Sarcopenia as a risk factor of progression-free survival in patients with metastases: a systematic review and meta-analysis

Sarcopenia as a risk factor of progression-free survival in patients with metastases: a systematic review and meta-analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Sarcopenia as a risk factor of progression-free survival in patients with metastases: a systematic review and meta-analysis Meijun Zhou, Xiangru Shen, Shuai Fang, Teng Wan, Pan Liu, Peiling Li, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2319788/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 07 Feb, 2023 Read the published version in BMC Cancer → Version 1 posted 8 You are reading this latest preprint version Abstract Background Metastasis of cancer causes more than 90% of cancer deaths and is severely damaging to human health. In recent years, several studies have linked sarcopenia to shorter survival in patients with metastatic cancer. Several predictive models exist to predict mortality in patients with metastatic cancer, but have reported limited accuracy. Methods We systematically searched PubMed, EMBASE, and the Cochrane Library for articles published on or before October 14, 2022. Pooled Hazard Ratio (HR) estimates with 95% confidence intervals (CIs) were calculated using a random effects model. The primary outcome was an increased risk of death or tumor progression in patients with metastatic cancer. In addition, we performed subgroup analyses and leave-one-out sensitivity analyses to explore the main sources of heterogeneity and the stability of the results. Results Sixteen retrospective cohort studies with 1,675 patients were included in the 888 papers screened. The results showed that sarcopenia was associated with lower progression-free survival (HR = 1.56, 95% CI = 1.19–2.03, I2 = 76.3%, P < 0.001). This result was further confirmed by trim-and-fill procedures and leave-one-out sensitivity analysis. Conclusions This study suggests that sarcopenia may be a risk factor for reduced progression-free survival in patients with metastatic cancer. Further studies are still needed to explain the reason for this high heterogeneity in outcome. Trial Registration: CRD42022325910 sarcopenia metastases progression-free survival meta retrospective study Figures Figure 1 Figure 2 Figure 3 Background Sarcopenia, from the Greek word "sarx" meaning "meat" and "penia" meaning loss, was first defined by Rosenberg in 1988 ( 1 ). It is defined as a progressive, systemic skeletal muscle disease involving progressive and systemic loss of skeletal muscle mass and function ( 2 , 3 ). Sarcopenia is associated with a variety of diseases, including but not limited to natural aging, functional, metabolic and immune disorders, increased muscle catabolism due to cancer, and toxicity of anti-cancer treatments ( 2 , 4 , 5 ). Previous studies have often confused cachexia with sarcopenia, a syndrome of weight loss and reduced muscle mass, and have been associated with poor prognosis ( 6 , 7 ). However, recent studies have shown that cachexia and sarcopenia represent different aspects of the muscle wasting spectrum ( 8 , 9 ). Approximately 15–50% of cancer patients with weight loss are sarcopenic rather than cachectic ( 10 ). With regard to the prognosis of cancer patients, the U.S. Food and Drug Administration's criteria for the effectiveness of cancer drug trials are whether the survival of cancer patients is prolonged and whether clinical symptoms improve after treatment ( 11 ). Although overall survival (OS) is the gold standard for evaluating clinical outcomes, the use of overall survival as a prognostic criterion for cancer patients may be biased. Possible reasons include the non-single nature of treatment for cancer patients from onset to end of life, the combination of other basic diseases and the use of other drugs during the course of the disease ( 12 , 13 ). Therefore, progression-free survival of tumor patients in clinical studies can be a better proxy for overall survival ( 14 ). Progression-free survival is defined as the time from the time when a patient is randomly enrolled to the time when the patient is first proved to have tumor progression or death without tumor progression. It allows the trial data to be obtained over a relatively short follow-up period compared to OS as the trial endpoint. Progression-free survival to be the endpoint reduces the impact of subsequent treatments and is usually based on results obtained from objective and quantitative evaluations ( 15 ). Many studies have been conducted to assess the predictive roles of sarcopenia in the occurrence of adverse events in cancer patients. Current systematic review suggests that sarcopenia negatively affects prognostic outcomes of cancer patients in terms of survival, physical activity, length of hospital stay and other complications ( 16 – 22 ). However, we found that current studies were limited to specific primary tumors or site-specific metastatic cancers ( 23 – 25 ). While sarcopenia as a systemic disease, we hypothesize that it is closely associated with the prognosis of multiple metastatic cancers. There is still controversy regarding the impact of sarcopenia on the prognosis and survival of patients with metastatic cancer. In the Lee et al. study, sarcopenia was not considered to be a potential factor in the patients' reduced PFS, which contradicts the findings of several other similar studies ( 26 – 28 ). Therefore, to elucidate whether sarcopenia and progression-free survival have a potential relationship in patients with metastatic cancer, we performed a systematic review and meta-analysis of studies focusing on the relationship between sarcopenia and progression-free survival in patients with metastatic cancer. Methods Standard Protocol Approvals This systematic review was conducted based on a predefined protocol and in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)( 29 ) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) recommendations( 30 ). The review protocol was registered in PROSPERO with the registration unique identifying number (UIN) of CRD42022325910. Search strategy and selection criteria Databases of Pubmed, Embase and Cochrane Central Register of Controlled Trials were systematically searched from inception to October 14, 2022 by two independent investigators (MZ and XS) without language or time restrictions. We used MeSH (for Pubmed and Cochrane)/Emtree (for Embase) terms combined with free-text words (including synonyms and closely related words) that were associated with metastases and sarcopenia.The detailed search strategy and specific terms were used, which were searched as free text words and as MeSH/Entrée terms without language restrictions. In addition, we also performed manual reference check of relevant articles, meta-analyses, reviews, and meeting abstracts. When two or more articles used the same cohort data, we preferred the most up-to-date ones with full-text information available. We perform study selection by a series of consecutive stages including duplicate checking using Endnote software, titles and abstracts screening, full-text article selection according to the eligibility criteria. These processes were conducted independently by two investigators (XS and TW). Conflicts were handled by consensus, and an adjudicator (WG) was consulted when necessary. If different opinions were encountered, senior experts would be consulted (SF or YF). Eligibility criteria Studies were considered appropriate and were included in the analysis if they satisfied the following established inclusion criteria. ( 1 ) prospective or retrospective population-based cohort study design; ( 2 ) participants: Patients diagnosed with metastatic cancer, with or without sarcopenia. Sarcopenia was diagnosed according to the criteria given by EWGSOP in 2019 ( 2 , 31 ); ( 3 ) outcome: progression-free survival; ( 4 ) the measure of association: hazard ratio (HR) and corresponding 95% CIs provided from the original studies or having related data that could be used to calculate the risk ratios. We excluded hospital-based on community-based observational studies and those providing inadequate data to generate risk ratio for the association between sarcopenia and metastases. Study selection, data collection, and data extraction Two investigators (XS and TW) independently read through, screened, extracted data from the included studies, and filled in the pre-designed data extraction excel forms. If there were any discrepancies, we would consult a third senior investigator (WG) until a consensus was reached. The following study characteristics were abstracted including study author, publication year, study design, study period, geographical region, observation period, population characteristics and age at cancer diagnosis, main treatment, measurements and definitions of sarcopenia, original cancer type, metastatic site of cancer and outcome. Quality assessment The methodological quality for the included studies was evaluated using the Newcastle–Ottawa scale (NOS)( 32 ) tool based on the main aspects in terms of representativeness of the patients, ascertainment of exposure and outcomes, adequacy of follow-up. Statistical analysis All statistical analyses were performed using Stata statistical software (version 15.1). The primary outcome was the PFS, defined as the length of time during and after the treatment of cancer, that a patient lives with the disease but the disease does not get worse. We applied the DerSimonian and Laird random effects meta-analysis to pool HRs along with the corresponding 95% CIs due to the anticipated substantial heterogeneity in terms of the enrolled populations( 33 ). To meta-analyze the HRs of PFS, we converted reported HRs to log HRs and used a generalized inverse variance method with a random effects model combining data. Results are reported with both effect estimates and 95% CIs. We used the I 2 statistic to assess heterogeneity between studies, with I 2 values > 50% indicating significant heterogeneity( 34 ). To explore the sources of heterogeneity, we carried out a series of subgroup analyses based on geographical regions (Europe and Asia), gender (male or female), original cancer type, and methodological quality (low or high). Sensitivity analysis was performed by applying the leave-one-out method. Begg’s funnel plot was used to detect publication bias in studies reporting overall survival, with a P-value < 0.1 indicating a significant difference( 35 ). Results Literature search and study characteristics The initial literature search identified a total of 888 citations. After duplication removal, 756 studies remained for title and abstract review. During this process, we excluded 688 irrelevant citations and 68 potentially relevant studies were selected for full-text review. Due to non-population-based cohorts, reviews, meta-analyses or no outcome data reported, 16 studies(26-28, 36-48) involving 1,675 participants satisfied the inclusion criteria and were eligible to be included in the final meta-analysis (Figure 1). Table 1 presents the baseline characteristics of the included studies. Among the studies published between 20 16 and 2022, 8 studies(26-28, 36, 39, 41, 44, 45) were from Asia, 7 studies(38, 40, 42, 43, 46-48) were from Europe and a separate study(37) from Brazil. All of the studies were retrospective cohort, and 68.75% of the included studies (11/16) were of high quality with an NOS score of≥7). The sample size of the included studies ranged from 29 to 353 participants. Original cancer type included hormone-sensitive prostate cancer, renal cell carcinoma, head cancer, lung cancer, renal cell cancer, bladder cancer, colorectal cancer, gastrointestinal stromal tumor, esophago–gastric junction cancer, proximal gastric cancer, distal gastric cancer, thyroid cancer, upper tract urothelial carcinoma, bile duct cancer, ampullary cancer, breast cancer and pancreatic cancer. 14 studies used the L3 skeletal muscle index (L3-SMI) to measure sarcopenia, 1 study used L3 psoas muscle index (L3-PMI) and 1 study used the total psoas area index (TPI). L3-SMI meant measuring the cross-section area of skeletal muscles (cm²) at L3 disc space divided by the square of the height of the patient (m²), the muscles are mainly the psoas major, and also include erector spinae, quadratus lumborum, transversus abdominis, external and internal oblique, and rectus abdominis muscles, for L3-PMI, the muscle is only the psoas; TPI meant measuring the total area of psoas area (cm²) divided by the square of the height of the patient (m²). For groups used L3-SMI, sarcopenia was defined as L3-SMI <41 cm²/m² in women, <43 cm²/m² in men with BMI <25 kg/m², and 25 kg/ m²; For group used L3-PMI, sarcopenia was defined as L3-PMI≤6.36 cm²/m² for men and ≤ 3.92 cm²/m² for women; For group used TPI, sarcopenia was defined as TPI < 5.73 cm²/m² for men and < 4.37 cm²/m² for women. Methodological quality (risk of bias) Using the NOS tool for cohort studies, a total of 5 studies(36, 39, 41, 43, 47) had a high risk of bias, with each study having 2 to 3 possible sources of bias, bias was most common in adequacy of follow-up. A total of 9 scores were assigned to 9 item questions, and a score of less than 7 was defined as high risk of bias(Table 2). Associations between sarcopenia and the risk of poor PFS When we meta-analyzed the 16 studies, the results showed that the pooled HR of progression-free survival reached 1.56 (95% CI = 1.19-2.03) in all site cancer survivors compared with noncancer controls. Heterogeneity among studies was high (I2= 76.3%; P< 0.001) (Figure 2). Subgroup analysis In the subgroup analysis, we found that the risk of reduced PFS was significant in two subgroups: the Asian population (HR 1.98, 1.18-3.31) and the study with low risk of bias (HR 1.56, 1.10-2.21). In addition, subgroup analysis did not show a significant correlation between patient gender and lower PFS (Table 3). For specific cancer sites, we noted a significant correlation between lower PFS and urologic cancer (HR 1.57, 1.02-2.41), endocrine gland cancer (HR2.16, 1.36-3.43). After observing and categorizing the gastrointestinal cancer subgroup, we found that colorectal cancer (HR 1.55, 1.18-2.04) was significantly associated with lower PFS, while gastric cancer (HR 1.36 0.49-3.74) did not show an increased risk of lower PFS (HR1.36 0.49-3.74) (Table 3). Sensitivity analyses and publication bias Sensitivity analyses were performed using the leave-one-out method to further examine the stability of the result. We found some studies that significantly changed the pooled HR (lowest HR 1.19, 0.92-1.47; highest HR 1.41, 1.07-1.76), and after a careful reading of the included articles and excluding one low-quality study, we obtained robust results (lowest HR 1.36, 1.01-1.70; highest HR 1.58, 1.15-2.00)(43). Visual inspection of the contour enhanced funnel plot for the outcome revealed asymmetry, indicating potential evidence of publication bias. Publication bias analysis indicated that no potential missing studies were identified in the funnel plot region, and therefore publication bias is unlikely to be the underlying cause of asymmetry. Both Begg’s test(p=0.027) and Egger’s test(p<0.001) were significant. Trim-and-fill technique adjusted for publication bias, found funnel plot region contained only two potentially missing studies, but all were located at the bottom of the funnel plot(49). After adjusting for publication bias, HR= 1.472, 95% CI 1.140-1.901, which is consistent with our previous results, indicating that our results are still reliable (Figure 3). Discussion Principal findings This systematic review and meta-analysis of 16 population-based cohort studies demonstrated a statistically significant increased risk of reduced PFS in metastatic cancer patients with concomitant sarcopenia compared with non-sarcopenic patients, with results remaining consistent after adjusting for potential publication bias. Furthermore, our results suggest that sarcopenia has a stronger contribution to worsening PFS in Asian populations, a finding that is stable in high-quality studies. Our findings regarding the association between sarcopenia and the risk of worsening PFS in patients with metastatic cancer are consistent with a systematic review and multiple clinical studies, all of which suggest that patients with sarcopenia have a risk of worsening PFS ( 47 , 50 , 51 ). However, the results of most of these studies were from cohorts with high limitations. These studies were limited to specific cancer types and cancer patients treated with chemotherapy or radiation (e.g., patients with metastatic renal cell carcinoma treated with cabozantinib). To our knowledge, this study is one of the few studies involving a representative population of multiple cancer types, with meta-analysis and systematic review from high-quality population-based cohort studies, rather than previous individual or narrative studies. Potential mechanisms Originally used to describe the loss of muscle mass with age, the European Working Group on Sarcopenia in Older People (EWGSOP) has recently defined sarcopenia to include impaired muscle strength and poor physical performance ( 2 ). Previously, most people considered sarcopenia as an inevitable part of aging. However, the degree of sarcopenia is highly variable and depends on the presence of certain risk factors, such as lack of exercise, age-related decreases in hormone concentrations and cytokine imbalances, decreased ability to synthesize proteins, failure of satellite cell activation, potential effects of microRNA, oxidative stress due to chronic diseases, etc ( 52 – 56 ). There are two broad types of sarcopenias, primary sarcopenia caused by aging and secondary sarcopenia mainly caused by malignancy ( 57 ). In cancer patients, the adverse effects of sarcopenia include increased susceptibility to adverse events, increased complications from cancer surgery and chemotherapy toxicity, and difficulty in pursuing further cancer-directed therapy ( 58 ). Sarcopenia is characterized by a decrease in both muscle strength and mass, and therefore may increase the risk of falls and fractures in older adults ( 59 , 60 ). In addition, decreased muscle function can affect swallowing and breathing, which can aggravate or cause respiratory disease ( 61 ). At the same time, we note that sarcopenia may interact with certain underlying diseases in patients, leading to a poor prognosis. In one study, it was confirmed that patients with COPD are often associated with sarcopenia and negatively affect important clinical outcomes ( 62 ). For the heart, sarcopenia is thought to be closely associated with heart failure (HF) ( 63 )。