Elevated fibrinogen-albumin ratio is an adverse prognostic factor for patients with primarily resected gastroesophageal adenocarcinoma

Elevated fibrinogen-albumin ratio is an adverse prognostic factor for patients with primarily resected gastroesophageal adenocarcinoma | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Elevated fibrinogen-albumin ratio is an adverse prognostic factor for patients with primarily resected gastroesophageal adenocarcinoma Gerd Jomrich, Winny Yan, Dagmar Kollmann, Ivan Kristo, Daniel Winkler, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4755706/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 14 Oct, 2024 Read the published version in Journal of Cancer Research and Clinical Oncology → Version 1 posted 11 You are reading this latest preprint version Abstract Purpose : Serum fibrinogen and albumin play important roles in systemic inflammation and are implicated in tumor progression. The fibrinogen-to-albumin ratio (FAR) has shown a prognostic impact in several malignancies. This study aims to assess the prognostic value of the pretherapeutic FAR in patients with adenocarcinoma of the gastroesophageal junction (AEG) who underwent upfront resection. Methods: Consecutive patients who underwent surgical resection at the Department of Surgery at the Medical University of Vienna between 1992 and 2014 were included into this study. Optimal cut-off values were determined with the receiver-operating characteristic (ROC) curve, uni- and multivariate analyzes were calculated by the Cox proportional hazard regression model for overall survival (OS). Results: Among 135 included patients, the majority were male (79.26%), with a mean age of 66.53 years. Elevated FAR correlated significantly ( p=0.002 ) with shorter OS in univariate analysis, also confirmed as independent prognostic factor ( p=0.005 ) in multivariable analysis. The ROC curve of FAR (AUC=0.744) outperformed fibrinogen (AUC=0.738) and albumin (AUC=0.378) in predicting OS for AEG patients. Conclusion: The FAR serves as an independent prognostic factor for OS in patients undergoing primarily resection for AEG. Given its routine availability and ease of calculation, FAR could help in diagnosis and treatment selection for AEG patients. Further validation studies are warranted to confirm these findings conclusively. esophageal cancer fibrinogen to albumin ratio prognostic parameter malignant tumor prognosis Figures Figure 1 Figure 2 Figure 3 Introduction According to the latest GLOBOCAN analysis, esophageal cancer (EC) is the seventh most common type of cancer worldwide (Sung et al., 2021 ). Two histological subtypes are distinguishable, differing geographically, genetically, and in risk factors: esophageal squamous cell carcinoma (ESCC) and adenocarcinoma of the gastroesophageal junction (AEG). ESCC generally prevails, however, recent decades have seen a notable rise in AEG diagnoses, especially in western nations, surpassing ESCC (Arnold et al., 2015 ). Although survival rates for AEG have improved with multimodal therapies, the prognosis remains poor with a maximum 5-year survival rate of 20% in high-income countries (Morgan et al. 2020). Despite improvements in the treatment of AEG combining surgical resection and new systemic therapy regimens, approximately 50% of patients experience disease recurrence (Dhakras et al., 2020 ). Currently, conventional tumor-based histopathologic risk factors, including tumor and lymph node staging, tumor differentiation, and resection margin status, are the sole prognostic indicators only accessible post-surgery. Therefore, identifying prognostic markers before surgery can enhance treatment approaches for patients with EAG (Dhakras et al., 2020 ). Over the past decade, numerous biomarkers have emerged to predict patients survival rates in various malignancies (An et al., 2022 ; Jomrich et al., 2021 , 2020 , 2019 ; Tada et al., 2023). Among these parameters aiding in individual risk assessment in EC is the FAR, which is calculated using preoperative available laboratory tests reflecting the influence of immune response on tumor progression and survival (Diakos et al., 2014 ; Dinca et al., 2023 ). Elevated FAR is associated with decreased OS across various cancers including esophageal squamous cell carcinoma and gastric carcinoma, confirming its potential as a prognostic marker for patients suffering from malignant diseases (Zhang and Xiao, 2019 ). Additionally, inflammatory parameters are linked to decreased disease-free survival (DFS) and OS in patients with AEG (Powell et al., 2021). Fibrinogen is an acute-phase protein, which acts as a key role in the coagulation cascade and hemostasis. It has been ascribed an important role in the stabilization of tumor cells, their cell invasion, the metastasis process and the promotion of blood vessel formation in malignant lesions (Palumbo et al., 2000 ). The correlation between plasma fibrinogen levels and prognosis has been observed in several types of cancers including AEG (Jagadesham et al., 2017 ). Serum-albumin is being used to determine the nutritional status since malnutrition and chronic systemic inflammation in cancer affect albumin synthesis (Simons et al., 1999 ). Cytokines like interleukin-6 or tumor necrosis factor, released during the systemic inflammatory response, stimulate acute-phase protein production such as fibrinogen. This increases amino acid demand and alters vascular wall permeability, enhancing albumin uptake into cells (Barber et al., 1999 ). Serum albumin has been identified as an independent predictor of survival in different cancer types (Maltoni and Amadori, 2002 ), including lung (Yuan et al., 2022 ), gastric (Oñate-Ocaña et al., 2007 ) and pancreatic (Siddiqui et al., 2007 ) cancer. Thus, pretreatment serum albumin levels offer valuable prognostic significance in cancer, showing the less the albumin value, the worse the prognosis (Gupta and Lis, 2010 ). The aim of this study was to assess whether the FAR, obtained preoperatively from patients with AEG, can predict survival rates. While it has demonstrated a prognostic value in ESCC (Tan et al., 2017 ), significance of FAR for AEG remains uncertain, driving the focus of this study. To the best of our knowledge, this is the first study investigating the prognostic role of FAR in primarily resected AEG. Methods This retrospective study uses data from a prospectively maintained database from the Department of General Surgery at the Medical University of Vienna, of patients who underwent primarily resection for AEG between 1992 and 2014. The classification of the primary tumor was based on the eighth edition of the American Joint Committee on Cancer (AJCC) (Rice et al., 2017 ). Inclusion criteria comprised availability of serum fibrinogen and albumin laboratory values obtained within two weeks before surgery, histologically confirmed diagnosis of AEG, and absence of neoadjuvant therapy. Exclusion criteria included pregnancy, age under 18 years at disease onset. Patients with fever or signs of active or chronic inflammatory disease during laboratory data collection were excluded as well. Serum fibrinogen and albumin were analyzed in the central laboratory of the Vienna General Hospital, which has a certified (ISO 9001) and accredited (ISO 15189 since 2008) quality management system. The baseline clinicopathological values were retrospectively reviewed and collected from the local database and electronical patients records. The patients' baseline clinicopathologic values were retrospectively reviewed and collected from the local database and electronic patient records. Follow-up appointments were scheduled every three months for the first two years and every six months for the subsequent three years. Statistical analysis The analysis and correlation of the data used was carried out using IBM SPSS Statistics 29.0 (Armonk, New York, USA) software for Windows. A significance threshold of p < 0.05 was applied for statistical significance. Categorical variables were described by absolute and relative frequencies, and metric variables were described by mean and median minimum and maximum. The FAR was defined as the fibrinogen levels divided by the serum albumin levels. Receiver-operating characteristic (ROC) curve analysis was used to determine the optimal cut-off values for fibrinogen, albumin, and FAR. The determination of these cut-off values was considered by maximizing Youden’s index (sensitivity + specificity − 1). Univariate and multivariate analyses were conducted to assess the prognostic value of FAR. In the multivariate analysis, each parameter - FAR, albumin, and fibrinogen - was individually evaluated using the Cox regression proportional hazard model to ascertain their independent prognostic significance for OS. The association between FAR and clinicopathologic factors was evaluated through the Chi-square and Kruskal-Wallis tests. Survival analysis, including OS and survival curves, was performed using the Kaplan-Meier survival curves. The disparity in survival outcomes between various groups was determined using the log-rank test. Given the exploratory nature of the study, no adjustments for multiple testing were made unless explicitly stated (Bender and Lange, 2001 ). Results In the present study, a total of 135 patients (107, 79.26% male) were included (suppl. Figure 1). Mean age at the time of surgery was 66.53 years (range 44–90 years), 81 patients (60%) were 65 years old or older on the day of surgery. The correlation between the clinicopathological parameters and FAR are compiled in Table 1 . The OS was settled as the endpoint, using the ROC analysis to determine the cut-off value of FAR. The Youden index calculated revealed an optimal cut-off for FAR = 7.77 (Fig. 1 ), fibrinogen = 340 (Fig. 2 a) and albumin = 40.55 (Fig. 2 b), respectively. For all patients the median survival of all patients was 37.4 months, and the Kaplan-Meier analysis shows that the group with high FAR has a significantly ( p < 0.001) worse outcome compared to the group with low FAR (Fig. 3 ). The univariate analysis shows significant correlation of OS and preoperative UICC stage ( p < 0.001), clinical tumor stage ( p < 0.001), clinical lymph node stage ( p < 0.001), postoperative UICC stage ( p < 0.001), pathologic tumor stage ( p < 0.001), pathologic lymph node stage ( p < 0.001), tumor grading ( p = 0.002), adjuvant therapy ( p < 0.001), fibrinogen ( p = 0.013), and FAR ( p = 0.002). Multivariate analysis was conducted using two models: one incorporating clinical staging, and another one incorporating pathological staging. In the multivariate Cox regression model with clinical staging (cT, cN) ( Table 2 ), FAR was an independent predictor of OS with a hazard ratio (HR) of 2.456 ( p < 0.001 ), indicating a 145.6% higher risk of earlier death. The clinical tumor stage (cT) was also significant ( p = 0.005 ), particularly for cT2 with an HR of 2.768 ( p = 0.001 ), indicating a 176.8% higher risk of earlier death. Clinical lymph node involvement (cN) was not significant overall ( p = 0.246 ), although cN2 approached significance (HR = 2.489, p = 0.051 ). In the pathological staging model (pT, pN) (Table 3 ), FAR remained a significant predictor with an HR of 2.170 ( p = 0.004 ), indicating a 117% higher risk of earlier death. The pathological tumor stage (pT) was highly significant overall ( p < 0.001 ), with pT 1 (HR = 3.434, p < 0.001 ), pT 2 (HR = 4.289, p < 0.001 ), and pT3 (HR = 4.512, p = 0.014 ) all showing substantial increased risks of earlier death. Pathological lymph node involvement (pN) was not significant overall ( p = 0.056 ), but pN1 (HR = 1.889, p = 0.029 ) and pN2 (HR = 2.701, p = 0.011 ) were significant. Furthermore, the ROC curve analysis was conducted to assess the predictive value of various biomarkers for OS in patients with AEG. The AUC for fibrinogen was determined to be 0.738, ( p < 0.001; 95% CI [0.627 to 0.849]) (Fig. 2 a). Conversely, albumin (Fig. 2 b) exhibited an AUC of 0.378, with a p -value of 0.047 and a 95% CI spanning from 0.267 to 0.488. The AUC for the FAR was 0.744 ( p < 0.001, 95% CI 0.637–0.851) (Fig. 1 ) , indicating superior predictive performance compared to both albumin and fibrinogen alone. Consequently, FAR emerges as a better predictor of OS in patients with AEG. Discussion This study investigated the clinical impact of the FAR in patients who underwent primarily resection of AEG. Our findings showed that higher FAR values were significantly ( p < 0.001) associated with lower survival rates in these patients, suggesting the potential of FAR as an independent prognostic parameter. Moreover, FAR outperformed albumin and fibrinogen in predicting patient outcomes, highlighting its enhanced predictive value for AEG patients. The response of the immunes system inflammation, and initiation of the coagulation cascade play important roles in tumor development, with fibrinogen being primarily responsible for platelet aggregation during hemostasis. As an essential hemostatic factor, it is involved in various mechanisms that hinder antitumor immunity and therefore promoting tumor progression (Mosesson, 2005 ). For instance, it may inhibit macrophage migration and disrupt fibrinogen-leukocyte interactions by modifying the leukocyte integrin binding motif and compromising the ability of the host to mount an effective immune response against tumors (Silva et al., 2019 ). Additionally, fibrinogen can inhibit the clearance of tumor cells by natural killer (NK) cells, facilitating immune evasion and metastasis (Palumbo et al., 2005 ). Moreover, fibrinogen has been shown to promote epithelial-mesenchymal transition (EMT) through the AKT-mTOR pathway in ESCC, contributing to tumor aggressiveness prognosis (Zhang et al., 2017 ). Therefore aiming a decrease of fibrinogen could be an approach for minimizing poor prognosis (Deng et al., 2023 ). Similarly, there is consensus in the literature regarding the poor prognosis associated with low albumin concentrations in cancer patients (Gupta and Lis, 2010 ), reflecting the nutritional status of patients. Malnutrition and inflammatory processes suppress albumin synthesis over time, contributing to tumor cachexia (Ballmer et al., 1994 ). The prognostic relevance of albumin levels in esophageal carcinomas has been well documented (Otowa et al., 2017 ). While previous studies have explored the role of fibrinogen in various malignancies, including esophageal tumors, the specific prognostic value of the FAR in patients with AEG has not been investigated yet, highlighting the significance of our study. Several studies and meta-analyses have demonstrated the negative impact of high FAR values on OS in various cancers including gastrointestinal cancers (Zhang and Xiao, 2019 ). Our study aligns with these findings, revealing significant results for several prognostic factors, including fibrinogen, albumin and FAR. Furthermore, the results of ROC curve analysis suggest that both fibrinogen and FAR outperform albumin in terms of predicting prognosis, underscoring the potential relevance of these parameters. However, further research is warranted to fully evaluate the prognostic impact of FAR in AEG and other malignancies. The findings of our study emphasize the importance of considering FAR, especially in clinical practice for AEG patients. Patients with high preoperative FAR values may benefit from closer monitoring and tailored therapeutic interventions to address potential complications or infections. Finally, our study highlights the underexplored prognostic significance of systemic inflammatory parameters in large western