# Pre-Therapeutic Sarcopenia among Cancer Patients: An Up-to-Date Meta-Analysis of Prevalence and Predictive Value during Cancer Treatment

Anne-Laure Couderc, Evelyne Liuu, Pascaline Boudou-Rouquette, Johanne Poisson, Maxime Frelaut, Coline Montégut, Soraya Mebarki, Romain Geiss, Zoé Ap Thomas, Aurélien Noret, et al.

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Anne-Laure Couderc, Evelyne Liuu, Pascaline Boudou-Rouquette, Johanne Poisson, Maxime Frelaut, et al. Pre-Therapeutic Sarcopenia among Cancer Patients: An Up-to-Date Meta-Analysis of Prevalence and Predictive Value during Cancer Treatment. Nutrients, 2023, 15 (5), pp.1193. 10.3390/nu15051193. [hal-04092423](https://hal-04092423)

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Systematic Review

# Pre-Therapeutic Sarcopenia among Cancer Patients: An Up-to-Date Meta-Analysis of Prevalence and Predictive Value during Cancer Treatment

Anne-Laure Couderc<sup>1,2,†,‡ ID</sup>, Evelyne Liuu<sup>3,4,†,‡ ID</sup>, Pascaline Boudou-Rouquette<sup>5,6,‡ ID</sup>, Johanne Poisson<sup>7,8</sup>, Maxime Frelaut<sup>9,‡</sup>, Coline Montégut<sup>1,10,‡</sup>, Soraya Mebarki<sup>7,‡</sup>, Romain Geiss<sup>11,‡</sup>, Zoé ap Thomas<sup>12 ID</sup>, Aurélien Noret<sup>7</sup>, Monica Pierro<sup>7</sup>, Capucine Baldini<sup>13,‡ ID</sup>, Elena Paillaud<sup>7,14,‡,§ ID</sup> and Frédéric Pamoukdjian<sup>15,16,*‡,§ ID</sup>

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**Citation:** Couderc, A.-L.; Liuu, E.; Boudou-Rouquette, P.; Poisson, J.; Frelaut, M.; Montégut, C.; Mebarki, S.; Geiss, R.; ap Thomas, Z.; Noret, A.; et al. Pre-Therapeutic Sarcopenia among Cancer Patients: An Up-to-Date Meta-Analysis of Prevalence and Predictive Value during Cancer Treatment. *Nutrients* **2023**, *15*, 1193. https://doi.org/10.3390/nu15051193

Academic Editor: Line Merethe Oldervoll

Received: 3 February 2023

Revised: 18 February 2023

Accepted: 21 February 2023

Published: 27 February 2023

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**Copyright:** © 2023 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).

¹ Internal Medicine Geriatrics and Therapeutic Unit, APHM, 13009 Marseille, France

2 CNRS, EFS, ADES, Aix-Marseille University, 13015 Marseille, France

3 Department of Geriatrics, CHU Poitiers, 86000 Poitiers, France

4 CIC1402 INSERM Unit, Poitiers University Hospital, 86000 Poitiers, France

5 Ariane Program, Department of Medical Oncology, Cochin Hospital, Paris Cancer Institute CARPEM, APHP, 75014 Paris, France

6 INSERM U1016-CNRS UMR8104, Cochin Institute, Paris Cancer Institute CARPEM, Paris Cité University, 75015 Paris, France

7 Department of Geriatrics, Georges Pompidou European Hospital, Paris Cancer Institute CARPEM, APHP, 75015 Paris, France

8 Faculty of Health, Paris Cité University, 75006 Paris, France

9 Department of Medical Oncology, Gustave Roussy Institute, 94805 Villejuif, France

10 Coordination Unit for Geriatric Oncology (UCOG), PACA West, 13009 Marseille, France

11 Department of Medical Oncology, Curie Institute, 92210 Saint-Cloud, France

12 Department of Cancer Medicine, Gustave Roussy Institute, 94805 Villejuif, France

13 Drug Development Department, Gustave Roussy Institute, 94805 Villejuif, France

14 INSERM, IMRB, Clinical, Epidemiology and Ageing, Université Paris-Est Creteil, 94010 Creteil, France

15 Department of Geriatrics, Avicenne Hospital, APHP, 93000 Bobigny, France

16 INSERM UMR_S942 Cardiovascular Markers in Stressed Conditions MASCOT, Sorbonne Paris Nord University, 93000 Bobigny, France

* Correspondence: frederic.pamoukdjian@aphp.fr

† These authors contributed equally to this work.

‡ Current address: French Society of Geriatric Oncology (SoFOG), F-63122 Ceyrat, France.

§ These authors contributed equally to this work.

**Abstract:** This study will address the prevalence of pre-therapeutic sarcopenia (PS) and its clinical impact during cancer treatment among adult cancer patients ≥ 18 years of age. A meta-analysis (MA) with random-effect models was performed via a MEDLINE systematic review, according to the PRISMA statement, focusing on articles published before February 2022 that reported observational studies and clinical trials on the prevalence of PS and the following outcomes: overall survival (OS), progression-free survival (PFS), post-operative complications (POC), toxicities (TOX), and nosocomial infections (NI). A total of 65,936 patients (mean age: 45.7–85 y) with various cancer sites and extensions and various treatment modes were included. Mainly defined by CT scan-based loss of muscle mass only, the pooled prevalence of PS was 38.0%. The pooled relative risks were 1.97, 1.76, 2.70, 1.47, and 1.76 for OS, PFS, POC, TOX, and NI, respectively (moderate-to-high heterogeneity, I²: 58–85%). Consensus-based algorithm definitions of sarcopenia, integrating low muscle mass and low levels of muscular strength and/or physical performance, lowered the prevalence (22%) and heterogeneity (I² < 50%). They also increased the predictive values with RRs ranging from 2.31 (OS) to 3.52 (POC). PS among cancer patients is prevalent and strongly associated with poor outcomes during cancer treatment, especially when considering a consensus-based algorithm approach.

**Keywords:** sarcopenia; cancer; prevalence; risk factor; survival; post-operative complications; toxicities; hospital-acquired infections; disability
# 1. Introduction

Since its first definition, introduced in 1989 as an age-associated loss of muscle mass, the definition of sarcopenia has been gradually refined [1]. In 2010, 2011, and 2014, the European Working Group On Sarcopenia (namely EWGOS 1), the International Working Group on Sarcopenia (IWGS), and the Asian Working Group on Sarcopenia (AWGS 1) agreed to define sarcopenia as a syndrome characterized by an age-related loss of skeletal muscle mass (quantitatively assessed by the skeletal muscle index (SMI) or appendicular skeletal muscle mass (ASM) using CT scan, and bioelectrical impedance analysis (BIA) or dual-energy X-ray absorptiometry (DXA) methods), and by loss of function (loss of muscle strength and/or physical performance) using a screening-based approach targeting gait speed measurement [2–4]. In 2019, the AWGS updated the threshold values of the operational criteria (then termed AWGS 2). The EWGOS definition was also updated (EWGOS 2), now defining sarcopenia as a muscle disease characterized by the association of low levels of muscle strength (handgrip strength) and low muscle mass, with low physical performance (typically slow gait speed) becoming an indicator of severity [5,6]. In addition, the condition does not affect solely older adults ≥65 years and it has now been recognized that sarcopenia can begin earlier in life. In particular, sarcopenia is considered as primary or age-related, and as secondary when a specific cause (mainly driven by inflammatory processes) is evidenced (Table A1).

Cancer is frequently considered to be a major cause of secondary sarcopenia. In our previous systematic review including 35 observational studies or clinical trials and 6894 patients with cancer before 2016, sarcopenia concerned 38.6% of patients before cancer treatment [7]. We found that pre-therapeutic sarcopenia (PS) was associated with poor survival rates, post-operative complications and chemotherapy-related toxicities during cancer treatment, but with a strong between-study heterogeneity with respect to cancer site or extension and the definitions of sarcopenia. Since this review, with the arrival of immune-therapies and an update in the consensuses, there has been a considerable increase in the number of additional studies among cancer patients, but no comprehensive analysis has been conducted to date.

We therefore aimed to update our previous systematic review and to decipher heterogeneity in the prevalence of PS and its predictive values for overall survival, progression-free survival, post-operative complications, treatment-related toxicities, disability, and nosocomial infections among cancer patients using a meta-analysis including research published before 2022.

# 2. Materials and Methods

We followed the recommendations of the preferred reporting items for systematic reviews and meta-analyses (PRISMA) method for reporting this systematic review with meta-analysis [8]. The protocol was registered on 6 February 2023 and is available on the OSF platform: https://doi.org/10.17605/OSF.IO/H7PUZ, accessed on 13 February 2023.

## 2.1. *Information Sources*

This meta-analysis was based on a systematic, comprehensive search on MEDLINE via PubMed for articles published in English or French from 31 March 2016 to 31 December 2021. Due to a considerable increase in the number of studies addressing sarcopenia among cancer patients, we chose only to consult the PubMed database. The following research algorithm was used: sarcopenia AND (cancer OR tumors OR malignancies) AND (death OR overall survival OR progression-free survival OR relapse OR chemotherapy OR targeted therapy OR radiotherapy OR hormonal therapy OR surgery OR immunotherapy OR toxicity OR disability OR infection) AND human NOT review NOT letter. All articles retrieved from our previous systematic review were also included [7].

## 2.2. *Search Strategy*

For this meta-analysis, the following issues were addressed:
(a) What is the most commonly encountered definition of PS among patients with cancer?

(b) What is the pooled prevalence of PS among patients with cancer, and what is the prevalence according to the definition of sarcopenia?

(c) What are the mean differences in muscle strength (i.e., grip-strength) and physical performance (i.e., gait speed) between sarcopenic and non-sarcopenic groups of patients with cancer?

(d) What is the predictive value of PS for overall survival (OS) and progression-free survival (PFS) among patients with cancer?

(e) What is the predictive value of PS for severe post-operative complications (POC) among patients with cancer?

(f) What is the predictive value of PS for severe treatment-related toxicities and/or dose-limiting toxicities (TOX) among patients with cancer?

(g) What is the predictive value of PS for disability and nosocomial infections (NI) among patients with cancer?

To answer these questions, we pre-defined eligibility criteria for the articles: *patients* (adults 18 y and over with cancer), *intervention* (pre-therapeutic sarcopenia assessed using a consensual measurement), *comparator* (sarcopenia vs. no sarcopenia), *outcomes* (prevalence of sarcopenia, OS and PFS, severe post-operative complications defined as a Clavien-Dindo scale score $\ge$ 3a, $\ge$grade 3 treatment-related toxicities (CTCAE) and/or dose-limiting toxicities, disability defined in terms of an activities of daily living score (ADL) of $\le 5/6$, and nosocomial infections defined as hospital-acquired infections), and *study design* (clinical trials, prospective or retrospective studies with consecutive inclusions) (PICOS) criteria.

## 2.3. *Selection Process*

Articles meeting the eligibility criteria were first selected on the basis of titles and abstracts (FP) then on the basis of perusal of the full text by 5 independent groups (PBR/MF, ALC/CM, SM/RG, FP/JP, EL/ZapT, and EP/AN/MP). The term sarcopenia was to be clearly defined in the articles. If several articles reported similar results, only the article with the most complete information was retained. Duplicates were screened for and removed. Disagreements were resolved by consensus in each reviewing group.

## 2.4. *Data Collection*

The data recorded included publication date, country, study design, follow-up time, number of patients, number of men and women, cancer site, cancer extension (classified as local, locally advanced, or metastatic), treatment modes, mean or median age at inclusion, the definition of sarcopenia used (low muscle mass quantity only or consensus-based algorithm), cut-off values for quantitative muscle mass indices (arm muscle area (AMA, cm²), ASM (kg/m²), psoas muscle index (PMI, cm²/m²), SMI (cm²/m²) or total psoas area (TPA, cm²)), muscle strength assessed by handgrip-strength (kg), physical performance assessed by gait speed (m/s), number of sarcopenic patients, number of sarcopenic men and women, number of sarcopenic patients with a body mass index $\ge 30$ kg/m² (i.e., sarcopenic obesity), and finally the outcomes associated with either the PS values (%) or the hazard ratios or the odds ratios.

## 2.5. *Meta-Analysis Endpoints*

The primary endpoint was the pooled prevalence of PS among cancer patients.

The secondary endpoints were: mean differences in handgrip strength (kg) and gait speed (m/s) between sarcopenic and non-sarcopenic patients; OS; PFS; grade $\ge$ 3a post-operative complications (Clavien-Dindo scale); grade $\ge$ 3 treatment-related toxicities (CTCAE) and/or dose-limiting toxicities; ADL-score $\le 5/6$; and hospital-acquired infections.

## 2.6. *Quality Assessment*

We used the Newcastle-Ottawa quality assessment scale (NOS) designed for cohort studies which was the case for all patients, even for those recruited from RCTs [9]. Based
on a risk-of-bias assessment, this scale rates the quality of studies with scores ranging from 0 to 9. The quality of the studies was classified as good (≥7), fair (4–6), or poor (0–3).

## 2.7. *Effect Measures*

The prevalence of PS was summarized as a pooled prevalence with 95% confidence interval (95% CI) using logit transformation.

Handgrip strength and gait speed were summarized as a pooled mean difference (MD) with 95% CI with reference to non-sarcopenic patients using the inverse variance method.

OS and PFS were summarized as a pooled risk ratio (RR) with 95% CI with reference to non-sarcopenic patients using the inverse variance method.

The remaining outcomes were summarized as a pooled RR with 95% CI with reference to non-sarcopenic patients using the Mantel–Haenszel method.

## 2.8. *Synthesis Method*

The data were analyzed using R statistical software (version 4.1.0; R Foundation for Statistical Computing, Vienna, Austria; http://www.r-project.org, accessed on 1 September 2022). All tests were 2-sided and statistical significance was set at *p* < 0.05.

Regarding the study characteristics, categorical variables were summarized as the numbers (%), and continuous variables were summarized as the means ± standard deviation (SD) or medians [Q1–Q3] as appropriate. The studies were described in descending order according to their publication date.

To detect a non-linear relationship between sarcopenia prevalence and the muscle mass indices (using reported cut-off values), we used a non-parametric regression via smoothing splines when possible.

On the basis of the selected articles, and given that between-study heterogeneity was expected, we performed a meta-analysis with random-effect models (with the package "meta") to assess the prevalence of PS, the mean difference in muscle strength and physical performance indices (grip strength and gait speed), and the predictive value of PS for OS, PFS, Clavien–Dindo scale ≥grade 3 for POC, ≥grade-3 for TOX, disability (ADL score ≤ 5/6), and NI among cancer patients. As there was a single study addressing disability, we did not conduct a meta-analysis on this outcome. With regard to the prevalence of PS (first endpoint), we first ran a funnel plot to detect graphical asymmetry. Statistically, the funnel plot asymmetry was assessed using the Peters' test, which is appropriate for meta-analyses of single proportion. We addressed the heterogeneity of the study results using the I² indicator and the Cochran's Q test. I² values of 0%, 25%, 50%, and 75% were considered to indicate none, low, moderate, and high heterogeneity, respectively. A *p* value ≤ 0.05 in the Q test indicated a significant heterogeneity. Due to the heterogeneous nature of sarcopenia and the variety of the contexts assessed, we anticipated the need for subgroup analyses according to a sensitivity analysis, excluding studies over the 95% confidence interval from the funnel plot, according to the following: study quality (good, fair or poor), the mean or median age at inclusion classified as < or ≥65 y, sex, BMI (< or ≥30 kg/m²), cancer site, cancer extension, treatment mode, definition of sarcopenia (low muscle mass quantity only or consensus-based algorithm), and the cut-off values for muscle mass indices. We also considered post hoc subgroup analyses according to the publication date (2008–2012, 2013–2017, and 2018–2022), the number of patients included (<100, 100–200, 200–400, and ≥400), and world regions (Asian vs. non-Asian).

To decipher the factors that could explain heterogeneity, we then ran a multivariate meta-regression with a mixed-effect model for the first endpoint (prevalence). Factors (study groups) yielding *p* values under 0.20 in the univariate analysis were considered for inclusion in the multivariate analysis. A backward selection process of the highest *p* values was performed to retain the final multivariate model.
## 3. Results

### 3.1. Study Selection and Quality Rating of the Studies Included

As of 31 December 2021, including the final publications in 2022, the comprehensive search yielded 1318 articles potentially eligible for this review (Figure A1). After excluding non-eligible articles, 226 remained for review and meta-analysis, dated from 2008 to 2022 as follows: 5 in 2022 [10–14], 60 in 2021 [15–74], 36 in 2020 [75–110], 31 in 2019 [111–141], 29 in 2018 [142–170], 18 in 2017 [171–187], 15 in 2016 [188–202], 15 in 2015 [203–217], 2 in 2014 [218,219], 5 in 2013 [220–224], 6 in 2012 [225–230], none in 2011, 1 in 2010 [231], 2 in 2009 [232,233], and 1 in 2008 [234] (Table 1).

According to the NOS score, 151/226 studies (67%) were rated as good quality (NOS ≥ 7) meaning there was a low risk of bias (Table 1).

### 3.2. Patient and Study Characteristics

In all, 65,936 patients were included in this meta-analysis with sample sizes ranging from 16 to 6447 patients (Table 1). Overall, 118 studies were retrospective, 95 were prospective, and 13 were clinical trials. The studies were mainly from Asia, Europe, and North-America, while only two studies were from Africa [75,101]. The follow-up time ranged from 0 to 200 months. The mean or median age at inclusion ranged from 45.7 to 85 y. Thirty-three per cent (17,295/65,936) of the patients had a mean or median age at inclusion ≥65 years. A total of 419/65,936 patients had a mean or median age at inclusion ≥75 years. Most of the studies also included patients younger than 65 years (64%, 30,691/47,986 patients), Asians (51%, 33,453/65,936), men (66%, 30,424/46,265), and with a body mass index < 30 kg/m² (69.5%, 2628/8627). The studies mainly included cancers in various sites (22%, 14,600/65,936), gastric (20.5%, 13,513/65,936), or colorectal (17%, 11,419/65,936), and with various extensions (82%, 54,269/65,936). The treatment modes observed were mainly surgery (61%, 40,486/65,936), chemotherapy (6%, 4169/65,936), immune therapy (1%, 909/65,936), and targeted therapy (1%, 634/65,936).

### 3.3. Definition of Sarcopenia among Cancer Patients

Sarcopenia was mainly defined from muscle mass measurement only (190/226 studies, 84%), from CT scan (n = 178), BIA (n = 11), or DXA (n = 1) (Table 1). Sixteen studies did not specify the muscle mass index used [43,45,68,85,86,95,96,120,122,123,139,141,147,148,186,207]. Of the 210 remaining studies, regardless of the sarcopenia definition used, the SMI by CT scan at lumbar three was the main muscle mass quantity index used (171/210, 81.5%) followed by the ASM (21/210, 10%), the PMI (13/210, 6%), the TPA (4/210 studies, 2%), and the AMA (1/226 studies, 0.5%). The SMI cut-off values ranged from 29.0 to 48.4 cm²/m² (37 thresholds in all) for women (median [Q1–Q3] = 38.5 [37.5–41.0]), and from 36.0 to 68.9 cm²/m² (43 thresholds in all) for men (median [Q1–Q3] = 47.3 [43.0–52.4]).

From 2015 to the present, of the 36 studies applying a consensus-based algorithm definition of sarcopenia, 17, 9, 6, and 2 studies respectively used the AWGS1, the EWGOS2, the EWGOS1, and the AWGS2 guidelines. The IWGS was not used.

