
==== Front
Adv Nutr
Adv Nutr
Advances in Nutrition
2161-8313
2156-5376
American Society for Nutrition

S2161-8313(24)00116-9
10.1016/j.advnut.2024.100282
100282
Review
Prevalence of and Survival with Cachexia among Patients with Cancer: A Systematic Review and Meta-Analysis
Takaoka Tomoya 12
Yaegashi Akinori 34
Watanabe Daiki d2watanabe@aoni.waseda.jp
56⁎
1 Medical Science Division, Department of Medical Science, Graduate School of Medicine, Science and Technology, Shinshu University, Nagano, Japan
2 Division of Clinical Nutrition, Shinshu University Hospital, Nagano, Japan
3 Department of Health and Nutrition, Faculty of Human Science, Hokkaido Bunkyo University, Hokkaido, Japan
4 Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
5 Faculty of Sport Sciences, Waseda University, Saitama, Japan
6 National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan
⁎ Corresponding author. d2watanabe@aoni.waseda.jp
08 8 2024
9 2024
08 8 2024
15 9 10028213 5 2024
31 7 2024
5 8 2024
© 2024 The Author(s)
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Cachexia is associated with lower overall survival (OS) in patients with cancer; however, the relationship between the two is reported to differ according to the definitive criteria for diagnosing cachexia.

We aimed to investigate 1) the difference in the prevalence of cachexia in patients with cancer and 2) the association between cachexia and OS, depending on the definitive criteria for diagnosing cachexia in patients with cancer. We searched PubMed and Web of Science from their inception until July 31, 2023, to identify eligible studies. We conducted a systematic review of the prevalence of cachexia in patients with cancer and performed a meta-analysis to investigate its relationship with OS. A total of 125 articles comprising 137,960 patients were included in the systematic review, and 26 articles consisting of 11,118 patients underwent meta-analysis. The overall prevalence of cachexia in patients with cancer was 33.0% (95% confidence interval [CI]: 32.8, 33.3); however, it varied according to the definitive criteria for diagnosing cachexia (13.9%–56.5%). According to the Fearon 2011 criteria, the prevalence of cachexia was associated with a high hazard ratio (HR) for OS compared with that of noncachexia [HR: 1.58 (95% CI: 1.45, 1.73)]; according to the other criteria, the HR was 2.78 (95% CI: 1.88, 4.11), indicating significant subgroup differences (P = 0.006). The dose–response curve indicated that the HR for OS plateaued at a cachexia prevalence range of 40%–50% (l-shaped relationship). The prevalence of cachexia in patients with cancer may vary depending on the definitive criteria used to diagnose cachexia. The HR for OS was higher for low cachexia prevalence. The definitive criteria should be carefully considered when assessing cachexia in patients with cancer.

This trial was registered at the PROSPERO as CRD42023435474.

Keywords

cancer cachexia
diagnostic accuracy
definitive criteria
prognosis
heterogeneity
Abbreviations

CI confidence interval

EPCRC European Palliative Care Research Collaborative

HR hazard ratio

OS overall survival

RevMan Review Manager

RoBANS Risk of Bias Assessment Tool for Nonrandomized Studies
==== Body
pmc Statement of Significance

This study provides crucial insights into the prognostic impact of differential diagnostic criteria for cancer cachexia in clinical practice. We provide quantitative and qualitative evidence of a significant difference in overall survival and prevalence of cachexia depending on the definitive criteria for diagnosing cachexia in patients with cancer.

Introduction

Cancer is the leading cause of death worldwide and a significant public health concern [1]. The number of patients with cancer is projected to continue to rise [1], and it is crucial to develop strategies that enhance the survival rate of these patients through early detection of cancer and effective treatment.

Cancer cachexia has been defined by the European Palliative Care Research Collaborative (EPCRC) as a “multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment” [2]. The prevalence of cachexia in patients with cancer is 11%–71% [3] and may result in interrupted chemotherapy, poorer quality of life, and decreased overall survival (OS) [2]. Therefore, accurate diagnosis and early treatment of cachexia in patients with cancer are crucial in cancer treatment.

Several definitive criteria for diagnosing cachexia are available [2,4,5]. The EPCRC (Fearon 2011 criteria [2]) proposes definitive criteria comprising 3 items: weight loss, low BMI, and low skeletal muscle mass (sarcopenia) because of insufficient energy (food) intake or increased energy expenditure. Other definitive criteria for diagnosing cachexia (for example, Fearon 2006 criteria [4]) include inadequate energy or food intake, inflammation, and weight loss. When assessing the prevalence of cachexia based on Fearon 2011 and Fearon 2006 criteria, Thoresen et al. [6] reported a prevalence of 53.2% and 20.8% and hazard ratios (HRs) for OS of 1.54 and 2.26, respectively, in patients with colorectal cancer.

Differences in the diagnostic criteria can influence the prevalence estimates of cachexia, potentially hindering the translation of research findings into clinical practice. Although a systematic review has documented the prevalence of cachexia in patients with cancer [3], to the best of our knowledge, no study has extensively examined it according to different definitive criteria for cachexia diagnosis. In addition, the disparities between the association of cancer-related cachexia and OS have not been widely explored.

This study aimed to identify differences in the prevalence of cachexia using a systematic review (Aim 1) and to evaluate the relationship between cachexia and OS using a meta-analysis (Aim 2) on the basis of the definitive criteria for cachexia diagnosis in patients with cancer. We hypothesized that the prevalence of cachexia would vary depending on the definitive criteria and that a lower prevalence would result in a higher HR for OS. This is because high-risk populations can be more accurately identified [6].

Methods

This systematic review and meta-analysis followed the PRISMA 2020 guidelines and was registered in PROSPERO (CRD42023435474; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=435474). The PRISMA 2020 checklist of items included in this systematic review and meta-analysis is presented in Supplemental Table 1.

Search strategy

We conducted a systematic review of the diagnostic and assessment methods of cachexia and its prevalence in patients with cancer. Additionally, we performed a meta-analysis to investigate the association between cancer-related cachexia and OS. We searched the PubMed and Web of Science databases from their inception until 31 July, 2023. The electronic literature search was conducted by 1 researcher (TT.).

The basic strategy entailed searching for “Cancer” AND “Cachexia” AND “Assessment” OR “Diagnosis” AND “Study design” using Medical Subject Heading terms and free text terms appropriate to each database. The search was designed to be broad enough to identify all assessment methods. A full copy of the search strategy used for PubMed and Web of Science is presented in Supplemental Table 2.