cohorts with AEG. The optimal inflammatory parameter for predicting overall survival remains uncertain (Puhr et al., 2023 ). However, our findings contribute valuable insights by identifying the FAR as a promising prognostic indicator for estimating OS in a sizable and representative European cohort of AEG patients. Limitations The main limitation of this study was the retrospective design of our study which introduces inherent biases, notably selection bias, compounded by partial accessibility to pretherapeutic laboratory data. Additionally, being conducted solely at one center may limit the broader applicability of our findings. Furthermore, our study's modest sample size and extended duration could impact result reliability. To substantiate the clinical relevance of FAR, further investigations involving larger and more diverse patient cohorts are needed to validate this finding. Conclusion In conclusion, elevated FAR values are linked to decreased OS in AEG patients undergoing primary surgery. Our study suggests that preoperative FAR serves as an independent prognostic factor in AEG patients, indicating that lower FAR levels may improve OS in this population. Declarations Author contributions: The manuscript has been read and approved by all authors. All authors contributed to the preparation of the manuscript significantly and agree with the content of the manuscript. All authors confirm that the manuscript has not been submitted elsewhere. Study concepts: G.J., S.F.S.; Study design: G.J., S.F.S.; Data acquisition: G.J., W.Y., D.K., I.K., H.P.; Quality control of data and algorithms: D.W., A.I-M., R.A., S.F.S.; Data analysis and interpretation: G.J., D.W., A.I-M., R.A., S.F.S.; Statistical analysis: G.J., D.W.; Manuscript preparation: G.J.; Manuscript editing: G.J.; Manuscript review: A.I-M., R.A., S.F.S. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Conflicts of interest AIM declares following general COIs which are not directly related to the content of the manuscript: Participation in advisory boards organized by MSD, Servier, Daiichi Sankyo, BMS and Astellas, lecture honoraria from Eli Lilly, Servier, BMS, MSD, Astellas, Astra Zeneca and Daiichi Sankyo, consulting for Astellas, MSD, Amgen, Astra Zeneca and BeiGene, travel support from BMS, Roche, Eli Lilly, Daiichi Sankyo and BeiGene. The other authors declare that they have no conflicts of interest. Consent to participate According to its retrospective nature and in line with the ethics committees approval, written patient consent was not applicable to this study. This is in line with local ethical standards and was approved based on the ethical principles of the World Medical Association Declaration of Helsinki by the Ethics Committee of the Medical University of Vienna with the ethics vote 1132/2023. All procedures were in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1964 and later versions. References An S, Shim H, Kim K, Kim B, Bang H-J, Do H, Lee H-R, Kim Y (2022) Pretreatment inflammatory markers predicting treatment outcomes in colorectal cancer. 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Variable High FAR (%) Low FAR (%) p-value mean Age (SD) 67.2 (10.92) 64.84 (8.49) 0.053 Sex 0.021 Male 72 (0.67) 35 (0.33) Female 25 (0.89) 3 (0.11) cT 0.2 1 23 (0.62) 14 (0.38) 2 41 (0.72) 16 (0.28) 3 33 (0.80) 8 (0.20) cN 0.026 0 25 (0.56) 20 (0.44) 1 62 (0.79) 16 (0.077) 2 8 (0.80) 2 (0.2) 3 2 (1) 0 (0) pT 0.022 1 24 (0.56) 19 (0.44) 2 33 (0.73) 12 (0.27) 3 36 (0.86) 6 (0.14) 4 4 (0.8) 1 (0.2) pN 0.120 0 40 (0.63) 23 (0.37) 1 34 (0.74) 12 (0.26) 2 14 (0.88) 2 (0.13) 3 9 (0.9) 1 (0.1) Adjuvant therapy 0.020 Yes 54 (0.79) 14 (0.21) No 41 (0.61) 26 (0.39) ASA 0.438 I 10 (0.59) 7 (0.41) II 73 (0.72) 28 (0.28) III 12 (0.8) 3 (0.2) IV 2 (1) 0 (0) ECOG PS 0.828 0 36 (0.72) 14 (0.28) 2 14 (0.74) 5 (0.26) 3 2 (1) 0 (0) Abbreviations: SD standard deviation, c clinical staging, p pathological staging, ASA American society of anesthesiologists classification, ECOG Eastern Cooperative Oncology Group Performance Status, HR hazard ratio, CI confidential interval; Table 2 Clinical staging model - univariate and multivariate Cox regression analyses estimating the influence of the FAR and clinicopathologic parameters on OS in patients with primarily resected AEG Variable Univariate Multivariate HR 95% CI p -Value HR 95% CI p -Value Age (years) 1.013 0.992–1.034 0.222 NI SEX (ref. male) 1.202 0.757–1.909 0.437 0.671 0.408–1.106 0.118 G (ref. G3) 0.002 0.010 1 vs. 3 0.421 0.151–1.174 0.098 2.471 0.792–7.377 0.121 2 vs. 3 0.501 0.336–0.747 0.001 1.748 1.292–2.363 < 0.001 cN (ref. cN0) 1.840 1.406–2.408 < 0.001 1.391 1.040–1.860 0.026 pT < 0.001 NI 1 vs. 4 0.099 0.036–0.272 < 0.001 2 vs. 4 0.325 0.125–0.843 0.021 3 vs. 4 0.595 0.232–1.523 0.279 pN < 0.001 NI 1 vs. 0 0.157 0.075–0.328 < 0.001 2 vs. 0 0.517 0.257–1.040 0.064 3 vs. 0 0.998 0.451–2.208 0.996 Adjuvant therapy (ref. yes) 0.239 0.157–0.364 < 0.001 ASA 0.507 0.550 I 1.088 0.610–1.940 0.776 1.001 0.515–1.949 0.997 II 1.651 0.765–5.651 0.202 0.689 0.265–1.789 0.444 III 0.739 0.097–5.651 0.770 0.261 0.029–2.348 0.231 ECOG < 0.001 0.001 ECOG 1 0.950 0.627–1.438 0.808 0.711 0.457–1.106 0.130 ECOG 2 1.063 0.578–1.956 0.844 0.831 0.402–1.716 