intervention	DXA / 6 min walk test, 1 rep maximum seated leg press, height & weight	Lean body mass (kg) E: 43.1 (1.8) C: 45.4 (5.0)	Lean body mass (kg) E: 43.2 (2.2) C: 45.1 (0.8) (6 months)
Demark-Wahnefried et al30 (2008) US	Breast cancer US White (85) US Black (12) US Other (3)	T: 90 Groups: 1) CA (29) 2) CA+EX (29) 3) CA+EX+FVLF (32)	RCT: 1 attention control arm, 2 experimental arms	1) CA: intakes of 1200–1500 mg calcium 2) CA+EX: CA + aerobic exercise ≥ 30 minutes per day ≥ 3 times per week and strength-training exercises every other day 3) CA+EX+FVLF: CA + EX + high fruit and vegetable, low-fat diet; goal of ≤ 20% of energy from fat and ≥ 5 servings of fruits and vegetables per day	DXA / Diet History Questionnaire, Longitudinal Study Physical Activity Questionnaire, Hospital Anxiety and Depression Scale, Functional Assessment of Cancer Therapy–Breast Cancer (for quality of life)	Total lean mass (kg) CA: 42.51 (6.61) CA+EX: 41.06 (7.08) CA+EX+FVLF: 41.57 (5.68)	Total lean mass (kg) CA: 43.2 (7.42) CA+EX: 40.62 (7.08) CA+EX+FVLF: 41.28 (7.04) (6 months)
Adams et al31 (2016) Canada	Breast cancer Canadian (200)	T: 200 Groups: 1) AET (64) 2) RET (66) 3) UC (70)	RCT: 3 arms	1) AET: 60 mins (15 mins at 60% of VO2peak and 45 mins at 80% of VO2peak) of either treadmill, cycle ergometer, or elliptical-based exercise 2) RET: 2 sets of 8–12 repetitions of 9 exercises, performed between 60% and 70% of their predicted single-repetition maximum and progressed throughout the intervention period 3) UC: avoid beginning any new exercise	DXA / Patient-reported outcomes (quality of life, physical function, fatigue)	SMI (kg/m2) RET: 14.93 (1.6) AET: 15.31 (1.8) UC: 15.26 (1.7)	SMI (kg/m2) RET: 15.29 (1.6) AET: 15.52 (2.0) UC:15.29 (1.7) (4 weeks)
Yamamoto et al19 (2017) Japan	Gastric cancer Japanese (90)	T: 90 Groups: 1) Sarcopenia (22) 2) Non-sarcopenia (68)	Case-control study	1) Sarcopenia: resistance training: hand grip (10 kg, 20 reps), walking (1 hr); nutritional support: ≥ 28 kcal/IBW of energy, ≥ 1.2 g/IBW of protein, oral supplementation with 2.4 g HMB 2) Non-sarcopenia: No intervention	Bioimpedance analysis / 4 m gait speed and hand grip strength testing	SMI (kg/m2) / lean body mass (kg) Group of ≤ 3 wks (n = 14): 6.2 (0.5) / 39.1 (4.3) Group of > 3 wks (n = 8): 5.9 (0.9) / 37.5 (7.2)	SMI (kg/m2) / lean body mass (kg) Group of ≤ 3 wks (n = 14): 6.3 (0.6) / 38.8 (4.2) Group of > 3 wks (n = 8): 6.2 (0.9) / 38.4 (7.3) (median 16 days)
Aredes et al32 (2019) Brazil	Cervical cancer Brazilian (40)	T: 40 Groups: 1) E (20) 2) C (20)	Randomized triple-blind clinical trial	1) E: 4 capsules of ω−3 fatty acids (2.5 g/day), containing 2 g EPA and 450 mg DHA 2) C: 4 identical-looking capsules containing olive oil Both groups also received an oral isocaloric nutritional supplement in powder form, containing an additional 430 kcal and 16 g of protein per day	CT / Anthropometry / Patient-Generated Subjective Global Assessment, Common Toxicity Criteria for Adverse Events, plasma long-chain polyunsaturated fatty acids	SMI (cm2/m2) E: 45.11 (6.15) C: 44.60 (8.11) High-compliance group (≥80%): E: 45.34 (5.33) C: 45.84 (8.45)	SMI (cm2/m2) E: 41.67 (6.53) C: 41.44 (7.01) High compliance group (≥80%): E: 45.34 (5.33) C: 45.84 (8.45) (45 days)
Naito et al33 (2019) Japan	Advanced pancreatic and non-small cell lung cancer Japanese (30)	T: 30 (single-arm study)	Prospective single-arm study	Combined exercise and nutritional intervention: Exercise: combined home-based low-intensity resistance training and counseling to promote physical activity Nutrition: standard nutritional counseling and instruction on how to manage symptoms (appetite and oral intake); supplements rich in branched-chain amino acids provided (1 pack of Inner Power (139 kcal/125 g) per day for 8 weeks; contains branched-chain amino acids (2500 mg), coenzyme Q10 (30 mg), and L-carnitine (50 mg)	CT / 6 min walk distance, 5 m gait speed, hand grip strength, 5x sit-to-stand test, exercise diary collection, physical activity measurement, physical activity interview, Food intake, nutritional status (Mini Nutritional Assessment), nutritional checklist, diet diary collection	SMI (cm2/m2) 40.7 (1.0)	SMI (cm2/m2) 39.6 (0.5) (8 ± 4 weeks)