### 3.4. PS Is Prevalent among Cancer Patients

All the studies were used to assess the prevalence. The pooled prevalence of PS among cancer patients was 38.0% (95% CI: 36.0–41.0) with a high between-study heterogeneity (I² = 97%) (Table 2). Figure A2 shows a significant funnel plot asymmetry (*p* < 0.0001).
<table><caption>Table 1. Study characteristics.</caption><thead><tr><th rowspan="2">Reference</th><th rowspan="2">Asia (Y/N)</th><th rowspan="2">Recruitment RCT/P/RP</th><th rowspan="2">Follow-Up (m)</th><th colspan="3">Patients</th><th rowspan="2">Site</th><th rowspan="2">Extension</th><th rowspan="2">Treatment</th><th rowspan="2">Mean or Median Age (y)</th><th rowspan="2">Definition of Sarcopenia/Muscle Mass Index</th><th colspan="3">Sarcopenia</th><th rowspan="2">Over the 95% CI (Y/N)</th><th rowspan="2">NOS G/F/P</th></tr><tr><th>Total</th><th>M</th><th>F</th><th>Total</th><th>M</th><th>F</th></tr></thead><tbody><tr><td>Takagi A et al., 2022 [10]</td><td>Y</td><td>P</td><td>1.0</td><td>114</td><td>74</td><td>40</td><td>Various</td><td>Various</td><td>Various</td><td>68.4</td><td>CT scan/SMI</td><td>57</td><td>NA</td><td>NA</td><td>N</td><td>G</td></tr><tr><td>Lu JL et al., 2022 [11]</td><td>Y</td><td>P</td><td>0.0</td><td>260</td><td>196</td><td>64</td><td>Gastric</td><td>Locally advanced</td><td>Surgery</td><td>62.4</td><td>EWGOS 2/ASM</td><td>41</td><td>22</td><td>19</td><td>Y</td><td>G</td></tr><tr><td>Deluche E et al., 2022 [12]</td><td>N</td><td>P</td><td>1.0</td><td>139</td><td>2</td><td>137</td><td>Breast</td><td>Metastatic</td><td>Various</td><td>61.2</td><td>EWGOS 1/SMI</td><td>41</td><td>1</td><td>40</td><td>N</td><td>F</td></tr><tr><td>Tagliafico AS et al., 2022 [13]</td><td>N</td><td>P</td><td>200.0</td><td>74</td><td>37</td><td>37</td><td>Myeloma</td><td>Metastatic</td><td>Chemotherapy</td><td>60.8</td><td>CT scan/SMI</td><td>18</td><td>6</td><td>12</td><td>Y</td><td>G</td></tr><tr><td>Orzell S et al., 2022 [14]</td><td>N</td><td>P</td><td>72.0</td><td>251</td><td>191</td><td>58</td><td>Head and neck</td><td>Various</td><td>Surgery</td><td>67.4</td><td>EWGOS 2/SMI</td><td>39</td><td>21</td><td>18</td><td>Y</td><td>G</td></tr><tr><td>Bajric T et al., 2021 [15]</td><td>N</td><td>RP</td><td>63.6</td><td>355</td><td>135</td><td>220</td><td>Colorectal</td><td>Metastatic</td><td>Surgery</td><td>68.0</td><td>CT scan/SMI</td><td>78</td><td>65</td><td>13</td><td>Y</td><td>F</td></tr><tr><td>Cárcamo L. et al., 2021 [16]</td><td>N</td><td>RP</td><td>72.0</td><td>359</td><td>193</td><td>166</td><td>Colorectal</td><td>Various</td><td>Surgery</td><td>64.0</td><td>CT scan/SMI</td><td>85</td><td>NA</td><td>NA</td><td>Y</td><td>G</td></tr><tr><td>Catanese S et al., 2021 [17]</td><td>N</td><td>RP</td><td>87.6</td><td>78</td><td>56</td><td>22</td><td>Gastric</td><td>Metastatic</td><td>Various</td><td>67.0</td><td>CT scan/SMI</td><td>34</td><td>22</td><td>12</td><td>N</td><td>G</td></tr><tr><td>Chai VW et al., 2021 [18]</td><td>N</td><td>RP</td><td>12.0</td><td>228</td><td>139</td><td>89</td><td>Colorectal</td><td>Various</td><td>Surgery</td><td>69.0</td><td>CT scan/SMI</td><td>36</td><td>24</td><td>12</td><td>Y</td><td>G</td></tr><tr><td>Chang YR et al., 2021 [19]</td><td>Y</td><td>RP</td><td>141.6</td><td>109</td><td>63</td><td>46</td><td>Sarcoma</td><td>Metastatic</td><td>Targeted therapy</td><td>61.0</td><td>CT scan/PMI</td><td>25</td><td>NA</td><td>NA</td><td>Y</td><td>F</td></tr><tr><td>Chen HW et al., 2021 [20]</td><td>Y</td><td>RP</td><td>86.4</td><td>163</td><td>NA</td><td>NA</td><td>Urothelial</td><td>Various</td><td>Surgery</td><td>64.3</td><td>CT scan/SMI</td><td>132</td><td>NA</td><td>NA</td><td>Y</td><td>F</td></tr><tr><td>Daffrè E et al., 2021 [21]</td><td>N</td><td>RP</td><td>60.0</td><td>238</td><td>169</td><td>69</td><td>Lung NSC</td><td>Various</td><td>Surgery</td><td>63.0</td><td>CT scan/SMI</td><td>47</td><td>36</td><td>11</td><td>Y</td><td>G</td></tr><tr><td>Ferini G et al., 2021 [22]</td><td>N</td><td>RP</td><td>70.0</td><td>28</td><td>25</td><td>3</td><td>Urothelial</td><td>Various</td><td>Radiotherapy</td><td>85.0</td><td>CT scan/SMI</td><td>8</td><td>8</td><td>0</td><td>N</td><td>F</td></tr><tr><td>Haik L et al., 2021 [23]</td><td>N</td><td>RP</td><td>60.0</td><td>261</td><td>198</td><td>63</td><td>Various</td><td>Various</td><td>Immunotherapy</td><td>61.9</td><td>CT scan/SMI</td><td>122</td><td>87</td><td>35</td><td>N</td><td>F</td></tr><tr><td>Harry Hsu TM et al., 2021 [24]</td><td>N</td><td>P</td><td>33.6</td><td>136</td><td>63</td><td>73</td><td>Pancreas</td><td>Various</td><td>Not specified</td><td>67.0</td><td>CT scan/SMI</td><td>21</td><td>9</td><td>12</td><td>Y</td><td>F</td></tr><tr><td>Hu WH et al., 2021 [25]</td><td>Y</td><td>RP</td><td>80.4</td><td>114</td><td>68</td><td>46</td><td>Colorectal</td><td>Various</td><td>Surgery</td><td>63.2</td><td>CT scan/SMI</td><td>52</td><td>NA</td><td>NA</td><td>N</td><td>G</td></tr><tr><td>Huang DD et al., 2021 [26]</td><td>Y</td><td>P</td><td>67.2</td><td>419</td><td>282</td><td>137</td><td>Gastric</td><td>Various</td><td>Surgery</td><td>72.0</td><td>CT scan/SMI</td><td>285</td><td>208</td><td>77</td><td>Y</td><td>G</td></tr><tr><td>Kim J et al., 2021 [27]</td><td>Y</td><td>RP</td><td>41.0</td><td>840</td><td>526</td><td>534</td><td>Gastric</td><td>Various</td><td>Various</td><td>60.4</td><td>CT scan/SMI</td><td>119</td><td>110</td><td>9</td><td>Y</td><td>G</td></tr><tr><td>Kim GH et al., 2021 [28]</td><td>Y</td><td>RP</td><td>70.5</td><td>280</td><td>182</td><td>98</td><td>Gastric</td><td>Local</td><td>Surgery</td><td>82.0</td><td>CT scan/SMI</td><td>173</td><td>NA</td><td>NA</td><td>Y</td><td>G</td></tr><tr><td>Kawaguchi Y et al., 2021 [29]</td><td>Y</td><td>RP</td><td>60.0</td><td>256</td><td>173</td><td>83</td><td>Lung NSC</td><td>Various</td><td>Surgery</td><td>68.5</td><td>CT scan/PMI</td><td>128</td><td>89</td><td>39</td><td>Y</td><td>F</td></tr><tr><td>Juris A et al., 2021 [30]</td><td>N</td><td>RP</td><td>48.0</td><td>89</td><td>40</td><td>49</td><td>Various</td><td>Various</td><td>Surgery</td><td>57.0</td><td>CT scan/SMI</td><td>22</td><td>11</td><td>11</td><td>Y</td><td>F</td></tr><tr><td>Jullien M et al., 2021 [31]</td><td>N</td><td>P</td><td>36.6</td><td>656</td><td>367</td><td>289</td><td>Lymphoma</td><td>Various</td><td>Various</td><td>49.0</td><td>CT scan/SMI</td><td>225</td><td>179</td><td>46</td><td>N</td><td>G</td></tr><tr><td>Jalal M et al., 2021 [32]</td><td>N</td><td>RP</td><td>0.0</td><td>204</td><td>114</td><td>90</td><td>Pancreas</td><td>Locally advanced</td><td>Various</td><td>69.0</td><td>CT scan/SMI</td><td>111</td><td>41</td><td>70</td><td>Y</td><td>F</td></tr><tr><td>Kirsten J et al., 2021 [33]</td><td>N</td><td>P</td><td>12.0</td><td>178</td><td>109</td><td>69</td><td>Leukemia</td><td>Metastatic</td><td>Chemotherapy</td><td>58.3</td><td>EWGOS1</td><td>49</td><td>42</td><td>7</td><td>Y</td><td>G</td></tr><tr><td>Kim N et al., 2021 [34]</td><td>Y</td><td>RP</td><td>30.1</td><td>185</td><td>120</td><td>65</td><td>Gastric</td><td>Metastatic</td><td>Immunotherapy</td><td>59.0</td><td>CT scan/SMI</td><td>93</td><td>85</td><td>8</td><td>Y</td><td>G</td></tr><tr><td>Leone R et al., 2021 [35]</td><td>N</td><td>RP</td><td>40.0</td><td>43</td><td>15</td><td>28</td><td>Lymphoma</td><td>Various</td><td>Chemotherapy</td><td>61.0</td><td>CT scan/SMI</td><td>13</td><td>NA</td><td>NA</td><td>N</td><td>F</td></tr><tr><td>Lee CH et al., 2021 [36]</td><td>Y</td><td>RP</td><td>57.1</td><td>78</td><td>59</td><td>19</td><td>Kidney</td><td>Metastatic</td><td>Targeted therapy</td><td>61.6</td><td>CT scan/SMI</td><td>41</td><td>28</td><td>13</td><td>N</td><td>G</td></tr><tr><td>Liang H et al., 2021 [37]</td><td>Y</td><td>RP</td><td>17.7</td><td>100</td><td>93</td><td>7</td><td>Esophageal</td><td>Various</td><td>Radiotherapy</td><td>59.0</td><td>CT scan/SMI</td><td>77</td><td>74</td><td>3</td><td>Y</td><td>F</td></tr><tr><td>Makal GB et al., 2021 [38]</td><td>Y</td><td>RP</td><td>1.0</td><td>225</td><td>141</td><td>84</td><td>Various</td><td>Various</td><td>Surgery</td><td>58.7</td><td>CT scan/TPA</td><td>102</td><td>42</td><td>60</td><td>N</td><td>P</td></tr><tr><td>Nilsson M et al., 2021 [39]</td><td>N</td><td>RP</td><td>60.0</td><td>106</td><td>22</td><td>84</td><td>Anal</td><td>Various</td><td>Radiotherapy</td><td>63.8</td><td>CT scan/SMI</td><td>41</td><td>11</td><td>30</td><td>N</td><td>G</td></tr><tr><td>Takeda T et al., 2021 [40]</td><td>Y</td><td>RP</td><td>63.6</td><td>80</td><td>35</td><td>45</td><td>Pancreas</td><td>Metastatic</td><td>Chemotherapy</td><td>77.0</td><td>CT scan/SMI</td><td>61</td><td>25</td><td>36</td><td>Y</td><td>G</td></tr><tr><td>Takiguchi K et al., 2021 [41]</td><td>Y</td><td>RP</td><td>96.0</td><td>209</td><td>116</td><td>93</td><td>Colorectal</td><td>Locally advanced</td><td>Surgery</td><td>NA</td><td>CT scan/PMI</td><td>81</td><td>50</td><td>31</td><td>N</td><td>F</td></tr><tr><td>Thureau S et al., 2021 [42]</td><td>N</td><td>P</td><td>60.0</td><td>243</td><td>187</td><td>56</td><td>Head and neck</td><td>Various</td><td>Various</td><td>61.0</td><td>CT scan/SMI</td><td>88</td><td>NA</td><td>NA</td><td>N</td><td>G</td></tr><tr><td>Troschel FM et al., 2021 [43]</td><td>N</td><td>RP</td><td>96.0</td><td>367</td><td>247</td><td>120</td><td>Lung NSC</td><td>Various</td><td>Surgery</td><td>62.2</td><td>CT scan/NA</td><td>104</td><td>86</td><td>18</td><td>Y</td><td>G</td></tr><tr><td>Trussardi Fayh AP et al., 2021 [44]</td><td>N</td><td>P</td><td>0.0</td><td>108</td><td>51</td><td>57</td><td>Various</td><td>Various</td><td>Various</td><td>70.6</td><td>EWGOS 2/SMI</td><td>26</td><td>NA</td><td>NA</td><td>Y</td><td>F</td></tr><tr><td>van den Berg I et al., 2021 [45]</td><td>N</td><td>RP</td><td>60.0</td><td>754</td><td>352</td><td>306</td><td>Colorectal</td><td>Various</td><td>Surgery</td><td>NA</td><td>CT scan/NA</td><td>266</td><td>NA</td><td>NA</td><td>N</td><td>F</td></tr><tr><td>Wu WY et al., 2021 [46]</td><td>Y</td><td>P</td><td>67.2</td><td>648</td><td>486</td><td>162</td><td>Gastric</td><td>Various</td><td>Surgery</td><td>64.3</td><td>AWGS2/ EWGOS2/SMI</td><td>133</td><td>91</td><td>42</td><td>Y</td><td>G</td></tr><tr><td>Xu YY et al., 2021 [47]</td><td>Y</td><td>RP</td><td>50.0</td><td>184</td><td>141</td><td>43</td><td>Esophageal</td><td>Various</td><td>Various</td><td>62.0</td><td>CT scan/SMI</td><td>94</td><td>75</td><td>19</td><td>Y</td><td>F</td></tr><tr><td>Yamashita S et al., 2021 [48]</td><td>Y</td><td>RP</td><td>72.0</td><td>123</td><td>103</td><td>20</td><td>Urothelial</td><td>Various</td><td>Surgery</td><td>74.0</td><td>CT scan/SMI</td><td>48</td><td>NA</td><td>NA</td><td>N</td><td>F</td></tr><tr><td>Zhang FM et al., 2021 [49]</td><td>Y</td><td>P</td><td>80.0</td><td>507</td><td>367</td><td>140</td><td>Gastric</td><td>Local</td><td>Surgery</td><td>63.0</td><td>CT scan/SMI</td><td>73</td><td>53</td><td>20</td><td>Y</td><td>F</td></tr><tr><td>Zilioli VR et al., 2021 [50]</td><td>N</td><td>RP</td><td>144.0</td><td>154</td><td>78</td><td>76</td><td>Lymphoma</td><td>Various</td><td>Various</td><td>71.0</td><td>CT scan/SMI</td><td>66</td><td>42</td><td>24</td><td>N</td><td>G</td></tr><tr><td>Zou HB et al., 2021 [51]</td><td>Y</td><td>P</td><td>6.0</td><td>135</td><td>91</td><td>44</td><td>Gastric</td><td>Various</td><td>Surgery</td><td>64.0</td><td>AWGS 2/SMI</td><td>27</td><td>14</td><td>13</td><td>Y</td><td>F</td></tr></tbody></table>
<table><caption>Table 1. *Cont.*</caption><thead><tr><th rowspan="2">Reference</th><th rowspan="2">Asia (Y/N)</th><th rowspan="2">Recruitment RCT/P/RP</th><th rowspan="2">Follow-Up (m)</th><th colspan="3">Patients</th><th rowspan="2">Site</th><th rowspan="2">Extension</th><th rowspan="2">Treatment</th><th rowspan="2">Mean or Median Age (y)</th><th rowspan="2">Definition of Sarcopenia/Muscle Mass Index</th><th colspan="3">Sarcopenia</th><th rowspan="2">Over the 95% CI (Y/N)</th><th rowspan="2">NOS G/F/P</th></tr><tr><th>Total</th><th>M</th><th>F</th><th>Total</th><th>M</th><th>F</th></tr></thead><tbody><tr><td>Peng H et al., 2021 [52]</td><td>Y</td><td>RP</td><td>82.0</td><td>121</td><td>96</td><td>25</td><td>Esophageal</td><td>Various</td><td>Surgery</td><td>70.3</td><td>CT scan/SMI</td><td>65</td><td>52</td><td>13</td><td>Y</td><td>F</td></tr><tr><td>Rinninella E et al., 2021 [53]</td><td>N</td><td>RP</td><td>0.0</td><td>26</td><td>18</td><td>8</td><td>Gastric</td><td>Locally advanced</td><td>Various</td><td>63.3</td><td>CT scan/SMI</td><td>19</td><td>NA</td><td>NA</td><td>Y</td><td>F</td></tr><tr><td>Runkel M et al., 2021 [54]</td><td>N</td><td>RP</td><td>0.0</td><td>94</td><td>58</td><td>36</td><td>Colorectal</td><td>Metastatic</td><td>Surgery</td><td>61.4</td><td>CT scan/SMI</td><td>34</td><td>NA</td><td>NA</td><td>N</td><td>F</td></tr><tr><td>Sakurai K et al., 2021 [55]</td><td>Y</td><td>RP</td><td>127.0</td><td>1054</td><td>691</td><td>363</td><td>Gastric</td><td>Various</td><td>Surgery</td><td>NA</td><td>CT scan/SMI</td><td>193</td><td>117</td><td>76</td><td>Y</td><td>G</td></tr><tr><td>Sehouli J et al., 2021 [56]</td><td>N</td><td>P</td><td>59.0</td><td>226</td><td>0</td><td>226</td><td>Various</td><td>Various</td><td>Surgery</td><td>59.0</td><td>BIA/ASM</td><td>68</td><td>0</td><td>68</td><td>N</td><td>G</td></tr><tr><td>Şengül Ayçiçek G et al., 2021 [57]</td><td>N</td><td>P</td><td>0.0</td><td>49</td><td>25</td><td>24</td><td>Various</td><td>Various</td><td>Surgery</td><td>70.0</td><td>BIA/ASM</td><td>14</td><td>1</td><td>13</td><td>N</td><td>F</td></tr><tr><td>Sun X et al., 2021 [58]</td><td>Y</td><td>P</td><td>50.0</td><td>267</td><td>202</td><td>65</td><td>Gastric</td><td>Various</td><td>Surgery</td><td>64.8</td><td>AWGS 1/SMI</td><td>49</td><td>32</td><td>17</td><td>Y</td><td>G</td></tr><tr><td>Pessia B et al., 2021 [59]</td><td>N</td><td>RP</td><td>48.0</td><td>68</td><td>NA</td><td>NA</td><td>Pancreas</td><td>Local</td><td>Surgery</td><td>63.0</td><td>CT scan/SMI</td><td>32</td><td>NA</td><td>NA</td><td>N</td><td>G</td></tr><tr><td>Choi H et al., 2021 [60]</td><td>Y</td><td>RP</td><td>60.0</td><td>440</td><td>243</td><td>197</td><td>Lung NSC</td><td>Local</td><td>Surgery</td><td>65.0</td><td>CT scan/SMI</td><td>246</td><td>NA</td><td>NA</td><td>Y</td><td>G</td></tr><tr><td>Jang HY et al., 2021 [61]</td><td>Y</td><td>RP</td><td>120.0</td><td>160</td><td>120</td><td>40</td><td>Liver</td><td>Local</td><td>Surgery</td><td>55.2</td><td>CT scan/SMI</td><td>28</td><td>17</td><td>11</td><td>Y</td><td>G</td></tr><tr><td>Tenuta M et al., 2021 [62]</td><td>N</td><td>P</td><td>62.5</td><td>47</td><td>27</td><td>20</td><td>Lung NSC</td><td>Locally advanced</td><td>Immunotherapy</td><td>67.0</td><td>EWGOS 2/ASM</td><td>19</td><td>10</td><td>9</td><td>N</td><td>G</td></tr><tr><td>Lee JH et al., 2021 [63]</td><td>Y</td><td>P</td><td>36.0</td><td>70</td><td>70</td><td>0</td><td>Prostate</td><td>Metastatic</td><td>Various</td><td>66.5</td><td>CT scan/SMI</td><td>47</td><td>47</td><td>0</td><td>Y</td><td>G</td></tr><tr><td>Taniguchi Y et al., 2021 [64]</td><td>Y</td><td>RP</td><td>72.0</td><td>567</td><td>393</td><td>174</td><td>Gastric</td><td>Various</td><td>Surgery</td><td>NA</td><td>CT scan/PMI</td><td>88</td><td>81</td><td>7</td><td>Y</td><td>G</td></tr><tr><td>Deng L et al., 2021 [65]</td><td>Y</td><td>P</td><td>80.0</td><td>121</td><td>52</td><td>69</td><td>Cholangio-carcinoma</td><td>Various</td><td>Surgery</td><td>65.0</td><td>CT scan/PMI</td><td>53</td><td>NA</td><td>NA</td><td>N</td><td>G</td></tr><tr><td>Uemura S et al., 2021 [66]</td><td>Y</td><td>RP</td><td>60.0</td><td>69</td><td>38</td><td>31</td><td>Pancreas</td><td>Various</td><td>Chemotherapy</td><td>63.0</td><td>CT scan/SMI</td><td>33</td><td>12</td><td>21</td><td>N</td><td>F</td></tr><tr><td>Jung AR et al., 2021 [67]</td><td>Y</td><td>P</td><td>96.0</td><td>190</td><td>156</td><td>34</td><td>Head and neck</td><td>Various</td><td>Various</td><td>71.9</td><td>CT scan/SMI</td><td>64</td><td>56</td><td>8</td><td>N</td><td>G</td></tr><tr><td>Huang X et al., 2021 [68]</td><td>Y</td><td>P</td><td>3.0</td><td>82</td><td>55</td><td>27</td><td>Head and neck</td><td>Various</td><td>Chemotherapy</td><td>45.7</td><td>AWGS 1//NA</td><td>37</td><td>17</td><td>20</td><td>N</td><td>G</td></tr><tr><td>Regnier R et al., 2021 [69]</td><td>N</td><td>RP</td><td>3.0</td><td>82</td><td>62</td><td>20</td><td>Kidney</td><td>Locally advanced</td><td>Various</td><td>65.0</td><td>CT scan/SMI</td><td>47</td><td>39</td><td>8</td><td>Y</td><td>G</td></tr><tr><td>Jin K et al., 2021 [70]</td><td>Y</td><td>RP</td><td>0.0</td><td>119</td><td>59</td><td>60</td><td>Pancreas</td><td>Locally advanced</td><td>Various</td><td>60.2</td><td>CT scan/SMI</td><td>57</td><td>NA</td><td>NA</td><td>N</td><td>G</td></tr><tr><td>Miura A et al., 2021 [71]</td><td>Y</td><td>RP</td><td>79.6</td><td>259</td><td>155</td><td>104</td><td>Lung NSC</td><td>Various</td><td>Surgery</td><td>73.0</td><td>CT scan/PMI</td><td>179</td><td>127</td><td>52</td><td>Y</td><td>F</td></tr><tr><td>Takahashi Y et al., 2021 [72]</td><td>Y</td><td>RP</td><td>137.0</td><td>315</td><td>192</td><td>123</td><td>Lung NSC</td><td>Local</td><td>Surgery</td><td>70.0</td><td>CT scan/PMI</td><td>79</td><td>46</td><td>33</td><td>Y</td><td>G</td></tr><tr><td>Silva PB et al., 2021 [73]</td><td>N</td><td>P</td><td>0.0</td><td>71</td><td>71</td><td>0</td><td>Head and neck</td><td>Various</td><td>Not specified</td><td>66.9</td><td>EWGOS 1/ASM</td><td>32</td><td>32</td><td>0</td><td>N</td><td>F</td></tr><tr><td>Seror M et al., 2021 [74]</td><td>N</td><td>RP</td><td>60.0</td><td>110</td><td>92</td><td>18</td><td>Liver</td><td>Local</td><td>Surgery</td><td>67.7</td><td>CT scan/SMI</td><td>26</td><td>25</td><td>1</td><td>Y</td><td>G</td></tr><tr><td>Badran H et al., 2020 [75]</td><td>N</td><td>P</td><td>12.0</td><td>262</td><td>96</td><td>53</td><td>Liver</td><td>Locally advanced</td><td>Various</td><td>59.6</td><td>CT scan/SMI</td><td>113</td><td>86</td><td>27</td><td>N</td><td>F</td></tr><tr><td>Chen WS et al., 2020 [76]</td><td>Y</td><td>P</td><td>0.0</td><td>360</td><td>214</td><td>146</td><td>Colorectal</td><td>Various</td><td>Surgery</td><td>72.0</td><td>AWGS 1/SMI</td><td>133</td><td>76</td><td>57</td><td>N</td><td>G</td></tr><tr><td>Fraisse G et al., 2020 [77]</td><td>N</td><td>RP</td><td>64.8</td><td>146</td><td>126</td><td>20</td><td>Urothelial</td><td>Various</td><td>Various</td><td>NA</td><td>CT scan/SMI</td><td>67</td><td>59</td><td>8</td><td>N</td><td>P</td></tr><tr><td>Hirsch L et al., 2020 [78]</td><td>N</td><td>P</td><td>18.0</td><td>92</td><td>58</td><td>34</td><td>Various</td><td>Metastatic</td><td>Immunotherapy</td><td>64.6</td><td>CT scan/SMI</td><td>45</td><td>NA</td><td>NA</td><td>N</td><td>G</td></tr><tr><td>Huang CH et al., 2020 [79]</td><td>Y</td><td>RP</td><td>84.0</td><td>107</td><td>101</td><td>6</td><td>Esophageal</td><td>Various</td><td>Various</td><td>54.1</td><td>CT scan/SMI</td><td>65</td><td>63</td><td>2</td><td>Y</td><td>P</td></tr><tr><td>Lanza E et al., 2020 [80]</td><td>N</td><td>RP</td><td>60.0</td><td>142</td><td>110</td><td>32</td><td>Liver</td><td>Various</td><td>Intra-arterial infusion for hepatocellular carcinoma</td><td>73.0</td><td>CT scan/SMI</td><td>121</td><td>97</td><td>24</td><td>Y</td><td>G</td></tr><tr><td>Tsukagoshi M et al., 2020 [81]</td><td>Y</td><td>RP</td><td>36.0</td><td>30</td><td>23</td><td>7</td><td>Lung NSC</td><td>Various</td><td>Immunotherapy</td><td>67.0</td><td>CT scan/PMI</td><td>13</td><td>10</td><td>3</td><td>N</td><td>G</td></tr><tr><td>Ueno A et al., 2020 [82]</td><td>Y</td><td>RP</td><td>0.0</td><td>82</td><td>0</td><td>82</td><td>Breast</td><td>Various</td><td>Chemotherapy</td><td>54.0</td><td>CT scan/SMI</td><td>10</td><td>NA</td><td>10</td><td>Y</td><td>F</td></tr><tr><td>Pielkenrood BJ et al., 2020 [83]</td><td>N</td><td>P</td><td>19.2</td><td>310</td><td>194</td><td>116</td><td>Various</td><td>Metastatic</td><td>Radiotherapy</td><td>67.0</td><td>CT scan/SMI</td><td>119</td><td>NA</td><td>NA</td><td>N</td><td>G</td></tr><tr><td>Wang PY et al., 2020 [84]</td><td>Y</td><td>P</td><td>0.2</td><td>212</td><td>145</td><td>67</td><td>Esophageal</td><td>Various</td><td>Surgery</td><td>64.9</td><td>AWGS 1/ASM</td><td>55</td><td>37</td><td>18</td><td>Y</td><td>G</td></tr><tr><td>Martini K et al., 2020 [85]</td><td>N</td><td>RP</td><td>1.0</td><td>234</td><td>69</td><td>165</td><td>Lung NSC</td><td>Various</td><td>Surgery</td><td>NA</td><td>CT scan/NA</td><td>78</td><td>23</td><td>55</td><td>N</td><td>F</td></tr><tr><td>Berardi G et al., 2020 [86]</td><td>N</td><td>P</td><td>3.0</td><td>234</td><td>158</td><td>76</td><td>Various</td><td>Various</td><td>Surgery</td><td>66.5</td><td>EWGOS 2/NA</td><td>68</td><td>31</td><td>37</td><td>Y</td><td>G</td></tr><tr><td>den Boer RB et al., 2020 [87]</td><td>N</td><td>P</td><td>3.0</td><td>199</td><td>158</td><td>41</td><td>Gastric</td><td>Various</td><td>Various</td><td>66.1</td><td>CT scan/SMI</td><td>84</td><td>67</td><td>17</td><td>N</td><td>F</td></tr><tr><td>Xu LB et al., 2020 [88]</td><td>Y</td><td>P</td><td>48.0</td><td>749</td><td>499</td><td>250</td><td>Gastric</td><td>Various</td><td>Surgery</td><td>NA</td><td>AWGS 2/SMI</td><td>134</td><td>91</td><td>43</td><td>Y</td><td>G</td></tr></tbody></table>
<table><caption>Table 1. *Cont.*</caption><thead><tr><th rowspan="2">Reference</th><th rowspan="2">Asia (Y/N)</th><th rowspan="2">Recruitment RCT/P/RP</th><th rowspan="2">Follow-Up (m)</th><th colspan="3">Patients</th><th rowspan="2">Site</th><th rowspan="2">Extension</th><th rowspan="2">Treatment</th><th rowspan="2">Mean or Median Age (y)</th><th rowspan="2">Definition of Sarcopenia/Muscle Mass Index</th><th colspan="3">Sarcopenia</th><th rowspan="2">Over the 95% CI (Y/N)</th><th rowspan="2">NOS G/F/P</th></tr><tr><th>Total</th><th>M</th><th>F</th><th>Total</th><th>M</th><th>F</th></tr></thead><tbody><tr><td>Yu J II et al., 2020 [89]</td><td>Y</td><td>RCT</td><td>192.0</td><td>458</td><td>282</td><td>176</td><td>Gastric</td><td>Various</td><td>Various</td><td>NA</td><td>CT scan/SMI</td><td>75</td><td>74</td><td>1</td><td>Y</td><td>G</td></tr><tr><td>Mishra A et al., 2020 [90]</td><td>N</td><td>P</td><td>0.0</td><td>296</td><td>161</td><td>135</td><td>Leukemia</td><td>Metastatic</td><td>Chemotherapy</td><td>52.4</td><td>CT scan/SMI</td><td>132</td><td>75</td><td>57</td><td>N</td><td>G</td></tr><tr><td>Choi K et al., 2020 [91]</td><td>Y</td><td>P</td><td>72.0</td><td>238</td><td>193</td><td>45</td><td>Liver</td><td>Various</td><td>Various</td><td>59.0</td><td>CT scan/PMI</td><td>135</td><td>130</td><td>5</td><td>Y</td><td>G</td></tr><tr><td>Benadon B et al., 2020 [92]</td><td>N</td><td>P</td><td>60.0</td><td>104</td><td>72</td><td>32</td><td>Esophageal</td><td>Locally advanced</td><td>Various</td><td>63.0</td><td>CT scan/SMI</td><td>84</td><td>NA</td><td>NA</td><td>Y</td><td>G</td></tr><tr><td>Mallet R et al., 2020 [93]</td><td>N</td><td>P</td><td>120.0</td><td>97</td><td>81</td><td>16</td><td>Esophageal</td><td>Various</td><td>Various</td><td>63.6</td><td>CT scan/SMI</td><td>54</td><td>49</td><td>5</td><td>Y</td><td>G</td></tr><tr><td>Ryu Y et al., 2020 [94]</td><td>Y</td><td>P</td><td>60.0</td><td>548</td><td>326</td><td>222</td><td>Pancreas</td><td>Various</td><td>Various</td><td>62.5</td><td>CT scan/SMI</td><td>252</td><td>186</td><td>66</td><td>Y</td><td>G</td></tr><tr><td>Giani A et al., 2020 [95]</td><td>N</td><td>P</td><td>0.0</td><td>173</td><td>111</td><td>62</td><td>Colorectal</td><td>Local</td><td>Surgery</td><td>70.0</td><td>CT scan/NA</td><td>43</td><td>NA</td><td>NA</td><td>Y</td><td>F</td></tr><tr><td>van Rijn-Dekker MI et al., 2020 [96]</td><td>N</td><td>P</td><td>60.0</td><td>750</td><td>555</td><td>195</td><td>Head and neck</td><td>Various</td><td>Various</td><td>NA</td><td>CT scan/NA</td><td>189</td><td>143</td><td>46</td><td>Y</td><td>G</td></tr><tr><td>Srpcc M et al., 2020 [97]</td><td>N</td><td>P</td><td>120.0</td><td>139</td><td>117</td><td>22</td><td>Esophageal</td><td>Various</td><td>Surgery</td><td>63.9</td><td>CT scan/SMI</td><td>23</td><td>20</td><td>3</td><td>Y</td><td>G</td></tr><tr><td>Roch B et al., 2020 [98]</td><td>N</td><td>RP</td><td>30.0</td><td>142</td><td>93</td><td>49</td><td>Lung NSC</td><td>Metastatic</td><td>Immunotherapy</td><td>63.5</td><td>CT scan/SMI</td><td>92</td><td>NA</td><td>NA</td><td>Y</td><td>G</td></tr><tr><td>Agalar C et al., 2020 [99]</td><td>N</td><td>P</td><td>36.0</td><td>65</td><td>23</td><td>42</td><td>Colorectal</td><td>Metastatic</td><td>Various</td><td>56.0</td><td>CT scan/SMI</td><td>20</td><td>6</td><td>14</td><td>N</td><td>F</td></tr><tr><td>Shinohara S et al., 2020 [100]</td><td>Y</td><td>RP</td><td>96.0</td><td>391</td><td>275</td><td>116</td><td>Lung NSC</td><td>Various</td><td>Surgery</td><td>69.3</td><td>CT scan/PMI</td><td>198</td><td>160</td><td>38</td><td>Y</td><td>G</td></tr><tr><td>Salman MA et al., 2020 [101]</td><td>N</td><td>P</td><td>12.0</td><td>52</td><td>38</td><td>14</td><td>Liver</td><td>Local</td><td>Surgery</td><td>53.9</td><td>CT scan/SMI</td><td>27</td><td>18</td><td>9</td><td>N</td><td>G</td></tr><tr><td>Stangl-Kremser J et al., 2020 [102]</td><td>N</td><td>RCT</td><td>60.0</td><td>186</td><td>186</td><td>0</td><td>Prostate</td><td>Metastatic</td><td>Chemotherapy</td><td>68.8</td><td>CT scan/SMI</td><td>154</td><td>154</td><td>NA</td><td>Y</td><td>G</td></tr><tr><td>Zhuang CL et al., 2020 [103]</td><td>Y</td><td>RP</td><td>36.0</td><td>883</td><td>619</td><td>264</td><td>Gastric</td><td>Various</td><td>Surgery</td><td>65.0</td><td>EWGOS 1/EWGOS 2/SMI</td><td>150</td><td>103</td><td>47</td><td>Y</td><td>G</td></tr><tr><td>Hendrickson NR et al., 2020 [104]</td><td>N</td><td>RP</td><td>12.0</td><td>145</td><td>83</td><td>62</td><td>Sarcoma</td><td>Various</td><td>Surgery</td><td>NA</td><td>CT scan/PMI</td><td>38</td><td>21</td><td>17</td><td>Y</td><td>G</td></tr><tr><td>Yumioka T et al., 2020 [105]</td><td>Y</td><td>RP</td><td>0.0</td><td>80</td><td>55</td><td>25</td><td>Various</td><td>Various</td><td>Chemotherapy</td><td>71.6</td><td>CT scan/TPA</td><td>39</td><td>NA</td><td>NA</td><td>N</td><td>F</td></tr><tr><td>Oflazoglu U et al., 2020 [106]</td><td>N</td><td>P</td><td>0.0</td><td>461</td><td>203</td><td>258</td><td>Various</td><td>Various</td><td>Not specified</td><td>58.2</td><td>EWGOS 1/ASM</td><td>77</td><td>59</td><td>18</td><td>Y</td><td>G</td></tr><tr><td>Lee EC et al., 2020 [107]</td><td>Y</td><td>P</td><td>60.0</td><td>158</td><td>73</td><td>85</td><td>Urothelial</td><td>Various</td><td>Surgery</td><td>64.0</td><td>CT scan/SMI</td><td>88</td><td>58</td><td>30</td><td>Y</td><td>F</td></tr><tr><td>Martin L et al., 2020 [108]</td><td>N</td><td>P</td><td>19.6</td><td>1157</td><td>744</td><td>413</td><td>Various</td><td>Various</td><td>Surgery</td><td>63.6</td><td>CT scan/SMI</td><td>173</td><td>NA</td><td>NA</td><td>Y</td><td>F</td></tr><tr><td>Couderc AL et al., 2020 [109]</td><td>N</td><td>P</td><td>0.0</td><td>31</td><td>31</td><td>0</td><td>Prostate</td><td>Various</td><td>Various</td><td>80.4</td><td>EWGOS 2/ASM</td><td>8</td><td>8</td><td>NA</td><td>N</td><td>F</td></tr><tr><td>He WZ et al., 2020 [110]</td><td>Y</td><td>P</td><td>144.0</td><td>1767</td><td>1382</td><td>385</td><td>Head and neck</td><td>Various</td><td>Various</td><td>NA</td><td>CT scan/SMI</td><td>683</td><td>573</td><td>110</td><td>N</td><td>G</td></tr><tr><td>Chen XY et al., 2019 [111]</td><td>Y</td><td>P</td><td>0.0</td><td>313</td><td>229</td><td>84</td><td>Gastric</td><td>Various</td><td>Surgery</td><td>62.0</td><td>AWGS 1/SMI</td><td>37</td><td>23</td><td>14</td><td>Y</td><td>G</td></tr><tr><td>Dijkstrauis WPM et al., 2019 [112]</td><td>N</td><td>P</td><td>0.0</td><td>88</td><td>66</td><td>22</td><td>Various</td><td>Metastatic</td><td>Chemotherapy</td><td>63.0</td><td>CT scan/SMI</td><td>43</td><td>29</td><td>14</td><td>N</td><td>F</td></tr><tr><td>Dolan RD et al., 2019 [113]</td><td>N</td><td>P</td><td>109.2</td><td>650</td><td>354</td><td>296</td><td>Colorectal</td><td>Various</td><td>Surgery</td><td>NA</td><td>CT scan/SMI</td><td>283</td><td>150</td><td>133</td><td>N</td><td>G</td></tr><tr><td>de Paula N et al., 2019 [114]</td><td>N</td><td>RP</td><td>13.0</td><td>232</td><td>0</td><td>232</td><td>Uterus</td><td>Various</td><td>Various</td><td>64.3</td><td>CT scan/SMI</td><td>60</td><td>0</td><td>60</td><td>Y</td><td>F</td></tr><tr><td>Griffin OM et al., 2019 [115]</td><td>N</td><td>P</td><td>48.0</td><td>78</td><td>37</td><td>41</td><td>Pancreas</td><td>Various</td><td>Chemotherapy</td><td>64.2</td><td>CT scan/SMI</td><td>39</td><td>NA</td><td>NA</td><td>N</td><td>F</td></tr><tr><td>Hopkins JJ et al., 2019 [116]</td><td>N</td><td>RP</td><td>123.0</td><td>968</td><td>589</td><td>379</td><td>Colorectal</td><td>Various</td><td>Surgery</td><td>65.8</td><td>CT scan/SMI</td><td>488</td><td>262</td><td>226</td><td>Y</td><td>G</td></tr><tr><td>Jung A et al., 2019 [117]</td><td>Y</td><td>P</td><td>70.5</td><td>258</td><td>223</td><td>35</td><td>Head and neck</td><td>Various</td><td>Various</td><td>64.0</td><td>CT scan/SMI</td><td>17</td><td>NA</td><td>NA</td><td>Y</td><td>G</td></tr><tr><td>Huillard O et al., 2019 [118]</td><td>N</td><td>RCT</td><td>0.0</td><td>180</td><td>NA</td><td>NA</td><td>Thyroid</td><td>Metastatic</td><td>Targeted therapy</td><td>63.0</td><td>CT scan/SMI</td><td>89</td><td>NA</td><td>NA</td><td>Y</td><td>G</td></tr><tr><td>Kitano Y et al., 2019 [119]</td><td>Y</td><td>RP</td><td>94.1</td><td>110</td><td>75</td><td>35</td><td>Cholangio-carcinoma</td><td>Locally advanced</td><td>Surgery</td><td>71.0</td><td>CT scan/SMI</td><td>31</td><td>17</td><td>14</td><td>N</td><td>G</td></tr><tr><td>Kurk S et al., 2019 [120]</td><td>N</td><td>RCT</td><td>57.0</td><td>182</td><td>115</td><td>67</td><td>Colorectal</td><td>Metastatic</td><td>Chemotherapy</td><td>64.0</td><td>CT scan/NA</td><td>99</td><td>63</td><td>36</td><td>Y</td><td>G</td></tr><tr><td>Lin J et al., 2019 [121]</td><td>Y</td><td>P</td><td>0.0</td><td>594</td><td>448</td><td>146</td><td>Gastric</td><td>Locally advanced</td><td>Surgery</td><td>64.3</td><td>CT scan/SMI</td><td>195</td><td>NA</td><td>NA</td><td>N</td><td>G</td></tr><tr><td>Matsunaga T et al., 2019 [122]</td><td>Y</td><td>RP</td><td>54.0</td><td>163</td><td>128</td><td>35</td><td>Esophageal</td><td>Various</td><td>Various</td><td>64.7</td><td>BIA/NA</td><td>82</td><td>64</td><td>18</td><td>Y</td><td>G</td></tr><tr><td>Tamura T et al., 2019 [123]</td><td>Y</td><td>RP</td><td>1.0</td><td>153</td><td>101</td><td>52</td><td>Gastric</td><td>Various</td><td>Surgery</td><td>NA</td><td>BIA/NA</td><td>24</td><td>17</td><td>7</td><td>Y</td><td>G</td></tr><tr><td>Vashi PG et al., 2019 [124]</td><td>N</td><td>RP</td><td>70.0</td><td>112</td><td>63</td><td>49</td><td>Colorectal</td><td>Various</td><td>Various</td><td>56.3</td><td>CT scan/SMI</td><td>46</td><td>26</td><td>20</td><td>N</td><td>G</td></tr><tr><td>Yamamoto K et al., 2019 [125]</td><td>Y</td><td>RP</td><td>60.0</td><td>90</td><td>61</td><td>29</td><td>Gastric</td><td>Various</td><td>Surgery</td><td>NA</td><td>EWGOS 1/ASM</td><td>19</td><td>17</td><td>2</td><td>Y</td><td>G</td></tr><tr><td>Yang J et al., 2019 [126]</td><td>Y</td><td>RP</td><td>1.0</td><td>417</td><td>251</td><td>166</td><td>Colorectal</td><td>Various</td><td>Surgery</td><td>57.9</td><td>CT scan/SMI</td><td>61</td><td>42</td><td>19</td><td>Y</td><td>G</td></tr><tr><td>Okabe H et al., 2019 [127]</td><td>Y</td><td>RP</td><td>0.0</td><td>269</td><td>167</td><td>102</td><td>Colorectal</td><td>Various</td><td>Surgery</td><td>74.0</td><td>CT scan/SMI</td><td>159</td><td>81</td><td>78</td><td>Y</td><td>G</td></tr><tr><td>Otten L et al., 2019 [128]</td><td>N</td><td>P</td><td>12.0</td><td>439</td><td>248</td><td>191</td><td>Various</td><td>Various</td><td>Various</td><td>69.6</td><td>EWGOS 1/ASM</td><td>119</td><td>82</td><td>37</td><td>Y</td><td>G</td></tr></tbody></table>