0.616 ECOG 3 39.862 7.050-225.383 < 0.001 23.421 3.602-152.297 < 0.001 Fibrinogen 1.002 1.000-1.004 0.013 See suppl. Table 1 Albumin 0.969 0.939-1.000 0.053 See suppl. Table 2 FAR 0.1082 1.030–1.136 0.002 1.102 1.040–1.168 0.001 Abbreviations: NI not included, c clinical staging, p pathological staging, OP operation, HR hazard ratio, CI confidence interval, ASA American society of anesthesiologists classification, ECOG Eastern Cooperative Oncology Group Bold values indicate statistical significance Table 3: Pathological staging model - univariate and multivariate Cox regression analyses estimating the FAR and clinicopathologic parameters on OS in patients with primarily resected AEG Variable Univariate Multivariate HR 95% CI p -Value HR 95% CI p -Value Age (years) 1.013 0.992–1.034 0.222 NI SEX 1.202 0.757–1.909 0.437 0.734 0.434–1.242 0.249 G (ref. 3) 0.002 0.162 1 vs. 3 0.421 0.151–1.174 0.098 1.370 0.474–3.959 0.561 2 vs. 3 0.501 0.336–0.747 0.001 NI cN (ref. cN0) 1.840 1.406–2.408 < 0.001 NI pT < 0.001 < 0.001 1 vs.4 0.099 0.036–0.272 < 0.001 3.434 1.771–6.657 < 0.001 2 vs. 4 0.325 0.125–0.843 0.021 4.289 2.060–8.926 < 0.001 3 vs. 4 0.595 0.232–1.523 0.279 4.512 1.354–15.039 0.072 pN < 0.001 0.056 1 vs. 0 0.157 0.075–0.328 < 0.001 1.889 1.067–3.345 0.290 2 vs. 0 0.517 0.257–1.040 0.064 2.701 1.255–5.424 0.011 3 vs. 0 0.998 0.451–2.208 0.996 2.246 0.930–5.424 0.071 Adjuvant therapy (ref. yes) 0.239 0.157–0.364 < 0.001 ASA 0.507 0.167 I 1.088 0.610–1.940 0.776 0.454 0.220–0.938 0.033 II 1.651 0.765–5.651 0.202 0.374 0.127-1.100 0.074 III 0.739 0.097–5.651 0.770 0.493 0.051–4.786 0.542 ECOG < 0.001 0.002 ECOG 1 0.950 0.627–1.438 0.808 0.688 0.433–1.092 0.113 ECOG 2 1.063 0.578–1.956 0.844 0.785 0.336–1.835 0.576 ECOG 3 39.862 7.050-225.383 < 0.001 21.268 2.916-155.098 0.003 Fibrinogen 1.002 1.000-1.004 0.013 See suppl. Table 1 Albumin 0.969 0.939-1.000 0.053 See suppl. Table 2 FAR 0.1082 1.030–1.136 0.002 2.170 1.278–3.683 0.004 Abbreviations: NI not included, c clinical staging, p pathological staging, OP operation, HR hazard ratio, CI confidence interval, ASA American society of anesthesiologists classification, ECOG Eastern Cooperative Oncology Group Bold values indicate statistical significance Additional Declarations No competing interests reported. Supplementary Files SupplementaryFigure1.jpg Supplementarytable1.odt Supplementarytable2.odt Cite Share Download PDF Status: Published Journal Publication published 14 Oct, 2024 Read the published version in Journal of Cancer Research and Clinical Oncology → Version 1 posted Editorial decision: Revision requested 13 Aug, 2024 Reviews received at journal 13 Aug, 2024 Reviews received at journal 01 Aug, 2024 Reviewers agreed at journal 01 Aug, 2024 Reviewers agreed at journal 01 Aug, 2024 Reviewers agreed at journal 31 Jul, 2024 Reviewers agreed at journal 21 Jul, 2024 Reviewers invited by journal 18 Jul, 2024 Editor assigned by journal 18 Jul, 2024 Submission checks completed at journal 18 Jul, 2024 First submitted to journal 17 Jul, 2024 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. 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Vienna","correspondingAuthor":false,"prefix":"","firstName":"Winny","middleName":"","lastName":"Yan","suffix":""},{"id":338078226,"identity":"a66fbd45-c70e-4ef0-a83c-9d55c85dc398","order_by":2,"name":"Dagmar Kollmann","email":"","orcid":"","institution":"Medical University of Vienna","correspondingAuthor":false,"prefix":"","firstName":"Dagmar","middleName":"","lastName":"Kollmann","suffix":""},{"id":338078227,"identity":"c37c678b-af63-4a4f-9b8d-719f59731123","order_by":3,"name":"Ivan Kristo","email":"","orcid":"","institution":"Medical University of Vienna","correspondingAuthor":false,"prefix":"","firstName":"Ivan","middleName":"","lastName":"Kristo","suffix":""},{"id":338078228,"identity":"ed730187-f942-4b91-91ad-b7d9afcad6bd","order_by":4,"name":"Daniel Winkler","email":"","orcid":"","institution":"Vienna University of Economics and Business","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"","lastName":"Winkler","suffix":""},{"id":338078229,"identity":"917e73a2-611c-49c2-b6ce-815dd76c1974","order_by":5,"name":"Hannah Puhr","email":"","orcid":"","institution":"Medical University of Vienna","correspondingAuthor":false,"prefix":"","firstName":"Hannah","middleName":"","lastName":"Puhr","suffix":""},{"id":338078230,"identity":"25a102a3-0b00-4afe-91b2-ce6690c9469f","order_by":6,"name":"Aysegül Ihan-Mutlu","email":"","orcid":"","institution":"Medical University of Vienna","correspondingAuthor":false,"prefix":"","firstName":"Aysegül","middleName":"","lastName":"Ihan-Mutlu","suffix":""},{"id":338078231,"identity":"44c5b0fc-27ea-4003-8bcd-8233a78a24f7","order_by":7,"name":"Marlene Hollenstein","email":"","orcid":"","institution":"Medical University of Vienna","correspondingAuthor":false,"prefix":"","firstName":"Marlene","middleName":"","lastName":"Hollenstein","suffix":""},{"id":338078232,"identity":"07514a9a-9e5f-4858-ab57-83dbee03d950","order_by":8,"name":"Reza Asari","email":"","orcid":"","institution":"Medical University of Vienna","correspondingAuthor":false,"prefix":"","firstName":"Reza","middleName":"","lastName":"Asari","suffix":""},{"id":338078233,"identity":"16972218-053e-47fe-bbf6-2befebddbb07","order_by":9,"name":"Sebastian 