Eligibility criteria

Table 1 presents the criteria used in this study for the population, intervention/exposure, comparison, outcome, and study design. The inclusion criteria for Aim 1 encompassed both observational and interventional studies that 1) involved the assessment or diagnosis of cachexia in patients with cancer and 2) included patients aged ≥18 y. Aim 2 had similar criteria with the addition of 3) OS as a condition. The exclusion criteria for both aims were 1) cachexia in patients without cancer, 2) patients aged <18 y, 3) unspecified assessment or diagnosis methods for cachexia, 4) studies in which all patients had cachexia, 5) nonhuman studies (for example, in vivo and in vitro), 6) nonoriginal articles (for example, reviews), and 7) articles not published in English or Japanese.TABLE 1 PECOS criteria for inclusion and exclusion of studies.

TABLE 1Parameter	Inclusion criteria	Exclusion criteria	
Aim 1 (systematic review)	Aim 2 (meta-analysis)	Aims 1 and 2	
Population	Adult patients with cancer, aged ≥18 y	Adult patients with cancer, aged ≥18 y	Patients without cancer, patients with only cachexia, aged <18 y	
Exposure	Definition and their assessment items of cachexia	Cachexia	Unclear details on definition and assessment items for cachexia	
Comparison		Noncachexia		
Outcome	Prevalence of cachexia	Overall survival		
Study design	Observational (cross-sectional, prospective cohort, and retrospective) and interventional studies	Observational (prospective cohort and retrospective) and interventional studies	Nonhuman studies (for example, in vivo and in vitro) and nonoriginal articles (for example, review articles)	
Other			Not published in English or Japanese	
Abbreviations: PECOS, participants, exposure, comparison, outcomes, and study design.

Data extraction

The retrieved articles were imported into a Google Sheet spreadsheet (Alphabet Inc.). Subsequently, duplicates were manually removed by 1 researcher (TT), and 2 researchers (TT and AY) independently screened the literature for titles and abstracts and reviewed the full text. Any disagreements were resolved by consensus with a third researcher (DW).

One researcher (TT) extracted the following data from the included studies: the last name of the first author, publication year, country, study design, sample size, number of patients with and without cachexia, sex, age, height, body weight (at assessment), BMI, cancer type, cancer stage, reference article for the assessment or diagnosis of cachexia, assessment or diagnosis subdomains (items) of cachexia, prevalence of cachexia, and multivariable-adjusted HR and 95% confidence interval (CI) of OS (the noncachexia group was used as a reference category). Another researcher (AY) confirmed this process.

The assessment items in each set of definitive criteria for cachexia diagnosis were summarized by the frequency of use for classifying frailty, sarcopenia, and malnutrition by the Global Leadership Initiative on Malnutrition [[7], [8], [9]]. Each country was classified into one of the following 7 regions: Europe, North America, South America, Asia, Africa, Oceania, and Multiple regions. The cancer types were classified with reference to the International Classification of Diseases, 10th revision. If the assessment or diagnosis item was listed in the article, only that item was obtained; otherwise, all the items listed in the references were obtained. OS was noted only for assessments or diagnoses of cachexia and noncachexia at baseline or pretreatment.

Quality assessment

The quality assessments of studies reporting prevalence and OS data were performed using Hoy’s risk bias tool [10] and Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS), respectively [11]. Two researchers (TT and AY) independently scored each article, and any disagreements were resolved by consensus with a third researcher (DW).

Hoy’s risk of bias tool, which comprising 10 domains, was applied to assess the studies reporting on the prevalence of cachexia in patients with cancer [10]. The respective domains were assessed using the following questions: 1) Was the study’s target population a close representation of the national population in relation to relevant variables, such as age, sex, and occupation? 2) Was the sampling frame a true or close representation of the target population? 3) Was some form of random selection used to select the sample or was a census undertaken? 4) Was the likelihood of nonresponse bias minimal? 5) Were data collected directly from the patients (rather than through a proxy)? 6) Was an acceptable case definition used in the study? 7) Was the study instrument that measured the parameter of interest (for example, prevalence of low back pain) shown to have reliability and validity (if necessary)? 8) Was the same mode of data collection used for all patients? 9) Was the length of the shortest prevalence period for the parameter of interest appropriate? 10) Were the numerator(s) and denominator(s) for the parameter of interest appropriate? Each domain was evaluated as having a “low,” “high,” or “unclear” risk, with the “unclear risk” rating added by Petermann-Rocha et al. [12] when there was insufficient information to make a judgment. Overall, each study was rated as having a “low,” “moderate,” or “high” risk of bias. Studies with ≥8 domains scored as low risk were categorized as “low risk,” those with 6–7 domains as low risk were classified as “moderate risk,” and those with ≤5 domains as low risk were classified as “high risk.”

RoBANS was used to assess 6 domains in observational studies reporting on OS [11], with each domain classified as “low risk,” “high risk,” or “unknown.” These domains include participant selection, confounding variables, exposure measurement, outcome assessment blinding, incomplete outcome data, and selective reporting of outcomes.

Statistical analysis

The weighted mean age and BMI of the patients were calculated using either the mean or median values in each article. Each weighted mean was calculated by multiplying the weight associated with the value of each study by the number of participants. The frequency of use of the diagnostic criteria items for cachexia outlined in each study was summarized. The prevalence of cachexia in patients with cancer and the criteria for cachexia used in ≥2 articles in the systematic review are presented as percentages (%) and 95% CIs.

A meta-analysis, including forest and funnel plots, was conducted using Review Manager (RevMan) Version 5.4.1 (Nordic Cochrane Centre; Cochrane Collaboration). Subgroup analyses were performed based on different assessment criteria for cachexia (Fearon 2011 criteria [2] or others). We used the Fearon 2011 criteria as a reference because they are the standard in the field of cachexia. The association between cancer cachexia and OS was summarized by pooling adjusted HRs with 95% CIs using a random-effects generic inverse variance method for the cachexia compared with the noncachexia group at baseline or pretreatment. Random-effects models were applied, considering the presence or absence of significant heterogeneity. We assessed the heterogeneity across studies using Cochran’s Q test and I2 statistic. The level of heterogeneity (I2) was measured as a percentage, with 25% indicating low heterogeneity, 50% indicating moderate heterogeneity, and 75% indicating high heterogeneity. To visually evaluate publication bias, we used a funnel plot. We fitted meta-regression using a nonlinear model in STATA MP, Version 15.0 (StataCorp LP).

Sensitivity analyses were performed using the following 3 methods: 1) a meta-analysis using a fixed-effect model to verify the robustness of the results, 2) exclusion of studies rated as high or unknown in any of the RoBANS domains (14 of 26 articles) to eliminate the possible influence of low-quality studies, and 3) exclusion of the bottom 50% of studies with the smallest sample sizes in the meta-analysis (13 of 26 articles) to eliminate the possible influence of studies with small sample sizes.