<table><caption>Table 1. *Cont.*</caption><thead><tr><th rowspan="2">Reference</th><th rowspan="2">Asia (Y/N)</th><th rowspan="2">Recruitment RCT/P/RP</th><th rowspan="2">Follow-Up (m)</th><th colspan="3">Patients</th><th rowspan="2">Site</th><th rowspan="2">Extension</th><th rowspan="2">Treatment</th><th rowspan="2">Mean or Median Age (y)</th><th rowspan="2">Definition of Sarcopenia/Muscle Mass Index</th><th colspan="3">Sarcopenia</th><th rowspan="2">Over the 95% CI (Y/N)</th><th rowspan="2">NOS G/F/P</th></tr><tr><th>Total</th><th>M</th><th>F</th><th>Total</th><th>M</th><th>F</th></tr></thead><tbody><tr><td>Panje CM et al., 2019 [129]</td><td>N</td><td>RCT</td><td>84.0</td><td>61</td><td>57</td><td>4</td><td>Esophageal</td><td>Locally advanced</td><td>Various</td><td>61.0</td><td>CT scan/SMI</td><td>31</td><td>NA</td><td>NA</td><td>N</td><td>G</td></tr><tr><td>Sasaki S et al., 2019 [130]</td><td>Y</td><td>RCT</td><td>6.0</td><td>219</td><td>143</td><td>76</td><td>Colorectal</td><td>Various</td><td>Various</td><td>64.0</td><td>CT scan/SMI</td><td>135</td><td>109</td><td>26</td><td>Y</td><td>G</td></tr><tr><td>Shi B et al., 2019 [131]</td><td>Y</td><td>RP</td><td>0.0</td><td>279</td><td>205</td><td>74</td><td>Gastric</td><td>Various</td><td>Surgery</td><td>56.2</td><td>CT scan/SMI</td><td>125</td><td>106</td><td>19</td><td>N</td><td>G</td></tr><tr><td>da Silva JR et al., 2019 [132]</td><td>N</td><td>P</td><td>13.0</td><td>334</td><td>151</td><td>183</td><td>Various</td><td>Various</td><td>Palliative</td><td>63.0</td><td>CT scan/ASM</td><td>219</td><td>NA</td><td>NA</td><td>Y</td><td>G</td></tr><tr><td>Charette N et al., 2019 [133]</td><td>N</td><td>RCT</td><td>30.0</td><td>217</td><td>123</td><td>94</td><td>Colorectal</td><td>Locally advanced</td><td>Chemotherapy</td><td>63.0</td><td>CT scan/SMI</td><td>150</td><td>NA</td><td>NA</td><td>Y</td><td>G</td></tr><tr><td>Jang M et al., 2019 [134]</td><td>Y</td><td>RP</td><td>0.0</td><td>284</td><td>163</td><td>121</td><td>Pancreas</td><td>Local</td><td>Surgery</td><td>62.6</td><td>CT scan/SMI</td><td>191</td><td>NA</td><td>NA</td><td>Y</td><td>G</td></tr><tr><td>Kiss N et al., 2019 [135]</td><td>N</td><td>P</td><td>80.0</td><td>41</td><td>29</td><td>12</td><td>Lung NSC</td><td>Various</td><td>Various</td><td>65.6</td><td>CT scan/SMI</td><td>25</td><td>NA</td><td>NA</td><td>Y</td><td>G</td></tr><tr><td>Kurita Y et al., 2019 [136]</td><td>Y</td><td>RP</td><td>66.0</td><td>82</td><td>60</td><td>22</td><td>Pancreas</td><td>Metastatic</td><td>Chemotherapy</td><td>64.0</td><td>CT scan/SMI</td><td>42</td><td>31</td><td>11</td><td>N</td><td>F</td></tr><tr><td>Nakamura N et al., 2019 [137]</td><td>Y</td><td>RP</td><td>146.5</td><td>90</td><td>51</td><td>39</td><td>Lymphoma</td><td>Metastatic</td><td>Chemotherapy</td><td>59.0</td><td>CT scan/SMI</td><td>39</td><td>25</td><td>14</td><td>N</td><td>F</td></tr><tr><td>Ma BW et al., 2019 [138]</td><td>Y</td><td>P</td><td>1.0</td><td>545</td><td>418</td><td>127</td><td>Gastric</td><td>Locally advanced</td><td>Surgery</td><td>62.6</td><td>EWGOS 1/SMI</td><td>40</td><td>25</td><td>15</td><td>Y</td><td>G</td></tr><tr><td>Wang P et al., 2019 [139]</td><td>Y</td><td>P</td><td>12.0</td><td>44</td><td>26</td><td>18</td><td>Esophageal</td><td>Various</td><td>Surgery</td><td>65.7</td><td>BIA/NA</td><td>18</td><td>NA</td><td>NA</td><td>N</td><td>G</td></tr><tr><td>Soma D et al., 2019 [140]</td><td>Y</td><td>P</td><td>0.0</td><td>102</td><td>89</td><td>13</td><td>Esophageal</td><td>Various</td><td>Various</td><td>67.3</td><td>CT scan/SMI</td><td>45</td><td>34</td><td>11</td><td>N</td><td>G</td></tr><tr><td>Zhang S et al., 2019 [141]</td><td>Y</td><td>RP</td><td>43.2</td><td>6447</td><td>4317</td><td>2130</td><td>Various</td><td>Various</td><td>Surgery</td><td>NA</td><td>CT scan/NA</td><td>1638</td><td>1109</td><td>529</td><td>Y</td><td>F</td></tr><tr><td>Ataseven B et al., 2018 [142]</td><td>N</td><td>RP</td><td>0.0</td><td>323</td><td>0</td><td>323</td><td>Ovary</td><td>Various</td><td>Surgery</td><td>60.0</td><td>CT scan/SMI</td><td>152</td><td>NA</td><td>152</td><td>Y</td><td>G</td></tr><tr><td>Banaste N et al., 2018 [143]</td><td>N</td><td>RP</td><td>81.6</td><td>214</td><td>105</td><td>109</td><td>Colorectal</td><td>Metastatic</td><td>Various</td><td>59.5</td><td>CT scan/SMI</td><td>90</td><td>NA</td><td>NA</td><td>N</td><td>G</td></tr><tr><td>Chambard LC et al., 2018 [144]</td><td>N</td><td>P</td><td>50.0</td><td>64</td><td>48</td><td>16</td><td>Lung NSC</td><td>Metastatic</td><td>Various</td><td>65.1</td><td>DXA/ASM</td><td>16</td><td>NA</td><td>NA</td><td>N</td><td>G</td></tr><tr><td>Chen WZ et al., 2018 [145]</td><td>Y</td><td>P</td><td>0.0</td><td>376</td><td>228</td><td>148</td><td>Colorectal</td><td>Various</td><td>Surgery</td><td>64.3</td><td>AWGS 1/SMI</td><td>92</td><td>44</td><td>48</td><td>Y</td><td>G</td></tr><tr><td>Kawamura T et al., 2018 [146]</td><td>Y</td><td>RP</td><td>66.5</td><td>951</td><td>660</td><td>291</td><td>Gastric</td><td>Various</td><td>Surgery</td><td>74.2</td><td>AWGS 1/AMA</td><td>111</td><td>69</td><td>42</td><td>Y</td><td>G</td></tr><tr><td>Ní Bhuachalla EB et al., 2018 [147]</td><td>N</td><td>P</td><td>26.1</td><td>725</td><td>433</td><td>292</td><td>Various</td><td>Various</td><td>Chemotherapy</td><td>64.3</td><td>CT scan/NA</td><td>274</td><td>144</td><td>130</td><td>N</td><td>G</td></tr><tr><td>Kim YR et al., 2018 [148]</td><td>Y</td><td>RP</td><td>80.0</td><td>92</td><td>92</td><td>0</td><td>Liver</td><td>Metastatic</td><td>Surgery</td><td>54.0</td><td>CT scan/NA</td><td>72</td><td>72</td><td>0</td><td>Y</td><td>G</td></tr><tr><td>Lee JS et al., 2018 [149]</td><td>Y</td><td>RP</td><td>31.9</td><td>140</td><td>106</td><td>34</td><td>Gastric</td><td>Various</td><td>Chemotherapy</td><td>67.0</td><td>CT scan/SMI</td><td>67</td><td>66</td><td>1</td><td>N</td><td>F</td></tr><tr><td>Mayr R et al., 2018 [150]</td><td>N</td><td>RP</td><td>3.0</td><td>327</td><td>262</td><td>65</td><td>Urothelial</td><td>Various</td><td>Surgery</td><td>70.0</td><td>CT scan/SMI</td><td>108</td><td>81</td><td>27</td><td>N</td><td>G</td></tr><tr><td>Mao CC et al., 2018 [151]</td><td>Y</td><td>P</td><td>1.2</td><td>682</td><td>513</td><td>169</td><td>Gastric</td><td>Various</td><td>Surgery</td><td>64.5</td><td>AWGS 1/SMI</td><td>132</td><td>90</td><td>42</td><td>Y</td><td>F</td></tr><tr><td>Motoori M et al., 2018 [152]</td><td>Y</td><td>RP</td><td>0.0</td><td>83</td><td>66</td><td>17</td><td>Esophageal</td><td>Various</td><td>Various</td><td>65.0</td><td>BIA/ASM</td><td>28</td><td>55</td><td>NA</td><td>N</td><td>P</td></tr><tr><td>McSorley ST et al., 2018 [153]</td><td>N</td><td>P</td><td>96.0</td><td>322</td><td>174</td><td>148</td><td>Colorectal</td><td>Various</td><td>Surgery</td><td>NA</td><td>CT scan/SMI</td><td>158</td><td>NA</td><td>NA</td><td>Y</td><td>F</td></tr><tr><td>van der Kroft G et al., 2018 [154]</td><td>N</td><td>P</td><td>1.0</td><td>63</td><td>39</td><td>24</td><td>Colorectal</td><td>Various</td><td>Surgery</td><td>69.0</td><td>CT scan/SMI</td><td>33</td><td>20</td><td>13</td><td>N</td><td>F</td></tr><tr><td>van Vugt JLA et al., 2018 [155]</td><td>N</td><td>P</td><td>1.0</td><td>816</td><td>440</td><td>376</td><td>Colorectal</td><td>Various</td><td>Surgery</td><td>NA</td><td>CT scan/SMI</td><td>411</td><td>NA</td><td>NA</td><td>Y</td><td>G</td></tr><tr><td>Williams GR et al., 2018 [156]</td><td>N</td><td>P</td><td>0.1</td><td>25</td><td>12</td><td>13</td><td>Colorectal</td><td>Various</td><td>Chemotherapy</td><td>59.0</td><td>CT scan/SMI</td><td>12</td><td>NA</td><td>NA</td><td>N</td><td>F</td></tr><tr><td>Zhang WT et al., 2018 [157]</td><td>Y</td><td>RP</td><td>1.0</td><td>636</td><td>478</td><td>158</td><td>Gastric</td><td>Various</td><td>Surgery</td><td>NA</td><td>AWGS 1/SMI</td><td>86</td><td>64</td><td>22</td><td>Y</td><td>G</td></tr><tr><td>Zhang Y et al., 2018 [158]</td><td>Y</td><td>RP</td><td>0.2</td><td>156</td><td>115</td><td>41</td><td>Gastric</td><td>Various</td><td>Surgery</td><td>59.1</td><td>CT scan/SMI</td><td>24</td><td>17</td><td>7</td><td>Y</td><td>G</td></tr><tr><td>Okugawa Y et al., 2018 [159]</td><td>Y</td><td>P</td><td>60.0</td><td>167</td><td>99</td><td>68</td><td>Colorectal</td><td>Various</td><td>Various</td><td>67.0</td><td>CT scan/PMI</td><td>55</td><td>20</td><td>35</td><td>N</td><td>F</td></tr><tr><td>Rier HN et al., 2018 [160]</td><td>N</td><td>P</td><td>0.0</td><td>131</td><td>73</td><td>58</td><td>Various</td><td>Various</td><td>Various</td><td>72.0</td><td>EWGOS 1/SMI</td><td>34</td><td>18</td><td>16</td><td>Y</td><td>F</td></tr><tr><td>Sato S et al., 2018 [161]</td><td>Y</td><td>RP</td><td>36.0</td><td>48</td><td>32</td><td>16</td><td>Esophageal</td><td>Locally advanced</td><td>Various</td><td>65.5</td><td>CT scan/SMI</td><td>34</td><td>23</td><td>11</td><td>Y</td><td>F</td></tr><tr><td>Stretch C et al., 2018 [162]</td><td>N</td><td>RP</td><td>120.0</td><td>123</td><td>61</td><td>52</td><td>Pancreas</td><td>Various</td><td>Surgery</td><td>68.5</td><td>CT scan/SMI</td><td>50</td><td>29</td><td>21</td><td>N</td><td>F</td></tr><tr><td>Sugimoto M et al., 2018 [163]</td><td>N</td><td>RP</td><td>60.0</td><td>323</td><td>176</td><td>147</td><td>Pancreas</td><td>Various</td><td>Various</td><td>65.0</td><td>CT scan/SMI</td><td>200</td><td>NA</td><td>NA</td><td>Y</td><td>G</td></tr><tr><td>Sui K et al., 2018 [164]</td><td>Y</td><td>P</td><td>60.0</td><td>354</td><td>203</td><td>151</td><td>Pancreas</td><td>Various</td><td>Surgery</td><td>70.0</td><td>CT scan/SMI</td><td>87</td><td>51</td><td>36</td><td>Y</td><td>G</td></tr><tr><td>Limpawattana P et al., 2018 [165]</td><td>Y</td><td>P</td><td>30.0</td><td>75</td><td>58</td><td>17</td><td>Bile ducts</td><td>Various</td><td>Various</td><td>57.0</td><td>AWGS 1/ASM</td><td>40</td><td>40</td><td>6</td><td>Y</td><td>F</td></tr><tr><td>Caan BJ et al., 2018 [166]</td><td>N</td><td>RP</td><td>120.0</td><td>3241</td><td>0</td><td>3241</td><td>Breast</td><td>Various</td><td>Various</td><td>54.1</td><td>CT scan/SMI</td><td>1086</td><td>0</td><td>1086</td><td>N</td><td>G</td></tr><tr><td>Ha Y et al., 2018 [167]</td><td>Y</td><td>RP</td><td>96.0</td><td>178</td><td>141</td><td>37</td><td>Liver</td><td>Various</td><td>Various</td><td>NA</td><td>CT scan/SMI</td><td>62</td><td>43</td><td>19</td><td>N</td><td>G</td></tr><tr><td>Nakashima Y et al., 2018 [168]</td><td>Y</td><td>RP</td><td>60.0</td><td>341</td><td>289</td><td>52</td><td>Esophageal</td><td>Various</td><td>Surgery</td><td>NA</td><td>CT scan/SMI</td><td>171</td><td>NA</td><td>NA</td><td>Y</td><td>G</td></tr><tr><td>Makiura D et al., 2018 [169]</td><td>Y</td><td>P</td><td>60.0</td><td>98</td><td>83</td><td>15</td><td>Esophageal</td><td>Various</td><td>Surgery</td><td>67.0</td><td>AWGS 1/ASM</td><td>31</td><td>24</td><td>7</td><td>N</td><td>F</td></tr><tr><td>Mason RJ et al., 2018 [170]</td><td>N</td><td>RP</td><td>84.0</td><td>698</td><td>698</td><td>0</td><td>Prostate</td><td>Various</td><td>Surgery</td><td>61.8</td><td>CT scan/SMI</td><td>388</td><td>388</td><td>0</td><td>Y</td><td>G</td></tr><tr><td>Begini P et al., 2017 [171]</td><td>N</td><td>RP</td><td>100.0</td><td>92</td><td>65</td><td>27</td><td>Liver</td><td>Various</td><td>Various</td><td>71.6</td><td>CT scan/SMI</td><td>37</td><td>20</td><td>17</td><td>N</td><td>G</td></tr><tr><td>Black D et al., 2017 [172]</td><td>N</td><td>RP</td><td>61.0</td><td>447</td><td>256</td><td>191</td><td>Various</td><td>Various</td><td>Various</td><td>NA</td><td>CT scan/SMI</td><td>104</td><td>NA</td><td>NA</td><td>Y</td><td>G</td></tr><tr><td>Daly LE et al., 2017 [173]</td><td>N</td><td>RP</td><td>0.0</td><td>84</td><td>52</td><td>32</td><td>Melanoma</td><td>Metastatic</td><td>Immunotherapy</td><td>54.0</td><td>CT scan/SMI</td><td>20</td><td>10</td><td>10</td><td>Y</td><td>G</td></tr></tbody></table>
<table><caption>Table 1. *Cont.*</caption><thead><tr><th rowspan="2">Reference</th><th rowspan="2">Asia (Y/N)</th><th rowspan="2">Recruitment RCT/P/RP</th><th rowspan="2">Follow-Up (m)</th><th colspan="3">Patients</th><th rowspan="2">Site</th><th rowspan="2">Extension</th><th rowspan="2">Treatment</th><th rowspan="2">Mean or Median Age (y)</th><th rowspan="2">Definition of Sarcopenia/Muscle Mass Index</th><th colspan="3">Sarcopenia</th><th rowspan="2">Over the 95% CI (Y/N)</th><th rowspan="2">NOS G/F/P</th></tr><tr><th>Total</th><th>M</th><th>F</th><th>Total</th><th>M</th><th>F</th></tr></thead><tbody><tr><td>Endo T et al., 2017 [174]</td><td>Y</td><td>P</td><td>0.0</td><td>121</td><td>81</td><td>40</td><td>Various</td><td>Various</td><td>Surgery</td><td>70.3</td><td>BIA/ASM</td><td>29</td><td>NA</td><td>NA</td><td>Y</td><td>F</td></tr><tr><td>Härter J et al., 2017 [175]</td><td>N</td><td>P</td><td>5.0</td><td>60</td><td>34</td><td>26</td><td>Various</td><td>Various</td><td>Surgery</td><td>NA</td><td>BIA/ASM</td><td>11</td><td>NA</td><td>NA</td><td>Y</td><td>P</td></tr><tr><td>Heidelberger V et al., 2017 [176]</td><td>N</td><td>RP</td><td>17.0</td><td>68</td><td>36</td><td>32</td><td>Melanoma</td><td>Various</td><td>Immunotherapy</td><td>65.0</td><td>CT scan/SMI</td><td>34</td><td>NA</td><td>NA</td><td>N</td><td>F</td></tr><tr><td>Huang DD et al., 2017 [177]</td><td>Y</td><td>P</td><td>1.0</td><td>470</td><td>364</td><td>106</td><td>Gastric</td><td>Various</td><td>Surgery</td><td>65.0</td><td>AWGS 1/SMI</td><td>79</td><td>59</td><td>20</td><td>Y</td><td>F</td></tr><tr><td>Imai K et al., 2017 [178]</td><td>Y</td><td>RP</td><td>0.0</td><td>351</td><td>242</td><td>109</td><td>Liver</td><td>Various</td><td>Various</td><td>70.4</td><td>CT scan/SMI</td><td>33</td><td>30</td><td>3</td><td>Y</td><td>G</td></tr><tr><td>Paireder M et al., 2017 [235]</td><td>N</td><td>RP</td><td>99.4</td><td>130</td><td>106</td><td>24</td><td>Esophageal</td><td>Various</td><td>Various</td><td>61.4</td><td>CT scan/SMI</td><td>80</td><td>68</td><td>12</td><td>Y</td><td>G</td></tr><tr><td>Lou N et al., 2017 [179]</td><td>Y</td><td>P</td><td>1.0</td><td>206</td><td>161</td><td>45</td><td>Gastric</td><td>Various</td><td>Surgery</td><td>64.0</td><td>AWGS 1/SMI</td><td>14</td><td>9</td><td>5</td><td>Y</td><td>G</td></tr><tr><td>Cushen SJ et al., 2017 [180]</td><td>N</td><td>RP</td><td>0.0</td><td>55</td><td>43</td><td>12</td><td>Kidney</td><td>Metastatic</td><td>Targeted therapy</td><td>66.0</td><td>CT scan/SMI</td><td>18</td><td>18</td><td>0</td><td>N</td><td>G</td></tr><tr><td>Cespedes Feliciano EMC et al., 2017 [181]</td><td>N</td><td>P</td><td>120.0</td><td>2470</td><td>1251</td><td>1219</td><td>Colorectal</td><td>Various</td><td>Surgery</td><td>63.0</td><td>CT scan/SMI</td><td>1133</td><td>NA</td><td>NA</td><td>Y</td><td>G</td></tr><tr><td>Elliott JA et al., 2017 [182]</td><td>N</td><td>P</td><td>60.0</td><td>207</td><td>165</td><td>42</td><td>Esophageal</td><td>Various</td><td>Surgery</td><td>61.6</td><td>CT scan/SMI</td><td>49</td><td>45</td><td>4</td><td>Y</td><td>F</td></tr><tr><td>Wendrich AW et al., 2017 [183]</td><td>N</td><td>RP</td><td>90.0</td><td>112</td><td>72</td><td>40</td><td>Head and neck</td><td>Various</td><td>Chemotherapy</td><td>54.5</td><td>CT scan/SMI</td><td>61</td><td>23</td><td>38</td><td>Y</td><td>G</td></tr><tr><td>Bronger H et al., 2017 [184]</td><td>N</td><td>RP</td><td>60.0</td><td>128</td><td>0</td><td>128</td><td>Ovary</td><td>Various</td><td>Various</td><td>65.0</td><td>CT scan/SMI</td><td>16</td><td>0</td><td>16</td><td>Y</td><td>G</td></tr><tr><td>Ishihara H et al., 2017 [185]</td><td>Y</td><td>RP</td><td>58.0</td><td>137</td><td>89</td><td>48</td><td>Urothelial</td><td>Locally advanced</td><td>Surgery</td><td>72.8</td><td>CT scan/SMI</td><td>90</td><td>48</td><td>42</td><td>Y</td><td>F</td></tr><tr><td>Miyata H et al., 2017 [186]</td><td>Y</td><td>P</td><td>0.0</td><td>94</td><td>76</td><td>18</td><td>Esophageal</td><td>Various</td><td>Various</td><td>64.2</td><td>BIA/NA</td><td>44</td><td>NA</td><td>NA</td><td>N</td><td>G</td></tr><tr><td>Zhou CJ et al., 2017 [187]</td><td>Y</td><td>P</td><td>1.0</td><td>240</td><td>190</td><td>50</td><td>Gastric</td><td>Various</td><td>Surgery</td><td>73.0</td><td>AWGS 1/SMI</td><td>69</td><td>52</td><td>17</td><td>Y</td><td>F</td></tr><tr><td>Chemama S et al., 2016 [188]</td><td>N</td><td>RP</td><td>0.0</td><td>97</td><td>37</td><td>60</td><td>Colorectal</td><td>Metastatic</td><td>Various</td><td>53.0</td><td>CT scan/SMI</td><td>39</td><td>6</td><td>33</td><td>N</td><td>G</td></tr><tr><td>Grotenhuis BA et al., 2016 [189]</td><td>N</td><td>RCT</td><td>104.0</td><td>120</td><td>88</td><td>32</td><td>Esophageal</td><td>Locally advanced</td><td>Various</td><td>62.0</td><td>CT scan/SMI</td><td>54</td><td>42</td><td>12</td><td>N</td><td>G</td></tr><tr><td>Nishigori T et al., 2016 [190]</td><td>Y</td><td>RP</td><td>0.0</td><td>199</td><td>164</td><td>35</td><td>Esophageal</td><td>Various</td><td>Surgery</td><td>65.0</td><td>CT scan/SMI</td><td>149</td><td>133</td><td>16</td><td>Y</td><td>G</td></tr><tr><td>Okumura S et al., 2016 [191]</td><td>Y</td><td>RP</td><td>60.0</td><td>207</td><td>111</td><td>96</td><td>Bile ducts</td><td>Various</td><td>Surgery</td><td>68.0</td><td>CT scan/SMI</td><td>71</td><td>36</td><td>35</td><td>N</td><td>G</td></tr><tr><td>Pecorelli N et al., 2016 [192]</td><td>N</td><td>RP</td><td>2.0</td><td>202</td><td>108</td><td>94</td><td>Pancreas</td><td>Various</td><td>Surgery</td><td>66.8</td><td>CT scan/SMI</td><td>132</td><td>79</td><td>53</td><td>Y</td><td>F</td></tr><tr><td>Park I et al., 2016 [193]</td><td>Y</td><td>P</td><td>44.3</td><td>88</td><td>59</td><td>29</td><td>Various</td><td>Metastatic</td><td>Chemotherapy</td><td>65.0</td><td>CT scan/ASM</td><td>76</td><td>57</td><td>19</td><td>Y</td><td>F</td></tr><tr><td>Suzuki Y et al., 2016 [194]</td><td>Y</td><td>RP</td><td>100.0</td><td>90</td><td>52</td><td>38</td><td>Lung NSC</td><td>Local</td><td>Surgery</td><td>68.7</td><td>CT scan/SMI</td><td>38</td><td>16</td><td>22</td><td>N</td><td>F</td></tr><tr><td>Takeoka Y et al. 2016 [195]</td><td>Y</td><td>RP</td><td>60.0</td><td>56</td><td>19</td><td>37</td><td>Myeloma</td><td>Metastatic</td><td>Chemotherapy</td><td>71.0</td><td>CT scan/SMI</td><td>37</td><td>8</td><td>29</td><td>Y</td><td>F</td></tr><tr><td>Fukushima H et al., 2016 [196]</td><td>Y</td><td>RP</td><td>96.0</td><td>81</td><td>53</td><td>28</td><td>Urothelial</td><td>Various</td><td>Surgery</td><td>71.0</td><td>CT scan/SMI</td><td>47</td><td>28</td><td>19</td><td>Y</td><td>G</td></tr><tr><td>Go SI et al., 2016 [197]</td><td>Y</td><td>RP</td><td>132.0</td><td>187</td><td>112</td><td>75</td><td>Lymphoma</td><td>Metastatic</td><td>Chemotherapy</td><td>NA</td><td>CT scan/SMI</td><td>46</td><td>28</td><td>18</td><td>Y</td><td>G</td></tr><tr><td>Kumar A et al., 2016 [198]</td><td>N</td><td>P</td><td>60.0</td><td>296</td><td>0</td><td>296</td><td>Ovary</td><td>Metastatic</td><td>Chemotherapy</td><td>64.6</td><td>CT scan/SMI</td><td>132</td><td>0</td><td>132</td><td>N</td><td>G</td></tr><tr><td>Pedzwiatr M et al., 2016 [199]</td><td>N</td><td>P</td><td>1.0</td><td>124</td><td>73</td><td>51</td><td>Colorectal</td><td>Various</td><td>Surgery</td><td>65.9</td><td>CT scan/SMI</td><td>34</td><td>12</td><td>22</td><td>Y</td><td>G</td></tr><tr><td>Rollins KE et al., 2016 [200]</td><td>N</td><td>RP</td><td>66.0</td><td>228</td><td>124</td><td>104</td><td>Pancreas</td><td>Various</td><td>Chemotherapy</td><td>NA</td><td>CT scan/SMI</td><td>138</td><td>NA</td><td>NA</td><td>Y</td><td>G</td></tr><tr><td>Yabusaki N et al., 2016 [201]</td><td>Y</td><td>RP</td><td>60.0</td><td>195</td><td>157</td><td>38</td><td>Liver</td><td>Local</td><td>Surgery</td><td>66.0</td><td>CT scan/SMI</td><td>89</td><td>57</td><td>32</td><td>N</td><td>F</td></tr><tr><td>Buettner S et al., 2016 [202]</td><td>N</td><td>P</td><td>12.0</td><td>1326</td><td>730</td><td>596</td><td>Various</td><td>Various</td><td>Surgery</td><td>62.5</td><td>CT scan/TPA</td><td>398</td><td>219</td><td>179</td><td>Y</td><td>G</td></tr><tr><td>Amini N et al., 2015 [203]</td><td>N</td><td>RP</td><td>60.0</td><td>763</td><td>418</td><td>345</td><td>Pancreas</td><td>Various</td><td>Surgery</td><td>67.0</td><td>CT scan/TPA</td><td>192</td><td>NA</td><td>NA</td><td>Y</td><td>G</td></tr><tr><td>Anandavadivelan P et al., 2015 [204]</td><td>N</td><td>RCT</td><td>0.0</td><td>72</td><td>61</td><td>11</td><td>Esophageal</td><td>Various</td><td>Chemotherapy</td><td>67.0</td><td>CT scan/SMI</td><td>31</td><td>NA</td><td>NA</td><td>N</td><td>G</td></tr><tr><td>Fukuda Y et al., 2015 [205]</td><td>Y</td><td>P</td><td>0.0</td><td>99</td><td>66</td><td>33</td><td>Gastric</td><td>Various</td><td>Surgery</td><td>NA</td><td>AWGS 1/ASM</td><td>21</td><td>19</td><td>2</td><td>Y</td><td>G</td></tr><tr><td>Huang DD et al., 2015 [206]</td><td>Y</td><td>P</td><td>1.0</td><td>142</td><td>88</td><td>54</td><td>Colorectal</td><td>Various</td><td>Surgery</td><td>62.0</td><td>AWGS 1/SMI</td><td>17</td><td>11</td><td>6</td><td>Y</td><td>G</td></tr><tr><td>Ida S et al., 2015 [207]</td><td>Y</td><td>P</td><td>0.0</td><td>138</td><td>121</td><td>17</td><td>Esophageal</td><td>Various</td><td>Surgery</td><td>NA</td><td>BIA/NA</td><td>61</td><td>47</td><td>14</td><td>N</td><td>G</td></tr><tr><td>Kim EY et al., 2015 [208]</td><td>Y</td><td>RP</td><td>38.0</td><td>149</td><td>127</td><td>22</td><td>Lung SC</td><td>Various</td><td>Various</td><td>68.6</td><td>CT scan/SMI</td><td>118</td><td>110</td><td>8</td><td>Y</td><td>G</td></tr><tr><td>Levolger S et al., 2015 [209]</td><td>N</td><td>P</td><td>36.0</td><td>90</td><td>63</td><td>27</td><td>Liver</td><td>Various</td><td>Various</td><td>62.0</td><td>CT scan/SMI</td><td>52</td><td>39</td><td>13</td><td>Y</td><td>G</td></tr><tr><td>Reisinger KW et al., 2015 [210]</td><td>N</td><td>RP</td><td>1.0</td><td>310</td><td>155</td><td>155</td><td>Esophageal</td><td>Various</td><td>Surgery</td><td>69.0</td><td>CT scan/SMI</td><td>148</td><td>90</td><td>58</td><td>Y</td><td>G</td></tr><tr><td>Tamandl D et al., 2015 [211]</td><td>N</td><td>RP</td><td>60.0</td><td>200</td><td>151</td><td>49</td><td>Esophageal</td><td>Various</td><td>Surgery</td><td>63.9</td><td>CT scan/SMI</td><td>130</td><td>107</td><td>23</td><td>Y</td><td>G</td></tr><tr><td>Tegels JJ et al., 2015 [212]</td><td>N</td><td>RP</td><td>6.0</td><td>149</td><td>NA</td><td>NA</td><td>Gastric</td><td>Various</td><td>Surgery</td><td>69.8</td><td>EWGOS 1/SMI</td><td>86</td><td>NA</td><td>NA</td><td>Y</td><td>G</td></tr><tr><td>Voron T et al., 2015 [213]</td><td>N</td><td>RP</td><td>70.0</td><td>109</td><td>92</td><td>17</td><td>Liver</td><td>Local</td><td>Surgery</td><td>61.7</td><td>CT scan/SMI</td><td>59</td><td>53</td><td>6</td><td>Y</td><td>G</td></tr><tr><td>Lodewic TM et al., 2015 [214]</td><td>N</td><td>P</td><td>60.0</td><td>171</td><td>104</td><td>67</td><td>Colorectal</td><td>Metastatic</td><td>Surgery</td><td>64.0</td><td>CT scan/SMI</td><td>80</td><td>45</td><td>35</td><td>N</td><td>G</td></tr></tbody></table>
<table><caption>Table 1. *Cont.*</caption><thead><tr><th rowspan="2">Reference</th><th rowspan="2">Asia (Y/N)</th><th rowspan="2">Recruitment RCT/P/RP</th><th rowspan="2">Follow-Up (m)</th><th colspan="3">Patients</th><th rowspan="2">Site</th><th rowspan="2">Extension</th><th rowspan="2">Treatment</th><th rowspan="2">Mean or Median Age (y)</th><th rowspan="2">Definition of Sarcopenia/Muscle Mass Index</th><th colspan="3">Sarcopenia</th><th rowspan="2">Over the 95% CI (Y/N)</th><th rowspan="2">NOS G/F/P</th></tr><tr><th>Total</th><th>M</th><th>F</th><th>Total</th><th>M</th><th>F</th></tr></thead><tbody><tr><td>Tan BH et al., 2015 [215]</td><td>N</td><td>RP</td><td>83.3</td><td>89</td><td>67</td><td>22</td><td>Various</td><td>Various</td><td>Chemotherapy</td><td>65.8</td><td>CT scan/SMI</td><td>44</td><td>34</td><td>10</td><td>N</td><td>G</td></tr><tr><td>Wang SL et al., 2015 [216]</td><td>Y</td><td>P</td><td>1.0</td><td>255</td><td>190</td><td>65</td><td>Gastric</td><td>Various</td><td>Surgery</td><td>65.1</td><td>AWGS 1/SMI</td><td>32</td><td>26</td><td>6</td><td>Y</td><td>G</td></tr><tr><td>van Vugt JL et al., 2015 [217]</td><td>N</td><td>RP</td><td>1.0</td><td>206</td><td>100</td><td>106</td><td>Colorectal</td><td>Metastatic</td><td>Surgery</td><td>NA</td><td>CT scan/SMI</td><td>90</td><td>46</td><td>44</td><td>N</td><td>G</td></tr><tr><td>Gonzalez MC et al., 2014 [218]</td><td>N</td><td>P</td><td>36.0</td><td>175</td><td>60</td><td>115</td><td>Various</td><td>Various</td><td>Chemotherapy</td><td>56.9</td><td>BIA/ASM</td><td>22</td><td>NA</td><td>NA</td><td>Y</td><td>G</td></tr><tr><td>Barret M et al., 2014 [219]</td><td>N</td><td>P</td><td>2.0</td><td>51</td><td>38</td><td>13</td><td>Colorectal</td><td>Metastatic</td><td>Chemotherapy</td><td>65.0</td><td>CT scan/SMI</td><td>36</td><td>31</td><td>5</td><td>Y</td><td>G</td></tr><tr><td>Harimoto N et al., 2013 [220]</td><td>Y</td><td>RP</td><td>60.0</td><td>186</td><td>145</td><td>41</td><td>Liver</td><td>Various</td><td>Surgery</td><td>NA</td><td>CT scan/SMI</td><td>75</td><td>50</td><td>25</td><td>N</td><td>G</td></tr><tr><td>Huillard O et al., 2013 [221]</td><td>N</td><td>RP</td><td>52.0</td><td>61</td><td>38</td><td>59</td><td>Kidney</td><td>Metastatic</td><td>Targeted therapy</td><td>60.0</td><td>CT scan/SMI</td><td>32</td><td>24</td><td>8</td><td>N</td><td>G</td></tr><tr><td>Veasey-Rodrigues H et al., 2013 [222]</td><td>N</td><td>P</td><td>2.0</td><td>16</td><td>5</td><td>11</td><td>Various</td><td>Metastatic</td><td>Targeted therapy</td><td>60.0</td><td>CT scan/SMI</td><td>7</td><td>NA</td><td>NA</td><td>Y</td><td>F</td></tr><tr><td>Veasey-Rodrigues H et al., 2013 [223]</td><td>N</td><td>RCT</td><td>3.0</td><td>306</td><td>159</td><td>147</td><td>Various</td><td>Metastatic</td><td>Various</td><td>56.0</td><td>CT scan/SMI</td><td>144</td><td>93</td><td>51</td><td>Y</td><td>G</td></tr><tr><td>Meza-Junco J et al., 2013 [224]</td><td>N</td><td>RP</td><td>24.0</td><td>116</td><td>98</td><td>18</td><td>Liver</td><td>Various</td><td>Various</td><td>58.0</td><td>CT scan/SMI</td><td>35</td><td>30</td><td>5</td><td>N</td><td>F</td></tr><tr><td>Lieffers JR et al., 2012 [225]</td><td>N</td><td>RP</td><td>1.0</td><td>234</td><td>135</td><td>99</td><td>Colorectal</td><td>Various</td><td>Surgery</td><td>63.0</td><td>CT scan/SMI</td><td>91</td><td>57</td><td>34</td><td>N</td><td>G</td></tr><tr><td>Mir O et al., 2012 [226]</td><td>N</td><td>RP</td><td>16.0</td><td>18</td><td>15</td><td>3</td><td>Liver</td><td>Metastatic</td><td>Chemotherapy</td><td>64.0</td><td>CT scan/SMI</td><td>9</td><td>NA</td><td>NA</td><td>N</td><td>F</td></tr><tr><td>Parsons HA et al., 2012 [227]</td><td>N</td><td>RCT</td><td>26.6</td><td>104</td><td>65</td><td>39</td><td>Various</td><td>Metastatic</td><td>Various</td><td>NA</td><td>CT scan/SMI</td><td>53</td><td>36</td><td>17</td><td>N</td><td>G</td></tr><tr><td>Parsons HA et al., 2012 [228]</td><td>N</td><td>RP</td><td>26.6</td><td>48</td><td>19</td><td>29</td><td>Various</td><td>Metastatic</td><td>Intra-arterial infusion for hepatocellular carcinoma</td><td>56.0</td><td>CT scan/SMI</td><td>21</td><td>10</td><td>11</td><td>N</td><td>F</td></tr><tr><td>van Vledder MG et al., 2012 [229]</td><td>N</td><td>RP</td><td>97.0</td><td>196</td><td>120</td><td>76</td><td>Colorectal</td><td>Metastatic</td><td>Surgery</td><td>64.5</td><td>CT scan/SMI</td><td>38</td><td>11</td><td>27</td><td>Y</td><td>G</td></tr><tr><td>Dalal S et al., 2012 [230]</td><td>N</td><td>RCT</td><td>90.0</td><td>41</td><td>18</td><td>23</td><td>Pancreas</td><td>Locally advanced</td><td>Various</td><td>58.9</td><td>CT scan/SMI</td><td>26</td><td>NA</td><td>NA</td><td>Y</td><td>F</td></tr><tr><td>Antoun S et al., 2010 [231]</td><td>N</td><td>RCT</td><td>6.0</td><td>80</td><td>60</td><td>20</td><td>Kidney</td><td>Metastatic</td><td>Targeted therapy</td><td>59.8</td><td>CT scan/SMI</td><td>42</td><td>20</td><td>13</td><td>Y</td><td>G</td></tr><tr><td>Tan BH et al., 2009 [232]</td><td>N</td><td>P</td><td>42.0</td><td>111</td><td>52</td><td>59</td><td>Pancreas</td><td>Various</td><td>Palliative</td><td>64.4</td><td>CT scan/SMI</td><td>62</td><td>33</td><td>27</td><td>Y</td><td>G</td></tr><tr><td>Prado CM et al., 2009 [233]</td><td>N</td><td>P</td><td>19.2</td><td>55</td><td>NA</td><td>55</td><td>Breast</td><td>Metastatic</td><td>Targeted therapy</td><td>54.8</td><td>CT scan/SMI</td><td>14</td><td>NA</td><td>14</td><td>N</td><td>G</td></tr><tr><td>Prado CM et al., 2008 [234]</td><td>N</td><td>P</td><td>39.6</td><td>250</td><td>136</td><td>114</td><td>Various</td><td>Various</td><td>Not specified</td><td>63.9</td><td>CT scan/SMI</td><td>38</td><td>28</td><td>10</td><td>Y</td><td>F</td></tr></tbody></table>