Sarcopenia may promote HF development through different mechanisms, including pathological ergoreflex ( 63 , 64 ). At the same time, HF may induce sarcopenia through multiple pathways, such as hormonal changes, poor nutrition, lack of exercise and etc. Therefore, early identification and intervention for the basic diseases in patients with metastatic cancer may be necessary in the future. It is now generally accepted that chemotherapy is also a cause of sarcopenia in cancer patients ( 65 – 67 ). However, the relationship between the two is equally complex. One study found that patients with metastatic colorectal cancer (mCRC) had a significant reduction in muscle area during chemotherapy, and the rate of muscle loss observed in the study was 24 times faster than the normal rate of muscle loss (1% per year) ( 68 ). Another study of adjuvant chemotherapy in patients with colon cancer found that baseline sarcopenia was associated with an increased incidence of all grade 3–4 chemotherapy-induced toxicities ( 69 ). In addition, in patients with colon, lung, esophageal, gastric, and other types of cancer, mortality increases and progression-free survival decreases after chemotherapy, even if patients with sarcopenia do not exhibit lower overall survival ( 69 – 72 ). The current explanation for this phenomenon is that patients with sarcopenia are forced to reduce doses or delay dosing cycles due to excessive toxicity to oncology treatment ( 73 ). It is common practice to base chemotherapy on the body surface area of each patient, without taking into account the large and unpredictable fraction of body weight accounted for by adipose tissue ( 74 ). A large amount of evidence shows that this method fails especially in patients with sarcopenia, and the related toxicity risks cannot be solved ( 75 – 77 ). Obviously, although some physiological constants may be related to body surface area, they are not related to other anthropometric parameters, such as body mass index. Besides, sarcopenia also reduces the effective effect of chemotherapy. Studies have shown that among breast cancer patients with sarcopenia, many chemotherapeutic drugs such as capecitabine, paclitaxel, docetaxel, and nab-paclitaxel have poor effects ( 73 , 78 ). The reasonable explanation may be that the adverse outcome may be related to the high toxicity rate, which in turn may lead to the necessary dose reduction and the provision of effective tumor treatment at a lower dose, thus reducing the therapeutic benefit ( 79 ). To sum up, cancer patients are prone to sarcopenia before and after chemotherapy, and sarcopenia occurring or aggravated during chemotherapy will worsen the prognosis and aggravate the toxicity caused by chemotherapy. Therefore, chemotherapy cycles and doses need to be carefully set based on drug toxicity and therapeutic effects. In our study, we found that the risk of sarcopenia and reduced PFS was not significant in the European population. It was found that, with the exception of the study of Haik, the remaining studies that showed unstable results were low risk of bias studies, and sensitivity analysis also yielded relatively stable results after excluding this study ( 43 ). All patients in this study were from a single hospital cohort and did not target a specific cancer, but rather included multiple cancers. In addition, this study was the only cohort to use immune checkpoint therapy on patients, which has relatively few side effects. Other studies have commonly used chemotherapy, and patients may have been treated with the previously described, mutually reinforcing effect of sarcopenia and chemotherapy toxicity, but this was not a problem in immunotherapy. This could be a potential reason why this research concluded that sarcopenia was not significantly associated with PFS. Several studies have now demonstrated that cancer patients treated with immune checkpoint inhibitors alone or in combination with chemotherapy have significantly improved survival compared to chemotherapy alone( 80 – 82 ). Whether immunotherapy exerts a better improvement in PFS in patients with sarcopenia needs to be further explored in more clinical studies. Implications This meta-analysis provided important future clinical implications for the risk of worsening PFS in metastatic cancer patients with concomitant sarcopenia, yielding an approximate risk estimate with an HR of 1.56 (95% CI = 1.19–2.03) for PFS. Early screening and effective interventions are clinically important in the prevention and treatment of sarcopenia. Second, optimal strategies for prevention and management of sarcopenia have not been established due to the widespread neglect of sarcopenia in cancer. Due to the lack of reliable clinical data to guide clinicians, physicians may consider the use of specific treatment options based on the history of adjuvant therapy (e.g., chemotherapy or radiation therapy), baseline information, etc., in cancer patients. In addition, screening and treatment of individuals at high risk for stroke has implications for the prevention of sarcopenia and for reducing the burden of sarcopenia in the general elderly population. Strengths and limitations The current study has several advantages in the following aspects. First, the current systematic evaluation and meta-analysis includes a more representative population in the relevant field, providing up-to-date evidence on the association between the risk of worsening PFS in metastatic cancer patients with concomitant sarcopenia. Second, we developed a systematic and comprehensive database search strategy based on the major online databases (PubMed, Embase, and Cochrane Library) with no search date restrictions so that we could retrieve as many relevant articles from around the world as possible, avoiding publication bias on pooled results and improving the reproducibility of results. Third, almost all included studies were from national cohorts or population-based cohorts, thus minimizing potential selection bias stemming from study design. In addition, a transparent methodological quality assessment of the included studies was performed using the NOS list for cohort studies. Fourth, several methods, including subgroup analysis and sensitivity analysis, have been applied to thoroughly identify sources of heterogeneity based on abstract study-level baseline characteristics. In these sensitivity analyses, after excluding one low-quality study, our results remained stable and Egger's test combined with the cut-and-patch method found no evidence of publication bias. This study also has some limitations. First, significant heterogeneity was found in the included studies, which was predictable and may be partly due to differences in baseline characteristics of the population (sex, race, tumor primary site and metastatic site, etc.), exposure to treatment (adjuvant chemotherapy, radiation therapy, or hormonal therapy), and statistical methods (adjustment for confounders). Although several methods were applied to adjust for outcomes, considerable moderate to high heterogeneity remained. After careful study, we concluded that irregularities in PFS can introduce bias in the results, mainly due to differences in the interval between patient follow-up after treatment. For PFS, PFS is susceptible to the influence of the follow-up interval because the exact time point at which a patient progresses is uncertain. Different follow-up intervals may lead to highly variable trial results. For example, if patients are asked to follow up every 3 months, assuming a high degree of patient compliance, and if patients in the trial group have a prolonged survival of less than 3 months compared to the control group, it cannot be concluded that the trial group is better than the control group because tumor progression in both groups will be detected at the same review every 3 months, then PFS is recorded as No difference. In a more extreme case, if the tumor is reviewed every 3 months after treatment, and the tumor is determined to be progression-free at the first post-treatment review (3 months) in the trial group, but progression appears soon after the review (much less than 3 months, or even days) but is not detected, while tumor progression is detected at the first post-treatment review (nearly 3 months) in the control group, the difference in progression-free survival between the two groups is considered to be 3 months, while the true difference between the two groups is close to 0. The true difference is close to 0, which would result in a 3-month bias. Such differences can occur not only within studies, but also between studies due to inconsistent PFS intervals, and the shorter the follow-up interval for patients, the more reliable their trial results. This inference is supported by the fact that most of our studies did not mention the follow-up interval and that those that reported this element were at low risk of bias and had a higher degree of confidence, as other investigators have also mentioned this directly or indirectly ( 83 ). However, given that the results of most subgroup analyses and sensitivity analyses were highly consistent with the primary outcome, we believe that the impact of these heterogeneities on the primary outcome of the study is limited. Second, the results of this meta-analysis are based on observational cohort studies, which may be limited by confounding factors such as patient gender, adjuvant treatment modality, and follow-up interval. However, all included studies provided data comparing sarcopenic and non-sarcopenic populations and matched with a number of important covariates suggesting a consistently increased risk of worsening PFS in sarcopenic patients. Third, because our study was a single-study-level meta-analysis rather than an individual patient-level meta-analysis, we were unable to perform more detailed subgroup analyses (e.g., risk analyses based on events during cancer survival and follow-up) and were unable to explore progressive sarcopenia that occurred during follow-up. Fourth, some subgroup analyses found nonsignificant results, which we believe may be due to the relatively small sample size and low statistical efficacy. More evidence from high-quality prospective cohort studies on the impact of sarcopenia on the risk of death or progression in patients with metastatic cancer is needed. Finally, the meta-analysis was limited to studies published in peer-reviewed journals in English. We may have missed articles published in other languages or in journals outside of the three databases we searched. In addition, unpublished gray literature was not included. However, three major databases, PubMed, Embase, and the Cochrane Library, published the vast majority of available reports. Despite these limitations, the current study includes the vast majority of cancer types, which provides a largely adequate sample size for meaningful and robust statistical analyses. Conclusions In this article, we performed a systematic evaluation and meta-analysis of sarcopenia in metastatic cancer patients. The results suggest that sarcopenia might be an indicator of reduced progression-free survival in metastatic cancer patients. However, there is still a need to conduct larger prospective cohort studies to confirm the conclusion. Abbreviations Hazard Ratio, HR; confidence intervals, CIs; overall survival, OS; Newcastle–Ottawa scale, NOS; L3 skeletal muscle index, L3-SMI; L3 psoas muscle index, L3-PMI; total psoas area index, TPI; metastatic colorectal cancer, mCRC Declarations Ethics approval and consent to participate Not applicable Consent for publication Not applicable. Availability of data and material All data generated or analysed during this study are included in this published article. Competing interests The authors declare that they have no competing interests. Funding Not applicable. Authors' contributions MZ, TW and WG conceived and designed the article. XS and PL (Pan Liu) performed the retrieve. XS and PL (Pan Liu) contributed material/analysis tools. MZ, XS and PL (Peiling Li) wrote the manuscript. XS, PL (Pan Liu), HT and SF performed reference collection and data management. XS and PL (Pan Liu) performed statistical analyses. 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Sarcopenia's Prognostic Impact on Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis. Journal of clinical medicine. 2021;10(22). Tables Table 1. Characteristics of studies included in meta-analysis First author Year Study design Region Diagnosed period Sample size Female% Median/mean age Main Treatment Original cancer type cancer metastases Lee, J. H. 2021 Retrospective cohort study Korea 2018 to 2021 70 0 66 Chemotherapy Hormone-sensitive prostate cancer Bone, lung, liver, pleura, adrenal gland, peritoneum, ureter Lee, C. H. 2021 Retrospective cohort study Korea 2010 to 2017 78 24.4 61 Chemotherapy Renal cell carcinoma NR Haik 2021 Retrospective cohort study France 2013 to 2017 261 24 61.9 (mean) Immunity therapy Head, lung, renal, bladder cancer Liver, lung, bone, brain Gallois 2021 Prospective cohort study France 2013 to 2016 149 67 NR Chemotherapy Colorectal cancer NR Chang 2021 Retrospective cohort study China 2007 to 2018 109 42.2 60.9 (mean) Chemotherapy Gastrointestinal stromal tumor Liver Catanese 2021 Retrospective cohort study Italy 2010 to 2017 78 28.2 67 Chemotherapy Esophago–gastric junction cancer, proximal gastric cancer, distal gastric cancer Liver, lung, lymph nodes, peritoneum, bone Yamazaki 2020 Retrospective cohort study Japan 2015 to 2019 54 64.81 66.5 Chemotherapy Thyroid cancer Liver, lung, bone, brain, lymph node Shimizu 2020 Retrospective cohort study Japan 2017 to 2019 29 15 73 Chemotherapy Bladder tumor, upper tract urothelial carcinoma Liver, lung, lymph nodes, bone Lee, B. M. 2020 Retrospective cohort study Korea. 