Results

Study selection

Figure 1 shows a flow diagram of the study selection process. Our electronic literature search identified 1011 publications (excluding duplicates). After screening the titles and abstracts of 580 publications, 431 full-text articles were assessed in detail, and 306 articles were further identified as ineligible (Supplemental Table 3). Finally, 125 articles qualified for the systematic review, out of which 26 were included in the meta-analysis.FIGURE 1 Flow chart of the study search and selection process.

FIGURE 1

Quality assessment

According to Hoy’s risk of bias tool, the overall quality of studies included in the systematic review was distributed as follows: 9.6%: low risk, 46.4%: moderate risk, and 44.0%: high risk. In terms of domains, Q1 (representation of the national population) and Q3 (random sampling) for many studies were classified as high risk, whereas Q4 (nonresponse), Q7 (measurement methods of exposure), and Q8 (data collection consistency across subjects) were categorized as unclear (Supplemental Figure 1A and Supplemental Table 4).

Based on RoBANS, ∼54% of the studies included in the meta-analysis exhibited an unclear or high risk of bias. However, the selection of participants, blinding of outcome assessments, and incomplete outcome data were considered low risk across all studies (Supplemental Figure 1B and Supplemental Table 5).

Study characteristics

Table 2 summarizes the basic characteristics of the 125 and 26 articles in the systematic review and meta-analysis, respectively, with 137,960 patients in the systematic review and 11,118 patients in the meta-analysis. Patients in the meta-analysis were older (weighted mean 64 compared with 58 y), constituted a higher percentage of male (58.0 compared with 52.8%), and had a higher BMI (24.0 compared with 22.8 kg/m2) than those in the systematic review. Supplemental Table 6 lists the studies included in the systematic review.TABLE 2 Summary of the characteristics of studies included in the systematic review and meta-analysis.

TABLE 2	Aim 1 (systematic review)	Aim 2 (meta-analysis)	
All	Cachexia	Noncachexia1	All	Cachexia	Noncachexia1	
Age (y)2	
 Number of studies, n	113	53	49	21	10	10	
 Number of patients, n	100,132	26,970	33,277	5959	1444	1433	
 Mean (range)3	58 (50–83)	60 (47–83)	58 (48–83)	64 (58–80)	63 (59–72)	63 (57–70)	
Sex2	
 Number of studies, n	118	55	55	26	12	12	
 Number of patients, n	123,074	26,460	42,948	11,118	1476	2449	
 Male, n (%)	64,976 (52.8)	14,564 (55.0)	18,275 (42.6)	6447 (58.0)	1000 (67.8)	1797 (73.4)	
BMI (kg/m2)2	
 Number of studies, n	88	47	42	14	10	9	
 Number of patients, n	88,827	27,842	36,774	3528	2410	2481	
 Mean (range)3	22.8 (16.0–31.4)	22.9 (16.0–28.7)	24.2 (21.1–30.1)	24.0 (18.4–28.5)	23.0 (19.6–28.1)	23.5 (21.7–28.5)	
Regions4, n (%)	137,960	45,538	88,570	11,118	3956	5334	
 Europe	9467 (6.8)	4309 (9.4)	5096 (5.8)	2151 (19.3)	823 (20.8)	1319 (24.7)	
 North America	19,208 (13.9)	10,546 (23.2)	8228 (9.3)	913 (8.2)	336 (8.5)	376 (7.0)	
 South America	5035 (3.6)	1628 (3.6)	1648 (1.9)	4152 (37.3)	1181 (29.9)	1442 (27.0)	
 Asia	100,477 (72.5)	28,139 (61.8)	71,531 (80.8)	3748 (33.7)	1559 (39.4)	2106 (39.5)	
 Africa	1024 (0.7)	116 (0.3)	908 (1.0)	—	—	—	
 Oceania	12 (0.0)	6 (0.0)	6 (0.0)	—	—	—	
 Multiple regions5	2737 (2.0)	794 (1.7)	1153 (1.3)	154 (1.4)	57 (1.4)	91 (1.7)	
Cancer type6,7, n (%)	137,960	45,538	88,570	11,118	3956	5334	
 Lung cancer	7091 (5.1)	2256 (5.0)	4777 (5.4)	671 (6.0)	225 (5.7)	437 (8.2)	
 Gastrointestinal cancer	29,948 (21.7)	7674 (16.9)	22,057 (24.9)	4190 (37.7)	1654 (41.8)	2329 (43.7)	
 Head and neck cancer	751 (0.5)	314 (0.7)	428 (0.5)	426 (3.8)	212 (5.4)	214 (4.0)	
 Solid or hematopoietic	302 (0.2)	112 (0.2)	167 (0.2)	86 (0.8)	40 (1.0)	46 (0.9)	
 Urological cancer	304 (0.2)	61 (0.1)	212 (0.2)	141 (1.3)	16 (0.4)	125 (2.3)	
 Gynecological cancer	40 (0.0)	15 (0.0)	22 (0.0)	—	—	—	
 Multiple cancers8	99,524 (72.2)	35,106 (77.1)	60,907 (68.8)	5604 (50.4)	1809 (45.7)	2183 (40.9)	
Cancer stage2	
 Number of studies, n	65	30	26	11	5	4	
 Number of patients, n	93,806	25,459	29,653	3193	776	517	
 Stage Ⅰ, n (%)	12,804 (13.6)	2510 (9.9)	5166 (17.4)	639 (20.0)	106 (13.7)	56 (10.8)	
 Stage Ⅱ, n (%)	18,412 (19.6)	4972 (19.5)	6934 (23.4)	419 (13.1)	98 (12.6)	18 (3.5)	
 Stage Ⅲ, n (%)	26,096 (27.8)	8288 (32.6)	9663 (32.6)	1012 (31.7)	317 (40.9)	201 (38.9)	
 Stage Ⅳ, n (%)	20,613 (22.0)	9433 (37.1)	7009 (23.6)	1066 (33.4)	236 (30.4)	204 (39.5)	
1 Not included patient with precachexia or refractory cachexia.

2 Data were extracted from the article.

3 Data are shown as the mean values weighted by the number of patients.

4 The number of studies (systematic review, meta-analysis) are as follows: Europe (48, 8), North America (18, 4), South America (6, 1), Asia (48, 12), Africa (1, 0), Oceania (1, 0), and Multiple regions (3, 1).