Abbreviations: AET, aerobic exercise training; C, control group; CA, calcium-rich diet; DHA, docosahexaenoic acid; DXA, dual-energy X-ray absorptiometry; E, experimental group; EX, exercise; EPA, eicosapentaenoic acid; FVLF, high fruit and vegetable, low-fat diet; HMB, leucine metabolite β-hydroxy-β-methylbutyrate; hr, hours; IBW, ideal body weight; min, minutes; RCT, randomized controlled trial; RET, resistance exercise training; T, total; UC, usual care; VO2peak, peak oxygen uptake.

Effectiveness of interventions related to change in skeletal muscle mass index

The results of the meta-analyses for each dependent variable (SMI as skeletal muscle mass and/or lean body mass) are shown in Figure 2. For SMI change before and after a particular intervention, we did not find statistically significant heterogeneity (I² = 33.7%, Q = 7.54, P = 0.183).

Figure 2.

Results of random-effects meta-analysis of effects of sarcopenia interventions on muscle mass change during cancer treatment.

Because the studies discussed conceptually different, non-homogenous intervention groups, such as resistance exercise versus ω−3 fatty acid supplementation, we used a random effects model instead of a fixed model and constructed forest plots for each outcome using the mean effect size measured. The summary mean difference in SMI across four studies with six intervention groups (total of 196 participants with cancer undergoing chemotherapy) revealed a trend toward significantly increasing skeletal muscle mass (mean difference in SMI = 0.168, 95% CI −0.015–0.352, P = 0.072), with SMI being maintained after intervention. The effect sizes of the interventions on sarcopenia ranged from −2.75 to 0.36. In a funnel plot analysis, an asymmetric pattern was observed, with two studies falling on the left side rather than in the middle (Figure 3). The estimated heterogeneity variance between studies (P = 0.045) showed publication bias (Figure 3). Because the study of ω−3 fatty acid supplementation³² had a different intervention type than any of the other studies and was an outlier in Figure 3, we conducted an additional meta-analysis excluding the ω−3 supplementation study. This meta-analysis, using only three studies with five intervention groups (181 participants), found that skeletal muscle mass was significantly increased following the interventions (mean difference in SMI = 0.182, 95% CI −0.002–0.366, P = 0.052).

Figure 3.

Funnel plot for effects of sarcopenia interventions on muscle mass change during cancer treatment.

Effectiveness of interventions related to change in lean body mass

For change in lean body mass before and after the intervention (see Figure 2), we also did not find statistically significant heterogeneity (I² = 0%, Q = 0.47, P = 0.924). In Figure 2, a forest plot using lean body mass presents the mean effect size. The summary mean difference in lean body mass, derived from two studies with four intervention groups and a total of 91 participants, revealed no significant change (mean difference in lean body mass = −0.014, 95% CI −1.291–1.264, P = 0.983). The effect sizes of the two studies, which evaluated the effects of exercise and/or nutritional support on sarcopenia, ranged from −0.440 to 0.690. In a funnel plot analysis, a symmetric pattern was observed, and all four intervention groups were in the middle (Figure 3).

