{"paper_id":"4c6d6872-2299-4118-975d-bb3ad9f3addf","body_text":"The Impact of Sarcopenia on Overall Survival in Patients with Pan-RAS Wild-type Colorectal Liver Metastasis Receiving Hepatectomy | 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 Article The Impact of Sarcopenia on Overall Survival in Patients with Pan-RAS Wild-type Colorectal Liver Metastasis Receiving Hepatectomy Yao-Ren Yang, Chung-Sheng Shi, Sheng-Wei Chang, Yu-Ying Wu, Yu-Li Su, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2358572/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Apr, 2023 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Background Sarcopenia has been associated with conventional chemotherapy-related toxicity, postoperative complications and poor overall survival in patients with genotype-unselected metastatic colorectal cancer (mCRC). This study aimed to evaluate the prognostic implications of sarcopenia and its change after perioperative cetuximab plus doublet chemotherapy and hepatectomy in patients with RAS wild-type colorectal liver metastasis (CRLM). Methods Patients with CRLM from 2007 to 2018 in Chang Gung Research Database were retrospectively analyzed. Baseline characteristics as well as skeletal muscle index (SMI) at baseline and dynamic changes after interventions were collected. A multivariate Cox proportional hazard model was used to evaluate the effect of each parameter on overall survival (OS), and the Kaplan-Meier method was used to establish survival curves. A two-sided p value < 0.05 was considered statistically significance. Results Of 214 RAS wild-type mCRC patients who received both cetuximab and doublet chemotherapy, 77 who received upfront or subsequent hepatectomy were included in this study. The median follow-up time was 2.3 years. The rate of sarcopenia was higher in the patients who received neoadjuvant cetuximab-containing regimens than in those who received upfront hepatectomy (95% versus 63%, p = 0.001). Increased SMI after perioperative systemic therapy remained independently associated with better OS in multivariate analysis [hazard ratio (HR) = 0.88/10% increase, p = 0.013). The patients with sarcopenia had a trend of worse OS than those without sarcopenia (median OS: 4.5 versus 3.6 years, log-rank p = 0.282). Conclusions Improvement in sarcopenia ([SMI after intervention – initial SMI]/initial SMI x 100%) is an important prognostic factor for OS. Future research is warranted to investigate direct interventions for sarcopenia and the impact on OS. Biological sciences/Cancer Health sciences/Health care Health sciences/Risk factors Sarcopenia Colorectal liver metastasis Hepatectomy Cetuximab wild-type RAS Overall survival Figures Figure 1 Figure 2 Figure 3 Introduction Colorectal cancer (CRC) is the third most common cancer worldwide with the second highest mortality rate [ 1 , 2 ]. The overall survival (OS) of metastatic colorectal cancer (mCRC) has been extended from 21 months to 26–28 months after the addition of biologics to chemotherapy doublet [ 3 – 5 ]. The most common site of CRC metastasis is the liver, and surgical resection can further extend survival and is the only potential curative treatment for colorectal cancer with liver metastasis (CRLM).[ 6 , 7 ] Cetuximab, a monoclonal antibody targeting epidermal growth factor receptor (EGFR) signaling pathway, can improve the response rate, depth of response and conversion rate in patients with oncogene in the rat sarcoma virus (RAS) wild-type mCRC [ 8 , 9 ]. Sarcopenia is characterized by loss of skeletal muscle mass plus impaired muscle strength or physical performance [ 10 ], and it has been suggested to potentially be a poor prognostic factor for OS in both non-metastatic CRC and mCRC [ 11 – 17 ]. Higher postoperative complications, especially infectious complications, have been shown in CRC patients with sarcopenia [ 16 , 18 , 19 ]. In addition, sarcopenic patients are susceptible to the toxicity of chemotherapy, and higher rates of grade 3 and 4 toxicity, especially neutropenia, have been reported in patients with both non-metastatic CRC and mCRC [ 20 , 21 ]. A recent meta-analysis of studies with mostly conventional chemotherapy in RAS-unselected patients found that sarcopenia was associated with poorer OS in patients with CRLM after local therapy [ 22 ]. However, whether sarcopenia is a prognostic or predictive factor for RAS wild-type patients with CRLM undergoing liver resection and perioperative cetuximab-based treatment is largely unknown. Therefore, the aim of this retrospective study was to evaluate the prognostic and predictive roles of sarcopenia in mCRC and its treatment. Materials And Methods Data collection: This study was approved by the Ethics Committees of Chang Gung Memorial Hospital (CGMH-IRB No.201900703B0A3). Institutional Review Broad (IRB) approval was obtained, which included a waiver of individual patient consent. And the methods in this retrospective study were carried out in accordance with the approved guideline and regulation. Patients who were initially diagnosed with CRLM were identified from the Chang Gung Research Database (CGRD) [ 23 ]. Medical records were reviewed and patients who met the following criteria were enrolled: 1) CRLM with wild-type pan-RAS (including mutations of exon 2,3,4 in KRAS and NRAS), and 2) receiving cetuximab-containing regimens (FOLFOX/FOLFIRI) within 180 days after diagnosis and hepatic metastasectomy, including either upfront or subsequent hepatectomy. Patients without complete staging information, including abdominal and chest computed tomography and colonoscopy were excluded. Those without pathologic evidence of colorectal adenocarcinoma were also excluded. The included patients were arbitrarily divided into two groups: those who received neoadjuvant cetuximab plus doublet chemotherapy (CT) followed by hepatic (H) metastasectomy (CT-H group, n = 45), and those who received upfront hepatic metastasectomy followed by cetuximab plus doublet chemotherapy (H-CT group, n = 32). The patients’ demographic data were collected including sex and age (< 60 years or ≥ 60 years). Laboratory data at the initial diagnosis, including CEA (< 20 ng/ml or ≥ 20 ng/ml) and albumin (< 3.5 g/dl or ≥ 3.5 g/dl) were also recorded. Computed tomography taken within 3 months of the initial diagnosis was used to evaluate baseline skeletal muscle area (SMA). Corresponding follow-up images were collected at around 3 months after cetuximab plus doublet chemotherapy or hepatic metastasectomy to compare changes in muscle mass. Diagnosis of sarcopenia: measurement of muscle mass Two consecutive computed tomographic cross-sectional images extending from L3 to the iliac crest were used to measure SMA. A Hounsfield unit (HU) between − 29 and + 150 was identified as skeletal muscle [ 24 ]. Cross-sectional areas of all skeletal muscles, including the psoas muscle, abdominal wall muscles (rectus abdominus, internal and external obliques and transversus abdominus), and paraspinal muscles (erector spinae and quadratus lumborum) were summed. L3 skeletal muscle index (SMI) was calculated as all SMA/height (cm2/m2), and the cut-off point for sarcopenia was defined according to Prado’s study (38.5 cm2/m2 for females and 52.4 cm2/m2 for males) [ 24 ]. The change in SMI was defined as (SMI after intervention – initial SMI)/initial SMI x 100%. Statistical analysis Pearson’s chi-square test was used to compare differences between the two groups (H-CT group and CT-H group). OS was calculated from the date of initial diagnosis of CRLM to the date of death or loss of follow-up, whichever occurred first. The Kaplan-Meier method was used to establish survival curves, and the log-rank test was used to compare different curves. A multivariate Cox proportional hazard model was used to evaluate the effect of each parameter on OS. We considered a two-sided p value < 0.05 as statistically significance. All analyses were conducted using SAS version 9.4 (SAS Institute, Cary, NC, USA). Results A total of 3,880 patients who were initially diagnosed with colorectal cancer and liver metastasis between January 2007 and January 2018 were identified in the CGRD (Fig. 1 ). Frontline cetuximab was not reimbursed by the Taiwan National Health Insurance program until December 2012. Of the 3,880 patients, 214 had wild-type RAS and received both cetuximab and doublet chemotherapy in a perioperative setting. Among these patients, 77 received hepatic metastasectomy. There were 45 and 32 patients in the CT-H and H-CT groups, respectively, of whom 40 and 27 had baseline and follow-up images. Baseline Characteristics The demographics of the included patients are shown in Table 