5 Multiple regions entailed a collaborative study conducted in different regions.

6 Cancer types were classified with reference to the International Classification of Disease, 10th revision.

7 The number of studies (systematic review, meta-analysis) are as follows: lung cancer (including malignant mesothelioma) (18, 5), gastrointestinal cancer (37, 11), head and neck cancer (8, 2), solid or hematopoietic (3, 1), urological cancer (2, 1), gynecological cancer (1, 0), and multiple cancers (56, 6).

8 “Multiple cancers” were included in different cancer types.

Prevalence of cachexia in patients with cancer

A total of 30 definitive criteria for diagnosing cachexia were used in the study (excluding those without reference). Detailed definitions of each set of definitive criteria for cachexia diagnosis are provided in Supplemental Table 7.

Table 3 [2,5,4,[13], [14], [15], [16]] presents the prevalence of cachexia among patients with cancer according to the definitive criteria for cachexia diagnosis used in ≥2 articles in the systematic review. The overall prevalence of cachexia was 33.0% (95% CI: 32.8, 33.3) in the systematic review. Additionally, the most widely used definitive criteria were the Fearon 2011 [2] criteria, accounting for 58.4% in the systematic review and 69.2% in the meta-analysis, resulting in a cachexia prevalence of 30.2% and 40.4%, respectively. In the systematic review, the prevalence of cachexia according to the Evans 2008 [5] criteria (13.9%) was lower than that according to the Fearon 2011 [2] criteria (30.2%).TABLE 3 Prevalence of cachexia according to the definitive criteria for diagnosing cachexia.

TABLE 3Definitive criteria for cachexia (First author, publication year [reference])	Number of studies1	Number of patients	Number of patients with cachexia	Prevalence of cachexia	
n (%)2	n	(Range)	n	(Range)	%	(95% CI)	
Aim 1 (systematic review)	
All articles	125	137,960	(12–16,262)	45,538	(2–8649)	33.0	(32.8, 33.3)	
 Fearon K, 2011 [2]	73 (58.4)	100,350	(20–16,262)	30,284	(7–5261)	30.2	(29.9, 30.5)	
 No references3	18 (14.4)	3139	(12–1276)	912	(2–214)	29.1	(27.5, 30.7)	
 Evans WJ, 2008 [5]	9 (7.2)	5321	(33–4231)	742	(11–351)	13.9	(13.0, 14.9)	
 Fearon KC, 2006 [4]	3 (2.4)	167	(40–77)	45	(14–16)	26.9	(20.4, 34.3)	
 Bozzetti F, 2009 [13]	3 (2.4)	1754	(33–1307)	917	(13–523)	52.3	(49.9, 54.6)	
 Martin L, 2015 [14]	2 (1.6)	237	(92–145)	134	(55–79)	56.5	(50.0, 62.9)	
 Vigano AAL, 2017 [15]	2 (1.6)	1661	(277–1384)	350	(106–244)	21.1	(19.1, 23.1)	
 Zhou T, 2018 [16]	2 (1.6)	455	(196–259)	206	(103–103)	45.3	(40.6, 50.0)	
Aim 2 (meta-analysis)	
 All articles	26	11,118	(33–1384)	3956	(7–746)	35.6	(34.7, 36.5)	
 Fearon K, 2011 [2]	18 (69.2)	5437	(33–1215)	2196	(7–322)	40.4	(39.1, 41.7)	
 No references3	1 (3.8)	141		16		11.3	(6.6, 17.8)	
 Evans WJ, 2008 [5]	4 (15.4)	601	(33–361)	248	(11–192)	41.3	(37.3, 45.3)	
 Fearon KC, 2006 [4]	1 (3.8)	77		16		20.8	(12.4, 31.5)	
 Bozzetti F, 2009 [13]	1 (3.8)	33		13		39.4	(22.9, 57.9)	
 Vigano AAL, 2017 [15]	1 (3.8)	1384		244		17.6	(15.7, 19.7)	
 Zhou T, 2018 [16]	1 (3.8)	196		103		52.6	(45.3, 59.7)	
Abbreviation: CI, confidence interval.

Only definitions of cachexia used in ≥2 articles in the systematic review are shown. Detailed definitions of each diagnostic criterion of cachexia are summarized in Supplemental Table 7.

1 The number of studies and the total number of patients do not match because some studies were evaluated according to >1 criterion in 1 study.

2 Percentages shown in the systematic review and meta-analysis correspond to the total number of articles in each.

3 Studies that described criteria for evaluating cachexia but did not cite references.

Table 4 presents the assessment items for the definitive criteria for cachexia diagnosis and the prevalence of the condition, and Supplemental Table 8 provides a detailed breakdown of the frequency of use of these criteria across studies. The most commonly used items were weight loss (94.4%) and low BMI (68.0%). Conversely, fewer studies included items related to dietary intake, such as reduced energy intake and appetite (5.6% and 8.0%, respectively). The prevalence of cachexia was higher in studies that incorporated weight loss or low BMI into the criteria, and lower when the criteria included reduced energy intake, appetite, inflammation, low muscle strength, or fatigue.TABLE 4 Assessment items of the definitive criteria for diagnosing cachexia and prevalence of cachexia.

TABLE 4Domains	Number of studies1	Number of patients1	Number of patients with cachexia1	Prevalence of cachexia1	
n (%)2	n	(Range)	n	(Range)	%	(95% CI)	
All articles	125							
Low BMI	85 (68.0)	121,689	(12–16,262)	41,481	(2–8649)	34.1	(33.8, 34.4)	
Weight loss	118 (94.4)	137,465	(12–16,262)	45,443	(6–8649)	33.1	(32.8, 33.3)	
Low muscle mass	56 (44.8)	101,004	(12–16,262)	28,448	(6–5261)	28.2	(27.9, 28.4)	
Reduced energy intake	7 (5.6)	2269	(21–1384)	568	(7–244)	25.0	(23.3, 26.9)	
Reduced appetite	10 (8.0)	6051	(33–4231)	1033	(7–351)	17.1	(16.1, 18.0)	
Inflammation	17 (13.6)	10,767	(21–4231)	2378	(5–746)	22.1	(21.4, 22.9)	
Biochemical	16 (12.8)	9936	(33–4231)	2501	(5–746)	25.2	(24.3, 26.0)	
Screening tool3	5 (4.0)	1825	(70–1030)	874	(2–1030)	47.9	(45.6, 50.2)	
Low muscle strength	11 (8.8)	7031	(33–4231)	1577	(7–4231)	22.4	(21.5, 23.4)	
Low gait speed	1 (0.8)	1030		534		51.8	(48.7, 54.9)	
Fatigue	8 (6.4)	6940	(33–4231)	1007	(7–351)	14.5	(13.7, 15.4)	
Abbreviations: BMI, body mass index; CI, confidence interval.