Discussion

The most important findings from this review are that skeletal muscle mass and lean body mass did not significantly change after the interventions, despite the fact that participants were undergoing cancer treatment. Considering that a recent meta-analysis involving 2,662 cancer patients showed a significant average SMI loss during chemotherapy,²⁴ this review’s findings are encouraging with regard to the effectiveness of resistance exercise, either alone or combined with nutrition interventions, for reducing muscle mass loss in oncology practice. The intervention using nutritional supplementation alone did not demonstrate effectiveness.

Despite the fact that sarcopenia is known to be an important predictor of postoperative complications and overall survival during curative cancer treatment,^34–36 study findings regarding the condition remain controversial because of the lack of consensus regarding its definition and appropriate intervention strategies. Many past oncology studies have used the term sarcopenia, but generally have not made a distinction between what is now understood as primary versus secondary sarcopenia.³⁷ Secondary sarcopenia is now defined as loss of muscle mass—but not necessarily loss of muscle function—related to diseases such as cancer. Future oncology studies should employ precise terminology to help reach a consensus on the definition. In addition, because secondary sarcopenia can be affected by various disease-related factors,^2,3 it is advisable to clinically define what constitutes a high-risk group for this condition in oncological settings and manage such groups using a preliminary intervention that is preventive of sarcopenia. Accordingly, guidelines for managing clinically significant muscle loss are urgently needed to support oncology care.

Among the various types of interventions examined in our review, resistance training exercise showed a higher effect size in preserving SMI than other interventions for cancer patients undergoing treatment. Adams et al. employed a three-arm randomized controlled trial design that included aerobic exercise, resistance exercise, and usual care, and found that resistance exercise showed significant effectiveness in reversing sarcopenia compared to either aerobic exercise or usual care.³¹ The same study found sarcopenia to be related to lower quality of life among breast cancer patients initiating adjuvant chemotherapy, and the reversal of sarcopenia to be related to clinically meaningful improvements in quality of life. The researchers noted that few intervention studies have focused specifically on treating sarcopenia in cancer patients who are undergoing treatment.³¹ The conclusion is that, given the importance of preserving muscle mass in cancer patients undergoing treatment to reduce toxicity and maintain quality of life, resistance training should be implemented in the early stages of treatment.

Our review findings also reveal the importance of combining exercise and nutrition interventions. Compared to three interventions that combined exercise and nutrition, a nutrition-only intervention that involved ω−3 fatty acid supplementation showed the lowest effect size in preserving SMI (−2.75).³² The ω−3 supplementation used in that intervention had previously been found to positively affect skeletal muscle health,^38,39 and the intervention study itself showed the efficacy of ω−3 fatty acid supplementation for maintaining skeletal muscle quality and nutritional status as well as reducing chemoradiotherapy toxicities. However, our review shows that combined interventions should be considered a more effective strategy for preserving muscle mass. Recently, Bauer et al. suggested that resistance exercise combined with a protein intake of 1 to 1.5 g/kg/day would be reasonable for managing sarcopenia; in particular, they noted that the presence of secondary sarcopenia requires appropriate treatment of the underlying disease.² Future oncological studies of interventions involving combinations of protein intake with resistance exercise will need to precisely identify the interventions’ effects on retaining and building muscle mass.

Our review also indicates the importance of both intervention duration and high intervention compliance on maintenance of lean muscle mass. In Yamamoto et al.’s study, participants who completed more than 3 weeks of a combined exercise and nutritional support intervention showed significant increases in lean body mass (2.5 kg), whereas those who participated for less than 3 weeks lost lean body mass (−0.6 kg).¹⁹ Regarding intervention compliance, Aredes et al.’s study of prescribed fatty acid supplement capsules found that participants with cervical cancer who had high compliance (over 80%) showed lower SMI loss (−2.76 cm²/m²) compared to the total intervention group (−3.43 cm²/m²).³² In other words, combined exercise and nutrition interventions with durations greater than 3 weeks and consistent attendance showed the best outcomes.