Y = yes; N = no; RCT = randomized control trial; P = prospective observational study; RP = retrospective observational study with consecutive inclusion; M = male; F = female; NSC = non-small cell; SC = small cell; NA = not available; BIA = bioelectrical impedance analysis; DXA = dual energy X-ray absorptiometry; AMA = arm muscle area; ASM = appendicular skeletal muscle mass; SMI = skeletal muscle index; PMI = psoas muscle index; TPA = total psoas area; AWGS = Asian Working Group on Sarcopenia; EWGOS = European Working Group On Sarcopenia; NOS score: G = good; F = fair; P = poor.
<table><caption>**Table 2.** Prevalence of sarcopenia among cancer patients.</caption><thead><tr><th rowspan="2">Study Groups</th><th colspan="2">Patients</th><th rowspan="2">Prevalence<br>% [95% CI]</th><th rowspan="2">p Value for Subgroup<br>Differences</th><th colspan="2">Heterogeneity</th></tr><tr><th>N</th><th>(%)</th><th>I<sup>2</sup></th><th>p</th></tr></thead><tbody><tr><td><strong>Overall</strong></td><td></td><td></td><td></td><td>0.11</td><td></td><td></td></tr><tr><td>All studies</td><td>65,936</td><td>(100)</td><td>38.0 [36.0-41.0]</td><td></td><td>97%</td><td>&lt;0.01</td></tr><tr><td>Excluding studies over the 95% CI<br>(funnel plot)</td><td>18,935</td><td>(29)</td><td>40.5 [39.0-42.0]</td><td></td><td>66%</td><td>&lt;0.01</td></tr><tr><td><strong>Quality of study (NOS scale)</strong></td><td></td><td></td><td></td><td>0.75</td><td></td><td></td></tr><tr><td>Good</td><td>47,028</td><td>(71)</td><td>38.0 [34.0-41.0]</td><td></td><td>97%</td><td>&lt;0.01</td></tr><tr><td>Fair</td><td>18,287</td><td>(28)</td><td>40.0 [35.0-44.0]</td><td></td><td>96%</td><td>&lt;0.01</td></tr><tr><td>Poor</td><td>621</td><td>(1)</td><td>40.5 [28.5-54.0]</td><td></td><td>86.5%</td><td>&lt;0.01</td></tr><tr><td><strong>Year of publication</strong></td><td></td><td></td><td></td><td>0.80</td><td></td><td></td></tr><tr><td>2008-2012</td><td>1343</td><td>(2)</td><td>40.0 [30.0-50.0]</td><td></td><td>92%</td><td>&lt;0.01</td></tr><tr><td>2013-2017</td><td>13,411</td><td>(20)</td><td>40.0 [34.0-46.0]</td><td></td><td>96%</td><td>&lt;0.01</td></tr><tr><td>2018-2022</td><td>51,182</td><td>(78)</td><td>38.0 [35.0-41.0]</td><td></td><td>97%</td><td>&lt;0.01</td></tr><tr><td><strong>N° of patients included</strong></td><td></td><td></td><td></td><td>&lt;0.01</td><td></td><td></td></tr><tr><td>&lt;100</td><td>4364</td><td>(7)</td><td>45.0 [41.0-50.0]</td><td></td><td>84%</td><td>&lt;0.01</td></tr><tr><td>&lt;100-199</td><td>9606</td><td>(14.5)</td><td>41.0 [36.0-47.0]</td><td></td><td>95%</td><td>&lt;0.01</td></tr><tr><td>&lt;200-399</td><td>16,023</td><td>(24)</td><td>36.0 [31.0-42.0]</td><td></td><td>97%</td><td>&lt;0.01</td></tr><tr><td>≥400</td><td>35,943</td><td>(54.5)</td><td>27.0 [22.0-32.0]</td><td></td><td>99%</td><td>&lt;0.01</td></tr><tr><td><strong>World region</strong></td><td></td><td></td><td></td><td>0.26</td><td></td><td></td></tr><tr><td>Asia</td><td>33,453</td><td>(51)</td><td>37.0 [32.0-41.0]</td><td></td><td>97.5%</td><td>&lt;0.01</td></tr><tr><td>Not Asia</td><td>32,483</td><td>(49)</td><td>40.0 [37.0-43.0]</td><td></td><td>95%</td><td>&lt;0.01</td></tr><tr><td><strong>Mean or median age (y) at inclusion<br>(n = 47,986)</strong></td><td></td><td></td><td></td><td>0.21</td><td></td><td></td></tr><tr><td>&lt;65</td><td>30,691</td><td>(64)</td><td>38.0 [34.0-42.0]</td><td></td><td>96%</td><td>&lt;0.01</td></tr><tr><td>≥65</td><td>17,295</td><td>(36)</td><td>42.0 [37.0-46.0]</td><td></td><td>96%</td><td>&lt;0.01</td></tr><tr><td><strong>Sex (n = 46,265)</strong></td><td></td><td></td><td></td><td>0.22</td><td></td><td></td></tr><tr><td>Women</td><td>15,841</td><td>(34)</td><td>34.0 [30.0-38.0]</td><td></td><td>91%</td><td>&lt;0.01</td></tr><tr><td>Men</td><td>30,424</td><td>(66)</td><td>37.0 [34.0-41.0]</td><td></td><td>96%</td><td>&lt;0.01</td></tr><tr><td><strong>BMI (n = 8627)</strong></td><td></td><td></td><td></td><td>&lt;0.01</td><td></td><td></td></tr><tr><td>≥30 kg/m<sup>2</sup></td><td>2628</td><td>(30.5)</td><td>19.0 [13.0-27.0]</td><td></td><td>89.5%</td><td>&lt;0.01</td></tr><tr><td>&lt;30 kg/m<sup>2</sup></td><td>5999</td><td>(69.5)</td><td>39.0 [31.0-47.0]</td><td></td><td>96%</td><td>&lt;0.01</td></tr><tr><td><strong>Cancer site</strong></td><td></td><td></td><td></td><td>&lt;0.01</td><td></td><td></td></tr><tr><td>Gastric</td><td>13,513</td><td>(20.5)</td><td>24.0 [19.0-29.5]</td><td></td><td>97.5%</td><td>&lt;0.01</td></tr><tr><td>Breast</td><td>3517</td><td>(5)</td><td>25.0 [17.5-35.0]</td><td></td><td>82%</td><td>&lt;0.01</td></tr><tr><td>Sarcoma</td><td>254</td><td>(0.4)</td><td>25.0 [20.0-30.5]</td><td></td><td>0%</td><td>0.55</td></tr><tr><td>Uterus</td><td>232</td><td>(0.3)</td><td>26.0 [21.0-32.0]</td><td></td><td>-</td><td>-</td></tr><tr><td>Head and neck</td><td>3724</td><td>(6)</td><td>31.0 [21.0-43.0]</td><td></td><td>95%</td><td>&lt;0.01</td></tr><tr><td>Ovarian</td><td>747</td><td>(1)</td><td>33.0 [16.0-55.0]</td><td></td><td>95%</td><td>&lt;0.01</td></tr><tr><td>Lymphoma</td><td>1130</td><td>(2)</td><td>35.0 [29.0-41.5]</td><td></td><td>75%</td><td>&lt;0.01</td></tr><tr><td>Various</td><td>14,600</td><td>(22)</td><td>35.0 [29.0-41.0]</td><td></td><td>96%</td><td>&lt;0.01</td></tr><tr><td>Cholangiocarcinoma</td><td>231</td><td>(0.3)</td><td>36.0 [26.0-47.0]</td><td></td><td>83%</td><td>&lt;0.01</td></tr><tr><td>Melanoma</td><td>152</td><td>(0.2)</td><td>36.0 [20.0-56.0]</td><td></td><td>91%</td><td>&lt;0.01</td></tr><tr><td>Leukemia</td><td>474</td><td>(0.7)</td><td>36.0 [25.0-49.0]</td><td></td><td>93%</td><td>&lt;0.01</td></tr><tr><td>Colorectal</td><td>11,419</td><td>(17)</td><td>38.0 [33.0-44.0]</td><td></td><td>95%</td><td>&lt;0.01</td></tr><tr><td>Anal</td><td>106</td><td>(0.2)</td><td>39.0 [30.0-48.0]</td><td></td><td>-</td><td>-</td></tr><tr><td>Bile ducts</td><td>282</td><td>(0.4)</td><td>42.5 [30.0-56.0]</td><td></td><td>88%</td><td>&lt;0.01</td></tr><tr><td>Non-small cell lung</td><td>2914</td><td>(4)</td><td>43.0 [34.0-51.5]</td><td></td><td>95%</td><td>&lt;0.01</td></tr><tr><td>Liver</td><td>2391</td><td>(4)</td><td>44.0 [33.0-55.5]</td><td></td><td>95%</td><td>&lt;0.01</td></tr><tr><td>Myeloma</td><td>152</td><td>(0.2)</td><td>44.0 [18.0-74.0]</td><td></td><td>95%</td><td>&lt;0.01</td></tr><tr><td>Thyroids</td><td>180</td><td>(0.3)</td><td>49.5 [42.0-57.0]</td><td></td><td>-</td><td>-</td></tr><tr><td>Pancreatic</td><td>3813</td><td>(6)</td><td>49.5 [41.5-57.5]</td><td></td><td>96%</td><td>&lt;0.01</td></tr><tr><td>Kidney</td><td>356</td><td>(0.5)</td><td>50.0 [43.0-57.0]</td><td></td><td>53%</td><td>0.07</td></tr><tr><td>Esophageal</td><td>3474</td><td>(5)</td><td>50.0 [43.0-57.0]</td><td></td><td>92%</td><td>&lt;0.01</td></tr><tr><td>Urothelial</td><td>1163</td><td>(2)</td><td>52.0 [39.5-64.0]</td><td></td><td>94%</td><td>&lt;0.01</td></tr><tr><td>Prostatic</td><td>985</td><td>(1.5)</td><td>60.0 [38.0-79.0]</td><td></td><td>95%</td><td>&lt;0.01</td></tr><tr><td>Small cell lung</td><td>149</td><td>(0.2)</td><td>79.0 [72.0-85.0]</td><td></td><td>-</td><td>-</td></tr></tbody></table>
<table><caption>Table 2. *Cont.*</caption><thead><tr><th rowspan="2">Study Groups</th><th colspan="2">Patients</th><th rowspan="2">Prevalence % [95% CI]</th><th rowspan="2">p Value for Subgroup Differences</th><th colspan="2">Heterogeneity</th></tr><tr><th>N</th><th>(%)</th><th>I<sup>2</sup></th><th>p</th></tr></thead><tbody><tr><td><strong>Cancer extension</strong></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Various</td><td>54,269</td><td>(82)</td><td>35.0 [32.0-38.0]</td><td rowspan="4">&lt;0.01</td><td>97%</td><td>&lt;0.01</td></tr><tr><td>Local</td><td>2783</td><td>(4)</td><td>39.0 [30.0-50.0]</td><td>97%</td><td>&lt;0.01</td></tr><tr><td>Locally advanced</td><td>3186</td><td>(5)</td><td>48.0 [37.0-59.0]</td><td>96%</td><td>&lt;0.01</td></tr><tr><td>Metastatic</td><td>5698</td><td>(9)</td><td>46.0 [40.0-51.0]</td><td>92%</td><td>&lt;0.01</td></tr><tr><td><strong>Treatment modalities</strong></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Not specified</td><td>918</td><td>(1)</td><td>21.0 [12.5-33.0]</td><td rowspan="8">&lt;0.01</td><td>91%</td><td>&lt;0.01</td></tr><tr><td>Surgery</td><td>40,486</td><td>(61)</td><td>33.0 [30.0-37.0]</td><td>97%</td><td>&lt;0.01</td></tr><tr><td>Targeted therapy</td><td>634</td><td>(1)</td><td>41.0 [32.0-50.0]</td><td>81%</td><td>&lt;0.01</td></tr><tr><td>Various</td><td>17,641</td><td>(27)</td><td>41.0 [36.0-45.0]</td><td>96%</td><td>&lt;0.01</td></tr><tr><td>Immune therapy</td><td>909</td><td>(1)</td><td>46.0 [38.0-54.5]</td><td>80%</td><td>&lt;0.01</td></tr><tr><td>Radiotherapy</td><td>544</td><td>(0.8)</td><td>46.0 [28.0-66.0]</td><td>93%</td><td>&lt;0.01</td></tr><tr><td>Chemotherapy</td><td>4169</td><td>(6)</td><td>48.0 [41.0-56.0]</td><td>93%</td><td>&lt;0.01</td></tr><tr><td>Exclusive supportive care</td><td>445</td><td>(0.7)</td><td>62.0 [55.0-69.0]</td><td>70%</td><td>&lt;0.01</td></tr><tr><td>Intra-arterial infusion for hepatocellular carcinoma</td><td>190</td><td>(0.3)</td><td>68.0 [35.0-90.0]</td><td></td><td>96.5%</td><td>&lt;0.01</td></tr><tr><td><strong>Definition of sarcopenia</strong></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Consensus algorithm-based</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Overall</td><td>11,013</td><td>(17)</td><td>22.0 [19.0-26.0]</td><td rowspan="4">&lt;0.01</td><td>93%</td><td>&lt;0.01</td></tr><tr><td>AWGS</td><td>6996</td><td></td><td>20.5 [16.0-25.0]</td><td>93%</td><td>&lt;0.01</td></tr><tr><td>EWGOS 2</td><td>2462</td><td></td><td>20.5 [15.5-27.0]</td><td>88%</td><td>&lt;0.01</td></tr><tr><td>EWGOS 1</td><td>3086</td><td></td><td>25.0 [17.0-35.0]</td><td>96%</td><td>&lt;0.01</td></tr><tr><td>Muscle mass quantity only</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Overall</td><td>54,923</td><td>(83)</td><td>42.0 [39.0-45.0]</td><td rowspan="4">&lt;0.01</td><td>96%</td><td>&lt;0.01</td></tr><tr><td>DXA</td><td>64</td><td></td><td>25.0 [16.0-37.0]</td><td>-</td><td>-</td></tr><tr><td>BIA</td><td>1306</td><td></td><td>30.0 [23.0-38.0]</td><td>90%</td><td>&lt;0.01</td></tr><tr><td>CT scan</td><td>53,553</td><td></td><td>43.0 [40.0-46.0]</td><td>96.5%</td><td>&lt;0.01</td></tr><tr><td>Muscle mass indices (n = 55,304)</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>AMA (cm<sup>2</sup>)</td><td>951</td><td>(2)</td><td>12.0 [10.0-14.0]</td><td rowspan="5">&lt;0.01</td><td>-</td><td>-</td></tr><tr><td>ASM (kg/m<sup>2</sup>)</td><td>3261</td><td>(6)</td><td>31.0 [24.0-39.0]</td><td>95%</td><td>&lt;0.01</td></tr><tr><td>TPA (cm<sup>2</sup>/m<sup>2</sup>)</td><td>2394</td><td>(4)</td><td>36.0 [27.0-46.0]</td><td>93%</td><td>&lt;0.01</td></tr><tr><td>PMI (cm<sup>2</sup>/m<sup>2</sup>)</td><td>2967</td><td>(5)</td><td>36.5 [28.0-46.0]</td><td>96.5%</td><td>&lt;0.01</td></tr><tr><td>SMI (cm<sup>2</sup>/m<sup>2</sup>)</td><td>45,731</td><td>(83)</td><td>40.0 [37.0-43.0]</td><td>97%</td><td>&lt;0.01</td></tr><tr><td>Median cut-off values of CT scan-based SMI for women (n = 14,216)</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>&lt;38.5 (cm<sup>2</sup>/m<sup>2</sup>)</td><td>4609</td><td>(32)</td><td>25.0 [21.0-29.0]</td><td rowspan="2">&lt;0.01</td><td>87%</td><td>&lt;0.01</td></tr><tr><td>≥38.5 (cm<sup>2</sup>/m<sup>2</sup>)</td><td>9607</td><td>(68)</td><td>47.0 [40.0-54.0]</td><td>92%</td><td>&lt;0.01</td></tr><tr><td>Median cut-off values of CT scan-based SMI for men (n = 20,514)</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>&lt;47.3 (cm<sup>2</sup>/m<sup>2</sup>)</td><td>11,584</td><td>(56)</td><td>28.0 [24.0-32.0]</td><td rowspan="2">&lt;0.01</td><td>95%</td><td>&lt;0.01</td></tr><tr><td>≥47.3 (cm<sup>2</sup>/m<sup>2</sup>)</td><td>8930</td><td>(44)</td><td>52.0 [46.0-58.0]</td><td>95%</td><td>&lt;0.01</td></tr></tbody></table>