1 The numbers represent the sum of studies in which each item was included in the diagnostic category of cachexia.

2 Percentages shown correspond to the total number of articles in each.

3 Strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC-F) or subjective global assessment.

Association between the presence of cachexia and OS

Supplemental Table 9 presents the characteristics of the studies included in the meta-analysis. The estimated HR varied by study, and the number of adjusted confounders ranged from 2 to 12, with age being the most adjusted variable (13 articles; 50%).

Figure 2A [2,17] displays the forest plot of the meta-analysis examining the HR for OS [6,[18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41]]. Subgroup analysis based on the Fearon 2011 criteria and other criteria revealed HRs of 1.58 [95% CI: 1.45, 1.73; I2 = 1%; 18 articles (19 studies)] and 2.78 [95% CI: 1.88, 4.11; I2 = 86%; 12 articles (12 studies)], respectively. The Fearon 2011 criteria showed a significantly lower HR than the other criteria (subgroup differences: P = 0.006; I2 = 86.8%). Because the funnel plot showed asymmetry (Supplemental Figure 2), 3 sensitivity analyses were performed and all revealed similar results (Supplemental Figures 3–5).FIGURE 2 Meta-analysis and dose–response association between cachexia in patients with cancer and overall survival. (A) Forest plot for the effect of cachexia on overall survival. Subgroup analyses were carried out based on different definitive criteria for diagnosing cachexia (Fearon 2011 criteria [2] or others). Karmali et al. [17] did not report the 95% CI of the hazard ratio. We complemented it with a 95% CI using the mean and SD values calculated from the other group. (B) Meta-regression analysis. Circles represent hazard ratio point estimates for the prevalence of cancer cachexia in each study, with circle size representing sample size. Hazard ratios are displayed on a logarithmic scale. CI, confidence interval; IV, inverse variance; SD, standard deviation.

FIGURE 2

Figure 2B presents the meta-regression analysis. The HR for OS was higher when the prevalence of cachexia was low. The dose–response curve indicated that the HR for OS plateaued at a cachexia prevalence range of 40%–50%; nonetheless, the HR for OS remained consistently high across all cachexia prevalence levels.

Discussion

Main findings

We conducted a systematic review and meta-analysis to determine differences in the prevalence of cachexia and OS based on the definitive criteria for diagnosing cachexia in patients with cancer. The overall prevalence of cachexia was 33.0%, although it varied depending on the definitive criteria used. A higher HR for OS was found for cachexia than for noncachexia, which also varied based on the definitive criteria used. Additionally, the dose–response curve indicated that the HR for OS plateaued when the prevalence of cachexia reached 40%–50%. To the best of our knowledge, this is the first study to comprehensively evaluate different definitive criteria for cachexia diagnosis in patients with cancer and their impact on the association between prevalence and OS.

Differential prevalence of cachexia based on the definitive criteria

Previous studies have reported the prevalence of cachexia in patients with cancer in only 4 regions (Europe, North America, Asia, and Oceania) [3,42]. Anker et al. [3] reported that the prevalence of cachexia among patients with cancer in the United States, Canada, Australia, Europe, and Asia ranged from 11% to 74%, with the United States and the European Union having a prevalence of ∼30%. In Asia, the prevalence varied from 6.2% to 93% [42]. This study is the first to assess the global prevalence of cachexia in patients with cancer, revealing an overall prevalence of 33.0%, which is consistent with the findings of a previous study [3]. Our research estimated cachexia prevalence as 51.8% in North America and Europe and 28.8% in Asia. The variations in cachexia prevalence between our study and previous ones could be due to discrepancies in the inclusion criteria of the articles and the time frame of the systematic review.

Various definitive criteria are used for diagnosing cachexia. In our study, the Fearon 2011 criteria [2] were the most commonly used definitive criteria for diagnosing cachexia, and the Evans 2008 criteria were used less frequently (58.4% and 7.2%, respectively), consistent with the results of a previous study (57% and 6%, respectively) [42]. Of note, differences in the definitive criteria used to diagnose sarcopenia and frailty have been reported to affect their estimated prevalence [12,43]. In our study, the prevalence of cachexia according to the Fearon 2011 criteria was higher than that estimated using the Evans 2008 criteria (30.2% and 13.9%, respectively), as reported previously (49.7% and 17.9%, respectively) [37].

Our bias assessment also revealed variations in cachexia prevalence based on its definitive criteria, in addition to country/region, suggesting data heterogeneity and the limited availability of high-quality, nationally representative samples. Thus, future studies should focus on determining the prevalence of cachexia across diverse populations using different definitive criteria, ideally through national random sampling. In addition, more accurate definitive criteria for diagnosing cachexia should be established for onward application in clinical practice.

Assessment items in the definitive criteria for cachexia

Weight loss and low BMI were the frequently used items to define cachexia in our study, but items related to dietary intake and sarcopenia diagnosis were less frequently used. The phenotypic model of frailty includes 5 components (weight loss, low physical activity, exhaustion, slowness, and weakness) [7], whereas the diagnosis of sarcopenia includes 3 items (low muscle strength, physical performance, and low muscle mass) [8]. Although sarcopenia status (low muscle mass) serves as an assessment criterion for cachexia [4,5,9,31,[44], [45], [46], [47], [48]], it was only used in 44.8% of the studies in our systematic review. In contrast, weight loss, a key component in diagnosing frailty, was frequently adopted in defining cachexia in 94.4% of the studies. Consequently, the prevalence of cachexia varied depending on the assessment items included in the definitive criteria. A higher prevalence of cachexia was observed when low BMI or weight loss was included compared with that when reduced appetite (or dietary intake) or fatigue was considered.

Notably, Watanabe et al. [49] highlighted that the prevalence of frailty in the same individual can also vary according to the subdomain or definition method (phenotype model and accumulation deficit) used to assess frailty. Although our results are biased because we did not compare each item separately for the same individual, the creation and use of definitive criteria for cachexia diagnosis should consider the significance of each item for the prevalence and prognosis of cachexia. The definitive criteria for diagnosing cachexia among Asians have recently been published [50]. A study that used these criteria in patients with advanced cancer reported a high prevalence of cachexia (76%), although without comparison to the results of other definitive criteria [51]. Future research is warranted to examine differences in the prevalence of cachexia according to each item in the same individual and to determine whether regional adjustments are necessary in applying the definitive criteria.