2007 to 2016 353 42.5 67 Chemotherapy Gall bladder, intrahepatic bile duct, non-hilar bile duct, perihilar bile duct, ampullary cancer NR da Cunha 2019 Retrospective cohort study Brazil 2009 to 2015 72 44.4 59.4 (mean) Surgery and chemotherapy Colorectal cancer Peritoneum and other organs Franzoi 2020 Retrospective cohort study Belgium 2016 to 2019 50 100 61.2 (mean) Chemotherapy Breast cancer Visceral disease, bone only or locorregional Palleschi 2022 Retrospective cohort study Italy 2009 to 2020 43 100 58 Chemotherapy Breast cancer NR Williet 2021 Retrospective cohort study France 2012 to 2018 79 45.6 66 Chemotherapy Pancreatic cancer NR Ishihara 2016 Retrospective cohort study Japan 2007 to 2014 71 29.6 64 Chemotherapy Renal Cell Carcinoma NR Gu 2017 Retrospective cohort study China 2008 to 2014 101 35.6 59 Chemotherapy Renal cell carcinoma NR Malik 2021 Retrospective cohort study Poland 2017 to 2020 78 45 64.5 Chemotherapy Colorectal cancer Liver, lung, lymph node, peritoneum C ontinued. Characteristics of studies included in meta-analysis First author Measurements of sarcopenia Sarcopenia definition Outcomes median/mean Follow-up period Lee, J. H. L3-SMI SMI ≤ 52.4 cm2/m2 PFS 20.5 months Lee, C. H. L3-SMI SMI of < 43cm2/m2 and < 53 cm2/m2 for men with a BMI of < 25 kg/m2 and ≥ 25kg/m2, respectively, and < 41 cm2/m2 for women PFS 15.4 months Haik L3-SMI < 41 cm2/m2 for females and < 43 cm2/m2 for males if body mass index (BMI) < 25 kg/m2 or < 53 cm2/m2 if BMI ≥ 25 kg/m2 PFS NR Gallois L3-SMI men < 40.3 cm2/m2 and women < 32.0 cm2/m2 PFS 23 months Chang L3-PMI < 6.36 cm2/m2 for males and < 3.92 cm2/m2 for females PFS NR Catanese L3-SMI male patients as SMI < 43 cm2/m2 if BMI < 25 kg/m2 and SMI < 53 cm2/m2 if BMI ≥ 25 kg/m2, and in female patients as SMI < 41 cm2/m2 irrespective of BMI PFS 52.2 months Yamazaki L3-SMI < 42 cm2/m2 for males and < 38 cm2/m2 for females PFS NR Shimizu L3-PMI ≤ 6.36 cm2/m2 for men and ≤ 3.92 cm2/m2 for women PFS 7 months Lee, B. M. L3-SMI < 55 cm2/m2 for male and < 39 cm2/m2 for female PFS 7.77 months da Cunha L3-SMI SMI < 41 cm2/m2 for women; SMI < 43 cm2/m2 if BMI < 25 kg/m2 and SMI < 53 cm2/m2 if BMI ≤ 25 kg/m2 for men PFS 23.6 months Franzoi L3-SMI SMI < 40 cm2/m2 PFS 14.4 months Palleschi L3-SMI SMI < 40 cm2/m2 PFS 33 months Williet TPI < 5.73 cm2/m2 for men and < 4.37 cm2/m2 for women PFS NR Ishihara L3-SMI men with a BMI of < 25 kg/m2 and SMI 25 kg/m2 and SMI < 53 cm2/m2; women with SMI < 41 cm2/m2 PFS 20.2 months (mean) Gu L3-SMI < 40.8 cm2/m2 for males and < 34.9 cm2/m2 for females PFS NR Malik L3-SMI < 52.4 cm2/m2 for men and < 38.5 cm2/m2 for women PFS 19.1 months L3, 3rd lumbar spine; SMI, skeletal muscle index; PMI, psoas muscle index; BMI, body Mass Index; TPI, The total psoas area index; PFS, progression-free survival. Table 2. Methodological quality score of the included studies based on the Newcastle–Ottawa scale (NOS) tool. Author Year Study Design Selection Comparability Exposure/Outcome Total Score Risk of Bias Representative­ness of cohort * Selection of control cohort * Ascertainment of exposure * Outcome not present at start * Comparability of cohorts ** Assessment of outcome * Length of follow-up * Adequacy of follow-up * Total score Lee, J. H. 2021 Retrospective cohort study * * * ** * * * 8 Low Lee, C. H. 2021 Retrospective cohort study * * * ** * * * 8 Low Haik 2021 Retrospective cohort study * * * ** * 6 High Gallois 2021 Retrospective cohort study * * * ** * * * 8 Low Chang 2021 Retrospective cohort study * * * ** * 6 High Catanese 2021 Retrospective cohort study * * * ** * * 7 Low Yamazaki 2020 Retrospective cohort study * * * ** * 6 High Shimizu 2020 Retrospective cohort study * * * ** * * * 8 Low Lee, B. M. 2020 Retrospective cohort study * * * ** * * * 8 Low da Cunha 2019 Retrospective cohort study * * * ** * * * 8 Low Franzoi 2020 Retrospective cohort study * * * ** * * * 8 Low Palleschi 2022 Retrospective cohort study * * * ** * * * 8 Low Williet 2021 Retrospective cohort study * * * ** * 6 High Ishihara 2016 Retrospective cohort study * * * ** * * * 8 Low Gu 2017 Retrospective cohort study * * * ** * 6 High Malik 2021 Retrospective cohort study * * * ** * * * 8 Low Table 3. Subgroup analyses for the effect of sarcopenia on PFS in patients with metastases. Variables HR 95% CI I ² （ % ） No. studies P for interaction Regions ＜0.001 Asia 1.98 1.18 to 3.31 83.6 8 Europe 1.25 0.91 to 1.73 66.9 7 Gender ＜0.001 Female≤50% 1.53 1.12 to 2.11 79.8 12 Female＞50% 1.61 1.11 to 2.33 21.4 4 Original cancer type ＜0.001 Gastrointestinal 1.28 0.87 to 1.89 79.9 6 Urologic 1.57 1.02 to 2.41 7.3 5 Endocrine Gland 2.16 1.36 to 3.43 0 2 Breast 1.51 0.60 to 3.80 0 2 Quality assessment ＜0.001 Low risk of bias 1.56 1.10 to 2.21 77.1 11 High risk of bias 1.59 0.96 to 2.62 79.2 5 Continued. Subgroup analyses for Gastrointestinal Neoplasms. Cancer type HR 95% CI I ² （ % ） No. studies Colorectal 1.55 1.18 to 2.04 0 3 Gastric 1.36 0.49 to 3.74 85.5 2 Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2319788","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":158503717,"identity":"026c881c-69ac-4fb8-bb1e-31b5efd9a7e8","order_by":0,"name":"Meijun Zhou","email":"","orcid":"","institution":"Department of Ultrasound Medicine, Xiangnan College Affiliated Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Meijun","middleName":"","lastName":"Zhou","suffix":""},{"id":158503718,"identity":"7e2d98df-912e-4a91-a5a4-4ec427b56aeb","order_by":1,"name":"Xiangru Shen","email":"","orcid":"","institution":"Hengyang Medical College, University of South China","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiangru","middleName":"","lastName":"Shen","suffix":""},{"id":158503719,"identity":"1a51c833-a6cf-44b7-b032-d292e300f09e","order_by":2,"name":"Shuai Fang","email":"","orcid":"","institution":"Hengyang Medical College, University of South China","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Shuai","middleName":"","lastName":"Fang","suffix":""},{"id":158503720,"identity":"a983ebbd-5abf-4e7d-8afb-cda37671fd23","order_by":3,"name":"Teng Wan","email":"","orcid":"","institution":"Sports medicine department, Huazhong University of Science and Technology Union Shenzhen Hospital; the 6th Affiliated Hospital of Shenzhen University Health Science Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Teng","middleName":"","lastName":"Wan","suffix":""},{"id":158503721,"identity":"cfee3f48-67d3-4ff3-9c77-c52d8d68b53b","order_by":4,"name":"Pan Liu","email":"","orcid":"","institution":"Hengyang Medical College, University of South China","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Pan","middleName":"","lastName":"Liu","suffix":""},{"id":158503722,"identity":"e9587001-e88b-4f37-8171-330107cef29b","order_by":5,"name":"Peiling Li","email":"","orcid":"","institution":"Hengyang Medical College, University of South China","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Peiling","middleName":"","lastName":"Li","suffix":""},{"id":158503723,"identity":"4e4bb94d-143c-490e-977c-19ed240eca2d","order_by":6,"name":"Haifeng Tan","email":"","orcid":"","institution":"Hengyang Medical College, University of South China","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Haifeng","middleName":"","lastName":"Tan","suffix":""},{"id":158503724,"identity":"88ef32a5-3d86-484d-b273-dc49b76d1ca1","order_by":7,"name":"Yong Fu","email":"","orcid":"","institution":"The second affiliated Hospital, Department of Trauma orthopaedic, Hengyang Medical College","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yong","middleName":"","lastName":"Fu","suffix":""},{"id":158503725,"identity":"fed9173e-0bd8-47b5-b4f3-1b0e50cf683c","order_by":8,"name":"Weiming Guo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABFklEQVRIiWNgGAWjYNACAwYeBgbmA0DWAQY2qJgMgwRBLWwJKFp48GuBqDEAa4FzcWmRj0g+JvGhYJuMOf+ab9I8FXfk+SRyzCR+MNjxGNxuwKrF8EZamuQMg9s8ljPebjbmOfPMsA2oRbKHIZnH4M4B7Fpm5JjdBhrIY3Dj7MbHvG2HGdukgbbwMBwAiiTg1vIHrOXMg8O8/w7bg7RI/sGjRR7ojNsMIC3nexgf8zYcTgRpkcZniwHPs/SfPWBb2IwN5xw7nNwm/6zYWsYgmUcSh1/k25MPG/z4c9ve4PzhZxJvag7bzu85vPHmmwo7OT4cIWYAN0kC4QwWCQYDrKohtsBN4kc4g/kDbg2jYBSMglEwAgEAxEliddwVepEAAAAASUVORK5CYII=","orcid":"","institution":"Sports medicine department, Huazhong University of Science and Technology Union Shenzhen Hospital; the 6th Affiliated Hospital of Shenzhen University Health Science Center","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Weiming","middleName":"","lastName":"Guo","suffix":""}],"badges":[],"createdAt":"2022-11-28 07:44:32","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2319788/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2319788/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12885-023-10582-2","type":"published","date":"2023-02-07T18:44:21+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":30219873,"identity":"be1a22e7-8ce3-42d5-ba1d-91adcb7389fe","added_by":"auto","created_at":"2022-12-12 18:07:17","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":570551,"visible":true,"origin":"","legend":"\u003cp\u003eThe flow chart of the literature selection\u003c/p\u003e","description":"","filename":"Fig1.Flowdiagram.png","url":"https://assets-eu.researchsquare.com/files/rs-2319788/v1/9d8d9c6bc16e6392e08f51fe.png"},{"id":30220388,"identity":"43949edd-034d-48e5-a259-51ef60008a3e","added_by":"auto","created_at":"2022-12-12 18:15:17","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":518270,"visible":true,"origin":"","legend":"\u003cp\u003eHazard risk (HR) for association of sarcopenia with decrease of progression-free survival in patients with metastases\u003c/p\u003e","description":"","filename":"Fig2.ForestPlot.png","url":"https://assets-eu.researchsquare.com/files/rs-2319788/v1/737b2e3eeff45a4afff34da2.png"},{"id":30220390,"identity":"5dc94033-9bb0-4cbf-af77-391dcaf907eb","added_by":"auto","created_at":"2022-12-12 18:15:17","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":221374,"visible":true,"origin":"","legend":"\u003cp\u003eFunnel plots assessing the potential impact of publication bias.\u003c/p\u003e","description":"","filename":"Fig3.FunnelPlot.png","url":"https://assets-eu.researchsquare.com/files/rs-2319788/v1/a3f8f706eca6a5e3e2aae012.png"},{"id":44719130,"identity":"5e42f5c6-8d70-43d8-bc1a-bcece495babf","added_by":"auto","created_at":"2023-10-16 18:53:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1073268,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2319788/v1/b6743a52-4788-49e8-9286-6fcb62141764.pdf"},{"id":30219876,"identity":"b7c2558e-a0d2-42cf-88f7-55be8511b7cb","added_by":"auto","created_at":"2022-12-12 18:07:17","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":66231,"visible":true,"origin":"","legend":"","description":"","filename":"PRISMAchecklist2020.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2319788/v1/416d3d3e7ec7b5c8b669ec36.pdf"},{"id":30220858,"identity":"db7ba12b-d779-405d-bab8-5bdf89eac52f","added_by":"auto","created_at":"2022-12-12 18:23:17","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":26792,"visible":true,"origin":"","legend":"","description":"","filename":"Searchstrategy.docx","url":"https://assets-eu.researchsquare.com/files/rs-2319788/v1/cf0c08d126590427fd10fe1a.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Sarcopenia as a risk factor of progression-free survival in patients with metastases: a systematic review and meta-analysis","fulltext":[{"header":"Background","content":"\u003cp\u003eSarcopenia, from the Greek word \"sarx\" meaning \"meat\" and \"penia\" meaning loss, was first defined by Rosenberg in 1988 (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). It is defined as a progressive, systemic skeletal muscle disease involving progressive and systemic loss of skeletal muscle mass and function (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Sarcopenia is associated with a variety of diseases, including but not limited to natural aging, functional, metabolic and immune disorders, increased muscle catabolism due to cancer, and toxicity of anti-cancer treatments (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Previous studies have often confused cachexia with sarcopenia, a syndrome of weight loss and reduced muscle mass, and have been associated with poor prognosis (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). However, recent studies have shown that cachexia and sarcopenia represent different aspects of the muscle wasting spectrum (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Approximately 15\u0026ndash;50% of cancer patients with weight loss are sarcopenic rather than cachectic (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). With regard to the prognosis of cancer patients, the U.S. Food and Drug Administration's criteria for the effectiveness of cancer drug trials are whether the survival of cancer patients is prolonged and whether clinical symptoms improve after treatment (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Although overall survival (OS) is the gold standard for evaluating clinical outcomes, the use of overall survival as a prognostic criterion for cancer patients may be biased. Possible reasons include the non-single nature of treatment for cancer patients from onset to end of life, the combination of other basic diseases and the use of other drugs during the course of the disease (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Therefore, progression-free survival of tumor patients in clinical studies can be a better proxy for overall survival (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Progression-free survival is defined as the time from the time when a patient is randomly enrolled to the time when the patient is first proved to have tumor progression or death without tumor progression. It allows the trial data to be obtained over a relatively short follow-up period compared to OS as the trial endpoint. Progression-free survival to be the endpoint reduces the impact of subsequent treatments and is usually based on results obtained from objective and quantitative evaluations (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMany studies have been conducted to assess the predictive roles of sarcopenia in the occurrence of adverse events in cancer patients. Current systematic review suggests that sarcopenia negatively affects prognostic outcomes of cancer patients in terms of survival, physical activity, length of hospital stay and other complications (\u003cspan additionalcitationids=\"CR17 CR18 CR19 CR20 CR21\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). However, we found that current studies were limited to specific primary tumors or site-specific metastatic cancers (\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). While sarcopenia as a systemic disease, we hypothesize that it is closely associated with the prognosis of multiple metastatic cancers. There is still controversy regarding the impact of sarcopenia on the prognosis and survival of patients with metastatic cancer. In the Lee et al. study, sarcopenia was not considered to be a potential factor in the patients' reduced PFS, which contradicts the findings of several other similar studies (\u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Therefore, to elucidate whether sarcopenia and progression-free survival have a potential relationship in patients with metastatic cancer, we performed a systematic review and meta-analysis of studies focusing on the relationship between sarcopenia and progression-free survival in patients with metastatic cancer.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStandard Protocol Approvals\u003c/h2\u003e \u003cp\u003eThis systematic review was conducted based on a predefined protocol and in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)(\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) recommendations(\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). The review protocol was registered in PROSPERO with the registration unique identifying number (UIN) of CRD42022325910.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eSearch strategy and selection criteria\u003c/h2\u003e \u003cp\u003eDatabases of Pubmed, Embase and Cochrane Central Register of Controlled Trials were systematically searched from inception to October 14, 2022 by two independent investigators (MZ and XS) without language or time restrictions. We used MeSH (for Pubmed and Cochrane)/Emtree (for Embase) terms combined with free-text words (including synonyms and closely related words) that were associated with metastases and sarcopenia.The detailed search strategy and specific terms were used, which were searched as free text words and as MeSH/Entr\u0026eacute;e terms without language restrictions. In addition, we also performed manual reference check of relevant articles, meta-analyses, reviews, and meeting abstracts. When two or more articles used the same cohort data, we preferred the most up-to-date ones with full-text information available. We perform study selection by a series of consecutive stages including duplicate checking using Endnote software, titles and abstracts screening, full-text article selection according to the eligibility criteria. These processes were conducted independently by two investigators (XS and TW). Conflicts were handled by consensus, and an adjudicator (WG) was consulted when necessary. If different opinions were encountered, senior experts would be consulted (SF or YF).