1 . The baseline characteristics of the CT-H and H-CT groups were similar in sex, age, tumor sidedness, serum albumin and serum CEA, except for sarcopenia. Patients in the CT-H group had a significantly higher rate of sarcopenia (CT-H versus H-CT group: 95% versus 63%, p = 0.001). Table 1 Clinical characteristics of CT-H and H-CT patients Variables All CT-H H-CT p-value n % n % n % Total 77 45 32 Sex 0.389 Female 27 35.1 14 31.1 13 40.6 Male 50 64.9 31 68.9 19 59.4 Age, years 0.082 <60 45 58.4 30 66.7 15 46.9 ≥60 32 41.6 15 33.7 17 53.1 Sidedness of colon 0.422 Left 46 59.7 25 55.6 21 65.6 Right 8 10.4 4 8.9 7 21.9 Rectal 23 29.9 16 35.6 4 12.5 Albumin, g/dl 0.855 <3.5 43 61.4 28 62.2 15 60.0 ≥3.5 27 38.6 17 37.8 10 40.0 CEA, ng/ml 0.887 <20 49 73.1 29 72.5 20 74.1 ≥ 20 18 26.9 11 27.5 7 25.9 Sarcopenia 0.001 No 12 17.9 2 5.0 10 37.0 Yes 55 82.1 38 95.0 17 63.0 Mean SD Mean SD Mean SD SMI change after CT, % -1.3 16.0 -1.7 17.3 -0.7 14.3 0.803 SMI change after OP, % -5.4 17.2 -3.5 17.7 -14.8 11.4 0.094 The mean changes in SMI in the CT-H and H-CT groups after cetuximab plus doublet chemotherapy were − 1.7% and − 0.7%, respectively (p = 0.803), and the mean changes after hepatectomy were − 3.5% and − 14.8%, respectively (p = 0.094). Prognostic Factors for Overall Survival The median OS of the patients was 3.7 years, with a median follow-up of 2.3 years (Fig. 2 A). In univariate analysis of OS, tumor sidedness [left-sided and rectum versus right-sided cancer] (p = 0.009 and p = 0.048, respectively), and the changes in SMI after chemotherapy (HR: 0.72 per 10-unit increase in SMI, p = 0.027) and hepatectomy (HR: 0.72 per 10-unit increase of SMI, p = 0.028) were significant prognostic factors. In multivariate Cox proportional hazard analysis, improvement in SMI after chemotherapy remained the only significant prognostic factor for OS (HR: 0.88, p = 0.013) (Table 2 ). Table 2 Univariate and Multivariate analysis of prognostic Factors for Overall Survival Variables Crude HR p-value adjusted HR p-value HR 95% CI HR 95% CI Gender Female Ref. Ref. Male 1.25 (0.58–2.69) 0.574 1.18 (0.18–7.88) 0.866 Age, years <60 Ref. Ref. ≥60 0.66 (0.31–1.41) 0.282 0.64 (0.11–3.70) 0.622 Sidedness of tumor Left-sided colon 0.28 (0.11–0.73) 0.009 0.06 (0.01–1.06) 0.054 Right-sided colon Ref. Ref. Rectal 0.33 (0.11–0.99) 0.048 0.70 (0.05–9.46) 0.789 Albumin, g/dl <3.5 Ref. Ref. ≥3.5 1.00 (0.47–2.14) 0.998 0.38 (0.07–2.06) 0.263 CEA, ng/ml <20 Ref. Ref. ≥ 20 0.98 (0.41–2.38) 0.967 1.58 (0.21–11.8) 0.654 Sarcopenia No Ref. Ref. Yes 1.92 (0.57–6.44) 0.293 3.48 (0.26–47.2) 0.349 Treatment CT-H 0.78 (0.37–1.62) 0.505 0.35 (0.05–2.32) 0.274 H-CT Ref. Ref. SMI change after CT * 0.72 (0.53–0.96) 0.027 0.88 (0.79–0.97) 0.013 SMI change after OP * 0.72 (0.54–0.97) 0.028 1.04 (0.98–1.12) 0.226 * HRs were calculated by per 10 percent increase of SMI The OS rates of the patients with left-sided colon and rectal cancers were better than that of the patients with right-sided cancers (median OS: 4 and 2.9 years versus 1.5 years, log-rank p = 0.022) (Fig. 2 B). There was no significant difference in OS between the CT-H and H-CT groups (log-rank p = 0.508) (Fig. 2 C). There was a trend of better OS in the patients without sarcopenia (4.5 versus 3.6 years, log-rank p = 0.282) (Fig. 3 A). The magnitude of change in SMI was positively correlated with OS (Fig. 3 B and 3 C). Discussion To the best of our knowledge, this is the first study to show a positive correlation between increased OS and SMI after perioperative treatment with a cetuximab-containing regimen in patients with RAS wild-type CRLM. A previous study reported an independent association between losing more than 9% of skeletal muscle per 3 months during palliative chemotherapy with poor OS. However, none of the enrolled patients received a cetuximab-containing regimen, and RAS mutation status was not reported [ 15 ]. While both cetuximab combined with doublet chemotherapy and hepatic metastasectomy can improve the outcomes of mCRC, we focused on the prognostic implications of sarcopenia and its change after treatment in this study. Our results showed that change in sarcopenia was a strong prognostic factor for OS in patients with RAS wild-type CRLM. The operational definitions of sarcopenia are inconsistent across international working groups, but they are characterized by loss of muscle mass, muscle strength and performance [ 25 – 29 ]. Measuring the total muscle area around the third lumber vertebrae (L3) using computed tomography can strongly predict the ratio of whole-body fat to fat-free mass, and it has become a very convenient tool to evaluate secondary sarcopenia in patients with colorectal cancer [ 30 ]. The widely used cut-off point of skeletal mass loss in sarcopenia is according to Prado’s study (38.5 cm2/m2 for females and 52.4 cm2/m2 for males) [ 24 ]. The prevalence of sarcopenia in a recent meta-analysis of trials with heterogenous definitions of sarcopenia varied greatly in patients with CRLM ranging from 17–65% [ 22 ], due in part to different cut-off points. In the present study, approximately 82% of the patients had sarcopenia, and surprisingly the prevalence of sarcopenia was higher in the CT-H group than in the H-CT group (95% versus 63%, p = 0.001). This could be partially because those who received upfront cetuximab-containing systemic treatment had more severe initial involvement of the liver, which could cause physiologic derangements such as anorexia, organ dysfunction and decreased activity [ 10 ]. In addition, previous studies have suggested that CRLM is associated with an altered microenvironment with high levels of inflammatory cytokines such as TNF-alpha and IL-6, which could subsequently promote sarcopenia [ 31 , 32 ]. Previous studies have suggested that sarcopenia is a poor prognostic factor for OS in both non-metastatic CRC and mCRC [ 11 – 14 ]. However, the correlation between sarcopenia and OS is inconclusive in patients undergoing liver resection for CRLM. A recent meta-analysis concluded that sarcopenia is associated with a poorer OS based on trials including mostly RAS-unselected patients receiving conventional chemotherapy without the current widely used biologics [ 22 ]. Thus, whether this conclusion can be applied to patients with wild-type RAS receiving cetuximab is unknown. In the present study, the patients with sarcopenia had a trend of poorer OS compared to those without sarcopenia (median OS: 3.6 years versus 4.5 years, log-rank p = 0.282), and the difference (> 10 months) is of clinical significance. In addition, all eight patients with right-sided tumors had sarcopenia, which may have diluted the effect in multivariate analysis since sidedness has been reported to be an important prognostic factor in these patients [ 33 ]. Limitations This study has several limitations. First, this was a retrospective study with relatively small number of patients. However, we enrolled patients receiving both perioperative cetuximab-based doublet chemotherapy and hepatectomy, which are considered to be important prognostic factors for OS in modern real-world practice. Second, sarcopenia was evaluated only by skeletal muscle mass without performance status or strength. We used the widely accepted criteria for sarcopenia, and showed a higher prevalence in patients with more severe involvement of liver metastasis. Third, there was an association between an improvement in sarcopenia and better OS, however it is not clear whether interventions for sarcopenia can impact survival itself. Conclusion Improvement in sarcopenia after perioperative treatment with a cetuximab-containing regimen is an important prognostic factor for OS in patients with RAS wild-type CRLM after hepatectomy. Future research is warranted to investigate direct interventions for sarcopenia and the impact on OS. Declarations Acknowledgements None. Authors contributions Yao-Ren Yang and Chung-Sheng Shi designed and analyzed the study, and wrote the manuscript. Sheng-Wei Chang, Yu-Ying Wu and Yu-Li Su provided data curation and resources. Geng-ping Lin provided Formal analysis. Feng-Che Kuan provided supervision, project administration, manuscript editing. Corresponding author Correspondence to Feng-Che Kuan Data and code availability Data and codes can be provided by the corresponding author upon reasonable request Conflict of interest All authors declare that they have no conflict of interest References Sawicki, T., et al., A Review of Colorectal Cancer in Terms of Epidemiology, Risk Factors, Development, Symptoms and Diagnosis. Cancers (Basel), 2021. 13 (9). Bray, F., et al., Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018. 