Association between the definitive criteria for diagnosing cachexia and OS in patients with cancer

Cachexia in patients with cancer consistently showed an association with poor OS, although the effect varied depending on the definitive criteria used for diagnosis. Frailty has also been linked to mortality, and its impact on mortality risk differs depending on its definition. Similar to our findings, a lower prevalence of frailty may be associated with a higher risk of mortality [43,52]. Even when using the same term, “cachexia,” the prevalence can vary across various definitive criteria, potentially influencing prognosis outcomes. Our study revealed an L-shaped curve relationship between the HR for OS and the prevalence of cachexia. This association plateaued at a 40%–50% prevalence of cachexia. This finding is consistent with that of a study by Mytelka et al. [53], who reported a progressively worse survival with an increasing cachexia risk in patients with lung cancer.

Of concern, the Fearon 2011 criteria might overestimate the prevalence of cachexia, thereby diluting the true relationship between cachexia and adverse outcomes [37]. As such, the definitive criteria for cachexia should match the goal of diagnosis. For example, when the goal is to screen individuals at risk of cachexia, broader and more sensitive criteria (high-prevalence criteria) should be used. Conversely, when the goal is to select a high-risk population for treatment intervention, stricter and more specific criteria (low-prevalence criteria) should be used. Therefore, in clinical practice, it may be beneficial to screen populations at risk of cachexia using high-prevalence criteria, such as the Fearon 2011 criteria [2]. In contrast, the low-prevalence criteria can help to identify individuals requiring intensive treatment of cachexia, including dietary and drug therapy.

Strengths and limitations

The strength of this study lies in its ability to assess differences in characteristics between the large populations in the systematic review and the population used in the meta-analysis. This confirmed the representativeness of the relationship between cachexia and OS in the meta-analysis. Nevertheless, this study has some limitations. First, the systematic review was limited to articles published in 2 major databases, PubMed and Web of Science, leading to possible selection bias, as some relevant studies may have been omitted. Additionally, we were unable to obtain 1 article. Although this limitation may influence the estimation of the prevalence of cachexia and its association with OS, our results are consistent with previous reports [3,42]. Second, the funnel plot indicated asymmetry, suggesting publication bias. However, we could not use the trim-and-fill method to adjust the publication bias, because the RevMan software used for statistical analysis lacks this model. Nevertheless, we conducted thorough sensitivity analyses by excluding low-quality and small-sample-size studies. The sensitivity analyses yielded similar results to those of the main analysis. Third, our review was limited to articles in English or Japanese, which may introduce language selection bias. Finally, most of the studies included in the systematic review were classified as having a moderate or high risk of bias, and high heterogeneity was observed in the meta-analysis. Future studies with less bias are needed to accurately assess the prevalence of cachexia in patients with cancer.

In conclusion, this study provided the best available estimate of the prevalence of cachexia in patients with cancer, based on data from 137,960 patients across 6 regions (16 countries). Furthermore, it demonstrated that the OS varies depending on the prevalence of cachexia. These findings emphasize the importance of considering the definitive criteria used when evaluating the prognosis and prevalence of cachexia among patients with cancer.

Author contributions

The authors’ contributions were as follows – TT, AY, DW: contributed to the conception of this research; TT, AY, DW: designed the research; TT, AY, DW: screened the literature; TT, AY: selected and extracted the data; TT, AY, DW: performed quality assessment; TT, DW: conducted the analyses; TT: drafted the manuscript; all authors: contributed to the critical review of the manuscript; and all authors: read and approved the final manuscript.

Conflict of interest

The authors report no conflicts of interest.

Funding

The authors reported no funding received for this study.

Data availability

All data generated or analyzed during this study are included in this published article and the accompanying Supplementary Information files.

Appendix A Supplementary data

The following is the Supplementary data to this article:multimedia component 1

multimedia component 1

Acknowledgments

We would like to express our gratitude to all the individuals and research groups whose articles are included in this review. We also want to thank Dr Mitsuhisa Komatsu (Shinshu University) and Chieko Zakouji (Shinshu University Hospital) for their supportive comments and discussion on our work. Additionally, we would like to thank Editage (www.editage.jp) for the English-language editing.

Appendix A Supplementary data to this article can be found online at https://doi.org/10.1016/j.advnut.2024.100282.
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References