Our review also generated interesting findings regarding change in muscle mass. We note that although some interventions contributed to maintaining or increasing muscle mass during cancer treatment, no significant differences in SMI or lean body mass were observed. To be specific, Naito et al. identified no significant differences in skeletal muscle mass after an 8-week resistance training and nutrition intervention.³³ In Demark-Wahnefried et al.’s study involving breast cancer patients receiving adjuvant chemotherapy, the intervention group receiving exercise, a low-fat diet, and a calcium-rich diet showed a significantly lower percentage of body fat at the 6-month follow-up, but the change in lean body mass was not significant over time.³⁰ However, findings that the intervention group showed no significant reduction in muscle mass and that the control group showed greater lean body mass loss than the intervention group suggest that the intervention helped to prevent loss of muscle mass.²⁹

Overall, we found that four studies showed muscle mass increases^{19, 29–31} and that the interventions in all six studies helped to either increase muscle mass, maintain muscle mass, or lessen muscle mass loss compared to the control groups. In addition, although SMI changes were not statistically significant, we did find changes in other body composition parameters, such as body fat. We recommend that future studies evaluate how body composition changes during exercise and/or nutrition interventions and the relationships among changes in body fat, lean body mass, and SMI over time.

Lastly, our findings suggest that cancer type and related cancer treatment may play important roles in muscle mass change. Naito et al. employed a combined exercise and nutrition intervention for people with advanced pancreatic cancer and non-small cell lung cancer, but the effect size of SMI was −1.10, ranging from −3.06 to 0.86.³³ People with non-small cell lung cancer often show the highest prevalence of sarcopenia before treatment,⁴⁰ and given that lung cancer patients with sarcopenia show low functional status and overall survival,⁴¹ cancer type and initial lean muscle mass status may be related to intervention effectiveness. Findings were different in the two studies involving people with breast cancer,^29,30 which showed no significant lean body mass loss after the interventions. In a study that compared loss of SMI among patients with different cancer types, breast cancer patients were found to experience lower SMI loss compared to patients with rectal, prostate gland, lung, and colon cancer.⁴² Further research is needed to determine differences in SMI change following a given intervention among people with different types of cancer and different cancer treatments.

Limitations

This study has several limitations that should be considered when interpreting the results and planning future studies. First, we found only six relevant articles during the systematic review process, and they had small sample sizes (ranging from 30 to 200). The small number of included studies limits our understanding of intervention effectiveness. However, meta-analysis of even a small number of studies can generate meaningful findings,²⁸ thus we performed a meta-analysis to compare the effectiveness of the six interventions. Another limitation is that the six included studies varied considerably in terms of cancer and treatment types; research designs; intervention types, intensity and duration of the interventions; and methods of measuring muscle mass. These variations may affect the effect size of our review’s muscle mass findings, which should be interpreted with consideration of the circumstances and multiple factors of each study. To reach general conclusions about the effectiveness of interventions to maintain and reduce muscle mass loss, further randomized controlled trials involving participants with various cancer types will be required.

Implications for Nursing

The study findings contribute to better understanding of the general efficacy of existing interventions for secondary sarcopenia. Furthermore, with respect to oncology practice and research, the findings provide direction for future management of muscle mass loss to mitigate treatment toxicity and improve survivorship care. First, our observations suggest that clinical assessment instruments need to be developed or adapted specifically for cancer patients with sarcopenia. In addition, our results indicate that oncology nurse clinicians and physicians need to carefully assess cancer patients’ muscle mass before, during, and after chemotherapy; moreover, they need to support the most effective early sarcopenia intervention (i.e., a resistance exercise or combined exercise and nutrition intervention) to decrease adverse outcomes and improve quality of cancer care. However, given cancer patients’ physical condition, the safety of particular sarcopenia interventions should be considered to determine whether it is actually feasible to apply them. As a final point, oncology nurses and researchers need to bear in mind that although exercise and nutrition interventions are advantageous for maintaining muscle mass and decreasing adverse treatment effects, the evidence of their benefits in curative cancer treatment settings needs to be comprehensively examined. Further studies are needed to identify optimal combinations of interventions with consideration of intervention type, intensity, frequency, duration, and effectiveness in preserving muscle mass.

Conclusion

This systematic review and meta-analysis contributes up-to-date information about the effectiveness of exercise and nutrition interventions intended to preserve muscle mass in people who are undergoing cancer treatment. Early implementation of a resistance exercise intervention or a combined exercise and nutrition intervention is a promising strategy for avoiding muscle mass loss during treatment and for supporting cancer care. However, additional evidence-based assessment of interventions for secondary sarcopenia are needed to identify the most effective approach. The ultimate goal is to determine optimal methods of preserving muscle mass during cancer treatment in order to reduce chemotherapy toxicity and improve the quality of cancer care.