68 (6): p. 394-424. Aparicio, J., et al., Metastatic Colorectal Cancer. First Line Therapy for Unresectable Disease. J Clin Med, 2020. 9 (12). Tournigand, C., et al., FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol, 2004. 22 (2): p. 229-37. 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Cite Share Download PDF Status: Published Journal Publication published 27 Apr, 2023 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Major revision 22 Jan, 2023 Reviews received at journal 22 Jan, 2023 Reviewers agreed at journal 16 Jan, 2023 Reviews received at journal 11 Jan, 2023 Reviewers agreed at journal 09 Jan, 2023 Reviewers invited by journal 04 Jan, 2023 Editor assigned by journal 04 Jan, 2023 Editor invited by journal 15 Dec, 2022 Submission checks completed at journal 15 Dec, 2022 First submitted to journal 08 Dec, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-2358572\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Article\",\"associatedPublications\":[],\"authors\":[{\"id\":160328209,\"identity\":\"78a9b028-6c91-4881-98c6-2931d0f3fda1\",\"order_by\":0,\"name\":\"Yao-Ren Yang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Chang-Gung Memorial Hospital\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yao-Ren\",\"middleName\":\"\",\"lastName\":\"Yang\",\"suffix\":\"\"},{\"id\":160328210,\"identity\":\"d707899f-81c7-4e7f-a604-7354311cb49e\",\"order_by\":1,\"name\":\"Chung-Sheng Shi\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Chang Gung Memorial Hospital Chiayi Branch\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Chung-Sheng\",\"middleName\":\"\",\"lastName\":\"Shi\",\"suffix\":\"\"},{\"id\":160328211,\"identity\":\"b4736881-9020-47f6-88dd-cc922159d9b8\",\"order_by\":2,\"name\":\"Sheng-Wei Chang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Chang Gung Memorial Hospital\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Sheng-Wei\",\"middleName\":\"\",\"lastName\":\"Chang\",\"suffix\":\"\"},{\"id\":160328212,\"identity\":\"41718dbf-0b02-494e-9613-392c73f35a9b\",\"order_by\":3,\"name\":\"Yu-Ying Wu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Chang-Gung Memorial Hospital\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yu-Ying\",\"middleName\":\"\",\"lastName\":\"Wu\",\"suffix\":\"\"},{\"id\":160328213,\"identity\":\"7bd05444-766e-482a-9fb7-4d630040e2af\",\"order_by\":4,\"name\":\"Yu-Li Su\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Kaohsiung Chang Gung Memorial Hospital, Chang Gung University\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yu-Li\",\"middleName\":\"\",\"lastName\":\"Su\",\"suffix\":\"\"},{\"id\":160328214,\"identity\":\"14a398ed-38e2-4238-befb-acbebbf63446\",\"order_by\":5,\"name\":\"Geng-ping Lin\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Chang Gung Memorial Hospital, Chang Gung University\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Geng-ping\",\"middleName\":\"\",\"lastName\":\"Lin\",\"suffix\":\"\"},{\"id\":160328215,\"identity\":\"758ea3d8-3e01-4e6e-a4cc-7e98080ea430\",\"order_by\":6,\"name\":\"Feng-Che Kuan\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6ElEQVRIiWNgGAWjYBACfvbGxgcJFTZyQDYbcVokew4fNvhwJs0YoYWQToMbaWmSM9sOJzYQrUVyRo6BNA/b4fT+/tVpDxgq7tk1yPcY4NXCz/PGwJiHJz13xo232w0YzhQnN7Dx4Nci2Z5jkMwjYZ27QeLsNgnGtoRkBjbeDfj9ciDH4DCPAXO6AfFaTqQlNs5IcE4w4O8Fa7EjqAUUyAwfDqQZzrjBu00i4UxCAhtb/ge8WoBR2f4j8Z+NPH8/0GEfKhLs+ZmPJeDVggASQIVAlNhGpHqQfQfAlD3xOkbBKBgFo2CkAACJykiPX+xnKwAAAABJRU5ErkJggg==\",\"orcid\":\"\",\"institution\":\"Chang-Gung Memorial Hospital\",\"correspondingAuthor\":true,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Feng-Che\",\"middleName\":\"\",\"lastName\":\"Kuan\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2022-12-08 15:29:18\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-2358572/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-2358572/v1\",\"draftVersion\":[],\"editorialEvents\":[{\"content\":\"https://doi.org/10.1038/s41598-023-33439-x\",\"type\":\"published\",\"date\":\"2023-04-27T20:38:20+00:00\"}],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":30530613,\"identity\":\"f4c312c6-4baa-4058-ba70-629215e32577\",\"added_by\":\"auto\",\"created_at\":\"2022-12-19 18:17:03\",\"extension\":\"jpeg\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":195515,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eStep-wise inclusion process\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage1.jpeg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-2358572/v1/ee48c7b54e69b327f20230e5.jpeg\"},{\"id\":30530612,\"identity\":\"b7c050a4-7b46-4f78-8da3-eef27813b221\",\"added_by\":\"auto\",\"created_at\":\"2022-12-19 18:17:03\",\"extension\":\"jpeg\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":81648,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eA) Median survival time for all patients: 3.7 years. B) Median survival time for the patients with left-sided tumors: 4 years; rectal tumors: 2.9 years; right-sided tumors: 1.5 years; C) Median survival time for the CT-H group: 3.7 years and H-CT group: 4.0 years.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage2.jpeg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-2358572/v1/8113a45a4f72fd010be52371.jpeg\"},{\"id\":30530611,\"identity\":\"c3e25da9-48f7-4ef2-b54c-ca2c90b3706a\",\"added_by\":\"auto\",\"created_at\":\"2022-12-19 18:17:03\",\"extension\":\"png\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":74941,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eA) Median survival time of the patients with sarcopenia: 3.6 years: without sarcopenia: 4.5 years; B) Probability of death by percentage change in SMI after chemotherapy; C) Probability of death by percentage change in SMI after hepatectomy.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage3.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-2358572/v1/8af092c80a5c4ee4626a1b4b.png\"},{\"id\":44727839,\"identity\":\"1ef3e865-b29b-4a51-aaa9-5d287a6b862d\",\"added_by\":\"auto\",\"created_at\":\"2023-10-16 20:56:07\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":578887,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-2358572/v1/c010b122-4d05-458e-854c-c0707d1e56d8.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"The Impact of Sarcopenia on Overall Survival in Patients with Pan-RAS Wild-type Colorectal Liver Metastasis Receiving Hepatectomy\",\"fulltext\":[{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003eColorectal cancer (CRC) is the third most common cancer worldwide with the second highest mortality rate [\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e]. The overall survival (OS) of metastatic colorectal cancer (mCRC) has been extended from 21 months to 26\\u0026ndash;28 months after the addition of biologics to chemotherapy doublet [\\u003cspan additionalcitationids=\\\"CR4\\\" citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e]. The most common site of CRC metastasis is the liver, and surgical resection can further extend survival and is the only potential curative treatment for colorectal cancer with liver metastasis (CRLM).[\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e] Cetuximab, a monoclonal antibody targeting epidermal growth factor receptor (EGFR) signaling pathway, can improve the response rate, depth of response and conversion rate in patients with oncogene in the rat sarcoma virus (RAS) wild-type mCRC [\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eSarcopenia is characterized by loss of skeletal muscle mass plus impaired muscle strength or physical performance [\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e], and it has been suggested to potentially be a poor prognostic factor for OS in both non-metastatic CRC and mCRC [\\u003cspan additionalcitationids=\\\"CR12 CR13 CR14 CR15 CR16\\\" citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e]. Higher postoperative complications, especially infectious complications, have been shown in CRC patients with sarcopenia [\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e]. In addition, sarcopenic patients are susceptible to the toxicity of chemotherapy, and higher rates of grade 3 and 4 toxicity, especially neutropenia, have been reported in patients with both non-metastatic CRC and mCRC [\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e]. A recent meta-analysis of studies with mostly conventional chemotherapy in RAS-unselected patients found that sarcopenia was associated with poorer OS in patients with CRLM after local therapy [\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eHowever, whether sarcopenia is a prognostic or predictive factor for RAS wild-type patients with CRLM undergoing liver resection and perioperative cetuximab-based treatment is largely unknown. Therefore, the aim of this retrospective study was to evaluate the prognostic and predictive roles of sarcopenia in mCRC and its treatment.