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11:03:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4755706/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4755706/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00432-024-05976-z","type":"published","date":"2024-10-14T15:56:59+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":62732723,"identity":"9bf0233e-0b72-40ed-87df-514724c040d8","added_by":"auto","created_at":"2024-08-18 23:46:45","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":50633,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve analysis of serum FAR\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4755706/v1/9959d07ed8f1b67eb014f704.png"},{"id":62732729,"identity":"8b416ba3-d640-459b-817e-1ca750527a48","added_by":"auto","created_at":"2024-08-18 23:46:46","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":55356,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve analysis. a. serum albumin\u003cstrong\u003e \u003c/strong\u003eand b. serum fibrinogen\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4755706/v1/1f815cc51739844f2ae9f6ac.jpg"},{"id":62732724,"identity":"6ee90a2e-1b6a-4d8e-a0a7-5aee8916751d","added_by":"auto","created_at":"2024-08-18 23:46:45","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":18525,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier survival curves stratified by serum FAR in primarily resected AEG patients\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4755706/v1/6bcffc889f28c7c86d0a6d06.png"},{"id":67149549,"identity":"5b22eed1-53bc-4a3d-80e7-ec9e64ca1daf","added_by":"auto","created_at":"2024-10-21 16:13:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":926135,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4755706/v1/5f2c0b7d-79a3-4cd6-83c6-9cd30f7e178f.pdf"},{"id":62733187,"identity":"6758270a-3c33-4af5-90a5-406514c1320f","added_by":"auto","created_at":"2024-08-18 23:54:45","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":26261,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4755706/v1/d2ad02844b9ea73f68a55274.jpg"},{"id":62733188,"identity":"546ab7a0-94ea-461f-a2b6-26baec863715","added_by":"auto","created_at":"2024-08-18 23:54:45","extension":"odt","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":9374,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarytable1.odt","url":"https://assets-eu.researchsquare.com/files/rs-4755706/v1/5bcf2e68754818c5d7f89eaf.odt"},{"id":62732726,"identity":"fd47908d-da7c-475a-b747-3c6eb8022d64","added_by":"auto","created_at":"2024-08-18 23:46:45","extension":"odt","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":9630,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarytable2.odt","url":"https://assets-eu.researchsquare.com/files/rs-4755706/v1/e830987999071ff56108ef2f.odt"}],"financialInterests":"No competing interests reported.","formattedTitle":"Elevated fibrinogen-albumin ratio is an adverse prognostic factor for patients with primarily resected gastroesophageal adenocarcinoma","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAccording to the latest GLOBOCAN analysis, esophageal cancer (EC) is the seventh most common type of cancer worldwide (Sung et al., \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Two histological subtypes are distinguishable, differing geographically, genetically, and in risk factors: esophageal squamous cell carcinoma (ESCC) and adenocarcinoma of the gastroesophageal junction (AEG). ESCC generally prevails, however, recent decades have seen a notable rise in AEG diagnoses, especially in western nations, surpassing ESCC (Arnold et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). Although survival rates for AEG have improved with multimodal therapies, the prognosis remains poor with a maximum 5-year survival rate of 20% in high-income countries (Morgan et al. 2020). Despite improvements in the treatment of AEG combining surgical resection and new systemic therapy regimens, approximately 50% of patients experience disease recurrence (Dhakras et al., \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2020\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCurrently, conventional tumor-based histopathologic risk factors, including tumor and lymph node staging, tumor differentiation, and resection margin status, are the sole prognostic indicators only accessible post-surgery. Therefore, identifying prognostic markers before surgery can enhance treatment approaches for patients with EAG (Dhakras et al., \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2020\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOver the past decade, numerous biomarkers have emerged to predict patients survival rates in various malignancies (An et al., \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Jomrich et al., \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2021\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2020\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Tada et al., 2023). Among these parameters aiding in individual risk assessment in EC is the FAR, which is calculated using preoperative available laboratory tests reflecting the influence of immune response on tumor progression and survival (Diakos et al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2014\u003c/span\u003e; Dinca et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Elevated FAR is associated with decreased OS across various cancers including esophageal squamous cell carcinoma and gastric carcinoma, confirming its potential as a prognostic marker for patients suffering from malignant diseases (Zhang and Xiao, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Additionally, inflammatory parameters are linked to decreased disease-free survival (DFS) and OS in patients with AEG (Powell et al., 2021).