1 Sung H. Ferlay J. Siegel R.L. Laversanne M. Soerjomataram I. Jemal A. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries CA Cancer J. Clin. 71 3 2021 209 249 10.3322/caac.21660 33538338
2 Fearon K. Strasser F. Anker S.D. Bosaeus I. Bruera E. Fainsinger R.L. Definition and classification of cancer cachexia: an international consensus Lancet Oncol 12 5 2011 489 495 10.1016/S1470-2045(10)70218-7 21296615
3 Anker M.S. Holcomb R. Muscaritoli M. von Haehling S. Haverkamp W. Jatoi A. Orphan disease status of cancer cachexia in the USA and in the European Union: a systematic review J. Cachexia Sarcopenia Muscle 10 1 2019 22 34 10.1002/jcsm.12402 30920776
4 Fearon K.C. Voss A.C. Hustead D.S. Cancer Cachexia Study Group Definition of cancer cachexia: effect of weight loss, reduced food intake, and systemic inflammation on functional status and prognosis Am. J. Clin. Nutr. 83 6 2006 1345 1350 10.1093/ajcn/83.6.1345 16762946
5 Evans W.J. Morley J.E. Argilés J. Bales C. Baracos V. Guttridge D. Cachexia: a new definition Clin. Nutr. 27 6 2008 793 799 10.1016/j.clnu.2008.06.013 18718696
6 Thoresen L. Frykholm G. Lydersen S. Ulveland H. Baracos V. Prado C.M. Nutritional status, cachexia and survival in patients with advanced colorectal carcinoma. Different assessment criteria for nutritional status provide unequal results Clin. Nutr. 32 1 2013 65 72 10.1016/j.clnu.2012.05.009 22695408
7 Dent E. Lien C. Lim W.S. Wong W.C. Wong C.H. Ng T.P. The Asia-Pacific Clinical Practice Guidelines for the management of frailty J. Am. Med. Dir. Assoc. 18 7 2017 564 575 10.1016/j.jamda.2017.04.018 28648901
8 Chen L.K. Woo J. Assantachai P. Auyeung T.W. Chou M.Y. Iijima K. Asian Working Group for Sarcopenia: 2019 consensus update on sarcopenia diagnosis and treatment J. Am. Med. Dir. Assoc. 21 3 2020 300 307.e2 10.1016/j.jamda.2019.12.012 32033882
9 Jensen G.L. Cederholm T. Correia M.I.T.D. Gonzalez M.C. Fukushima R. Higashiguchi T. GLIM criteria for the diagnosis of malnutrition: a consensus report from the Global Clinical Nutrition Community JPEN J. Parenter. Enteral Nutr. 43 1 2019 32 40 10.1002/jpen.1440 30175461
10 Hoy D. Brooks P. Woolf A. Blyth F. March L. Bain C. Assessing risk of bias in prevalence studies: modification of an existing tool and evidence of interrater agreement J. Clin. Epidemiol. 65 9 2012 934 939 10.1016/j.jclinepi.2011.11.014 22742910
11 Kim S.Y. Park J.E. Lee Y.J. Seo H.J. Sheen S.S. Hahn S. Testing a tool for assessing the risk of bias for nonrandomized studies showed moderate reliability and promising validity J. Clin. Epidemiol. 66 4 2013 408 414 10.1016/j.jclinepi.2012.09.016 23337781
12 Petermann-Rocha F. Balntzi V. Gray S.R. Lara J. Ho F.K. Pell J.P. Global prevalence of sarcopenia and severe sarcopenia: a systematic review and meta-analysis J. Cachexia Sarcopenia Muscle 13 1 2022 86 99 10.1002/jcsm.12783 34816624
13 Bozzetti F. Mariani L. Defining and classifying cancer cachexia: a proposal by the SCRINIO Working Group, JPEN J. Parenter Enteral Nutr. 33 4 2009 361 367 10.1177/0148607108325076
14 Martin L. Senesse P. Gioulbasanis I. Antoun S. Bozzetti F. Deans C. Diagnostic criteria for the classification of cancer-associated weight loss J. Clin. Oncol. 33 1 2015 90 99 10.1200/JCO.2014.56.1894 25422490
15 Vigano A.A.L. Morais J.A. Ciutto L. Rosenthall L. di Tomasso J. Khan S. Use of routinely available clinical, nutritional, and functional criteria to classify cachexia in advanced cancer patients Clin. Nutr. 36 5 2017 1378 1390 10.1016/j.clnu.2016.09.008 27793524
16 Zhou T. Wang B. Liu H. Yang K. Thapa S. Zhang H. Development and validation of a clinically applicable score to classify cachexia stages in advanced cancer patients J. Cachexia Sarcopenia Muscle 9 2 2018 306 314 10.1002/jcsm.12275 29372594
17 Karmali R. Alrifai T. Fughhi I.A.M. Ng R. Chukkapalli V. Shah P. Impact of cachexia on outcomes in aggressive lymphomas Ann. Hematol. 96 6 2017 951 956 10.1007/s00277-017-2958-1 28417157
18 Avan A. Avan A. Le Large T.Y. Mambrini A. Funel N. Maftouh M. AKT1 and SELP polymorphisms predict the risk of developing cachexia in pancreatic cancer patients PLOS ONE 9 9 2014 e108057 10.1371/journal.pone.0108057
19 Blauwhoff-Buskermolen S. Langius J.A.E. Becker A. Verheul H.M.W. de van der Schueren M.A.E. The influence of different muscle mass measurements on the diagnosis of cancer cachexia J. Cachexia Sarcopenia Muscle 8 4 2017 615 622 10.1002/jcsm.12200 28447434
20 Cavka L. Pohar Perme M. Rotovnik Kozjek N. Seruga B. Prognostic impact of nutritional status on overall survival and health-related quality of life in men with advanced prostate cancer Nutrients 15 4 2023 1044 10.3390/nu15041044 36839402
21 Dijksterhuis W.P.M. Latenstein A.E.J. van Kleef J.J. Verhoeven R.H.A. de Vries J.H.M. Slingerland M. Cachexia and dietetic interventions in patients with esophagogastric cancer: a multicenter cohort study J. Natl. Compr. Canc. Netw. 19 2 2021 144 152 10.6004/jnccn.2020.7615 33418527
22 Dunne R.F. Roussel B. Culakova E. Pandya C. Fleming F.J. Hensley B. Characterizing cancer cachexia in the geriatric oncology population J. Geriatr. Oncol. 10 3 2019 415 419 10.1016/j.jgo.2018.08.008 30196027
23 Hou Y.C. Chen C.Y. Huang C.J. Wang C.J. Chao Y.J. Chiang N.J. The differential clinical impacts of cachexia and sarcopenia on the prognosis of advanced pancreatic cancer Cancers (Basel) 14 13 2022 3137 10.3390/cancers14133137 35804906
24 Jo H. Yoshida T. Horinouchi H. Yagishita S. Matsumoto Y. Shinno Y. Prognostic significance of cachexia in advanced non-small cell lung cancer patients treated with pembrolizumab Cancer Immunol. Immunother. 71 2 2022 387 398 10.1007/s00262-021-02997-2 34180007
25 Kimura M. Naito T. Kenmotsu H. Taira T. Wakuda K. Oyakawa T. Prognostic impact of cancer cachexia in patients with advanced non-small cell lung cancer Support Care Cancer 23 6 2015 1699 1708 10.1007/s00520-014-2534-3 25430482
26 Kwon M. Kim R.B. Roh J.L. Lee S.W. Kim S.B. Choi S.H. Prevalence and clinical significance of cancer cachexia based on time from treatment in advanced-stage head and neck squamous cell carcinoma Head Neck 39 4 2017 716 723 10.1002/hed.24672 28000343
27 Matsuo N. Azuma K. Murotani K. Murata D. Matama G. Kawahara A. Prognostic effect of cachexia in patients with non-small cell lung cancer receiving immune checkpoint inhibitors Thorac. Cancer. 14 15 2023 1362 1367 10.1111/1759-7714.14881 37037511