\\u003c/p\\u003e\"},{\"header\":\"Materials And Methods\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eData collection:\\u003c/h2\\u003e \\u003cp\\u003e This study was approved by the Ethics Committees of Chang Gung Memorial Hospital (CGMH-IRB No.201900703B0A3). Institutional Review Broad (IRB) approval was obtained, which included a waiver of individual patient consent. And the methods in this retrospective study were carried out in accordance with the approved guideline and regulation.\\u003c/p\\u003e \\u003cp\\u003ePatients who were initially diagnosed with CRLM were identified from the Chang Gung Research Database (CGRD) [\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e]. Medical records were reviewed and patients who met the following criteria were enrolled: 1) CRLM with wild-type pan-RAS (including mutations of exon 2,3,4 in KRAS and NRAS), and 2) receiving cetuximab-containing regimens (FOLFOX/FOLFIRI) within 180 days after diagnosis and hepatic metastasectomy, including either upfront or subsequent hepatectomy. Patients without complete staging information, including abdominal and chest computed tomography and colonoscopy were excluded. Those without pathologic evidence of colorectal adenocarcinoma were also excluded. The included patients were arbitrarily divided into two groups: those who received neoadjuvant cetuximab plus doublet chemotherapy (CT) followed by hepatic (H) metastasectomy (CT-H group, n\\u0026thinsp;=\\u0026thinsp;45), and those who received upfront hepatic metastasectomy followed by cetuximab plus doublet chemotherapy (H-CT group, n\\u0026thinsp;=\\u0026thinsp;32).\\u003c/p\\u003e \\u003cp\\u003eThe patients\\u0026rsquo; demographic data were collected including sex and age (\\u0026lt;\\u0026thinsp;60 years or \\u0026ge;\\u0026thinsp;60 years). Laboratory data at the initial diagnosis, including CEA (\\u0026lt;\\u0026thinsp;20 ng/ml or \\u0026ge;\\u0026thinsp;20 ng/ml) and albumin (\\u0026lt;\\u0026thinsp;3.5 g/dl or \\u0026ge;\\u0026thinsp;3.5 g/dl) were also recorded. Computed tomography taken within 3 months of the initial diagnosis was used to evaluate baseline skeletal muscle area (SMA). Corresponding follow-up images were collected at around 3 months after cetuximab plus doublet chemotherapy or hepatic metastasectomy to compare changes in muscle mass.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec4\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eDiagnosis of sarcopenia: measurement of muscle mass\\u003c/h2\\u003e \\u003cp\\u003eTwo consecutive computed tomographic cross-sectional images extending from L3 to the iliac crest were used to measure SMA. A Hounsfield unit (HU) between \\u0026minus;\\u0026thinsp;29 and +\\u0026thinsp;150 was identified as skeletal muscle [\\u003cspan citationid=\\\"CR24\\\" class=\\\"CitationRef\\\"\\u003e24\\u003c/span\\u003e]. Cross-sectional areas of all skeletal muscles, including the psoas muscle, abdominal wall muscles (rectus abdominus, internal and external obliques and transversus abdominus), and paraspinal muscles (erector spinae and quadratus lumborum) were summed. L3 skeletal muscle index (SMI) was calculated as all SMA/height (cm2/m2), and the cut-off point for sarcopenia was defined according to Prado\\u0026rsquo;s study (38.5 cm2/m2 for females and 52.4 cm2/m2 for males) [\\u003cspan citationid=\\\"CR24\\\" class=\\\"CitationRef\\\"\\u003e24\\u003c/span\\u003e]. The change in SMI was defined as (SMI after intervention \\u0026ndash; initial SMI)/initial SMI x 100%.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec5\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStatistical analysis\\u003c/h2\\u003e \\u003cp\\u003ePearson\\u0026rsquo;s chi-square test was used to compare differences between the two groups (H-CT group and CT-H group). OS was calculated from the date of initial diagnosis of CRLM to the date of death or loss of follow-up, whichever occurred first. The Kaplan-Meier method was used to establish survival curves, and the log-rank test was used to compare different curves. A multivariate Cox proportional hazard model was used to evaluate the effect of each parameter on OS. We considered a two-sided p value\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05 as statistically significance. All analyses were conducted using SAS version 9.4 (SAS Institute, Cary, NC, USA).\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cp\\u003eA total of 3,880 patients who were initially diagnosed with colorectal cancer and liver metastasis between January 2007 and January 2018 were identified in the CGRD (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). Frontline cetuximab was not reimbursed by the Taiwan National Health Insurance program until December 2012. Of the 3,880 patients, 214 had wild-type RAS and received both cetuximab and doublet chemotherapy in a perioperative setting. Among these patients, 77 received hepatic metastasectomy. There were 45 and 32 patients in the CT-H and H-CT groups, respectively, of whom 40 and 27 had baseline and follow-up images.\\u003c/p\\u003e \\u003cdiv id=\\\"Sec7\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eBaseline Characteristics\\u003c/h2\\u003e \\u003cp\\u003eThe demographics of the included patients are shown in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e. The baseline characteristics of the CT-H and H-CT groups were similar in sex, age, tumor sidedness, serum albumin and serum CEA, except for sarcopenia. Patients in the CT-H group had a significantly higher rate of sarcopenia (CT-H versus H-CT group: 95% versus 63%, p\\u0026thinsp;=\\u0026thinsp;0.001).\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eClinical characteristics of CT-H and H-CT patients\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"8\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" 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\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e0.389\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eFemale\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e27\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e35.1\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e14\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e31.1\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e13\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e40.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMale\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e50\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e64.9\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e31\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e68.9\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e19\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e59.4\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAge, years\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e0.082\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u0026lt;60\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e45\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e58.4\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e30\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e66.7\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e15\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e46.9\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u0026ge;60\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e32\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e41.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e15\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e33.7\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e17\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e53.1\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSidedness of colon\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e0.422\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eLeft\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e46\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e59.7\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e25\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e55.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e21\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e65.