\u003c/p\u003e \u003cp\u003eFibrinogen is an acute-phase protein, which acts as a key role in the coagulation cascade and hemostasis. It has been ascribed an important role in the stabilization of tumor cells, their cell invasion, the metastasis process and the promotion of blood vessel formation in malignant lesions (Palumbo et al., \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2000\u003c/span\u003e). The correlation between plasma fibrinogen levels and prognosis has been observed in several types of cancers including AEG (Jagadesham et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2017\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSerum-albumin is being used to determine the nutritional status since malnutrition and chronic systemic inflammation in cancer affect albumin synthesis (Simons et al., \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e1999\u003c/span\u003e). Cytokines like interleukin-6 or tumor necrosis factor, released during the systemic inflammatory response, stimulate acute-phase protein production such as fibrinogen. This increases amino acid demand and alters vascular wall permeability, enhancing albumin uptake into cells (Barber et al., \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e1999\u003c/span\u003e). Serum albumin has been identified as an independent predictor of survival in different cancer types (Maltoni and Amadori, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2002\u003c/span\u003e), including lung (Yuan et al., \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2022\u003c/span\u003e), gastric (O\u0026ntilde;ate-Oca\u0026ntilde;a et al., \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2007\u003c/span\u003e) and pancreatic (Siddiqui et al., \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2007\u003c/span\u003e) cancer. Thus, pretreatment serum albumin levels offer valuable prognostic significance in cancer, showing the less the albumin value, the worse the prognosis (Gupta and Lis, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2010\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe aim of this study was to assess whether the FAR, obtained preoperatively from patients with AEG, can predict survival rates. While it has demonstrated a prognostic value in ESCC (Tan et al., \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2017\u003c/span\u003e), significance of FAR for AEG remains uncertain, driving the focus of this study. To the best of our knowledge, this is the first study investigating the prognostic role of FAR in primarily resected AEG.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis retrospective study uses data from a prospectively maintained database from the Department of General Surgery at the Medical University of Vienna, of patients who underwent primarily resection for AEG between 1992 and 2014. The classification of the primary tumor was based on the eighth edition of the American Joint Committee on Cancer (AJCC) (Rice et al., \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). Inclusion criteria comprised availability of serum fibrinogen and albumin laboratory values obtained within two weeks before surgery, histologically confirmed diagnosis of AEG, and absence of neoadjuvant therapy. Exclusion criteria included pregnancy, age under 18 years at disease onset. Patients with fever or signs of active or chronic inflammatory disease during laboratory data collection were excluded as well. Serum fibrinogen and albumin were analyzed in the central laboratory of the Vienna General Hospital, which has a certified (ISO 9001) and accredited (ISO 15189 since 2008) quality management system.\u003c/p\u003e \u003cp\u003e The baseline clinicopathological values were retrospectively reviewed and collected from the local database and electronical patients records. The patients' baseline clinicopathologic values were retrospectively reviewed and collected from the local database and electronic patient records. Follow-up appointments were scheduled every three months for the first two years and every six months for the subsequent three years.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe analysis and correlation of the data used was carried out using IBM SPSS Statistics 29.0 (Armonk, New York, USA) software for Windows. A significance threshold of \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/em\u003e was applied for statistical significance. Categorical variables were described by absolute and relative frequencies, and metric variables were described by mean and median minimum and maximum.