Bold = grouping data, and significant *p* value at the threshold of 5%; BIA = bioelectrical impedance analysis; DXA = dual energy X-ray sbsorptiometry; AWGS = Asian Working Group on Sarcopenia; EWGOS = European Working Group On Sarcopenia; AMA = arm muscle area; ASM = appendicular skeletal muscle mass; SMI = skeletal muscle index; PMI = psoas muscle index; TPA = total psoas area.

Although the sensitivity analysis excluding studies over the 95% confidence interval from the funnel plot (n = 137 studies) led to less heterogeneity (I² = 66%), the 40.5% prevalence was not significantly different (*p* = 0.11).

The prevalence was significantly lower (*p* < 0.01) for consensus-based algorithm definitions of sarcopenia (22.0%) than for definitions based on muscle mass measures only (42.0%).

Using the muscle mass measurement-based definition only, the prevalence differed significantly (*p* < 0.01), ranging from 12.0% (AMA) to 40.0% (SMI). Above the SMI medians of 38.5 cm²/m² and 47.3 cm²/m² for women and men, respectively, the prevalence was
47.0% and 52.0%. Figure 1 shows the smoothing splines for the relationship between the prevalence of sarcopenia and muscle mass index measures for women and men (SMI, ASM, and PMI). Regarding SMI, up to the third quartiles of 41.0 cm²/m² and 52.4 cm²/m² for women and men, respectively, the association was linear with a tight confidence interval. Regarding ASM, the association was paradoxical for both women and men. For PMI, the association was strictly linear for women and men, but it resulted in a large confidence interval.