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eEligibility criteria\u003c/h2\u003e \u003cp\u003eStudies were considered appropriate and were included in the analysis if they satisfied the following established inclusion criteria. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) prospective or retrospective population-based cohort study design; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) participants: Patients diagnosed with metastatic cancer, with or without sarcopenia. Sarcopenia was diagnosed according to the criteria given by EWGSOP in 2019 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e); (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) outcome: progression-free survival; (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) the measure of association: hazard ratio (HR) and corresponding 95% CIs provided from the original studies or having related data that could be used to calculate the risk ratios. We excluded hospital-based on community-based observational studies and those providing inadequate data to generate risk ratio for the association between\u003c/p\u003e \u003cp\u003esarcopenia and metastases.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStudy selection, data collection, and data extraction\u003c/h2\u003e \u003cp\u003eTwo investigators (XS and TW) independently read through, screened, extracted data from the included studies, and filled in the pre-designed data extraction excel forms. If there were any discrepancies, we would consult a third senior investigator (WG) until a consensus was reached. The following study characteristics were abstracted including study author, publication year, study design, study period, geographical region, observation period, population characteristics and age at cancer diagnosis, main treatment, measurements and definitions of sarcopenia, original cancer type, metastatic site of cancer and outcome.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eQuality assessment\u003c/h2\u003e \u003cp\u003eThe methodological quality for the included studies was evaluated using the Newcastle\u0026ndash;Ottawa scale (NOS)(\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e) tool based on the main aspects in terms of representativeness of the patients, ascertainment of exposure and outcomes, adequacy of follow-up.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAll statistical analyses were performed using Stata statistical software (version 15.1). The primary outcome was the PFS, defined as the length of time during and after the treatment of cancer, that a patient lives with the disease but the disease does not get worse. We applied the DerSimonian and Laird random effects meta-analysis to pool HRs along with the corresponding 95% CIs due to the anticipated substantial heterogeneity in terms of the enrolled populations(\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). To meta-analyze the HRs of PFS, we converted reported HRs to log HRs and used a generalized inverse variance method with a random effects model combining data. Results are reported with both effect estimates and 95% CIs. We used the I\u003csup\u003e2\u003c/sup\u003e statistic to assess heterogeneity between studies, with I\u003csup\u003e2\u003c/sup\u003e values\u0026thinsp;\u0026gt;\u0026thinsp;50% indicating significant heterogeneity(\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). To explore the sources of heterogeneity, we carried out a series of subgroup analyses based on geographical regions (Europe and Asia), gender (male or female), original cancer type, and methodological quality (low or high). Sensitivity analysis was performed by applying the leave-one-out method. Begg\u0026rsquo;s funnel plot was used to detect publication bias in studies reporting overall survival, with a P-value\u0026thinsp;\u0026lt;\u0026thinsp;0.1 indicating a significant difference(\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eLiterature search and study characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe initial literature search identified a total of 888 citations. After duplication removal, 756 studies remained for title and abstract review. During this process, we excluded 688 irrelevant citations and 68 potentially relevant studies were selected for full-text review. Due to non-population-based cohorts, reviews, meta-analyses or no outcome data reported, 16 studies(26-28, 36-48) involving 1,675 participants satisfied the inclusion criteria and were eligible to be included in the final meta-analysis (Figure 1).\u003c/p\u003e\n\n\u003cp\u003eTable 1 presents the baseline characteristics of the included studies. Among the studies published between 20 16 and 2022, 8 studies(26-28, 36, 39, 41, 44, 45) were from Asia, 7 studies(38, 40, 42, 43, 46-48) were from Europe and a separate study(37) from Brazil. All of the studies were retrospective cohort, and 68.75% of the included studies (11/16) were of high quality with an NOS score of\u0026ge;7). The sample size of the included studies ranged from 29 to 353 participants. Original cancer type included hormone-sensitive prostate cancer, renal cell carcinoma, head cancer, lung cancer, renal cell cancer, bladder cancer, colorectal cancer, gastrointestinal stromal tumor, esophago\u0026ndash;gastric junction cancer, proximal gastric cancer, distal gastric cancer, thyroid cancer, upper tract urothelial carcinoma, bile duct cancer, ampullary cancer, breast cancer and pancreatic cancer. 14 studies used the L3 skeletal muscle index (L3-SMI) to measure sarcopenia, 1 study used L3 psoas muscle index (L3-PMI) and 1 study used the total psoas area index (TPI). L3-SMI meant measuring the cross-section area of skeletal muscles (cm\u0026sup2;) at L3 disc space divided by the square of the height of the patient (m\u0026sup2;), the muscles are mainly the psoas major, and also include erector spinae, quadratus lumborum, transversus abdominis, external and internal oblique, and rectus abdominis muscles, for L3-PMI, the muscle is only the psoas; TPI meant measuring the total area of psoas area (cm\u0026sup2;) divided by the square of the height of the patient (m\u0026sup2;). For groups used L3-SMI, sarcopenia was defined as L3-SMI \u0026lt;41 cm\u0026sup2;/m\u0026sup2; in women, \u0026lt;43 cm\u0026sup2;/m\u0026sup2; in men with BMI \u0026lt;25 kg/m\u0026sup2;, and \u0026lt;53 cm\u0026sup2;/m\u0026sup2; in men with BMI \u0026gt;25 kg/ m\u0026sup2;; For group used L3-PMI, sarcopenia was defined as L3-PMI\u0026le;6.36 cm\u0026sup2;/m\u0026sup2; for men and \u0026le; 3.92 cm\u0026sup2;/m\u0026sup2; for women; For group used TPI, sarcopenia was defined as TPI \u0026lt; 5.73 cm\u0026sup2;/m\u0026sup2; for men and \u0026lt; 4.37 cm\u0026sup2;/m\u0026sup2; for women.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eMethodological quality (risk of bias)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUsing the NOS tool for cohort studies, a total of 5 studies(36, 39, 41, 43, 47) had a high risk of bias, with each study having 2 to 3 possible sources of bias, bias was most common in adequacy of follow-up. A total of 9 scores were assigned to 9 item questions, and a score of less than 7 was defined as high risk of bias(Table 2).\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAssociations between sarcopenia and the risk of poor PFS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWhen we meta-analyzed the 16 studies, the results showed that the pooled HR of progression-free survival reached 1.56 (95% CI = 1.19-2.03) in all site cancer survivors compared with noncancer controls. Heterogeneity among studies was high (I2= 76.3%; P\u0026lt; 0.001) (Figure 2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSubgroup analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the subgroup analysis, we found that the risk of reduced PFS was significant in two subgroups: the Asian population (HR 1.98, 1.18-3.31) and the study with low risk of bias (HR 1.56, 1.10-2.21). In addition, subgroup analysis did not show a significant correlation between patient gender and lower PFS (Table 3). For specific cancer sites, we noted a significant correlation between lower PFS and urologic cancer (HR 1.57, 1.02-2.41), endocrine gland cancer (HR2.16, 1.36-3.43). After observing and categorizing the gastrointestinal cancer subgroup, we found that colorectal cancer (HR 1.55, 1.18-2.04) was significantly associated with lower PFS, while gastric cancer (HR 1.36 0.49-3.74) did not show an increased risk of lower PFS (HR1.36 0.49-3.74) (Table 3).\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eSensitivity analyses and publication bias \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSensitivity analyses were performed using the leave-one-out method to further examine the stability of the result. We found some studies that significantly changed the pooled HR (lowest HR 1.19, 0.92-1.47; highest HR 1.41, 1.07-1.76), and after a careful reading of the included articles and excluding one low-quality study, we obtained robust results (lowest HR 1.36, 1.01-1.70; highest HR 1.58, 1.15-2.00)(43). Visual inspection of the contour enhanced funnel plot for the outcome revealed asymmetry, indicating potential evidence of publication bias. Publication bias analysis indicated that no potential missing studies were identified in the funnel plot region, and therefore publication bias is unlikely to be the underlying cause of asymmetry. Both Begg\u0026rsquo;s test(p=0.027) and Egger\u0026rsquo;s test(p\u0026lt;0.001) were significant. Trim-and-fill technique adjusted for publication bias, found funnel plot region contained only two potentially missing studies, but all were located at the bottom of the funnel plot(49). After adjusting for publication bias, HR= 1.472, 95% CI 1.140-1.901, which is consistent with our previous results, indicating that our results are still reliable (Figure 3).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003ePrincipal findings\u003c/h2\u003e \u003cp\u003eThis systematic review and meta-analysis of 16 population-based cohort studies demonstrated a statistically significant increased risk of reduced PFS in metastatic cancer patients with concomitant sarcopenia compared with non-sarcopenic patients, with results remaining consistent after adjusting for potential publication bias. Furthermore, our results suggest that sarcopenia has a stronger contribution to worsening PFS in Asian populations, a finding that is stable in high-quality studies. Our findings regarding the association between sarcopenia and the risk of worsening PFS in patients with metastatic cancer are consistent with a systematic review and multiple clinical studies, all of which suggest that patients with sarcopenia have a risk of worsening PFS (\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e, \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e). However, the results of most of these studies were from cohorts with high limitations. These studies were limited to specific cancer types and cancer patients treated with chemotherapy or radiation (e.g., patients with metastatic renal cell carcinoma treated with cabozantinib). To our knowledge, this study is one of the few studies involving a representative population of multiple cancer types, with meta-analysis and systematic review from high-quality population-based cohort studies, rather than previous individual or narrative studies.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003ePotential mechanisms\u003c/h2\u003e \u003cp\u003eOriginally used to describe the loss of muscle mass with age, the European Working Group on Sarcopenia in Older People (EWGSOP) has recently defined sarcopenia to include impaired muscle strength and poor physical performance (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Previously, most people considered sarcopenia as an inevitable part of aging. However, the degree of sarcopenia is highly variable and depends on the presence of certain risk factors, such as lack of exercise, age-related decreases in hormone concentrations and cytokine imbalances, decreased ability to synthesize proteins, failure of satellite cell activation, potential effects of microRNA, oxidative stress due to chronic diseases, etc (\u003cspan additionalcitationids=\"CR53 CR54 CR55\" citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e). There are two broad types of sarcopenias, primary sarcopenia caused by aging and secondary sarcopenia mainly caused by malignancy (\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e). In cancer patients, the adverse effects of sarcopenia include increased susceptibility to adverse events, increased complications from cancer surgery and chemotherapy toxicity, and difficulty in pursuing further cancer-directed therapy (\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e). Sarcopenia is characterized by a decrease in both muscle strength and mass, and therefore may increase the risk of falls and fractures in older adults (\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e, \u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e). In addition, decreased muscle function can affect swallowing and breathing, which can aggravate or cause respiratory disease (\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e). At the same time, we note that sarcopenia may interact with certain underlying diseases in patients, leading to a poor prognosis. In one study, it was confirmed that patients with COPD are often associated with sarcopenia and negatively affect important clinical outcomes (\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e). For the heart, sarcopenia is thought to be closely associated with heart failure (HF) (\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e)。Sarcopenia may promote HF development through different mechanisms, including pathological ergoreflex (\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e, \u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e). At the same time, HF may induce sarcopenia through multiple pathways, such as hormonal changes, poor nutrition, lack of exercise and etc. Therefore, early identification and intervention for the basic diseases in patients with metastatic cancer may be necessary in the future.\u003c/p\u003e \u003cp\u003eIt is now generally accepted that chemotherapy is also a cause of sarcopenia in cancer patients (\u003cspan additionalcitationids=\"CR66\" citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e). However, the relationship between the two is equally complex. One study found that patients with metastatic colorectal cancer (mCRC) had a significant reduction in muscle area during chemotherapy, and the rate of muscle loss observed in the study was 24 times faster than the normal rate of muscle loss (1% per year) (\u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e). Another study of adjuvant chemotherapy in patients with colon cancer found that baseline sarcopenia was associated with an increased incidence of all grade 3\u0026ndash;4 chemotherapy-induced toxicities (\u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e). In addition, in patients with colon, lung, esophageal, gastric, and other types of cancer, mortality increases and progression-free survival decreases after chemotherapy, even if patients with sarcopenia do not exhibit lower overall survival (\u003cspan additionalcitationids=\"CR70 CR71\" citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR72\" class=\"CitationRef\"\u003e72\u003c/span\u003e). The current explanation for this phenomenon is that patients with sarcopenia are forced to reduce doses or delay dosing cycles due to excessive toxicity to oncology treatment (\u003cspan citationid=\"CR73\" class=\"CitationRef\"\u003e73\u003c/span\u003e). It is common practice to base chemotherapy on the body surface area of each patient, without taking into account the large and unpredictable fraction of body weight accounted for by adipose tissue (\u003cspan citationid=\"CR74\" class=\"CitationRef\"\u003e74\u003c/span\u003e). A large amount of evidence shows that this method fails especially in patients with sarcopenia, and the related toxicity risks cannot be solved (\u003cspan additionalcitationids=\"CR76\" citationid=\"CR75\" class=\"CitationRef\"\u003e75\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e). Obviously, although some physiological constants may be related to body surface area, they are not related to other anthropometric parameters, such as body mass index. Besides, sarcopenia also reduces the effective effect of chemotherapy. Studies have shown that among breast cancer patients with sarcopenia, many chemotherapeutic drugs such as capecitabine, paclitaxel, docetaxel, and nab-paclitaxel have poor effects (\u003cspan citationid=\"CR73\" class=\"CitationRef\"\u003e73\u003c/span\u003e, \u003cspan citationid=\"CR78\" class=\"CitationRef\"\u003e78\u003c/span\u003e). The reasonable explanation may be that the adverse outcome may be related to the high toxicity rate, which in turn may lead to the necessary dose reduction and the provision of effective tumor treatment at a lower dose, thus reducing the therapeutic benefit (\u003cspan citationid=\"CR79\" class=\"CitationRef\"\u003e79\u003c/span\u003e). To sum up, cancer patients are prone to sarcopenia before and after chemotherapy, and sarcopenia occurring or aggravated during chemotherapy will worsen the prognosis and aggravate the toxicity caused by chemotherapy. Therefore, chemotherapy cycles and doses need to be carefully set based on drug toxicity and therapeutic effects.