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eRight\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e8\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e10.4\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e4\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e8.9\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e7\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e21.9\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eRectal\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e23\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e29.9\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e16\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e35.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e4\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e12.5\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAlbumin, g/dl\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e0.855\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u0026lt;3.5\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e43\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e61.4\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e28\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e62.2\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e15\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e60.0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u0026ge;3.5\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e27\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e38.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e17\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e37.8\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e10\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e40.0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCEA, ng/ml\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e0.887\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u0026lt;20\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e49\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e73.1\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e29\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e72.5\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e20\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e74.1\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u0026ge; 20\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e18\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e26.9\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e11\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e27.5\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e7\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e25.9\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSarcopenia\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e0.001\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNo\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e12\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e17.9\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e2\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e5.0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e10\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e37.0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eYes\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e55\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e82.1\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e38\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e95.0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e17\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e63.0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eMean\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eSD\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eMean\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eSD\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003eMean\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003eSD\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSMI change after CT, %\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e-1.3\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e16.0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e-1.7\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e17.3\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e-0.7\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e14.3\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e0.803\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSMI change after OP, %\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e-5.4\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e17.2\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e-3.5\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e17.7\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e-14.8\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e11.4\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e0.094\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003eThe mean changes in SMI in the CT-H and H-CT groups after cetuximab plus doublet chemotherapy were \\u0026minus;\\u0026thinsp;1.7% and \\u0026minus;\\u0026thinsp;0.7%, respectively (p\\u0026thinsp;=\\u0026thinsp;0.803), and the mean changes after hepatectomy were \\u0026minus;\\u0026thinsp;3.5% and \\u0026minus;\\u0026thinsp;14.8%, respectively (p\\u0026thinsp;=\\u0026thinsp;0.094).\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec8\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003ePrognostic Factors for Overall Survival\\u003c/h2\\u003e \\u003cp\\u003eThe median OS of the patients was 3.7 years, with a median follow-up of 2.3 years (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003eA). In univariate analysis of OS, tumor sidedness [left-sided and rectum versus right-sided cancer] (p\\u0026thinsp;=\\u0026thinsp;0.009 and p\\u0026thinsp;=\\u0026thinsp;0.048, respectively), and the changes in SMI after chemotherapy (HR: 0.72 per 10-unit increase in SMI, p\\u0026thinsp;=\\u0026thinsp;0.027) and hepatectomy (HR: 0.72 per 10-unit increase of SMI, p\\u0026thinsp;=\\u0026thinsp;0.028) were significant prognostic factors. In multivariate Cox proportional hazard analysis, improvement in SMI after chemotherapy remained the only significant prognostic factor for OS (HR: 0.88, p\\u0026thinsp;=\\u0026thinsp;0.013) (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab2\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 2\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eUnivariate and Multivariate analysis of prognostic Factors for Overall Survival\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"7\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c6\\\" colnum=\\\"6\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c7\\\" colnum=\\\"7\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003eVariables\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003eCrude HR\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003ep-value\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c6\\\" namest=\\\"c5\\\"\\u003e \\u003cp\\u003eadjusted HR\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c7\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003ep-value\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eHR\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e95% CI\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eHR\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e95% CI\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eGender\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eFemale\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eRef.\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eRef.\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMale\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.25\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e(0.58\\u0026ndash;2.69)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.574\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.18\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e(0.18\\u0026ndash;7.88)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e0.866\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAge, years\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u0026lt;60\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eRef.\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eRef.\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u0026ge;60\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.66\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e(0.31\\u0026ndash;1.41)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.282\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.64\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e(0.11\\u0026ndash;3.70)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e0.622\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSidedness of tumor\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eLeft-sided colon\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.28\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e(0.11\\u0026ndash;0.73)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.009\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.06\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e(0.01\\u0026ndash;1.06)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e0.054\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eRight-sided colon\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eRef.