<figure><img src="image_5.png" /><figcaption>**Figure 1.** Non-parametric regression via smoothing splines for assessing the relationship between prevalence of pre-therapeutic sarcopenia and cut-off values of SMI (A,B), ASM (C,D), or PMI (E,F) in women and men with cancer, respectively.</figcaption></figure>

Depending on the cancer site, the prevalence varied very significantly from 24.0% (gastric) to 79.0% (small cell lung). In relation to cancer extension, the prevalence varied significantly from 39.0% (local) to 46.0% (metastatic). According to the treatment mode,
the pre-therapeutic prevalence of sarcopenia varied significantly from 33.0% (surgery) to 68% (intra-arterial infusion for hepatocellular carcinoma). In the 26 studies that reported prevalence according to BMI, the prevalence of sarcopenic obesity was significantly lower (*p* < 0.01) (19.0%) than for non-sarcopenic obesity (39.0%). The prevalence did not differ significantly with study quality, the year of publication, the world region, the age-threshold of 65 years at inclusion, or sex.

In multivariate meta-regression, consensus-based algorithm definitions of sarcopenia (as opposed to loss of muscle mass only), a sample size ≥ 400, and SMI based on CT scan cut-off values for women (not for men) as continuous variables were independently and significantly associated with the prevalence results (Table A2).

### 3.5. Muscle Strength and Physical Performance among Cancer Patients with Sarcopenia

Twelve studies including 3466 patients provided data on muscle strength and physical performance. Handgrip strength values among sarcopenic patients ranged from 17.7 to 22.6 kg and gait speed values among sarcopenic patients ranged from 0.72 to 1.00 m/s [26,51,58,111,138,145,169,177,179,187,206,216]. Figure 2 summarizes the mean differences in handgrip strength and gait speed between sarcopenic and non-sarcopenic patients.

#### A

<figure><img src="image_6.png" /></figure>

#### B

<figure><img src="image_7.png" /><figcaption>**Figure 2.** Pooled mean differences (MD) of handgrip strength (A, kg) and gait speed (B, m/s) between sarcopenic and non-sarcopenic groups among cancer patients [26,51,58,111,138,145,169,177,179,187,206,216].</figcaption></figure>
For handgrip strength, the pooled mean difference was −8.62 kg with a high between-study heterogeneity ($I^2$ = 91%). Regarding gait speed, the pooled mean difference was −0.19 m/s with a moderate between-study heterogeneity ($I^2$ = 68%).

### 3.6. Pre-Therapeutic Sarcopenia Is Associated with OS and PFS among Cancer Patients

Based on 101 studies including 28,995 patients, we found a strong, significant association between pre-therapeutic sarcopenia and OS with a pooled RR of 1.97 [1.79–2.17] and with a high between-study heterogeneity ($I^2$ = 85%, *p* < 0.01). Subgroup analyses are presented in Table 3 and Figure A3, showing a reduction in heterogeneity. The effect measure differed significantly (*p* < 0.01) according to sample size, world region, cancer site, and muscle mass index, while no significant differences were found for sensitivity analysis, study quality, year of publication, age threshold of 65 years at inclusion, cancer extension, treatment mode, and definition of sarcopenia. When low between-study heterogeneity was envisaged (i.e., $I^2$ < 50%), the greatest effects were associated with the PMI-based muscle index (RR = 2.76 [2.21–3.43]), bile duct cancers (RR = 2.71 [1.87–3.92]), and the consensus-based algorithm definitions of sarcopenia (RR = 2.31 [1.97–2.72]).

<table><caption>**Table 3.** Predictive value of pre-therapeutic sarcopenia on overall survival (OS) among cancer patients.</caption><thead><tr><th rowspan="2">Study Groups</th><th colspan="2">Patients</th><th rowspan="2">Relative Risk [95% CI] for OS</th><th rowspan="2">p Value for Subgroup Differences</th><th colspan="2">Heterogeneity</th></tr><tr><th>N</th><th>(%)</th><th>I<sup>2</sup></th><th>p</th></tr></thead><tbody><tr><td><strong>Overall</strong></td><td></td><td></td><td></td><td>0.37</td><td></td><td></td></tr><tr><td>All studies</td><td>28,995</td><td>(100)</td><td>1.97 [1.79–2.17]</td><td></td><td>85%</td><td>&lt;0.01</td></tr><tr><td>Excluding studies over the 95% CI (funnel plot)</td><td>7191</td><td>(25)</td><td>1.68 [1.55–1.80]</td><td></td><td>77%</td><td>&lt;0.01</td></tr><tr><td><strong>Quality of study (NOS)</strong></td><td></td><td></td><td></td><td>0.65</td><td></td><td></td></tr><tr><td>Good</td><td>22,939</td><td>(79)</td><td>1.94 [1.73–2.16]</td><td></td><td>75%</td><td>&lt;0.01</td></tr><tr><td>Fair</td><td>5803</td><td>(20)</td><td>2.10 [1.71–2.58]</td><td></td><td>90.5%</td><td>&lt;0.01</td></tr><tr><td>Poor</td><td>253</td><td>(1)</td><td>1.40 [0.47–4.20]</td><td></td><td>77%</td><td>0.04</td></tr><tr><td><strong>Year of publication</strong></td><td></td><td></td><td></td><td>0.93</td><td></td><td></td></tr><tr><td>2008–2012</td><td>598</td><td>(2)</td><td>1.85 [1.29–2.65]</td><td></td><td>54%</td><td>0.09</td></tr><tr><td>2013–2017</td><td>5977</td><td>(21)</td><td>1.97 [1.53–2.52]</td><td></td><td>93%</td><td>&lt;0.01</td></tr><tr><td>2018–2022</td><td>22,420</td><td>(77)</td><td>1.99 [1.78–2.22]</td><td></td><td>75%</td><td>&lt;0.01</td></tr><tr><td><strong>N° of patients included</strong></td><td></td><td></td><td></td><td>0.01</td><td></td><td></td></tr><tr><td>&lt;100</td><td>1718</td><td>(6)</td><td>2.24 [1.71–2.92]</td><td></td><td>87%</td><td>&lt;0.01</td></tr><tr><td>100–199</td><td>5150</td><td>(18)</td><td>2.17 [1.86–2.53]</td><td></td><td>61%</td><td>&lt;0.01</td></tr><tr><td>200–399</td><td>8417</td><td>(29)</td><td>1.90 [1.57–2.30]</td><td></td><td>81%</td><td>&lt;0.01</td></tr><tr><td>≥400</td><td>13,710</td><td>(47)</td><td>1.57 [1.35–1.82]</td><td></td><td>71%</td><td>&lt;0.01</td></tr><tr><td><strong>World region</strong></td><td></td><td></td><td></td><td>&lt;0.01</td><td></td><td></td></tr><tr><td>Asia</td><td>10,964</td><td>(38)</td><td>2.37 [2.07–2.71]</td><td></td><td>84%</td><td>&lt;0.01</td></tr><tr><td>Not Asia</td><td>18,031</td><td>(62)</td><td>1.69 [1.48–1.91]</td><td></td><td>72%</td><td>&lt;0.01</td></tr><tr><td><strong>Mean or median age (y) at inclusion (n = 23,630)</strong></td><td></td><td></td><td></td><td>0.09</td><td></td><td></td></tr><tr><td>&lt;65</td><td>14,384</td><td>(61)</td><td>1.87 [1.62–2.16]</td><td></td><td>75%</td><td>&lt;0.01</td></tr><tr><td>≥65</td><td>9246</td><td>(39)</td><td>2.24 [1.93–2.61]</td><td></td><td>89%</td><td>&lt;0.01</td></tr><tr><td><strong>Cancer site</strong></td><td></td><td></td><td></td><td>&lt;0.01</td><td></td><td></td></tr><tr><td>Gastric</td><td>5447</td><td>(19)</td><td>1.88 [1.46–2.44]</td><td></td><td>74%</td><td>&lt;0.01</td></tr><tr><td>Breast</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Sarcoma</td><td>145</td><td>(0.5)</td><td>3.42 [0.81–14.4]</td><td></td><td>-</td><td>-</td></tr><tr><td>Uterus</td><td>232</td><td>(0.8)</td><td>2.23 [1.18–3.92]</td><td></td><td>-</td><td>-</td></tr><tr><td>Head and neck</td><td>1692</td><td>(6)</td><td>2.75 [2.00–3.78]</td><td></td><td>62%</td><td>0.03</td></tr><tr><td>Ovarian</td><td>424</td><td>(1.5)</td><td>1.64 [0.53–5.06]</td><td></td><td>82.5%</td><td>0.02</td></tr><tr><td>Lymphoma</td><td>997</td><td>(3)</td><td>1.55 [0.89–2.70]</td><td></td><td>73%</td><td>0.02</td></tr><tr><td>Various</td><td>3649</td><td>(13)</td><td>1.72 [1.19–2.45]</td><td></td><td>96%</td><td>&lt;0.01</td></tr><tr><td>Cholangiocarcinoma</td><td>231</td><td>(0.8)</td><td>2.66 [1.85–3.81]</td><td></td><td>0%</td><td>0.69</td></tr></tbody></table>
<table><caption>Table 3. *Cont.*</caption><thead><tr><th rowspan="2">Study Groups</th><th colspan="2">Patients</th><th rowspan="2">Relative Risk [95% CI] for OS</th><th rowspan="2">p Value for Subgroup Differences</th><th colspan="2">Heterogeneity</th></tr><tr><th>N</th><th>(%)</th><th>I<sup>2</sup></th><th>p</th></tr></thead><tbody><tr><td>Melanoma</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Leukemia</td><td>178</td><td>(0.6)</td><td>3.12 [1.53–6.35]</td><td></td><td>-</td><td>-</td></tr><tr><td>Colorectal</td><td>7252</td><td>(25)</td><td>1.58 [1.28–1.95]</td><td></td><td>67%</td><td>&lt;0.01</td></tr><tr><td>Anal</td><td>106</td><td>(0.4)</td><td>4.50 [1.05–19.2]</td><td></td><td>-</td><td>-</td></tr><tr><td>Bile ducts</td><td>282</td><td>(1)</td><td>2.71 [1.87–3.92]</td><td></td><td>0%</td><td>0.49</td></tr><tr><td>Non-small cell lung</td><td>1440</td><td>(5)</td><td>2.92 [2.01–4.24]</td><td></td><td>53%</td><td>0.04</td></tr><tr><td>Liver</td><td>1422</td><td>(5)</td><td>2.56 [1.94–3.39]</td><td></td><td>43%</td><td>0.07</td></tr><tr><td>Myeloma</td><td>56</td><td>(0.2)</td><td>1.96 [0.78–5.00]</td><td></td><td>-</td><td>-</td></tr><tr><td>Thyroids</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Pancreatic</td><td>1789</td><td>(6)</td><td>1.45 [1.13–1.86]</td><td></td><td>71%</td><td>&lt;0.01</td></tr><tr><td>Kidney</td><td>78</td><td>(0.3)</td><td>2.63 [1.50–4.61]</td><td></td><td>-</td><td>-</td></tr><tr><td>Esophageal</td><td>1856</td><td>(6)</td><td>2.29 [1.77–2.95]</td><td></td><td>49%</td><td>0.03</td></tr><tr><td>Urothelial</td><td>835</td><td>(3)</td><td>1.87 [1.20–2.89]</td><td></td><td>51%</td><td>0.08</td></tr><tr><td>Prostatic</td><td>884</td><td>(3)</td><td>1.35 [0.89–2.03]</td><td></td><td>0%</td><td>0.52</td></tr><tr><td>Small cell lung</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td><strong>Cancer extension</strong></td><td></td><td></td><td></td><td>0.40</td><td></td><td></td></tr><tr><td>Various</td><td>23,842</td><td>(82)</td><td>1.86 [1.68–2.07]</td><td></td><td>72%</td><td>&lt;0.01</td></tr><tr><td>Local</td><td>1404</td><td>(5)</td><td>2.32 [1.71–3.15]</td><td></td><td>27%</td><td>0.23</td></tr><tr><td>Locally advanced</td><td>917</td><td>(3)</td><td>2.42 [1.50–3.92]</td><td></td><td>77%</td><td>&lt;0.01</td></tr><tr><td>Metastatic</td><td>2832</td><td>(10)</td><td>2.09 [1.53–2.86]</td><td></td><td>94%</td><td>&lt;0.01</td></tr><tr><td><strong>Treatment modalities</strong></td><td></td><td></td><td></td><td>0.74</td><td></td><td></td></tr><tr><td>Not specified</td><td>386</td><td>(1)</td><td>2.16 [1.49–3.13]</td><td></td><td>0%</td><td>0.50</td></tr><tr><td>Surgery</td><td>16,463</td><td>(57)</td><td>2.09 [1.84–2.37]</td><td></td><td>63%</td><td>&lt;0.01</td></tr><tr><td>Targeted therapy</td><td>78</td><td>(0.3)</td><td>2.63 [1.50–4.61]</td><td></td><td>-</td><td>-</td></tr><tr><td>Various</td><td>7798</td><td>(27)</td><td>1.85 [1.55–2.20]</td><td></td><td>77%</td><td>&lt;0.01</td></tr><tr><td>Immune therapy</td><td>618</td><td>(2)</td><td>2.37 [0.92–6.08]</td><td></td><td>92%</td><td>&lt;0.01</td></tr><tr><td>Radiotherapy</td><td>516</td><td>(2)</td><td>2.91 [1.23–6.90]</td><td></td><td>77%</td><td>0.01</td></tr><tr><td>Chemotherapy</td><td>2549</td><td>(9)</td><td>1.70 [1.23–2.36]</td><td></td><td>95%</td><td>&lt;0.01</td></tr><tr><td>Exclusive supportive care</td><td>445</td><td>(1.5)</td><td>1.62 [1.06–2.47]</td><td></td><td>64%</td><td>0.10</td></tr><tr><td>Intra-arterial infusion for hepatocellular carcinoma</td><td>142</td><td>(0.5)</td><td>2.22 [1.01–4.86]</td><td></td><td>-</td><td>-</td></tr><tr><td><strong>Definition of sarcopenia</strong></td><td></td><td></td><td></td><td>0.24</td><td></td><td></td></tr><tr><td>Muscle mass quantity only</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>CT scan</td><td>25,656</td><td>(88)</td><td>1.93 [1.74–2.15]</td><td></td><td>86%</td><td>&lt;0.01</td></tr><tr><td>BIA</td><td>347</td><td>(1)</td><td>1.77 [1.00–2.13]</td><td></td><td>35%</td><td>0.22</td></tr><tr><td>DXA</td><td>64</td><td>(0.2)</td><td>2.96 [1.40–6.27]</td><td></td><td>-</td><td>-</td></tr><tr><td>Consensus algorithm-based</td><td>2928</td><td>(10)</td><td>2.31 [1.97–2.72]</td><td></td><td>22%</td><td>0.25</td></tr><tr><td><strong>Muscle mass indices (n = 27,061)</strong></td><td></td><td></td><td></td><td>&lt;0.01</td><td></td><td></td></tr><tr><td>AMA (cm<sup>2</sup>)</td><td>951</td><td>(3)</td><td>2.26 [1.69–3.03]</td><td></td><td>-</td><td>-</td></tr><tr><td>ASM (kg/m<sup>2</sup>)</td><td>1274</td><td>(5)</td><td>2.84 [2.01–4.00]</td><td></td><td>87%</td><td>&lt;0.01</td></tr><tr><td>TPA (cm<sup>2</sup>/m<sup>2</sup>)</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>PMI (cm<sup>2</sup>/m<sup>2</sup>)</td><td>1567</td><td>(6)</td><td>2.76 [2.21–3.43]</td><td></td><td>0%</td><td>0.63</td></tr><tr><td>SMI (cm<sup>2</sup>/m<sup>2</sup>)</td><td>23,269</td><td>(86)</td><td>1.85 [1.66–2.07]</td><td></td><td>75%</td><td>&lt;0.01</td></tr></tbody></table>

Bold = grouping data, and significant *p* value at the threshold of 5%; BIA = bioelectrical impedance analysis; DXA = dual energy X-ray absorptiometry; AMA = arm muscle area; ASM = appendicular skeletal muscle mass; SMI = skeletal muscle index; PMI = psoas muscle index; TPA = total psoas area.

For 29 studies including 6546 patients, we found a strong and significant association between pre-therapeutic sarcopenia and PFS with a pooled RR of 1.76 [1.44–2.16] and a high between-study heterogeneity (I² = 85%, *p* < 0.01). Subgroup analyses are presented in Table 4 and Figure A4, showing a reduction in heterogeneity. The effect measure differed significantly (*p* < 0.01) according to the world region, cancer site, sarcopenia definition, and muscle mass index used, while no significant differences were found for sensitivity analysis, study quality, year of publication, sample size, age threshold of 65 years at inclusion, cancer extension, or treatment mode. When low between-study heterogeneity was envisaged (i.e., I² < 50%), the most marked effects were associated with the consensus-based algorithm
definitions of sarcopenia (RR = 3.59 [2.17–5.92]) and non-small cell lung cancer (RR = 2.43 [1.90–3.12]).

<table><caption>**Table 4.** Predictive value of pre-therapeutic sarcopenia on progression-free survival (PFS) among cancer patients.</caption><thead><tr><th rowspan="2">Study Groups</th><th colspan="2">Patients</th><th rowspan="2">Relative Risk [95% CI] for PFS</th><th rowspan="2">p Value for Subgroup Differences</th><th colspan="2">Heterogeneity</th></tr><tr><th>N</th><th>(%)</th><th>I<sup>2</sup></th><th>p</th></tr></thead><tbody><tr><td><strong>Overall</strong></td><td></td><td></td><td></td><td>0.23</td><td></td><td></td></tr><tr><td>All studies</td><td>6546</td><td>(100)</td><td>1.76 [1.44–2.16]</td><td></td><td>85%</td><td>&lt;0.01</td></tr><tr><td>Excluding studies over the 95% CI (funnel plot)</td><td>4008</td><td>(61)</td><td>1.35 [1.19–1.52]</td><td></td><td>80%</td><td>&lt;0.01</td></tr><tr><td><strong>Quality of study (NOS)</strong></td><td></td><td></td><td></td><td>0.15</td><td></td><td></td></tr><tr><td>Good</td><td>5055</td><td>(77)</td><td>1.83 [1.51–2.21]</td><td></td><td>75%</td><td>&lt;0.01</td></tr><tr><td>Fair</td><td>1345</td><td>(20.5)</td><td>1.68 [0.89–3.15]</td><td></td><td>94%</td><td>&lt;0.01</td></tr><tr><td>Poor</td><td>146</td><td>(2.5)</td><td>0.92 [0.48–1.78]</td><td></td><td>-</td><td>-</td></tr><tr><td><strong>Year of publication</strong></td><td></td><td></td><td></td><td>0.93</td><td></td><td></td></tr><tr><td>2008–2012</td><td>251</td><td>(4)</td><td>1.89 [1.34–2.64]</td><td></td><td>0%</td><td>0.98</td></tr><tr><td>2013–2017</td><td>693</td><td>(10)</td><td>1.83 [1.07–3.13]</td><td></td><td>83%</td><td>&lt;0.01</td></tr><tr><td>2018–2022</td><td>5602</td><td>(86)</td><td>1.75 [1.37–2.24]</td><td></td><td>87%</td><td>&lt;0.01</td></tr><tr><td><strong>N° of patients included</strong></td><td></td><td></td><td></td><td>0.73</td><td></td><td></td></tr><tr><td>&lt;100</td><td>489</td><td>(7.5)</td><td>2.22 [1.24–3.97]</td><td></td><td></td><td>&lt;0.01</td></tr><tr><td>100–199</td><td>1863</td><td>(28.5)</td><td>1.81 [1.35–2.42]</td><td></td><td></td><td>&lt;0.01</td></tr><tr><td>200–399</td><td>1922</td><td>(29)</td><td>1.49 [0.98–2.24]</td><td></td><td></td><td>&lt;0.01</td></tr><tr><td>≥400</td><td>2272</td><td>(35)</td><td>1.79 [0.97–3.29]</td><td></td><td></td><td>&lt;0.01</td></tr><tr><td><strong>World region</strong></td><td></td><td></td><td></td><td>&lt;0.01</td><td></td><td></td></tr><tr><td>Asia</td><td>2307</td><td>(35)</td><td>2.38 [1.81–3.13]</td><td></td><td>80%</td><td>&lt;0.01</td></tr><tr><td>Not Asia</td><td>4239</td><td>(65)</td><td>1.42 [1.12–1.81]</td><td></td><td>75.5%</td><td>&lt;0.01</td></tr><tr><td><strong>Mean or median age (y) at inclusion (n = 5891)</strong></td><td></td><td></td><td></td><td>0.78</td><td></td><td></td></tr><tr><td>&lt;65</td><td>3186</td><td>(54)</td><td>1.75 [1.28–2.40]</td><td></td><td>91%</td><td>&lt;0.01</td></tr><tr><td>≥65</td><td>2705</td><td>(46)</td><td>1.85 [1.43–2.39]</td><td></td><td>60%</td><td>0.01</td></tr><tr><td><strong>Cancer site</strong></td><td></td><td></td><td></td><td>&lt;0.01</td><td></td><td></td></tr><tr><td>Gastric</td><td>726</td><td>(11)</td><td>1.68 [0.43–6.50]</td><td></td><td>96%</td><td>&lt;0.01</td></tr><tr><td>Breast</td><td>55</td><td>(0.8)</td><td>1.90 [1.03–3.50]</td><td></td><td>-</td><td>-</td></tr><tr><td>Sarcoma</td><td>109</td><td>(2)</td><td>4.60 [3.53–6.00]</td><td></td><td>-</td><td>-</td></tr><tr><td>Uterus</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Head and neck</td><td>243</td><td>(3.5)</td><td>2.45 [1.58–3.78]</td><td></td><td>-</td><td>-</td></tr><tr><td>Ovarian</td><td>128</td><td>(2)</td><td>2.64 [1.23–5.64]</td><td></td><td>-</td><td>-</td></tr><tr><td>Lymphoma</td><td>1040</td><td>(16)</td><td>1.95 [1.19–3.20]</td><td></td><td>73%</td><td>0.01</td></tr><tr><td>Various</td><td>349</td><td>(5)</td><td>0.70 [0.54–0.93]</td><td></td><td>0%</td><td>0.92</td></tr><tr><td>Cholangiocarcinoma</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Melanoma</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Leukemia</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Colorectal</td><td>2512</td><td>(38)</td><td>1.35 [1.05–1.74]</td><td></td><td>55%</td><td>0.03</td></tr><tr><td>Anal</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Bile ducts</td><td>207</td><td>(3)</td><td>2.14 [1.46–3.13]</td><td></td><td>-</td><td>-</td></tr><tr><td>Non-small cell lung</td><td>534</td><td>(8)</td><td>2.43 [1.90–3.12]</td><td></td><td>0%</td><td>0.47</td></tr><tr><td>Liver</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Myeloma</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Thyroids</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Pancreatic</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Kidney</td><td>78</td><td>(1)</td><td>3.18 [1.85–5.47]</td><td></td><td>-</td><td>-</td></tr><tr><td>Esophageal</td><td>163</td><td>(2.5)</td><td>1.24 [0.71–2.17]</td><td></td><td>-</td><td>-</td></tr><tr><td>Urothelial</td><td>146</td><td>(2)</td><td>0.92 [0.47–1.78]</td><td></td><td>-</td><td>-</td></tr><tr><td>Prostatic</td><td>256</td><td>(4)</td><td>2.23 [0.69–7.18]</td><td></td><td>71%</td><td>0.06</td></tr><tr><td>Small cell lung</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr></tbody></table>
<table><caption>**Table 4.** *Cont.*</caption><thead><tr><th rowspan="2">Study Groups</th><th colspan="2">Patients</th><th rowspan="2">Relative Risk [95% CI] for PFS</th><th rowspan="2">p Value for Subgroup Differences</th><th colspan="2">Heterogeneity</th></tr><tr><th>N</th><th>(%)</th><th>I<sup>2</sup></th><th>p</th></tr></thead><tbody><tr><td><strong>Cancer extension</strong></td><td></td><td></td><td></td><td>0.13</td><td></td><td></td></tr><tr><td>Various</td><td>4469</td><td>(68)</td><td>1.62 [1.26–2.08]</td><td></td><td>81%</td><td>&lt;0.01</td></tr><tr><td>Local</td><td>315</td><td>(5)</td><td>2.32 [1.62–3.32]</td><td></td><td>-</td><td>-</td></tr><tr><td>Locally advanced</td><td>47</td><td>(1)</td><td>8.11 [1.61–41.0]</td><td></td><td>-</td><td>-</td></tr><tr><td>Metastatic</td><td>1715</td><td>(26)</td><td>1.84 [1.28–2.64]</td><td></td><td>89%</td><td>&lt;0.01</td></tr><tr><td><strong>Treatment modalities</strong></td><td></td><td></td><td></td><td>0.11</td><td></td><td></td></tr><tr><td>Not specified</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Surgery</td><td>3296</td><td>(50)</td><td>1.73 [1.28–2.35]</td><td></td><td>81%</td><td>&lt;0.01</td></tr><tr><td>Targeted therapy</td><td>242</td><td>(4)</td><td>3.21 [1.94–5.33]</td><td></td><td>73%</td><td>0.03</td></tr><tr><td>Various</td><td>2024</td><td>(31)</td><td>1.45 [1.10–1.91]</td><td></td><td>62%</td><td>&lt;0.01</td></tr><tr><td>Immune therapy</td><td>480</td><td>(7)</td><td>2.11 [0.84–5.29]</td><td></td><td>90%</td><td>&lt;0.01</td></tr><tr><td>Radiotherapy</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Chemotherapy</td><td>504</td><td>(8)</td><td>1.74 [0.83–3.64]</td><td></td><td>87%</td><td>&lt;0.01</td></tr><tr><td>Exclusive supportive care</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Intra-arterial infusion for hepatocellular carcinoma</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td><strong>Definition of sarcopenia</strong></td><td></td><td></td><td></td><td>&lt;0.01</td><td></td><td></td></tr><tr><td>Muscle mass quantity only</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>CT scan</td><td>5688</td><td>(87)</td><td>1.70 [1.38–2.10]</td><td></td><td>84%</td><td>&lt;0.01</td></tr><tr><td>BIA</td><td>163</td><td>(2.5)</td><td>1.24 [0.71–2.17]</td><td></td><td>-</td><td>-</td></tr><tr><td>DXA</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Consensus algorithm-based</td><td>695</td><td>(10.5)</td><td>3.59 [2.17–5.92]</td><td></td><td>12%</td><td>0.29</td></tr><tr><td><strong>Muscle mass indices (n = 6383)</strong></td><td></td><td></td><td></td><td>&lt;0.01</td><td></td><td></td></tr><tr><td>AMA (cm<sup>2</sup>)</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>ASM (kg/m<sup>2</sup>)</td><td>47</td><td>(1)</td><td>8.11 [1.61–40.9]</td><td></td><td>-</td><td>-</td></tr><tr><td>TPA (cm<sup>2</sup>/m<sup>2</sup>)</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>PMI (cm<sup>2</sup>/m<sup>2</sup>)</td><td>621</td><td>(9.5)</td><td>3.05 [2.01–4.62]</td><td></td><td>72%</td><td>0.01</td></tr><tr><td>SMI (cm<sup>2</sup>/m<sup>2</sup>)</td><td>5715</td><td>(87)</td><td>1.61 [1.30–1.99]</td><td></td><td>81%</td><td>&lt;0.01</td></tr></tbody></table>

Bold = grouping data, and significant *p* value at the threshold of 5%; BIA = bioelectrical impedance analysis; DXA = dual energy X-ray absorptiometry; AMA = arm muscle area; ASM = appendicular skeletal muscle mass; SMI = skeletal muscle index; PMI = psoas muscle index; TPA = total psoas area.