\u003c/p\u003e \u003cp\u003eIn our study, we found that the risk of sarcopenia and reduced PFS was not significant in the European population. It was found that, with the exception of the study of Haik, the remaining studies that showed unstable results were low risk of bias studies, and sensitivity analysis also yielded relatively stable results after excluding this study (\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e). All patients in this study were from a single hospital cohort and did not target a specific cancer, but rather included multiple cancers. In addition, this study was the only cohort to use immune checkpoint therapy on patients, which has relatively few side effects. Other studies have commonly used chemotherapy, and patients may have been treated with the previously described, mutually reinforcing effect of sarcopenia and chemotherapy toxicity, but this was not a problem in immunotherapy. This could be a potential reason why this research concluded that sarcopenia was not significantly associated with PFS. Several studies have now demonstrated that cancer patients treated with immune checkpoint inhibitors alone or in combination with chemotherapy have significantly improved survival compared to chemotherapy alone(\u003cspan additionalcitationids=\"CR81\" citationid=\"CR80\" class=\"CitationRef\"\u003e80\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR82\" class=\"CitationRef\"\u003e82\u003c/span\u003e). Whether immunotherapy exerts a better improvement in PFS in patients with sarcopenia needs to be further explored in more clinical studies.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eImplications\u003c/h2\u003e \u003cp\u003eThis meta-analysis provided important future clinical implications for the risk of worsening PFS in metastatic cancer patients with concomitant sarcopenia, yielding an approximate risk estimate with an HR of 1.56 (95% CI\u0026thinsp;=\u0026thinsp;1.19\u0026ndash;2.03) for PFS. Early screening and effective interventions are clinically important in the prevention and treatment of sarcopenia. Second, optimal strategies for prevention and management of sarcopenia have not been established due to the widespread neglect of sarcopenia in cancer. Due to the lack of reliable clinical data to guide clinicians, physicians may consider the use of specific treatment options based on the history of adjuvant therapy (e.g., chemotherapy or radiation therapy), baseline information, etc., in cancer patients. In addition, screening and treatment of individuals at high risk for stroke has implications for the prevention of sarcopenia and for reducing the burden of sarcopenia in the general elderly population.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eStrengths and limitations\u003c/h2\u003e \u003cp\u003eThe current study has several advantages in the following aspects. First, the current systematic evaluation and meta-analysis includes a more representative population in the relevant field, providing up-to-date evidence on the association between the risk of worsening PFS in metastatic cancer patients with concomitant sarcopenia. Second, we developed a systematic and comprehensive database search strategy based on the major online databases (PubMed, Embase, and Cochrane Library) with no search date restrictions so that we could retrieve as many relevant articles from around the world as possible, avoiding publication bias on pooled results and improving the reproducibility of results. Third, almost all included studies were from national cohorts or population-based cohorts, thus minimizing potential selection bias stemming from study design. In addition, a transparent methodological quality assessment of the included studies was performed using the NOS list for cohort studies. Fourth, several methods, including subgroup analysis and sensitivity analysis, have been applied to thoroughly identify sources of heterogeneity based on abstract study-level baseline characteristics. In these sensitivity analyses, after excluding one low-quality study, our results remained stable and Egger's test combined with the cut-and-patch method found no evidence of publication bias.\u003c/p\u003e \u003cp\u003eThis study also has some limitations. First, significant heterogeneity was found in the included studies, which was predictable and may be partly due to differences in baseline characteristics of the population (sex, race, tumor primary site and metastatic site, etc.), exposure to treatment (adjuvant chemotherapy, radiation therapy, or hormonal therapy), and statistical methods (adjustment for confounders). Although several methods were applied to adjust for outcomes, considerable moderate to high heterogeneity remained. After careful study, we concluded that irregularities in PFS can introduce bias in the results, mainly due to differences in the interval between patient follow-up after treatment. For PFS, PFS is susceptible to the influence of the follow-up interval because the exact time point at which a patient progresses is uncertain. Different follow-up intervals may lead to highly variable trial results. For example, if patients are asked to follow up every 3 months, assuming a high degree of patient compliance, and if patients in the trial group have a prolonged survival of less than 3 months compared to the control group, it cannot be concluded that the trial group is better than the control group because tumor progression in both groups will be detected at the same review every 3 months, then PFS is recorded as No difference. In a more extreme case, if the tumor is reviewed every 3 months after treatment, and the tumor is determined to be progression-free at the first post-treatment review (3 months) in the trial group, but progression appears soon after the review (much less than 3 months, or even days) but is not detected, while tumor progression is detected at the first post-treatment review (nearly 3 months) in the control group, the difference in progression-free survival between the two groups is considered to be 3 months, while the true difference between the two groups is close to 0. The true difference is close to 0, which would result in a 3-month bias. Such differences can occur not only within studies, but also between studies due to inconsistent PFS intervals, and the shorter the follow-up interval for patients, the more reliable their trial results. This inference is supported by the fact that most of our studies did not mention the follow-up interval and that those that reported this element were at low risk of bias and had a higher degree of confidence, as other investigators have also mentioned this directly or indirectly (\u003cspan citationid=\"CR83\" class=\"CitationRef\"\u003e83\u003c/span\u003e). However, given that the results of most subgroup analyses and sensitivity analyses were highly consistent with the primary outcome, we believe that the impact of these heterogeneities on the primary outcome of the study is limited. Second, the results of this meta-analysis are based on observational cohort studies, which may be limited by confounding factors such as patient gender, adjuvant treatment modality, and follow-up interval. However, all included studies provided data comparing sarcopenic and non-sarcopenic populations and matched with a number of important covariates suggesting a consistently increased risk of worsening PFS in sarcopenic patients. Third, because our study was a single-study-level meta-analysis rather than an individual patient-level meta-analysis, we were unable to perform more detailed subgroup analyses (e.g., risk analyses based on events during cancer survival and follow-up) and were unable to explore progressive sarcopenia that occurred during follow-up. Fourth, some subgroup analyses found nonsignificant results, which we believe may be due to the relatively small sample size and low statistical efficacy. More evidence from high-quality prospective cohort studies on the impact of sarcopenia on the risk of death or progression in patients with metastatic cancer is needed. Finally, the meta-analysis was limited to studies published in peer-reviewed journals in English. We may have missed articles published in other languages or in journals outside of the three databases we searched. In addition, unpublished gray literature was not included. However, three major databases, PubMed, Embase, and the Cochrane Library, published the vast majority of available reports. Despite these limitations, the current study includes the vast majority of cancer types, which provides a largely adequate sample size for meaningful and robust statistical analyses.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn this article, we performed a systematic evaluation and meta-analysis of sarcopenia in metastatic cancer patients. The results suggest that sarcopenia might be an indicator of reduced progression-free survival in metastatic cancer patients. However, there is still a need to conduct larger prospective cohort studies to confirm the conclusion.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eHazard Ratio, HR; confidence intervals, CIs; overall survival, OS; Newcastle\u0026ndash;Ottawa scale, NOS; L3 skeletal muscle index, L3-SMI; L3 psoas muscle index, L3-PMI; \u0026nbsp;total psoas area index, TPI; metastatic colorectal cancer, mCRC\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMZ, TW and WG conceived and designed the article. XS and PL (Pan Liu) performed the retrieve. XS and PL (Pan Liu) contributed material/analysis tools. MZ, XS and PL (Peiling Li) wrote the manuscript. XS, PL (Pan Liu), HT and SF performed reference collection and data management. XS and PL (Pan Liu) performed statistical analyses. TW and WG critically revised and edited successive drafts of the manuscript. All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eRosenberg IH. Sarcopenia: origins and clinical relevance. J Nutr. 1997;127(5 Suppl):990S-1S.\u003c/li\u003e\n\u003cli\u003eCruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, et al. Sarcopenia: revised European consensus on definition and diagnosis. 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J Gerontol A Biol Sci Med Sci. 2003;58(10):M911-6.\u003c/li\u003e\n\u003cli\u003eRyall JG, Schertzer JD, Lynch GS. Cellular and molecular mechanisms underlying age-related skeletal muscle wasting and weakness. Biogerontology. 2008;9(4):213-28.\u003c/li\u003e\n\u003cli\u003eDhillon RJ, Hasni S. Pathogenesis and Management of Sarcopenia. Clin Geriatr Med. 2017;33(1):17-26.\u003c/li\u003e\n\u003cli\u003eCannataro R, Carbone L, Petro JL, Cione E, Vargas S, Angulo H, et al. Sarcopenia: Etiology, Nutritional Approaches, and miRNAs. Int J Mol Sci. 2021;22(18).\u003c/li\u003e\n\u003cli\u003eBauer J, Morley JE, Schols A, Ferrucci L, Cruz-Jentoft AJ, Dent E, et al. Sarcopenia: A Time for Action. An SCWD Position Paper. Journal of cachexia, sarcopenia and muscle. 2019;10(5):956-61.\u003c/li\u003e\n\u003cli\u003eRyan AM, Prado CM, Sullivan ES, Power DG, Daly LE. Effects of weight loss and sarcopenia on response to chemotherapy, quality of life, and survival. Nutrition. 2019;67-68:110539.\u003c/li\u003e\n\u003cli\u003eBischoff-Ferrari HA, Orav JE, Kanis JA, Rizzoli R, Schlogl M, Staehelin HB, et al. Comparative performance of current definitions of sarcopenia against the prospective incidence of falls among community-dwelling seniors age 65 and older. Osteoporos Int. 2015;26(12):2793-802.\u003c/li\u003e\n\u003cli\u003eSchaap LA, van Schoor NM, Lips P, Visser M. Associations of Sarcopenia Definitions, and Their Components, With the Incidence of Recurrent Falling and Fractures: The Longitudinal Aging Study Amsterdam. J Gerontol A Biol Sci Med Sci. 2018;73(9):1199-204.\u003c/li\u003e\n\u003cli\u003eBone AE, Hepgul N, Kon S, Maddocks M. Sarcopenia and frailty in chronic respiratory disease. Chron Respir Dis. 2017;14(1):85-99.\u003c/li\u003e\n\u003cli\u003eSepulveda-Loyola W, Osadnik C, Phu S, Morita AA, Duque G, Probst VS. Diagnosis, prevalence, and clinical impact of sarcopenia in COPD: a systematic review and meta-analysis. Journal of cachexia, sarcopenia and muscle. 2020;11(5):1164-76.\u003c/li\u003e\n\u003cli\u003eCurcio F, Testa G, Liguori I, Papillo M, Flocco V, Panicara V, et al. Sarcopenia and Heart Failure. Nutrients. 2020;12(1).\u003c/li\u003e\n\u003cli\u003evon Haehling S. The wasting continuum in heart failure: from sarcopenia to cachexia. Proc Nutr Soc. 2015;74(4):367-77.\u003c/li\u003e\n\u003cli\u003eGrossberg AJ, Chamchod S, Fuller CD, Mohamed AS, Heukelom J, Eichelberger H, et al. Association of Body Composition With Survival and Locoregional Control of Radiotherapy-Treated Head and Neck Squamous Cell Carcinoma. JAMA Oncol. 2016;2(6):782-9.\u003c/li\u003e\n\u003cli\u003eHuang X, Ma J, Li L, Zhu XD. Severe muscle loss during radical chemoradiotherapy for non-metastatic nasopharyngeal carcinoma predicts poor survival. Cancer medicine. 2019;8(15):6604-13.\u003c/li\u003e\n\u003cli\u003eHua X, Liao JF, Huang X, Huang HY, Wen W, Long ZQ, et al. 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Negative Impact of Skeletal Muscle Loss after Systemic Chemotherapy in Patients with Unresectable Colorectal Cancer. PloS one. 2015;10(6):e0129742.\u003c/li\u003e\n\u003cli\u003eStene GB, Helbostad JL, Amundsen T, Sorhaug S, Hjelde H, Kaasa S, et al. Changes in skeletal muscle mass during palliative chemotherapy in patients with advanced lung cancer. Acta oncologica (Stockholm, Sweden). 2015;54(3):340-8.\u003c/li\u003e\n\u003cli\u003eTan BH, Brammer K, Randhawa N, Welch NT, Parsons SL, James EJ, et al. Sarcopenia is associated with toxicity in patients undergoing neo-adjuvant chemotherapy for oesophago-gastric cancer. Eur J Surg Oncol. 2015;41(3):333-8.\u003c/li\u003e\n\u003cli\u003ePrado CM, Baracos VE, McCargar LJ, Reiman T, Mourtzakis M, Tonkin K, et al. Sarcopenia as a determinant of chemotherapy toxicity and time to tumor progression in metastatic breast cancer patients receiving capecitabine treatment. Clinical cancer research : an official journal of the American Association for Cancer Research. 2009;15(8):2920-6.\u003c/li\u003e\n\u003cli\u003eDu Bois D, Du Bois EF. A formula to estimate the approximate surface area if height and weight be known. 1916. Nutrition. 1989;5(5):303-11; discussion 12-3.\u003c/li\u003e\n\u003cli\u003eBaker SD, Verweij J, Rowinsky EK, Donehower RC, Schellens JH, Grochow LB, et al. Role of body surface area in dosing of investigational anticancer agents in adults, 1991-2001. Journal of the National Cancer Institute. 2002;94(24):1883-8.\u003c/li\u003e\n\u003cli\u003eHendifar A, Yang D, Lenz F, Lurje G, Pohl A, Lenz C, et al. Gender disparities in metastatic colorectal cancer survival. Clinical cancer research : an official journal of the American Association for Cancer Research. 2009;15(20):6391-7.\u003c/li\u003e\n\u003cli\u003evan Vugt JL, Braam HJ, van Oudheusden TR, Vestering A, Bollen TL, Wiezer MJ, et al. 