\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eRef.\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eRectal\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.33\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e(0.11\\u0026ndash;0.99)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.048\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.70\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e(0.05\\u0026ndash;9.46)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e0.789\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAlbumin, g/dl\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u0026lt;3.5\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eRef.\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eRef.\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u0026ge;3.5\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e(0.47\\u0026ndash;2.14)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.998\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.38\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e(0.07\\u0026ndash;2.06)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e0.263\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCEA, ng/ml\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u0026lt;20\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eRef.\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eRef.\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u0026ge; 20\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.98\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e(0.41\\u0026ndash;2.38)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.967\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.58\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e(0.21\\u0026ndash;11.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e0.654\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSarcopenia\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNo\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eRef.\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eRef.\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eYes\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.92\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e(0.57\\u0026ndash;6.44)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.293\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e3.48\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e(0.26\\u0026ndash;47.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e0.349\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eTreatment\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCT-H\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.78\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e(0.37\\u0026ndash;1.62)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.505\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.35\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e(0.05\\u0026ndash;2.32)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e0.274\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eH-CT\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eRef.\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eRef.\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSMI change after CT\\u003csup\\u003e*\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.72\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e(0.53\\u0026ndash;0.96)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.027\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.88\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e(0.79\\u0026ndash;0.97)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e0.013\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSMI change after OP\\u003csup\\u003e*\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.72\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e(0.54\\u0026ndash;0.97)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.028\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.04\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e(0.98\\u0026ndash;1.12)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e0.226\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"7\\\" nameend=\\\"c7\\\" namest=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003csup\\u003e*\\u003c/sup\\u003e HRs were calculated by per 10 percent increase of SMI\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003eThe OS rates of the patients with left-sided colon and rectal cancers were better than that of the patients with right-sided cancers (median OS: 4 and 2.9 years versus 1.5 years, log-rank p\\u0026thinsp;=\\u0026thinsp;0.022) (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003eB). There was no significant difference in OS between the CT-H and H-CT groups (log-rank p\\u0026thinsp;=\\u0026thinsp;0.508) (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003eC). There was a trend of better OS in the patients without sarcopenia (4.5 versus 3.6 years, log-rank p\\u0026thinsp;=\\u0026thinsp;0.282) (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003eA). The magnitude of change in SMI was positively correlated with OS (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003eB and \\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003eC).\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eTo the best of our knowledge, this is the first study to show a positive correlation between increased OS and SMI after perioperative treatment with a cetuximab-containing regimen in patients with RAS wild-type CRLM. A previous study reported an independent association between losing more than 9% of skeletal muscle per 3 months during palliative chemotherapy with poor OS. However, none of the enrolled patients received a cetuximab-containing regimen, and RAS mutation status was not reported [\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e]. While both cetuximab combined with doublet chemotherapy and hepatic metastasectomy can improve the outcomes of mCRC, we focused on the prognostic implications of sarcopenia and its change after treatment in this study. Our results showed that change in sarcopenia was a strong prognostic factor for OS in patients with RAS wild-type CRLM.\\u003c/p\\u003e \\u003cp\\u003eThe operational definitions of sarcopenia are inconsistent across international working groups, but they are characterized by loss of muscle mass, muscle strength and performance [\\u003cspan additionalcitationids=\\\"CR26 CR27 CR28\\\" citationid=\\\"CR25\\\" class=\\\"CitationRef\\\"\\u003e25\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR29\\\" class=\\\"CitationRef\\\"\\u003e29\\u003c/span\\u003e]. Measuring the total muscle area around the third lumber vertebrae (L3) using computed tomography can strongly predict the ratio of whole-body fat to fat-free mass, and it has become a very convenient tool to evaluate secondary sarcopenia in patients with colorectal cancer [\\u003cspan citationid=\\\"CR30\\\" class=\\\"CitationRef\\\"\\u003e30\\u003c/span\\u003e]. The widely used cut-off point of skeletal mass loss in sarcopenia is according to Prado\\u0026rsquo;s study (38.5 cm2/m2 for females and 52.4 cm2/m2 for males) [\\u003cspan citationid=\\\"CR24\\\" class=\\\"CitationRef\\\"\\u003e24\\u003c/span\\u003e]. The prevalence of sarcopenia in a recent meta-analysis of trials with heterogenous definitions of sarcopenia varied greatly in patients with CRLM ranging from 17\\u0026ndash;65% [\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e], due in part to different cut-off points. In the present study, approximately 82% of the patients had sarcopenia, and surprisingly the prevalence of sarcopenia was higher in the CT-H group than in the H-CT group (95% versus 63%, p\\u0026thinsp;=\\u0026thinsp;0.001). This could be partially because those who received upfront cetuximab-containing systemic treatment had more severe initial involvement of the liver, which could cause physiologic derangements such as anorexia, organ dysfunction and decreased activity [\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e]. In addition, previous studies have suggested that CRLM is associated with