28 Morimoto K. Uchino J. Yokoi T. Kijima T. Goto Y. Nakao A. Impact of cancer cachexia on the therapeutic outcome of combined chemoimmunotherapy in patients with non-small cell lung cancer: a retrospective study Oncoimmunology 10 1 2021 1950411 10.1080/2162402X.2021.1950411
29 Namikawa T. Marui A. Yokota K. Fujieda Y. Munekage M. Uemura S. Frequency and prognostic impact of cachexia during drug treatment for unresectable advanced gastric cancer patients Surg. Today. 52 11 2022 1560 1567 10.1007/s00595-022-02493-9 35322296
30 Nemer L. Krishna S.G. Shah Z.K. Conwell D.L. Cruz-Monserrate Z. Dillhoff M. Predictors of pancreatic cancer-associated weight loss and nutritional interventions Pancreas 46 9 2017 1152 1157 10.1097/MPA.0000000000000898 28902785
31 Orell-Kotikangas H. Österlund P. Mäkitie O. Saarilahti K. Ravasco P. Schwab U. Cachexia at diagnosis is associated with poor survival in head and neck cancer patients Acta Otolaryngol 137 7 2017 778 785 10.1080/00016489.2016.1277263 28125312
32 Rich N.E. Phen S. Desai N. Mittal S. Yopp A.C. Yang J.D. Cachexia is prevalent in patients with hepatocellular carcinoma and associated with worse prognosis Clin. Gastroenterol. Hepatol. 20 5 2022 e1157 e1169 10.1016/j.cgh.2021.09.022 34555519
33 Shen X.D. Wang X. Zheng Z.J. Chen Y.H. Tan C.L. Liu X.B. The differential effects of sarcopenia and cachexia on overall survival for pancreatic ductal adenocarcinoma patients following pancreatectomy: a retrospective study based on a large population Cancer Med 12 9 2023 10438 10448 10.1002/cam4.5779 36938648
34 Shibata M. Fukahori M. Kasamatsu E. Machii K. Hamauchi S. A retrospective cohort study to investigate the incidence of cachexia during chemotherapy in patients with colorectal cancer Adv. Ther. 37 12 2020 5010 5022 10.1007/s12325-020-01516-6 33067699
35 Ueshima J. Maeda K. Shimizu A. Nagano A. Ishida Y. Takeuchi T. Cachexia staging score predicts survival in patients with cancer who receive palliative care Nutrition 106 2023 111880 10.1016/j.nut.2022.111880
36 van der Meij B.S. Schoonbeek C.P. Smit E.F. Muscaritoli M. van Leeuwen P.A. Langius J.A. Pre-cachexia and cachexia at diagnosis of stage III non-small-cell lung carcinoma: an exploratory study comparing two consensus-based frameworks Br. J. Nutr. 109 12 2013 2231 2239 10.1017/S0007114512004527 23153477
37 Vanhoutte G. van de Wiel M. Wouters K. Sels M. Bartolomeeussen L. De Keersmaecker S. Cachexia in cancer: what is in the definition? BMJ Open Gastroenterol 3 1 2016 e000097 10.1136/bmjgast-2016-000097
38 Wan Q. Wang Z. Zhao R. Tu T. Shen X. Shen Y. CT-determined low skeletal muscle mass predicts worse overall survival of gastric cancer in patients with cachexia Cancer Med 12 2 2023 1492 1500 10.1002/cam4.5040 35848533
39 Wiegert E.V.M. de Oliveira L.C. Calixto-Lima L. Mota E. Peres W.A.F. Cancer cachexia: comparing diagnostic criteria in patients with incurable cancer Nutrition 79–80 2020 110945 10.1016/j.nut.2020.110945
40 Zhuang C.L. Dong Q.T. Shi H.P. Zhang F.M. Luo X. Wang W.B. Cachexia versus sarcopenia in clinical characteristics and prognostic value after radical gastrectomy for gastric cancer: a large-scale prospective study Ann. Surg. Oncol. 29 4 2022 2348 2358 10.1245/s10434-021-11084-w 34797480
41 Zopf Y. Schink K. Reljic D. Herrmann H.J. Dieterich W. Kiesswetter E. Assessing cachexia in older patients: different definitions – but which one is the most practical for clinical routine? Arch. Gerontol. Geriatr. 86 2020 103943 10.1016/j.archger.2019.103943
42 Ueshima J. Inoue T. Saino Y. Kobayashi H. Murotani K. Mori N. Diagnosis and prevalence of cachexia in Asians: a scoping review Nutrition 119 2024 112301 10.1016/j.nut.2023.112301
43 Hanlon P. Fauré I. Corcoran N. Butterly E. Lewsey J. McAllister D. Frailty measurement, prevalence, incidence, and clinical implications in people with diabetes: a systematic review and study-level meta-analysis Lancet. Healthy Longev. 1 3 2020 e106 e116 10.1016/S2666-7568(20)30014-3 33313578
44 Huo Z. Chong F. Yin L. Li N. Zhang M. Guo J. Development and validation of an online dynamic nomogram system for predicting cancer cachexia among inpatients: a real-world cohort study in China, Support Care Cancer 31 1 2022 72 10.1007/s00520-022-07540-2
45 Cederholm T. Bosaeus I. Barazzoni R. Bauer J. Van Gossum A. Klek S. Diagnostic criteria for malnutrition – an ESPEN Consensus Statement Clin. Nutr. 34 3 2015 335 340 10.1016/j.clnu.2015.03.001 25799486
46 Jafri S.H. Previgliano C. Khandelwal K. Shi R. Cachexia index in advanced non-small-cell lung cancer patients Clin. Med. Insights Oncol. 9 2015 87 93 10.4137/CMO.S30891 26604850
47 Wiegert E.V.M. de Oliveira L.C. Calixto-Lima L. Chaves G.V. Silva Lopes M.S. Peres W.A.F. New cancer cachexia staging system for use in clinical practice Nutrition 90 2021 111271 10.1016/j.nut.2021.111271
48 Thoresen L. Frykholm G. Lydersen S. Ulveland H. Baracos V. Birdsell L. The association of nutritional assessment criteria with health-related quality of life in patients with advanced colorectal carcinoma Eur. J. Cancer Care (Engl). 21 4 2012 505 516 10.1111/j.1365-2354.2012.01327.x 22309292
49 Watanabe D. Yoshida T. Yamada Y. Watanabe Y. Yamada M. Fujita H. Combined use of two frailty tools in predicting mortality in older adults Sci. Rep. 12 1 2022 15042 10.1038/s41598-022-19148-x
50 Arai H. Maeda K. Wakabayashi H. Naito T. Konishi M. Assantachai P. Diagnosis and outcomes of cachexia in Asia: working consensus report from the Asian Working Group for Cachexia J. Cachexia Sarcopenia Muscle 14 5 2023 1949 1958 10.1002/jcsm.13323 37667992
51 Sakaguchi T. Maeda K. Takeuchi T. Mizuno A. Kato R. Ishida Y. Validity of the diagnostic criteria from the Asian Working Group for Cachexia in advanced cancer J. Cachexia Sarcopenia Muscle 15 1 2024 370 379 10.1002/jcsm.13408 38115133
52 Shamliyan T. Talley K.M. Ramakrishnan R. Kane R.L. Association of frailty with survival: a systematic literature review Ageing Res. Rev. 12 2 2013 719 736 10.1016/j.arr.2012.03.001 22426304
53 Mytelka D.S. Li L. Benoit K. Post-diagnosis weight loss as a prognostic factor in non-small cell lung cancer J. Cachexia Sarcopenia Muscle 9 1 2018 86 92 10.1002/jcsm.12253 29205930