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First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet (London, England). 2021;398(10294):27-40.\u003c/li\u003e\n\u003cli\u003eKang YK, Chen LT, Ryu MH, Oh DY, Oh SC, Chung HC, et al. Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. The Lancet Oncology. 2022;23(2):234-47.\u003c/li\u003e\n\u003cli\u003eKato K, Cho BC, Takahashi M, Okada M, Lin CY, Chin K, et al. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial. The Lancet Oncology. 2019;20(11):1506-17.\u003c/li\u003e\n\u003cli\u003eLee D, Kim NW, Kim JY, Lee JH, Noh JH, Lee H, et al. Sarcopenia\u0026apos;s Prognostic Impact on Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis. Journal of clinical medicine. 2021;10(22).\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Characteristics of studies included in meta-analysis\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003e\u003cstrong\u003eFirst author\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"4.775828460038986%\"\u003e\n \u003cp\u003e\u003cstrong\u003eYear\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.916179337231968%\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy design\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.432748538011696%\"\u003e\n \u003cp\u003e\u003cstrong\u003eRegion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiagnosed\u003cbr\u003e\u0026nbsp;period\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.555555555555555%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSample size\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian/mean age\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMain Treatment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003e\u003cstrong\u003eOriginal cancer type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.32748538011696%\"\u003e\n \u003cp\u003e\u003cstrong\u003ecancer metastases\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eLee, J. H.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"4.775828460038986%\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.916179337231968%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.432748538011696%\"\u003e\n \u003cp\u003eKorea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003e2018 to 2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.555555555555555%\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eChemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eHormone-sensitive prostate cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.32748538011696%\"\u003e\n \u003cp\u003eBone, lung, liver, pleura, adrenal gland, peritoneum, ureter\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eLee, C. H.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"4.775828460038986%\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.916179337231968%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.432748538011696%\"\u003e\n \u003cp\u003eKorea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003e2010 to 2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.555555555555555%\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e24.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eChemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eRenal cell carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.32748538011696%\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eHaik\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"4.775828460038986%\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.916179337231968%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.432748538011696%\"\u003e\n \u003cp\u003eFrance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003e2013 to 2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.555555555555555%\"\u003e\n \u003cp\u003e261\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e61.9 (mean)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eImmunity therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eHead, lung, renal, bladder cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.32748538011696%\"\u003e\n \u003cp\u003eLiver, lung, bone, brain\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eGallois\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"4.775828460038986%\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.916179337231968%\"\u003e\n \u003cp\u003eProspective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.432748538011696%\"\u003e\n \u003cp\u003eFrance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003e2013 to 2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.555555555555555%\"\u003e\n \u003cp\u003e149\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eChemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eColorectal cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.32748538011696%\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eChang\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"4.775828460038986%\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.916179337231968%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.432748538011696%\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003e2007 to 2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.555555555555555%\"\u003e\n \u003cp\u003e109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e42.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e60.9 (mean)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eChemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eGastrointestinal stromal tumor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.32748538011696%\"\u003e\n \u003cp\u003eLiver\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eCatanese\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"4.775828460038986%\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.916179337231968%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.432748538011696%\"\u003e\n \u003cp\u003eItaly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003e2010 to 2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.555555555555555%\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e28.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eChemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eEsophago\u0026ndash;gastric junction cancer, proximal gastric cancer, distal gastric cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.32748538011696%\"\u003e\n \u003cp\u003eLiver, lung, lymph nodes, peritoneum, bone\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eYamazaki\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"4.775828460038986%\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.916179337231968%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.432748538011696%\"\u003e\n \u003cp\u003eJapan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003e2015 to 2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.555555555555555%\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e64.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e66.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eChemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eThyroid cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.32748538011696%\"\u003e\n \u003cp\u003eLiver, lung, bone, brain, lymph node\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eShimizu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"4.775828460038986%\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.916179337231968%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.432748538011696%\"\u003e\n \u003cp\u003eJapan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003e2017 to 2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.555555555555555%\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eChemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eBladder tumor, upper tract urothelial carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.32748538011696%\"\u003e\n \u003cp\u003eLiver, lung, lymph nodes, bone\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eLee, B. M.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"4.775828460038986%\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.916179337231968%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.432748538011696%\"\u003e\n \u003cp\u003eKorea.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003e2007 to 2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.555555555555555%\"\u003e\n \u003cp\u003e353\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e42.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eChemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eGall bladder, intrahepatic bile duct, non-hilar bile duct, perihilar bile duct, ampullary cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.32748538011696%\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eda Cunha\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"4.775828460038986%\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.916179337231968%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.432748538011696%\"\u003e\n \u003cp\u003eBrazil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003e2009 to 2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.555555555555555%\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e44.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e59.4 (mean)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eSurgery and chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eColorectal cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.32748538011696%\"\u003e\n \u003cp\u003ePeritoneum and other organs\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eFranzoi\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"4.775828460038986%\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.916179337231968%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.432748538011696%\"\u003e\n \u003cp\u003eBelgium\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003e2016 to 2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.555555555555555%\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e61.2 (mean)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eChemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eBreast cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.32748538011696%\"\u003e\n \u003cp\u003eVisceral disease, bone only or locorregional\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003ePalleschi\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"4.775828460038986%\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.916179337231968%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.432748538011696%\"\u003e\n \u003cp\u003eItaly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003e2009 to 2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.555555555555555%\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eChemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eBreast cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.32748538011696%\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eWilliet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"4.775828460038986%\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.916179337231968%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.432748538011696%\"\u003e\n \u003cp\u003eFrance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003e2012 to 2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.555555555555555%\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e45.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eChemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003ePancreatic cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.32748538011696%\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eIshihara\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"4.775828460038986%\"\u003e\n \u003cp\u003e2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.916179337231968%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.432748538011696%\"\u003e\n \u003cp\u003eJapan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003e2007 to 2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.555555555555555%\"\u003e\n \u003cp\u003e71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e29.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eChemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eRenal Cell Carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.32748538011696%\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eGu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"4.775828460038986%\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.916179337231968%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.432748538011696%\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003e2008 to 2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.555555555555555%\"\u003e\n \u003cp\u003e101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e35.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eChemotherapy\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eRenal cell carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.32748538011696%\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eMalik\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"4.775828460038986%\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.916179337231968%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.432748538011696%\"\u003e\n \u003cp\u003ePoland\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003e2017 to 2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.555555555555555%\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.407407407407407%\"\u003e\n \u003cp\u003e64.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eChemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.865497076023392%\"\u003e\n \u003cp\u003eColorectal cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.32748538011696%\"\u003e\n \u003cp\u003eLiver, lung, lymph node, peritoneum\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eC\u003c/strong\u003e\u003cstrong\u003eontinued. Characteristics of studies included in meta-analysis\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003e\u003cstrong\u003eFirst author\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.331384015594542%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMeasurements of sarcopenia \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"58.771929824561404%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSarcopenia definition \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003e\u003cstrong\u003eOutcomes\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.450292397660819%\"\u003e\n \u003cp\u003e\u003cstrong\u003emedian/mean Follow-up period\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eLee, J. H.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.331384015594542%\"\u003e\n \u003cp\u003eL3-SMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"58.771929824561404%\"\u003e\n \u003cp\u003eSMI\u0026nbsp;\u0026le;\u0026nbsp;52.4 cm2/m2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.450292397660819%\"\u003e\n \u003cp\u003e20.5 months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eLee, C. H.