an altered microenvironment with high levels of inflammatory cytokines such as TNF-alpha and IL-6, which could subsequently promote sarcopenia [\\u003cspan citationid=\\\"CR31\\\" class=\\\"CitationRef\\\"\\u003e31\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR32\\\" class=\\\"CitationRef\\\"\\u003e32\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003ePrevious studies have suggested that sarcopenia is a poor prognostic factor for OS in both non-metastatic CRC and mCRC [\\u003cspan additionalcitationids=\\\"CR12 CR13\\\" citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e]. However, the correlation between sarcopenia and OS is inconclusive in patients undergoing liver resection for CRLM. A recent meta-analysis concluded that sarcopenia is associated with a poorer OS based on trials including mostly RAS-unselected patients receiving conventional chemotherapy without the current widely used biologics [\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e]. Thus, whether this conclusion can be applied to patients with wild-type RAS receiving cetuximab is unknown. In the present study, the patients with sarcopenia had a trend of poorer OS compared to those without sarcopenia (median OS: 3.6 years versus 4.5 years, log-rank p\\u0026thinsp;=\\u0026thinsp;0.282), and the difference (\\u0026gt;\\u0026thinsp;10 months) is of clinical significance. In addition, all eight patients with right-sided tumors had sarcopenia, which may have diluted the effect in multivariate analysis since sidedness has been reported to be an important prognostic factor in these patients [\\u003cspan citationid=\\\"CR33\\\" class=\\\"CitationRef\\\"\\u003e33\\u003c/span\\u003e].\\u003c/p\\u003e\"},{\"header\":\"Limitations\",\"content\":\"\\u003cp\\u003eThis study has several limitations. First, this was a retrospective study with relatively small number of patients. However, we enrolled patients receiving both perioperative cetuximab-based doublet chemotherapy and hepatectomy, which are considered to be important prognostic factors for OS in modern real-world practice. Second, sarcopenia was evaluated only by skeletal muscle mass without performance status or strength. We used the widely accepted criteria for sarcopenia, and showed a higher prevalence in patients with more severe involvement of liver metastasis. Third, there was an association between an improvement in sarcopenia and better OS, however it is not clear whether interventions for sarcopenia can impact survival itself.\\u003c/p\\u003e\"},{\"header\":\"Conclusion\",\"content\":\"\\u003cp\\u003eImprovement in sarcopenia after perioperative treatment with a cetuximab-containing regimen is an important prognostic factor for OS in patients with RAS wild-type CRLM after hepatectomy. Future research is warranted to investigate direct interventions for sarcopenia and the impact on OS.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgements\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNone.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthors contributions\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eYao-Ren Yang and Chung-Sheng Shi designed and analyzed the study, and wrote the manuscript. Sheng-Wei Chang, Yu-Ying Wu and Yu-Li Su provided data curation and resources. Geng-ping Lin provided Formal analysis. Feng-Che Kuan provided supervision, project administration, manuscript editing.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCorresponding author\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eCorrespondence to Feng-Che Kuan\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eData and code availability\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eData and codes can be provided by the corresponding author upon reasonable request\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConflict of interest\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAll authors declare that they have no conflict of interest\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eSawicki, T., et al., A Review of Colorectal Cancer in Terms of Epidemiology, Risk Factors, Development, Symptoms and Diagnosis. Cancers (Basel), 2021. \\u003cstrong\\u003e13\\u003c/strong\\u003e(9).\\u003c/li\\u003e\\n\\u003cli\\u003eBray, F., et al., Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018. \\u003cstrong\\u003e68\\u003c/strong\\u003e(6): p. 394-424.\\u003c/li\\u003e\\n\\u003cli\\u003eAparicio, J., et al., Metastatic Colorectal Cancer. First Line Therapy for Unresectable Disease. J Clin Med, 2020. \\u003cstrong\\u003e9\\u003c/strong\\u003e(12).\\u003c/li\\u003e\\n\\u003cli\\u003eTournigand, C., et al., FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol, 2004. \\u003cstrong\\u003e22\\u003c/strong\\u003e(2): p. 229-37.\\u003c/li\\u003e\\n\\u003cli\\u003eLenz, H.J., et al., Impact of Consensus Molecular Subtype on Survival in Patients With Metastatic Colorectal Cancer: Results From CALGB/SWOG 80405 (Alliance). J Clin Oncol, 2019. \\u003cstrong\\u003e37\\u003c/strong\\u003e(22): p. 1876-1885.\\u003c/li\\u003e\\n\\u003cli\\u003eJemal, A., et al., Cancer statistics, 2005. CA Cancer J Clin, 2005. \\u003cstrong\\u003e55\\u003c/strong\\u003e(1): p. 10-30.\\u003c/li\\u003e\\n\\u003cli\\u003eKopetz, S., et al., Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol, 2009. \\u003cstrong\\u003e27\\u003c/strong\\u003e(22): p. 3677-83.\\u003c/li\\u003e\\n\\u003cli\\u003eVan Cutsem, E., et al., Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med, 2009. \\u003cstrong\\u003e360\\u003c/strong\\u003e(14): p. 1408-17.\\u003c/li\\u003e\\n\\u003cli\\u003eVan Cutsem, E., et al., Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol, 2011. \\u003cstrong\\u003e29\\u003c/strong\\u003e(15): p. 2011-9.\\u003c/li\\u003e\\n\\u003cli\\u003eVergara-Fernandez, O., M. Trejo-Avila, and N. Salgado-Nesme, Sarcopenia in patients with colorectal cancer: A comprehensive review. World J Clin Cases, 2020. \\u003cstrong\\u003e8\\u003c/strong\\u003e(7): p. 1188-1202.\\u003c/li\\u003e\\n\\u003cli\\u003eChoi, M.H., et al., Sarcopenia is negatively associated with long-term outcomes in locally advanced rectal cancer. J Cachexia Sarcopenia Muscle, 2018. \\u003cstrong\\u003e9\\u003c/strong\\u003e(1): p. 53-59.\\u003c/li\\u003e\\n\\u003cli\\u003eHopkins, J.J., et al., The Impact of Muscle and Adipose Tissue on Long-term Survival in Patients With Stage I to III Colorectal Cancer. Dis Colon Rectum, 2019. \\u003cstrong\\u003e62\\u003c/strong\\u003e(5): p. 549-560.\\u003c/li\\u003e\\n\\u003cli\\u003eda Cunha, L.P., et al., Sarcopenia as an independent prognostic factor in patients with metastatic colorectal cancer: A retrospective evaluation. Clin Nutr ESPEN, 2019. \\u003cstrong\\u003e32\\u003c/strong\\u003e: p. 107-112.\\u003c/li\\u003e\\n\\u003cli\\u003eVashi, P.G., et al., Sarcopenia supersedes subjective global assessment as a predictor of survival in colorectal cancer. PLoS One, 2019. \\u003cstrong\\u003e14\\u003c/strong\\u003e(6): p. e0218761.\\u003c/li\\u003e\\n\\u003cli\\u003eBlauwhoff-Buskermolen, S., et al., Loss of Muscle Mass During Chemotherapy Is Predictive for Poor Survival of Patients With Metastatic Colorectal Cancer. J Clin Oncol, 2016. \\u003cstrong\\u003e34\\u003c/strong\\u003e(12): p. 1339-44.\\u003c/li\\u003e\\n\\u003cli\\u003eHuang, D.D., et al., Sarcopenia, as defined by low muscle mass, strength and physical performance, predicts complications after surgery for colorectal cancer. Colorectal Dis, 2015. \\u003cstrong\\u003e17\\u003c/strong\\u003e(11): p. O256-64.\\u003c/li\\u003e\\n\\u003cli\\u003ePeng, P.D., et al., Sarcopenia negatively impacts short-term outcomes in patients undergoing hepatic resection for colorectal liver metastasis. HPB (Oxford), 2011. \\u003cstrong\\u003e13\\u003c/strong\\u003e(7): p. 439-46.\\u003c/li\\u003e\\n\\u003cli\\u003eNakanishi, R., et al., Sarcopenia is an independent predictor of complications after colorectal cancer surgery. Surg Today, 2018. \\u003cstrong\\u003e48\\u003c/strong\\u003e(2): p. 151-157.\\u003c/li\\u003e\\n\\u003cli\\u003eLieffers, J.R., et al., Sarcopenia is associated with postoperative infection and delayed recovery from colorectal cancer resection surgery. Br J Cancer, 2012. \\u003cstrong\\u003e107\\u003c/strong\\u003e(6): p. 931-6.\\u003c/li\\u003e\\n\\u003cli\\u003eBarret, M., et al., Sarcopenia is linked to treatment toxicity in patients with metastatic colorectal cancer. Nutr Cancer, 2014. \\u003cstrong\\u003e66\\u003c/strong\\u003e(4): p. 583-9.\\u003c/li\\u003e\\n\\u003cli\\u003eJung, H.-W., et al., Effect of muscle mass on toxicity and survival in patients with colon cancer undergoing adjuvant chemotherapy. Supportive Care in Cancer, 2015. \\u003cstrong\\u003e23\\u003c/strong\\u003e(3): p. 687-694.