### 3.7. Pre-Therapeutic Sarcopenia Is Predictive of Severe Postoperative Complications among Cancer Patients

Based on 56 studies including 17,172 patients, we found a strong and significant association between pre-therapeutic sarcopenia and severe post-operative complications, with a pooled RR of 2.70 [2.33–3.12] involving a moderate heterogeneity (I² = 72%). Subgroup analyses are presented in Table 5 and Figure A5, showing a reduction in heterogeneity. The effect measure differed significantly (*p* < 0.01) according to sensitivity analysis, year of publication, sample size, world region, cancer site, and sarcopenia definition, while no significant differences were found for study quality, the age threshold of 65 years at inclusion, cancer extension, or muscle mass index. When low between-study heterogeneity was envisaged (i.e., I² < 50%), the most marked effects were associated with the consensus-based algorithm definitions of sarcopenia (RR = 3.62 [2.79–4.69]) and gastric cancer (RR = 3.09 [2.42–3.93]).
<table><caption>**Table 5.** Predictive value of pre-therapeutic sarcopenia on severe post-operative complications (POC) among cancer patients.</caption><thead><tr><th rowspan="2">Study Groups</th><th colspan="2">Patients</th><th rowspan="2">Relative Risk [95% CI] for POC</th><th rowspan="2">p Value for Subgroup Differences</th><th colspan="2">Heterogeneity</th></tr><tr><th>N</th><th>(%)</th><th>I<sup>2</sup></th><th>p</th></tr></thead><tbody><tr><td><strong>Overall</strong></td><td></td><td></td><td></td><td>0.02</td><td></td><td></td></tr><tr><td>All studies</td><td>17,172</td><td>(100)</td><td>2.70 [2.33-3.12]</td><td></td><td>72%</td><td>&lt;0.01</td></tr><tr><td>Excluding studies over the 95% CI (funnel plot)</td><td>3633</td><td>(21)</td><td>2.22 [1.84-2.68]</td><td></td><td>64%</td><td>&lt;0.01</td></tr><tr><td><strong>Quality of study (NOS)</strong></td><td></td><td></td><td></td><td>0.34</td><td></td><td></td></tr><tr><td>Good</td><td>14,555</td><td>(85)</td><td>2.75 [2.34-3.24]</td><td></td><td>75%</td><td>&lt;0.01</td></tr><tr><td>Fair</td><td>2411</td><td>(14)</td><td>2.67 [1.83-3.91]</td><td></td><td>60%</td><td>&lt;0.01</td></tr><tr><td>Poor</td><td>206</td><td>(1)</td><td>1.87 [1.16-3.04]</td><td></td><td>0%</td><td>0.51</td></tr><tr><td><strong>Year of publication</strong></td><td></td><td></td><td></td><td>0.02</td><td></td><td></td></tr><tr><td>2008-2012</td><td>0</td><td>(0)</td><td>-</td><td></td><td>48.5%</td><td>&lt;0.01</td></tr><tr><td>2013-2017</td><td>6355</td><td>(37)</td><td>1.39 [1.18-1.63]</td><td></td><td>81%</td><td>&lt;0.01</td></tr><tr><td>2018-2022</td><td>10,817</td><td>(63)</td><td>1.91 [1.53-2.38]</td><td></td><td></td><td></td></tr><tr><td><strong>N° of patients included</strong></td><td></td><td></td><td></td><td>0.04</td><td></td><td></td></tr><tr><td>&lt;100</td><td>806</td><td>(5)</td><td>1.78 [1.09-2.92]</td><td></td><td>72%</td><td>&lt;0.01</td></tr><tr><td>100-199</td><td>2425</td><td>(14)</td><td>1.30 [1.08-1.56]</td><td></td><td>41%</td><td>0.04</td></tr><tr><td>200-399</td><td>5407</td><td>(31)</td><td>1.95 [1.42-2.68]</td><td></td><td>85%</td><td>&lt;0.01</td></tr><tr><td>≥400</td><td>8534</td><td>(50)</td><td>1.87 [1.47-2.39]</td><td></td><td>58%</td><td>&lt;0.01</td></tr><tr><td><strong>World region</strong></td><td></td><td></td><td></td><td>&lt;0.01</td><td></td><td></td></tr><tr><td>Asia</td><td>10,092</td><td>(59)</td><td>2.02 [1.60-2.55]</td><td></td><td>81%</td><td>&lt;0.01</td></tr><tr><td>Not Asia</td><td>7080</td><td>(41)</td><td>1.38 [1.20-1.60]</td><td></td><td>57%</td><td>&lt;0.01</td></tr><tr><td><strong>Mean or median age (y) at inclusion (n = 13,209)</strong></td><td></td><td></td><td></td><td>0.39</td><td></td><td></td></tr><tr><td>&lt;65</td><td>6572</td><td>(50)</td><td>1.91 [1.49-2.44]</td><td></td><td>64%</td><td>&lt;0.01</td></tr><tr><td>≥65</td><td>6637</td><td>(50)</td><td>1.64 [1.28-2.10]</td><td></td><td>78%</td><td>&lt;0.01</td></tr><tr><td><strong>Cancer site</strong></td><td></td><td></td><td></td><td>&lt;0.01</td><td></td><td></td></tr><tr><td>Gastric</td><td>6856</td><td>(40)</td><td>3.09 [2.42-3.93]</td><td></td><td>43%</td><td>0.02</td></tr><tr><td>Breast</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Sarcoma</td><td>145</td><td>(1)</td><td>1.78 [1.22-2.59]</td><td></td><td>-</td><td>-</td></tr><tr><td>Uterus</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Head and neck</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Ovarian</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Lymphoma</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Various</td><td>1895</td><td>(11)</td><td>3.95 [1.97-7.95]</td><td></td><td>71%</td><td>&lt;0.01</td></tr><tr><td>Cholangiocarcinoma</td><td>110</td><td>(1)</td><td>2.44 [2.08-2.87]</td><td></td><td>0%</td><td>0.46</td></tr><tr><td>Melanoma</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Leukemia</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Colorectal</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Anal</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Bile ducts</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Non-small cell lung</td><td>808</td><td>(5)</td><td>3.66 [1.12-11.9]</td><td></td><td>93%</td><td>&lt;0.01</td></tr><tr><td>Liver</td><td>385</td><td>(2)</td><td>2.47 [0.90-6.77]</td><td></td><td>85%</td><td>&lt;0.01</td></tr><tr><td>Myeloma</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Thyroids</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Pancreatic</td><td>1629</td><td>(9)</td><td>1.86 [1.26-2.75]</td><td></td><td>51%</td><td>0.07</td></tr><tr><td>Kidney</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Esophageal</td><td>828</td><td>(5)</td><td>3.17 [1.82-5.52]</td><td></td><td>82%</td><td>&lt;0.01</td></tr><tr><td>Urothelial</td><td>473</td><td>(3)</td><td>1.68 [1.33-2.11]</td><td></td><td>0%</td><td>0.47</td></tr><tr><td>Prostatic</td><td>698</td><td>(4)</td><td>4.50 [1.76-11.5]</td><td></td><td>-</td><td>-</td></tr><tr><td>Small cell lung</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td><strong>Cancer extension</strong></td><td></td><td></td><td></td><td>0.06</td><td></td><td></td></tr><tr><td>Various</td><td>14,436</td><td>(84)</td><td>1.76 [1.46-2.11]</td><td></td><td>74%</td><td>&lt;0.01</td></tr><tr><td>Local</td><td>999</td><td>(6)</td><td>2.35 [1.14-4.86]</td><td></td><td>80%</td><td>&lt;0.01</td></tr><tr><td>Locally advanced</td><td>955</td><td>(6)</td><td>1.35 [0.85-2.14]</td><td></td><td>57%</td><td>0.05</td></tr><tr><td>Metastatic</td><td>782</td><td>(4)</td><td>1.30 [1.09-1.54]</td><td></td><td>0%</td><td>0.80</td></tr></tbody></table>
<table><caption>**Table 5.** *Cont.*</caption><thead><tr><th rowspan="2">Study Groups</th><th colspan="2">Patients</th><th rowspan="2">Relative Risk [95% CI] for POC</th><th rowspan="2">p Value for Subgroup Differences</th><th colspan="2">Heterogeneity</th></tr><tr><th>N</th><th>(%)</th><th>I<sup>2</sup></th><th>p</th></tr></thead><tbody><tr><td><strong>Treatment modalities</strong></td><td></td><td></td><td></td><td>0.04</td><td></td><td></td></tr><tr><td>Not specified</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Surgery</td><td>16,325</td><td>(95)</td><td>1.77 [1.50–2.09]</td><td></td><td>76%</td><td>&lt;0.01</td></tr><tr><td>Targeted therapy</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Various</td><td>847</td><td>(5)</td><td>1.26 [0.95–1.67]</td><td></td><td>43%</td><td>0.10</td></tr><tr><td>Immune therapy</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Radiotherapy</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Chemotherapy</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Exclusive supportive care</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Intra-arterial infusion for hepatocellular carcinoma</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td><strong>Definition of sarcopenia</strong></td><td></td><td></td><td></td><td>0.03</td><td></td><td></td></tr><tr><td>Muscle mass quantity only</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>CT scan</td><td>11,212</td><td>(65)</td><td>2.39 [2.01–2.83]</td><td></td><td>75%</td><td>&lt;0.01</td></tr><tr><td>BIA</td><td>626</td><td>(4)</td><td>3.16 [1.74–5.76]</td><td></td><td>65%</td><td>0.02</td></tr><tr><td>DXA</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Consensus algorithms</td><td>5334</td><td>(31)</td><td>3.62 [2.79–4.69]</td><td></td><td>36%</td><td>0.07</td></tr><tr><td>Muscle mass indices (n = 16,413)</td><td></td><td></td><td></td><td>0.06</td><td></td><td></td></tr><tr><td>AMA (cm<sup>2</sup>)</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>ASM (kg/m<sup>2</sup>)</td><td>834</td><td>(5)</td><td>3.26 [1.80–5.90]</td><td></td><td>72%</td><td>&lt;0.01</td></tr><tr><td>TPA (cm<sup>2</sup>/m<sup>2</sup>)</td><td>2089</td><td>(13)</td><td>1.60 [1.09–2.35]</td><td></td><td>72%</td><td>0.06</td></tr><tr><td>PMI (cm<sup>2</sup>/m<sup>2</sup>)</td><td>719</td><td>(4)</td><td>2.41 [0.99–5.91]</td><td></td><td>93%</td><td>&lt;0.01</td></tr><tr><td>SMI (cm<sup>2</sup>/m<sup>2</sup>)</td><td>12,771</td><td>(78)</td><td>1.48 [1.27–1.71]</td><td></td><td>61%</td><td>&lt;0.01</td></tr></tbody></table>

Bold = grouping data, and significant *p* value at the threshold of 5%; BIA = bioelectrical impedance analysis; DXA = dual energy X-ray absorptiometry; AMA = arm muscle area; ASM = appendicular skeletal muscle mass; SMI = skeletal muscle index; PMI = psoas muscle index; TPA = total psoas area.

### 3.8. Pre-Therapeutic Sarcopenia Is Predictive of Severe Treatment-Related Toxicity and/or Dose-Limiting Toxicity among Cancer Patients

Based on 19 studies including 2980 patients, we found a significant association between pre-therapeutic sarcopenia and severe treatment-related toxicities and/or dose-limiting toxicities, with a pooled RR of 1.47 [1.17–1.84] involving a moderate heterogeneity (I² = 71%). Subgroup analyses are presented in Table 6 and Figure A6, showing a reduction in heterogeneity. The effect measure differed significantly (*p* < 0.01) according to study quality, sample size, cancer site, cancer extension, and definition of sarcopenia, while no significant differences were found for sensitivity analysis, year of publication, world region, age threshold of 65 years at inclusion, or treatment mode. When low between-study heterogeneity was envisaged (i.e., I² < 50%), the most marked effects were associated with breast cancer (RR = 2.93 [1.82–4.73]), head and neck cancer (RR = 2.47 [1.65–3.69]), chemotherapy (RR = 1.98 [1.55–2.54]), and targeted therapy (RR = 1.63 [1.05–2.54]).

<table><caption>**Table 6.** Predictive value of pre-therapeutic sarcopenia on severe treatment-related toxicities and/or dose-limiting toxicities (TOX) among cancer patients.</caption><thead><tr><th rowspan="2">Study Groups</th><th colspan="2">Patients</th><th rowspan="2">Relative Risk [95% CI] for TOX</th><th rowspan="2">p Value for Subgroup Differences</th><th colspan="2">Heterogeneity</th></tr><tr><th>N</th><th>(%)</th><th>I<sup>2</sup></th><th>p</th></tr></thead><tbody><tr><td><strong>Overall</strong></td><td></td><td></td><td></td><td>0.49</td><td></td><td></td></tr><tr><td>All studies</td><td>2980</td><td>(100)</td><td>1.47 [1.17–1.84]</td><td></td><td>71%</td><td>&lt;0.01</td></tr><tr><td>Excluding studies over the 95% CI (funnel plot)</td><td>760</td><td>(25.5)</td><td>1.31 [1.11–1.57]</td><td></td><td>62%</td><td>&lt;0.01</td></tr></tbody></table>
<table><caption>Table 6. *Cont.*</caption><thead><tr><th rowspan="2">Study Groups</th><th colspan="2">Patients</th><th rowspan="2">Relative Risk [95% CI] for TOX</th><th rowspan="2">p Value for Subgroup Differences</th><th colspan="2">Heterogeneity</th></tr><tr><th>N</th><th>(%)</th><th>I<sup>2</sup></th><th>p</th></tr></thead><tbody><tr><td><strong>Quality of study (NOS)</strong></td><td></td><td></td><td></td><td>0.02</td><td></td><td></td></tr><tr><td>Good</td><td>2356</td><td>(79)</td><td>1.34 [1.01–1.77]</td><td></td><td>67%</td><td>&lt;0.01</td></tr><tr><td>Fair</td><td>517</td><td>(17)</td><td>1.78 [1.43–2.21]</td><td></td><td>24%</td><td>0.25</td></tr><tr><td>Poor</td><td>107</td><td>(4)</td><td>2.72 [1.76–4.21]</td><td></td><td>-</td><td>-</td></tr><tr><td><strong>Year of publication</strong></td><td></td><td></td><td></td><td>0.38</td><td></td><td></td></tr><tr><td>2008–2012</td><td>55</td><td>(2)</td><td>2.56 [1.14–5.78]</td><td></td><td>-</td><td>-</td></tr><tr><td>2013–2017</td><td>424</td><td>(14)</td><td>1.56 [0.94–2.60]</td><td></td><td>70%</td><td>&lt;0.01</td></tr><tr><td>2018–2022</td><td>2501</td><td>(84)</td><td>1.40 [1.07–1.84]</td><td></td><td>73%</td><td>&lt;0.01</td></tr><tr><td><strong>N° of patients included</strong></td><td></td><td></td><td></td><td>0.03</td><td></td><td></td></tr><tr><td>&lt;100</td><td>851</td><td>(28.5)</td><td>1.39 [1.01–1.91]</td><td></td><td>67%</td><td>&lt;0.01</td></tr><tr><td>100–199</td><td>702</td><td>(23.5)</td><td>1.92 [1.26–2.93]</td><td></td><td>68.5%</td><td>&lt;0.01</td></tr><tr><td>200–399</td><td>219</td><td>(7.5)</td><td>0.98 [0.78–1.25]</td><td></td><td>-</td><td>-</td></tr><tr><td>≥400</td><td>1208</td><td>(40.5)</td><td>1.42 [0.63–3.21]</td><td></td><td>88%</td><td>&lt;0.01</td></tr><tr><td><strong>World region</strong></td><td></td><td></td><td></td><td>0.80</td><td></td><td></td></tr><tr><td>Asia</td><td>1551</td><td>(52)</td><td>1.43 [1.04–1.98]</td><td></td><td>76.5%</td><td>&lt;0.01</td></tr><tr><td>Not Asia</td><td>1429</td><td>(48)</td><td>1.52 [1.08–2.13]</td><td></td><td>65%</td><td>&lt;0.01</td></tr><tr><td><strong>Mean or median age (y) at inclusion (n = 1772)</strong></td><td></td><td></td><td></td><td>0.44</td><td></td><td></td></tr><tr><td>&lt;65</td><td>1459</td><td>(82)</td><td>1.57 [1.18–2.11]</td><td></td><td>77%</td><td>&lt;0.01</td></tr><tr><td>≥65</td><td>313</td><td>(18)</td><td>1.26 [0.79–2.02]</td><td></td><td>0%</td><td>0.46</td></tr><tr><td><strong>Cancer site</strong></td><td></td><td></td><td></td><td>&lt;0.01</td><td></td><td></td></tr><tr><td>Gastric</td><td>458</td><td>(15)</td><td>0.96 [0.72–1.29]</td><td></td><td>-</td><td>-</td></tr><tr><td>Breast</td><td>137</td><td>(4.5)</td><td>2.93 [1.82–4.73]</td><td></td><td>0%</td><td>0.69</td></tr><tr><td>Sarcoma</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Uterus</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Head and neck</td><td>862</td><td>(29)</td><td>2.47 [1.65–3.69]</td><td></td><td>0%</td><td>0.40</td></tr><tr><td>Ovarian</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Lymphoma</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Various</td><td>89</td><td>(3)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Cholangiocarcinoma</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Melanoma</td><td>68</td><td>(2)</td><td>1.20 [0.40–3.56]</td><td></td><td>-</td><td>-</td></tr><tr><td>Leukemia</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Colorectal</td><td>244</td><td>(8)</td><td>1.00 [0.80–1.26]</td><td></td><td>0%</td><td>0.56</td></tr><tr><td>Anal</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Bile ducts</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Non-small cell lung</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Liver</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Myeloma</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Thyroids</td><td>180</td><td>(6)</td><td>1.20 [0.89–1.61]</td><td></td><td>-</td><td>-</td></tr><tr><td>Pancreatic</td><td>281</td><td>(9)</td><td>1.66 [1.13–2.42]</td><td></td><td>0%</td><td>0.47</td></tr><tr><td>Kidney</td><td>139</td><td>(5)</td><td>1.98 [0.99–3.98]</td><td></td><td>0%</td><td>0.71</td></tr><tr><td>Esophageal</td><td>494</td><td>(16.5)</td><td>1.17 [0.66–2.08]</td><td></td><td>86%</td><td>&lt;0.01</td></tr><tr><td>Urothelial</td><td>28</td><td>(1)</td><td>0.83 [0.21–3.29]</td><td></td><td>-</td><td>-</td></tr><tr><td>Prostatic</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Small cell lung</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td><strong>Cancer extension</strong></td><td></td><td></td><td></td><td>&lt;0.01</td><td></td><td></td></tr><tr><td>Various</td><td>2216</td><td>(74)</td><td>1.57 [1.16–2.12]</td><td></td><td>77%</td><td>&lt;0.01</td></tr><tr><td>Local</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Locally advanced</td><td>228</td><td>(8)</td><td>0.69 [0.47–1.02]</td><td></td><td>0%</td><td>0.62</td></tr><tr><td>Metastatic</td><td>536</td><td>(18)</td><td>1.57 [1.18–2.09]</td><td></td><td>28%</td><td>0.22</td></tr><tr><td><strong>Treatment modalities</strong></td><td></td><td></td><td></td><td>0.19</td><td></td><td></td></tr><tr><td>Not specified</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Surgery</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Targeted therapy</td><td>374</td><td>(12.5)</td><td>1.63 [1.05–2.54]</td><td></td><td>30%</td><td>0.23</td></tr><tr><td>Various</td><td>2040</td><td>(68.5)</td><td>1.22 [0.85–1.74]</td><td></td><td>79%</td><td>&lt;0.01</td></tr><tr><td>Immune therapy</td><td>68</td><td>(2)</td><td>1.20 [0.40–3.56]</td><td></td><td>-</td><td>-</td></tr><tr><td>Radiotherapy</td><td>28</td><td>(1)</td><td>0.83 [0.21–3.29]</td><td></td><td>-</td><td>-</td></tr></tbody></table>
<table><caption>**Table 6.** *Cont.*</caption><thead><tr><th rowspan="2">Study Groups</th><th colspan="2">Patients</th><th rowspan="2">Relative Risk [95% CI] for TOX</th><th rowspan="2">p Value for Subgroup Differences</th><th colspan="2">Heterogeneity</th></tr><tr><th>N</th><th>(%)</th><th>I<sup>2</sup></th><th>p</th></tr></thead><tbody><tr><td>Chemotherapy</td><td>470</td><td>(16)</td><td>1.98 [1.55–2.54]</td><td></td><td>32%</td><td>0.20</td></tr><tr><td>Exclusive supportive care</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Intra-arterial infusion for hepatocellular carcinoma</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td><strong>Definition of sarcopenia</strong></td><td></td><td></td><td></td><td>&lt;0.01</td><td></td><td></td></tr><tr><td>Muscle mass quantity only</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>CT scan</td><td>2886</td><td>(97)</td><td>1.53 [1.22–1.93]</td><td></td><td>70%</td><td>&lt;0.01</td></tr><tr><td>BIA</td><td>94</td><td>(3)</td><td>0.82 [0.56–1.21]</td><td></td><td>-</td><td>-</td></tr><tr><td>DXA</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Consensus algorithm-based</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td><strong>Muscle mass indices (n = 2136)</strong></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>AMA (cm<sup>2</sup>)</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>ASM (kg/m<sup>2</sup>)</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>TPA (cm<sup>2</sup>/m<sup>2</sup>)</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>PMI (cm<sup>2</sup>/m<sup>2</sup>)</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>SMI (cm<sup>2</sup>/m<sup>2</sup>)</td><td>2136</td><td>(100)</td><td>1.49 [1.18–1.90]</td><td></td><td>69%</td><td>&lt;0.01</td></tr></tbody></table>

Bold = grouping data, and significant *p* value at the threshold of 5%; BIA = bioelectrical impedance analysis; DXA = dual energy X-ray absorptiometry; AMA = arm muscle area; ASM = appendicular skeletal muscle mass; SMI = skeletal muscle index; PMI = psoas muscle index; TPA = total psoas area.