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.331384015594542%\"\u003e\n \u003cp\u003eL3-SMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"58.771929824561404%\"\u003e\n \u003cp\u003eSMI of \u0026lt; 43cm2/m2 and \u0026lt; 53 cm2/m2 for men with a BMI of \u0026lt; 25 kg/m2 and\u0026nbsp;\u0026ge;\u0026nbsp;25kg/m2, respectively, and \u0026lt; 41 cm2/m2 for women\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.450292397660819%\"\u003e\n \u003cp\u003e15.4 months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eHaik\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.331384015594542%\"\u003e\n \u003cp\u003eL3-SMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"58.771929824561404%\"\u003e\n \u003cp\u003e\u0026lt; 41 cm2/m2 for females and \u0026lt; 43 cm2/m2 for males if body mass index (BMI) \u0026lt; 25 kg/m2 or \u0026lt; 53 cm2/m2 if BMI\u0026nbsp;\u0026ge;\u0026nbsp;25 kg/m2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.450292397660819%\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eGallois\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.331384015594542%\"\u003e\n \u003cp\u003eL3-SMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"58.771929824561404%\"\u003e\n \u003cp\u003emen \u0026lt; 40.3 cm2/m2 and women \u0026lt; 32.0 cm2/m2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.450292397660819%\"\u003e\n \u003cp\u003e23 months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eChang\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.331384015594542%\"\u003e\n \u003cp\u003eL3-PMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"58.771929824561404%\"\u003e\n \u003cp\u003e\u0026lt; 6.36 cm2/m2 for males and \u0026lt; 3.92 cm2/m2 for females\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.450292397660819%\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eCatanese\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.331384015594542%\"\u003e\n \u003cp\u003eL3-SMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"58.771929824561404%\"\u003e\n \u003cp\u003emale patients as\u003cbr\u003e\u0026nbsp;SMI \u0026lt; 43 cm2/m2 if BMI \u0026lt; 25 kg/m2 and SMI \u0026lt; 53 cm2/m2 if BMI \u0026ge; 25 kg/m2, and in\u003cbr\u003e\u0026nbsp;female patients as SMI \u0026lt; 41 cm2/m2 irrespective of BMI\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.450292397660819%\"\u003e\n \u003cp\u003e52.2 months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eYamazaki\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.331384015594542%\"\u003e\n \u003cp\u003eL3-SMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"58.771929824561404%\"\u003e\n \u003cp\u003e\u0026lt; 42 cm2/m2 for males and \u0026lt; 38 cm2/m2 for females\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.450292397660819%\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eShimizu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.331384015594542%\"\u003e\n \u003cp\u003eL3-PMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"58.771929824561404%\"\u003e\n \u003cp\u003e\u0026le;\u0026nbsp;6.36 cm2/m2 for men and\u0026nbsp;\u0026le;\u0026nbsp;3.92 cm2/m2 for women\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.450292397660819%\"\u003e\n \u003cp\u003e7 months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eLee, B. M.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.331384015594542%\"\u003e\n \u003cp\u003eL3-SMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"58.771929824561404%\"\u003e\n \u003cp\u003e\u0026lt; 55 cm2/m2 for male and \u0026lt; 39 cm2/m2 for female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.450292397660819%\"\u003e\n \u003cp\u003e7.77 months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eda Cunha\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.331384015594542%\"\u003e\n \u003cp\u003eL3-SMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"58.771929824561404%\"\u003e\n \u003cp\u003eSMI \u0026lt; 41 cm2/m2 for women; SMI \u0026lt; 43 cm2/m2 if BMI \u0026lt; 25 kg/m2 and SMI \u0026lt; 53 cm2/m2 if BMI\u0026nbsp;\u0026le;\u0026nbsp;25 kg/m2 for men\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.450292397660819%\"\u003e\n \u003cp\u003e23.6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eFranzoi\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.331384015594542%\"\u003e\n \u003cp\u003eL3-SMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"58.771929824561404%\"\u003e\n \u003cp\u003eSMI \u0026lt; 40 cm2/m2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.450292397660819%\"\u003e\n \u003cp\u003e14.4 months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003ePalleschi\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.331384015594542%\"\u003e\n \u003cp\u003eL3-SMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"58.771929824561404%\"\u003e\n \u003cp\u003eSMI \u0026lt; 40 cm2/m2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.450292397660819%\"\u003e\n \u003cp\u003e33 months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eWilliet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.331384015594542%\"\u003e\n \u003cp\u003eTPI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"58.771929824561404%\"\u003e\n \u003cp\u003e\u0026lt; 5.73 cm2/m2 for men and \u0026lt; 4.37 cm2/m2 for women\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.450292397660819%\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eIshihara\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.331384015594542%\"\u003e\n \u003cp\u003eL3-SMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"58.771929824561404%\"\u003e\n \u003cp\u003emen with a BMI of \u0026lt; 25 kg/m2 and SMI \u0026lt; 43 cm2/m2; men with a BMI of \u0026gt; 25 kg/m2 and SMI \u0026lt; 53 cm2/m2; women with SMI \u0026lt; 41 cm2/m2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.450292397660819%\"\u003e\n \u003cp\u003e20.2 months (mean)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eGu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.331384015594542%\"\u003e\n \u003cp\u003eL3-SMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"58.771929824561404%\"\u003e\n \u003cp\u003e\u0026lt; 40.8 cm2/m2 for males and \u0026lt; 34.9 cm2/m2 for females\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.450292397660819%\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.309941520467836%\"\u003e\n \u003cp\u003eMalik\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.331384015594542%\"\u003e\n \u003cp\u003eL3-SMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"58.771929824561404%\"\u003e\n \u003cp\u003e\u0026lt; 52.4 cm2/m2 for men and \u0026lt; 38.5 cm2/m2 for women\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.1364522417154%\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.450292397660819%\"\u003e\n \u003cp\u003e19.1 months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eL3, 3rd lumbar spine; SMI, skeletal muscle index; PMI, psoas muscle index; BMI, body Mass Index; TPI, The total psoas area index; PFS, progression-free survival.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Methodological quality score of the included studies based on the Newcastle\u0026ndash;Ottawa scale (NOS) tool.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"6.2464183381088825%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAuthor\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"3.667621776504298%\"\u003e\n \u003cp\u003e\u003cstrong\u003eYear\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"10.773638968481375%\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy Design\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" width=\"37.363896848137536%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSelection\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.226361031518625%\"\u003e\n \u003cp\u003e\u003cstrong\u003eComparability\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"20.401146131805156%\"\u003e\n \u003cp\u003e\u003cstrong\u003eExposure/Outcome\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.042979942693409%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"7.277936962750716%\"\u003e\n \u003cp\u003e\u003cstrong\u003eRisk\u0026nbsp;\u003cbr\u003e\u0026nbsp;of Bias\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"12.181528662420382%\"\u003e\n \u003cp\u003e\u003cstrong\u003eRepresentative\u0026shy;ness of cohort *\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.5%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSelection of control cohort *\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.977707006369426%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAscertainment of exposure *\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.251592356687897%\"\u003e\n \u003cp\u003e\u003cstrong\u003eOutcome not present at start * \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.818471337579618%\"\u003e\n \u003cp\u003e\u003cstrong\u003eComparability of cohorts **\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.63375796178344%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAssessment of outcome * \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.678343949044587%\"\u003e\n \u003cp\u003e\u003cstrong\u003eLength of follow-up *\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.952229299363058%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdequacy of follow-up *\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.006369426751593%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003eLee, J. H.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.669724770642202%\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"19.55275229357798%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.002293577981652%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.346330275229358%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.263761467889909%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.23165137614679%\"\u003e\n \u003cp\u003e**\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.9380733944954125%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.16743119266055%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.045871559633028%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.282110091743119%\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003eLee, C. H.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.669724770642202%\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"19.55275229357798%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.002293577981652%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.346330275229358%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.263761467889909%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.23165137614679%\"\u003e\n \u003cp\u003e**\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.9380733944954125%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.16743119266055%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.045871559633028%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.282110091743119%\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003eHaik\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.669724770642202%\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"19.55275229357798%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.002293577981652%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.346330275229358%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.263761467889909%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.23165137614679%\"\u003e\n \u003cp\u003e**\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.9380733944954125%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.16743119266055%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.045871559633028%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.282110091743119%\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003eGallois\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.669724770642202%\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"19.55275229357798%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.002293577981652%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.346330275229358%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.263761467889909%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.23165137614679%\"\u003e\n \u003cp\u003e**\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.9380733944954125%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.16743119266055%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.045871559633028%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.282110091743119%\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003eChang\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.669724770642202%\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"19.55275229357798%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.002293577981652%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.346330275229358%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.263761467889909%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.23165137614679%\"\u003e\n \u003cp\u003e**\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.9380733944954125%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.16743119266055%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.045871559633028%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.282110091743119%\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003eCatanese\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.669724770642202%\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"19.55275229357798%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.002293577981652%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.346330275229358%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.263761467889909%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.23165137614679%\"\u003e\n \u003cp\u003e**\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.9380733944954125%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.16743119266055%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.045871559633028%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.282110091743119%\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003eYamazaki\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.669724770642202%\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"19.55275229357798%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.002293577981652%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.346330275229358%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.263761467889909%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.23165137614679%\"\u003e\n \u003cp\u003e**\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.9380733944954125%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.16743119266055%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.045871559633028%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.282110091743119%\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003eShimizu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.669724770642202%\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"19.55275229357798%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.002293577981652%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.346330275229358%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.263761467889909%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.23165137614679%\"\u003e\n \u003cp\u003e**\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.9380733944954125%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.16743119266055%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.045871559633028%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.282110091743119%\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003eLee, B. M.