\\u003c/li\\u003e\\n\\u003cli\\u003eWaalboer, R.B., et al., Sarcopenia and long-term survival outcomes after local therapy for colorectal liver metastasis: a meta-analysis. HPB (Oxford), 2022. \\u003cstrong\\u003e24\\u003c/strong\\u003e(1): p. 9-16.\\u003c/li\\u003e\\n\\u003cli\\u003eTsai, M.S., et al., Chang Gung Research Database: A multi-institutional database consisting of original medical records. Biomed J, 2017. \\u003cstrong\\u003e40\\u003c/strong\\u003e(5): p. 263-269.\\u003c/li\\u003e\\n\\u003cli\\u003ePrado, C.M., et al., Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol, 2008. \\u003cstrong\\u003e9\\u003c/strong\\u003e(7): p. 629-35.\\u003c/li\\u003e\\n\\u003cli\\u003eMuscaritoli, M., et al., Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by Special Interest Groups (SIG) \\\"cachexia-anorexia in chronic wasting diseases\\\" and \\\"nutrition in geriatrics\\\". Clin Nutr, 2010. \\u003cstrong\\u003e29\\u003c/strong\\u003e(2): p. 154-9.\\u003c/li\\u003e\\n\\u003cli\\u003eFielding, R.A., et al., Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia. J Am Med Dir Assoc, 2011. \\u003cstrong\\u003e12\\u003c/strong\\u003e(4): p. 249-56.\\u003c/li\\u003e\\n\\u003cli\\u003eMorley, J.E., et al., Sarcopenia with limited mobility: an international consensus. J Am Med Dir Assoc, 2011. \\u003cstrong\\u003e12\\u003c/strong\\u003e(6): p. 403-9.\\u003c/li\\u003e\\n\\u003cli\\u003eCruz-Jentoft, A.J., et al., Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing, 2019. \\u003cstrong\\u003e48\\u003c/strong\\u003e(1): p. 16-31.\\u003c/li\\u003e\\n\\u003cli\\u003eChen, L.K., et al., Recent Advances in Sarcopenia Research in Asia: 2016 Update From the Asian Working Group for Sarcopenia. J Am Med Dir Assoc, 2016. \\u003cstrong\\u003e17\\u003c/strong\\u003e(8): p. 767.e1-7.\\u003c/li\\u003e\\n\\u003cli\\u003eMourtzakis, M., et al., A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care. Appl Physiol Nutr Metab, 2008. \\u003cstrong\\u003e33\\u003c/strong\\u003e(5): p. 997-1006.\\u003c/li\\u003e\\n\\u003cli\\u003eGoodla, L. and X. Xue, The Role of Inflammatory Mediators in Colorectal Cancer Hepatic Metastasis. Cells, 2022. \\u003cstrong\\u003e11\\u003c/strong\\u003e(15).\\u003c/li\\u003e\\n\\u003cli\\u003eVisser, M., et al., Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the Health ABC Study. J Gerontol A Biol Sci Med Sci, 2002. \\u003cstrong\\u003e57\\u003c/strong\\u003e(5): p. M326-32.\\u003c/li\\u003e\\n\\u003cli\\u003eBajrić, T., et al., Sarcopenia and primary tumor location influence patients outcome after liver resection for colorectal liver metastases. Eur J Surg Oncol, 2022. \\u003cstrong\\u003e48\\u003c/strong\\u003e(3): p. 615-620.\\u003c/li\\u003e\\n\\u003c/ol\\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\":\"info@researchsquare.com\",\"identity\":\"scientific-reports\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"scirep\",\"sideBox\":\"Learn more about [Scientific Reports](http://www.nature.com/srep/)\",\"snPcode\":\"\",\"submissionUrl\":\"\",\"title\":\"Scientific Reports\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"stoa\",\"reportingPortfolio\":\"Scientific Reports\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Sarcopenia, Colorectal liver metastasis, Hepatectomy, Cetuximab, wild-type RAS, Overall survival\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-2358572/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-2358572/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003ch2\\u003eBackground\\u003c/h2\\u003e \\u003cp\\u003eSarcopenia has been associated with conventional chemotherapy-related toxicity, postoperative complications and poor overall survival in patients with genotype-unselected metastatic colorectal cancer (mCRC). This study aimed to evaluate the prognostic implications of sarcopenia and its change after perioperative cetuximab plus doublet chemotherapy and hepatectomy in patients with RAS wild-type colorectal liver metastasis (CRLM).\\u003c/p\\u003e\\u003ch2\\u003eMethods\\u003c/h2\\u003e \\u003cp\\u003ePatients with CRLM from 2007 to 2018 in Chang Gung Research Database were retrospectively analyzed. Baseline characteristics as well as skeletal muscle index (SMI) at baseline and dynamic changes after interventions were collected. A multivariate Cox proportional hazard model was used to evaluate the effect of each parameter on overall survival (OS), and the Kaplan-Meier method was used to establish survival curves. A two-sided p value\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05 was considered statistically significance.\\u003c/p\\u003e\\u003ch2\\u003eResults\\u003c/h2\\u003e \\u003cp\\u003eOf 214 RAS wild-type mCRC patients who received both cetuximab and doublet chemotherapy, 77 who received upfront or subsequent hepatectomy were included in this study. The median follow-up time was 2.3 years. The rate of sarcopenia was higher in the patients who received neoadjuvant cetuximab-containing regimens than in those who received upfront hepatectomy (95% versus 63%, p\\u0026thinsp;=\\u0026thinsp;0.001). Increased SMI after perioperative systemic therapy remained independently associated with better OS in multivariate analysis [hazard ratio (HR)\\u0026thinsp;=\\u0026thinsp;0.88/10% increase, p\\u0026thinsp;=\\u0026thinsp;0.013). The patients with sarcopenia had a trend of worse OS than those without sarcopenia (median OS: 4.5 versus 3.6 years, log-rank p\\u0026thinsp;=\\u0026thinsp;0.282).\\u003c/p\\u003e\\u003ch2\\u003eConclusions\\u003c/h2\\u003e \\u003cp\\u003eImprovement in sarcopenia ([SMI after intervention \\u0026ndash; initial SMI]/initial SMI x 100%) is an important prognostic factor for OS. Future research is warranted to investigate direct interventions for sarcopenia and the impact on OS.\\u003c/p\\u003e\",\"manuscriptTitle\":\"The Impact of Sarcopenia on Overall Survival in Patients with Pan-RAS Wild-type Colorectal Liver Metastasis Receiving Hepatectomy\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2022-12-19 18:16:58\",\"doi\":\"10.21203/rs.3.rs-2358572/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"decision\",\"content\":\"Major revision\",\"date\":\"2023-01-23T04:50:31+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2023-01-22T11:44:17+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"63624251-a50f-4e0d-ad48-88d2cb3bc5bf\",\"date\":\"2023-01-16T16:22:23+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2023-01-11T15:00:03+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"07f78f6f-c24e-4552-9da7-7af5477be0dd\",\"date\":\"2023-01-09T11:15:19+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2023-01-05T03:35:38+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2023-01-05T03:28:24+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvited\",\"content\":\"\",\"date\":\"2022-12-15T10:40:48+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"checksComplete\",\"content\":\"\",\"date\":\"2022-12-15T10:38:23+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"Scientific Reports\",\"date\":\"2022-12-08T15:18:55+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"scientific-reports\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"scirep\",\"sideBox\":\"Learn more about [Scientific Reports](http://www.nature.com/srep/)\",\"snPcode\":\"\",\"submissionUrl\":\"\",\"title\":\"Scientific Reports\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"stoa\",\"reportingPortfolio\":\"Scientific Reports\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"7fbc337a-a6bf-4692-ade4-20435a45f469\",\"owner\":[],\"postedDate\":\"December 19th, 2022\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"published-in-journal\",\"subjectAreas\":[{\"id\":17728907,\"name\":\"Biological sciences/Cancer\"},{\"id\":17728908,\"name\":\"Health sciences/Health care\"},{\"id\":17728909,\"name\":\"Health sciences/Risk factors\"}],\"tags\":[],\"updatedAt\":\"2023-10-16T20:46:56+00:00\",\"versionOfRecord\":{\"articleIdentity\":\"rs-2358572\",\"link\":\"https://doi.org/10.1038/s41598-023-33439-x\",\"journal\":{\"identity\":\"scientific-reports\",\"isVorOnly\":false,\"title\":\"Scientific Reports\"},\"publishedOn\":\"2023-04-27 20:38:20\",\"publishedOnDateReadable\":\"April 27th, 2023\"},\"versionCreatedAt\":\"2022-12-19 18:16:58\",\"video\":\"\",\"vorDoi\":\"10.1038/s41598-023-33439-x\",\"vorDoiUrl\":\"https://doi.org/10.1038/s41598-023-33439-x\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-2358572\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-2358572\",\"identity\":\"rs-2358572\",\"version\":[\"v1\"]},\"buildId\":\"7rjqhiLT3MXkJMwkYKINL\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}