### 3.9. Pre-Therapeutic Sarcopenia Is Associated with Disability among Cancer Patients

Only one study including 131 patients was found on the association between pre-therapeutic sarcopenia and disability (ADL ≤ 5/6) [160]. In this single-center prospective study including 40.5% of patients aged ≥ 75 years with cancers in various sites and with different extensions, baseline disability was noted for 30.5% of the patients. Compared to normal muscle mass and non-severe sarcopenia, severe sarcopenia is defined according to the EWGOS1 by low muscle mass (CT scan-based SMI), and both low handgrip strength and slow gait speed were significantly (*p* < 0.001) associated with disability (90% vs. 26% of patients) in univariate analysis.

### 3.10. Pre-Therapeutic Sarcopenia Is Predictive of Nosocomial Infections among Cancer Patients

Based on 22 studies including 6246 patients, we found a strong, significant association between pre-therapeutic sarcopenia and nosocomial infections with a pooled RR of 1.76 [1.41–2.22] and moderate heterogeneity (I² = 58%). Subgroup analyses are presented in Table 7 and Figure A7, showing a reduction in heterogeneity. The effect measure differed significantly (*p* < 0.01) according to sensitivity analysis, sample size, age threshold of 65 years at inclusion, cancer site, and definition of sarcopenia, while no significant differences were found for study quality, year of publication, world region, cancer extension, treatment mode, or muscle mass index. When low between-study heterogeneity was envisaged (i.e., I² < 50%), the most marked effects were associated with gastric cancer (RR = 2.55 [1.88–3.46]) and a sample size ≥ 400 (RR = 2.26 [1.66–3.07]).

<table><caption>**Table 7.** Predictive value of pre-therapeutic sarcopenia on severe treatment-related toxicities and/or dose-limiting toxicities (TOX) among cancer patients.</caption><thead><tr><th rowspan="2">Study Groups</th><th colspan="2">Patients</th><th rowspan="2">Relative Risk [95% CI] for NI</th><th rowspan="2">p Value for Subgroup Differences</th><th colspan="2">Heterogeneity</th></tr><tr><th>N</th><th>(%)</th><th>I<sup>2</sup></th><th>p</th></tr></thead><tbody><tr><td><strong>Overall</strong></td><td></td><td></td><td></td><td>&lt;0.01</td><td></td><td></td></tr><tr><td>All studies</td><td>6246</td><td>(100)</td><td>1.76 [1.41–2.22]</td><td></td><td>58%</td><td>&lt;0.01</td></tr><tr><td>Excluding studies over the 95% CI (funnel plot)</td><td>864</td><td>(14)</td><td>1.15 [0.87–1.52]</td><td></td><td></td><td></td></tr></tbody></table>
<table><caption>Table 7. *Cont.*</caption><thead><tr><th rowspan="2">Study Groups</th><th colspan="2">Patients</th><th rowspan="2">Relative Risk [95% CI] for NI</th><th rowspan="2">p Value for Subgroup Differences</th><th colspan="2">Heterogeneity</th></tr><tr><th>N</th><th>(%)</th><th>I<sup>2</sup></th><th>p</th></tr></thead><tbody><tr><td><strong>Quality of study (NOS)</strong></td><td></td><td></td><td></td><td>0.09</td><td></td><td></td></tr><tr><td>Good</td><td>4380</td><td>(70)</td><td>1.90 [1.45-2.49]</td><td></td><td>52%</td><td>0.01</td></tr><tr><td>Fair</td><td>1783</td><td>(28.5)</td><td>1.64 [1.02-2.65]</td><td></td><td>69%</td><td>&lt;0.01</td></tr><tr><td>Poor</td><td>83</td><td>(1.5)</td><td>0.83 [0.42-1.65]</td><td></td><td>-</td><td>-</td></tr><tr><td><strong>Year of publication</strong></td><td></td><td></td><td></td><td>0.63</td><td></td><td></td></tr><tr><td>2008-2012</td><td>234</td><td>(4)</td><td>1.83 [1.03-3.25]</td><td></td><td>-</td><td>-</td></tr><tr><td>2013-2017</td><td>2128</td><td>(34)</td><td>1.50 [1.20-1.87]</td><td></td><td>30%</td><td>0.17</td></tr><tr><td>2018-2022</td><td>3884</td><td>(62)</td><td>1.87 [1.56-2.23]</td><td></td><td>72%</td><td>&lt;0.01</td></tr><tr><td><strong>N° of patients included</strong></td><td></td><td></td><td></td><td>&lt;0.01</td><td></td><td></td></tr><tr><td>&lt;100</td><td>132</td><td>(2)</td><td>0.76 [0.44-1.32]</td><td></td><td>0%</td><td>0.71</td></tr><tr><td>100-199</td><td>1059</td><td>(17)</td><td>1.77 [1.22-2.56]</td><td></td><td>34%</td><td>0.17</td></tr><tr><td>200-399</td><td>2385</td><td>(38)</td><td>1.85 [1.23-2.80]</td><td></td><td>69%</td><td>&lt;0.01</td></tr><tr><td>≥400</td><td>2670</td><td>(43)</td><td>2.26 [1.66-3.07]</td><td></td><td>6%</td><td>0.36</td></tr><tr><td><strong>World region</strong></td><td></td><td></td><td></td><td>0.33</td><td></td><td></td></tr><tr><td>Asia</td><td>4817</td><td>(77)</td><td>1.91 [1.42-2.57]</td><td></td><td>66%</td><td>&lt;0.01</td></tr><tr><td>Not Asia</td><td>1429</td><td>(33)</td><td>1.53 [1.11-2.12]</td><td></td><td>36%</td><td>0.14</td></tr><tr><td><strong>Mean or median age (y) at inclusion (n = 5047)</strong></td><td></td><td></td><td></td><td>&lt;0.01</td><td></td><td></td></tr><tr><td>&lt;65</td><td>2126</td><td>(42)</td><td>2.60 [1.93-3.52]</td><td></td><td>41%</td><td>0.10</td></tr><tr><td>≥65</td><td>2921</td><td>(58)</td><td>1.36 [1.01-1.83]</td><td></td><td>45%</td><td>0.06</td></tr><tr><td><strong>Cancer site</strong></td><td></td><td></td><td></td><td>&lt;0.01</td><td></td><td></td></tr><tr><td>Gastric</td><td>3342</td><td>(53.5)</td><td>2.55 [1.88-3.46]</td><td></td><td>29%</td><td>0.21</td></tr><tr><td>Breast</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Sarcoma</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Uterus</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Head and neck</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Ovarian</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Lymphoma</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Various</td><td>49</td><td>(1)</td><td>0.67 [0.27-1.66]</td><td></td><td>-</td><td>-</td></tr><tr><td>Cholangiocarcinoma</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Melanoma</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Leukemia</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Colorectal</td><td>1033</td><td>(16.5)</td><td>1.80 [1.31-2.48]</td><td></td><td>14%</td><td>0.33</td></tr><tr><td>Anal</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Bile-ducts</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Non-small cell lung</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Liver</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Myeloma</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Thyroids</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Pancreatic</td><td>202</td><td>(3)</td><td>0.69 [0.32-1.49]</td><td></td><td>-</td><td>-</td></tr><tr><td>Kidney</td><td>0</td><td>(0)</td><td>0</td><td></td><td>-</td><td>-</td></tr><tr><td>Esophageal</td><td>1620</td><td>(26)</td><td>1.49 [1.02-2.18]</td><td></td><td>61%</td><td>0.01</td></tr><tr><td>Urothelial</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Prostatic</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Small cell lung</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td><strong>Cancer extension</strong></td><td></td><td></td><td></td><td>0.57</td><td></td><td></td></tr><tr><td>Various</td><td>6073</td><td>(97)</td><td>1.75 [1.38-2.22]</td><td></td><td>60%</td><td>&lt;0.01</td></tr><tr><td>Local</td><td>173</td><td>(3)</td><td>2.13 [1.11-4.10]</td><td></td><td>-</td><td>-</td></tr><tr><td>Locally-advanced</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Metastatic</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td><strong>Treatment modalities</strong></td><td></td><td></td><td></td><td>0.12</td><td></td><td></td></tr><tr><td>Not specified</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Surgery</td><td>6033</td><td>(97)</td><td>1.84 [1.45-2.32]</td><td></td><td>58%</td><td>&lt;0.01</td></tr><tr><td>Targeted therapy</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Various</td><td>213</td><td>(3)</td><td>1.05 [0.54-2.06]</td><td></td><td>19%</td><td>0.27</td></tr><tr><td>Immune-therapy</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr></tbody></table>
<table><caption>**Table 7.** *Cont.*</caption><thead><tr><th rowspan="2">Study Groups</th><th colspan="2">Patients</th><th rowspan="2">Relative Risk [95% CI] for NI</th><th rowspan="2">p Value for Subgroup Differences</th><th colspan="2">Heterogeneity</th></tr><tr><th>N</th><th>(%)</th><th>I<sup>2</sup></th><th>p</th></tr></thead><tbody><tr><td>Radiotherapy</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Chemotherapy</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Exclusive supportive care</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>Intra-arterial infusion for hepatocellular carcinoma</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td><strong>Definition of sarcopenia</strong></td><td></td><td></td><td></td><td>0.03</td><td></td><td></td></tr><tr><td>-Muscle mass quantity only</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>CT-scan</td><td>2487</td><td>(40)</td><td>1.59 [1.28-1.97]</td><td></td><td>0%</td><td>0.45</td></tr><tr><td>BIA</td><td>423</td><td>(7)</td><td>1.12 [0.62-2.02]</td><td></td><td>59%</td><td>0.06</td></tr><tr><td>DXA</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>-Consensus algorithm-based</td><td>3336</td><td>(53)</td><td>2.49 [1.75-3.54]</td><td></td><td>64%</td><td>&lt;0.01</td></tr><tr><td><strong>Muscle mass indices (n = 5782)</strong></td><td></td><td></td><td></td><td>0.92</td><td></td><td></td></tr><tr><td>AMA (cm<sup>2</sup>)</td><td>951</td><td>(16)</td><td>1.86 [1.10-3.16]</td><td></td><td>-</td><td>-</td></tr><tr><td>ASM (kg/m<sup>2</sup>)</td><td>344</td><td>(6)</td><td>1.34 [0.44-4.06]</td><td></td><td>88%</td><td>&lt;0.01</td></tr><tr><td>TPA (cm<sup>2</sup>/m<sup>2</sup>)</td><td>0</td><td>(0)</td><td>-</td><td></td><td>-</td><td>-</td></tr><tr><td>PMI (cm<sup>2</sup>/m<sup>2</sup>)</td><td>567</td><td>(10)</td><td>1.56 [0.73-3.30]</td><td></td><td>-</td><td>-</td></tr><tr><td>SMI (cm<sup>2</sup>/m<sup>2</sup>)</td><td>3920</td><td>(68)</td><td>1.85 [1.41-2.43]</td><td></td><td>53%</td><td>0.01</td></tr></tbody></table>

Bold = grouping data, and significant *p* value at the threshold of 5%; BIA = bioelectrical impedance analysis; DXA = Dual Energy X-Ray Absorptiometry; AMA = arm muscle area; ASM = appendicular skeletal muscle mass; SMI = skeletal muscle index; PMI = psoas muscle index; TPA = total psoas area.

## 4. Discussion

In this meta-analysis including 226 articles and 65,936 patients with various cancers, various extensions, and various treatment modes, PS was mainly defined as a loss of muscle mass using the SMI on CT scan-based assessment. PS was highly prevalent and was strongly associated with OS, PFS, POC, TOX, and NI during cancer treatment, with pooled relative risks ranging from 1.50 (toxicities) to 2.70 (post-operative complications).

To date, and despite successive sarcopenia consensus-based definitions of sarcopenia provided since 2010, the definition of sarcopenia mainly relies only on loss of muscle mass quantity among cancer patients. The standardized use of CT scans in pre-therapeutic oncological settings probably explains this. Unlike the ASM and the PMI indices, the SMI muscle mass index was linearly associated with the prevalence of sarcopenia for both women and men and had the tightest confidence interval, suggesting that it is probably the most suitable index for the quantification of muscle mass. However, homogeneous optimal cut-off thresholds remain to be clarified in the oncological setting.

As expected, we found great heterogeneity for all endpoints addressed here. Consistent with our previous review, the pooled prevalence of pre-therapeutic sarcopenia concerned 38% of cancer patients [7]. Using a multivariate meta-regression, we were able to identify sources of between-study heterogeneity as follows: consensus-based algorithm definitions of sarcopenia (as opposed to loss of muscle mass only), a powerful sample size (≥400), and the cut-off values of CT scan-based SMI for women (not for men) as continuous variables were independently and significantly associated with the prevalence results for pre-therapeutic sarcopenia. With respect to the prevalence results according to cancer localisation, our results require caution given the impact of the definition used. Strikingly, compared with definitions based on loss of muscle mass only (SMI), consensus-based algorithm definitions of sarcopenia reduced the prevalence significantly (42% vs. 22%), decreasing heterogeneity and increasing the predictive value for OS (RR = 1.85 vs. 2.31), PFS (RR = 1.61 vs. 3.59), post-operative complications (RR = 1.48 vs. 3.62), and nosocomial infections (RR = 1.85 vs. 2.49). This discrepancy could be explained by the additional criteria used for consensus algorithms, which consider both loss of muscle strength and/or physical performance and muscle mass. Indeed, it is known that grip strength and gait speed are independent factors associated with survival among cancer patients [236].
Surprisingly, except for nosocomial infections, we did not identify any significant difference for prevalence of sarcopenia, OS, PFS, post-operative complications, or severe treatment-related toxicities according to the age threshold of 65. This result highlights the leading role played by cancer (mainly due to cancer-related inflammatory processes) rather than age alone in promoting sarcopenia (namely secondary sarcopenia) and its clinical impact on adverse outcomes [6].

To our knowledge, although it was not performed on individual data, this is the largest and most powerful meta-analysis on this topic. It contains a stringent methodology, bringing together oncologists, geriatricians, and methodologists using data from many countries in numerous cancer settings, enabling us to provide a comprehensive up-to-date review of sarcopenia prevalence and its clinical impact in the course of cancer treatment. In particular, in a cancer setting we were able to highlight an association between pre-therapeutic sarcopenia and PFS on the one hand, and between pre-therapeutic sarcopenia and nosocomial infections on the other, subjects that have been studied infrequently to date. However, there are still insufficient data to provide a synthesis regarding the association between pre-therapeutic sarcopenia and disability.

On the basis of the findings of our meta-analysis, there clearly is an urgent need to agree on an operational definition of sarcopenia in oncological settings to improve study comparability. Given both the high prevalence and the strong clinical impact of pre-therapeutic sarcopenia during cancer treatment, we suggest that its detection should occur as early as possible. In agreement with the EWGOS 2 consensus, we support the use of the simple SARC-F (strength, assistance with walking, rise from a chair, climb stairs, and falls) screening tool, which has been previously validated in older cancer patients [237]. The early detection of sarcopenia can help to initiate early muscle rehabilitation combining protein supplementation and resistance exercise training in order to improve the healthcare trajectories during cancer treatment [238]. Finally, we encourage the use of sarcopenia as a stratification variable in the development of future clinical trial designs in oncology.

**5. Conclusions**

Using the findings of the largest and the most powerful meta-analysis on this topic to date, we conclude that pre-therapeutic sarcopenia among cancer patients, mainly defined as a loss of muscle mass quantity, is prevalent and strongly associated with OS, PFS, severe post-operative complications, severe treatment-related toxicities and/or dose-limiting toxicities, and nosocomial infections. We stress the need to agree on a consensual definition of sarcopenia in oncological settings.

**Author Contributions:** Conceptualization, E.P. and F.P.; methodology, F.P.; software, F.P.; validation, A.-L.C., E.L., P.B.-R., J.P., M.F., C.M., S.M., R.G., Z.a.T., A.N., M.P., C.B., E.P. and F.P.; formal analysis, F.P.; investigation, A.-L.C., E.L., P.B.-R., J.P., M.F., C.M., S.M., R.G., Z.a.T., A.N., M.P., E.P. and F.P.; resources, A.-L.C., E.L., P.B.-R., J.P., M.F., C.M., S.M., R.G., Z.a.T., A.N., M.P., E.P. and F.P.; data curation, A.-L.C., E.L., P.B.-R., J.P., M.F., C.M., S.M., R.G., Z.a.T., A.N., M.P., E.P. and F.P.; writing—original draft preparation, A.-L.C., E.L., P.B.-R., E.P. and F.P.; writing—review and editing, A.-L.C., E.L., P.B.-R., J.P., M.F., C.M., S.M., R.G., Z.a.T., A.N., M.P., C.B., E.P. and F.P.; visualization, A.-L.C., E.L., P.B.-R., J.P., M.F., C.M., S.M., R.G., Z.a.T., A.N., M.P., C.B., E.P. and F.P.; supervision, A.-L.C., E.L., P.B.-R., E.P. and F.P. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** The data presented in this study are available upon request from the corresponding author.

**Acknowledgments:** We thank the French Society of Geriatric Oncology (SoFOG) which supported this work. We thank Angela Swaine and Sarah Leyshon for revising the English language in the manuscript.
**Conflicts of Interest:** The authors declare no conflict of interest.

## Appendix A

<table><caption>**Table A1.** Consensus-based algorithm definition of sarcopenia.</caption><thead><tr><th rowspan="2">Consensus</th><th rowspan="2">Year</th><th rowspan="2">Screening</th><th colspan="3">Definition</th></tr><tr><th>Muscle Mass</th><th>Muscular Strength</th><th>Muscular Performance</th></tr></thead><tbody><tr><td>EWGOS 1</td><td>2010</td><td>No</td><td>↓<br>DXA, BIA,<br>CT or MRI</td><td>AND<br>Hand-grip strength (kg)<br>[M < 30, F < 20]</td><td>OR<br>GS < 0.8 m/s or SPPB <<br>9/12 or TGUG ≥ 20 s</td></tr><tr><td>IWGS</td><td>2011</td><td>No</td><td>↓<br>DXA</td><td>AND<br>No</td><td>-<br>GS < 1 m/s</td></tr><tr><td>AWGS 1</td><td>2014</td><td>No</td><td>↓<br>DXA or BIA</td><td>AND<br>Hand-grip strength (kg)<br>[M < 26, F < 18]</td><td>AND<br>GS < 0.8 m/s</td></tr><tr><td>EWGOS 2</td><td>2019</td><td>Yes<br>(SARCF)</td><td>↓<br>DXA, BIA,<br>CT or MRI</td><td>AND<br>Hand-grip strength (kg)<br>[M < 27, F < 16]<br>Or<br>5 Rising from a chair ><br>15 s</td><td>AND<br>(severity)<br>GS < 0.8 m/s or SPPB <<br>9/12 or TGUG ≥ 20 s</td></tr><tr><td>AWGS 2</td><td>2019</td><td>Yes<br>(SARCF)</td><td>↓<br>DXA or BIA</td><td>AND<br>Hand-grip strength (kg)<br>[M < 28, F < 18]<br>5 Rising from a chair ><br>12 s</td><td>AND<br>(severity)<br>GS < 1 m/s or SPPB <<br>9/12</td></tr></tbody></table>

EWGOS: European Working Group On Sarcopenia; IWGS: International Working Group on Sarcopenia; AWGS: Asian Working Group on Sarcopenia; DXA: dual-energy X-ray absorptiometry; BIA: bioelectrical impedance analysis; CT: computed tomography; MRI: magnetic resonance imagery. M: male; F: female. GS: gait speed; SPPB: short physical performance battery; TGUG: timed get up and go test. SARCF: strength, assistance with walking, rise from a chair, climb stairs, and falls. ↓: reduced muscle mass; Bold = consensus names, and syndromic combination.

<table><caption>**Table A2.** Multivariate meta-regression of factors significantly influencing the prevalence of pre-therapeutic sarcopenia among cancer patients.</caption><thead><tr><th>Study Groups</th><th>Estimates</th><th>Standard Error</th><th>p</th></tr></thead><tbody><tr><td>N° of patients included (n = 65,936)</td><td></td><td></td><td></td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;&lt;100</td><td>1 (reference)</td><td>-</td><td>-</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;100–199</td><td>0.02</td><td>0.15</td><td>0.89</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;200–300</td><td>-0.25</td><td>0.16</td><td>0.10</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;≥400</td><td>0.51</td><td>0.19</td><td><strong>&lt;0.01</strong></td></tr><tr><td>Definition of sarcopenia</td><td></td><td></td><td></td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Muscle mass only (n = 54,923)</td><td>1 (reference)</td><td>-</td><td>-</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Consensus algorithm-based (n = 11,013)</td><td>-0.85</td><td>0.18</td><td><strong>&lt;0.0001</strong></td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Cut-off values of CT scan-based SMI for<br>&nbsp;&nbsp;&nbsp;&nbsp;women (per 6.0 cm<sup>2</sup>/m<sup>2</sup> of more) (n = 14,216)</td><td>0.05</td><td>0.02</td><td><strong>&lt;0.01</strong></td></tr></tbody></table>

Bold = grouping data, and significant *p* value at the threshold of 5%.
Appendix B

<figure><img src="image_8.png" /><figcaption>Figure A1. Flaw chart of the meta-analysis.</figcaption></figure>

<figure><img src="image_9.png" /><figcaption>**Figure A2.** Funnel plot of the prevalence of pre-therapeutic sarcopenia among cancer patients (*p* value for asymmetry [Peters’ test] < 0.0001). Gold points = studies; blue dash lines = common effect with 95% CI; red dash lines = random effect.</figcaption></figure>
<figure><img src="image_10.png" /><figcaption>**Figure A3.** Pooled relative risk (RR) of the predictive value of pre-therapeutic sarcope- nia on overall survival among cancer patients [14–18,23–26,28,30,33,34,36,37,39,42,43,47– 52,55,56,58,61,65,67,70,72,75,77,79–81,83,89,91,93,94,96,98,100–104,107,108,112–117,119,125,130, 132,133,135,136,144,146–150,153,155,159,161–163,165,167–171,174,181,184,189,191,193–198,200,209– 211,214,224,229,230,232,234)].</figcaption></figure>
<figure><img src="image_11.png" /><figcaption>**Figure A4.** Pooled relative risk (RR) of the predictive value of pre-therapeutic sarcopenia on progression-free survival among cancer patients [15,17,19,23,25,31,35,36,42,46,50,62,63,72,77,81,98, 102,112,116,122,130,153,159,184,191,197,214,229,233].</figcaption></figure>
<figure><img src="image_12.png" /><figcaption>**Figure A5.** Pooled relative risk (RR) of the predictive value of pre-therapeutic sarcopenia on severe post-operative complications among cancer patients [18,26,49,51,54–59,70–72,76,77,84–86,103,104,111,119,123,125–127,129,131,138,143,150,155,157,158,162,164,169,170,175,177,179,184,187,188,190–192,199,202,203,205–207,209,212–214,216,217,220].</figcaption></figure>
<figure><img src="image_13.png" /><figcaption>**Figure A6.** Pooled relative risk (RR) of the predictive value of pre-therapeutic sarcopenia on severe treatment-related toxicity and/or dose limiting toxicity among cancer patients [22,36,40,47,70,79,82,89,96,118,129,130,136,156,161,176,183,186,215,221,233].</figcaption></figure>

<figure><img src="image_14.png" /><figcaption>**Figure A7.** Pooled relative risk (RR) of the predictive value of pre-therapeutic sarcopenia on nosocomial infections among cancer patients [57,64,76,84,95,111,123,146,151,152,168,177,179,182,190,192,199,206,207,210,225,235].</figcaption></figure>
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