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.669724770642202%\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"19.55275229357798%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.002293577981652%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.346330275229358%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.263761467889909%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.23165137614679%\"\u003e\n \u003cp\u003e**\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.9380733944954125%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.16743119266055%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.045871559633028%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.282110091743119%\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003eda Cunha\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.669724770642202%\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"19.55275229357798%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.002293577981652%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.346330275229358%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.263761467889909%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.23165137614679%\"\u003e\n \u003cp\u003e**\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.9380733944954125%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.16743119266055%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.045871559633028%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.282110091743119%\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003eFranzoi\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.669724770642202%\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"19.55275229357798%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.002293577981652%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.346330275229358%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.263761467889909%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.23165137614679%\"\u003e\n \u003cp\u003e**\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.9380733944954125%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.16743119266055%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.045871559633028%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.282110091743119%\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003ePalleschi\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.669724770642202%\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"19.55275229357798%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.002293577981652%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.346330275229358%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.263761467889909%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.23165137614679%\"\u003e\n \u003cp\u003e**\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.9380733944954125%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.16743119266055%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.045871559633028%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.282110091743119%\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003eWilliet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.669724770642202%\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"19.55275229357798%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.002293577981652%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.346330275229358%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.263761467889909%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.23165137614679%\"\u003e\n \u003cp\u003e**\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.9380733944954125%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.16743119266055%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.045871559633028%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.282110091743119%\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003eIshihara\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.669724770642202%\"\u003e\n \u003cp\u003e2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"19.55275229357798%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.002293577981652%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.346330275229358%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.263761467889909%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.23165137614679%\"\u003e\n \u003cp\u003e**\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.9380733944954125%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.16743119266055%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.045871559633028%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.282110091743119%\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003eGu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.669724770642202%\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"19.55275229357798%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.002293577981652%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.346330275229358%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.263761467889909%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.23165137614679%\"\u003e\n \u003cp\u003e**\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.9380733944954125%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.16743119266055%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.045871559633028%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.282110091743119%\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003eMalik\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.669724770642202%\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"19.55275229357798%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.002293577981652%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.346330275229358%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.263761467889909%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.23165137614679%\"\u003e\n \u003cp\u003e**\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.9380733944954125%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.25%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.16743119266055%\"\u003e\n \u003cp\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.045871559633028%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.282110091743119%\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Subgroup analyses for the effect of sarcopenia on PFS in patients with metastases.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"658\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.64437689969605%\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45288753799392%\"\u003e\n \u003cp\u003e\u003cstrong\u003e \u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.565349544072948%\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e\u003cstrong\u003eI\u003c/strong\u003e\u003cstrong\u003e\u0026sup2;\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo. studies\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.158054711246201%\"\u003e\n \u003cp\u003e\u003cstrong\u003eP for interaction\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.64437689969605%\"\u003e\n \u003cp\u003e\u003cstrong\u003eRegions\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45288753799392%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"16.565349544072948%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.158054711246201%\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.64437689969605%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"19.45288753799392%\"\u003e\n \u003cp\u003eAsia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e1.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.565349544072948%\"\u003e\n \u003cp\u003e1.18 to 3.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e83.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.158054711246201%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.64437689969605%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"19.45288753799392%\"\u003e\n \u003cp\u003eEurope\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e1.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.565349544072948%\"\u003e\n \u003cp\u003e0.91 to 1.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e66.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.158054711246201%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.64437689969605%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45288753799392%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"16.565349544072948%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.158054711246201%\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.64437689969605%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"19.45288753799392%\"\u003e\n \u003cp\u003eFemale\u0026le;50%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e1.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.565349544072948%\"\u003e\n \u003cp\u003e1.12 to 2.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e79.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.158054711246201%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.64437689969605%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"19.45288753799392%\"\u003e\n \u003cp\u003eFemale＞50%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e1.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.565349544072948%\"\u003e\n \u003cp\u003e1.11 to 2.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e21.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.158054711246201%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.64437689969605%\"\u003e\n \u003cp\u003e\u003cstrong\u003eOriginal cancer type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45288753799392%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"16.565349544072948%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.158054711246201%\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.64437689969605%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"19.45288753799392%\"\u003e\n \u003cp\u003eGastrointestinal\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e1.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.565349544072948%\"\u003e\n \u003cp\u003e0.87 to 1.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e79.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.158054711246201%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.64437689969605%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"19.45288753799392%\"\u003e\n \u003cp\u003eUrologic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e1.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.565349544072948%\"\u003e\n \u003cp\u003e1.02 to 2.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e7.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.158054711246201%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.64437689969605%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"19.45288753799392%\"\u003e\n \u003cp\u003eEndocrine Gland\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e2.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.565349544072948%\"\u003e\n \u003cp\u003e1.36 to 3.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.158054711246201%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"22.64437689969605%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"19.45288753799392%\"\u003e\n \u003cp\u003eBreast\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e1.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.565349544072948%\"\u003e\n \u003cp\u003e0.60 to 3.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.158054711246201%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"22.64437689969605%\"\u003e\n \u003cp\u003e\u003cstrong\u003eQuality assessment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45288753799392%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"16.565349544072948%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.72644376899696%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.158054711246201%\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"22.64437689969605%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"19.45288753799392%\"\u003e\n \u003cp\u003eLow risk of bias\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e1.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.565349544072948%\"\u003e\n \u003cp\u003e1.10 to 2.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e77.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.158054711246201%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"22.64437689969605%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45288753799392%\"\u003e\n \u003cp\u003eHigh risk of bias\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e1.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.565349544072948%\"\u003e\n \u003cp\u003e0.96 to 2.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e79.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72644376899696%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.158054711246201%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eContinued. Subgroup analyses for\u003c/strong\u003e \u003cstrong\u003eGastrointestinal Neoplasms.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"429\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.836829836829835%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCancer type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.918414918414918%\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.407925407925408%\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.918414918414918%\"\u003e\n \u003cp\u003e\u003cstrong\u003eI\u003c/strong\u003e\u003cstrong\u003e\u0026sup2;\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.918414918414918%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo. studies\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.836829836829835%\"\u003e\n \u003cp\u003eColorectal\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.918414918414918%\"\u003e\n \u003cp\u003e1.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.407925407925408%\"\u003e\n \u003cp\u003e1.18 to 2.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.918414918414918%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.918414918414918%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.836829836829835%\"\u003e\n \u003cp\u003eGastric\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.918414918414918%\"\u003e\n \u003cp\u003e1.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.407925407925408%\"\u003e\n \u003cp\u003e0.49 to 3.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.918414918414918%\"\u003e\n \u003cp\u003e85.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.918414918414918%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"sarcopenia, metastases, progression-free survival, meta, retrospective study","lastPublishedDoi":"10.21203/rs.3.rs-2319788/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2319788/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eMetastasis of cancer causes more than 90% of cancer deaths and is severely damaging to human health. In recent years, several studies have linked sarcopenia to shorter survival in patients with metastatic cancer. Several predictive models exist to predict mortality in patients with metastatic cancer, but have reported limited accuracy.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe systematically searched PubMed, EMBASE, and the Cochrane Library for articles published on or before October 14, 2022. Pooled Hazard Ratio (HR) estimates with 95% confidence intervals (CIs) were calculated using a random effects model. The primary outcome was an increased risk of death or tumor progression in patients with metastatic cancer. In addition, we performed subgroup analyses and leave-one-out sensitivity analyses to explore the main sources of heterogeneity and the stability of the results.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eSixteen retrospective cohort studies with 1,675 patients were included in the 888 papers screened. The results showed that sarcopenia was associated with lower progression-free survival (HR\u0026thinsp;=\u0026thinsp;1.56, 95% CI\u0026thinsp;=\u0026thinsp;1.19\u0026ndash;2.03, I2\u0026thinsp;=\u0026thinsp;76.3%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). This result was further confirmed by trim-and-fill procedures and leave-one-out sensitivity analysis.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis study suggests that sarcopenia may be a risk factor for reduced progression-free survival in patients with metastatic cancer. Further studies are still needed to explain the reason for this high heterogeneity in outcome.\u003c/p\u003e\u003ch2\u003eTrial Registration:\u003c/h2\u003e \u003cp\u003eCRD42022325910\u003c/p\u003e","manuscriptTitle":"Sarcopenia as a risk factor of progression-free survival in patients with metastases: a systematic review and meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-12-12 18:07:12","doi":"10.21203/rs.3.rs-2319788/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2023-01-11T11:59:53+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-01-02T21:33:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"8ae46eda-d765-4c5f-8b66-62efcaa3f416","date":"2022-12-22T13:32:24+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-12-19T12:18:01+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-12-08T18:19:36+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2022-12-08T12:59:38+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-12-08T12:47:35+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2022-11-28T07:42:09+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f73fa2e5-7fa7-4ebc-bdb4-2e3ca6840095","owner":[],"postedDate":"December 12th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-10-16T18:50:50+00:00","versionOfRecord":{"articleIdentity":"rs-2319788","link":"https://doi.org/10.1186/s12885-023-10582-2","journal":{"identity":"bmc-cancer","isVorOnly":false,"title":"BMC Cancer"},"publishedOn":"2023-02-07 18:44:21","publishedOnDateReadable":"February 7th, 2023"},"versionCreatedAt":"2022-12-12 18:07:12","video":"","vorDoi":"10.1186/s12885-023-10582-2","vorDoiUrl":"https://doi.org/10.1186/s12885-023-10582-2","workflowStages":[]},"version":"v1","identity":"rs-2319788","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2319788","identity":"rs-2319788","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}