\u003c/p\u003e \u003cp\u003eThe FAR was defined as the fibrinogen levels divided by the serum albumin levels. Receiver-operating characteristic (ROC) curve analysis was used to determine the optimal cut-off values for fibrinogen, albumin, and FAR. The determination of these cut-off values was considered by maximizing Youden\u0026rsquo;s index (sensitivity\u0026thinsp;+\u0026thinsp;specificity \u0026minus;\u0026thinsp;1). Univariate and multivariate analyses were conducted to assess the prognostic value of FAR. In the multivariate analysis, each parameter - FAR, albumin, and fibrinogen - was individually evaluated using the Cox regression proportional hazard model to ascertain their independent prognostic significance for OS.\u003c/p\u003e \u003cp\u003eThe association between FAR and clinicopathologic factors was evaluated through the Chi-square and Kruskal-Wallis tests. Survival analysis, including OS and survival curves, was performed using the Kaplan-Meier survival curves. The disparity in survival outcomes between various groups was determined using the log-rank test. Given the exploratory nature of the study, no adjustments for multiple testing were made unless explicitly stated (Bender and Lange, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2001\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eIn the present study, a total of 135 patients (107, 79.26% male) were included (suppl. Figure\u0026nbsp;1). Mean age at the time of surgery was 66.53 years (range 44\u0026ndash;90 years), 81 patients (60%) were 65 years old or older on the day of surgery. The correlation between the clinicopathological parameters and FAR are compiled in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. The OS was settled as the endpoint, using the ROC analysis to determine the cut-off value of FAR. The Youden index calculated revealed an optimal cut-off for FAR\u0026thinsp;=\u0026thinsp;7.77 (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e), fibrinogen\u0026thinsp;=\u0026thinsp;340 (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003ea) and albumin\u0026thinsp;=\u0026thinsp;40.55 (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eb), respectively.\u003c/p\u003e\n\u003cp\u003eFor all patients the median survival of all patients was 37.4 months, and the Kaplan-Meier analysis shows that the group with high FAR has a significantly (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) worse outcome compared to the group with low FAR (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eThe univariate analysis shows significant correlation of OS and preoperative UICC stage (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), clinical tumor stage (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), clinical lymph node stage (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), postoperative UICC stage (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), pathologic tumor stage (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), pathologic lymph node stage (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), tumor grading (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002), adjuvant therapy (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), fibrinogen (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013), and FAR (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002).\u003c/p\u003e\n\u003cp\u003eMultivariate analysis was conducted using two models: one incorporating clinical staging, and another one incorporating pathological staging. In the multivariate Cox regression model with clinical staging (cT, cN) (\u003cstrong\u003eTable\u0026nbsp;2\u003c/strong\u003e), FAR was an independent predictor of OS with a hazard ratio (HR) of 2.456 (\u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e), indicating a 145.6% higher risk of earlier death. The clinical tumor stage (cT) was also significant (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.005\u003c/em\u003e), particularly for cT2 with an HR of 2.768 (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.001\u003c/em\u003e), indicating a 176.8% higher risk of earlier death. Clinical lymph node involvement (cN) was not significant overall (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.246\u003c/em\u003e), although cN2 approached significance (HR\u0026thinsp;=\u0026thinsp;2.489, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.051\u003c/em\u003e).\u003c/p\u003e\n\u003cp\u003eIn the pathological staging model (pT, pN) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e), FAR remained a significant predictor with an HR of 2.170 (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.004\u003c/em\u003e), indicating a 117% higher risk of earlier death. The pathological tumor stage (pT) was highly significant overall (\u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e), with pT 1 (HR\u0026thinsp;=\u0026thinsp;3.434, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e), pT 2 (HR\u0026thinsp;=\u0026thinsp;4.289, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e), and pT3 (HR\u0026thinsp;=\u0026thinsp;4.512, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.014\u003c/em\u003e) all showing substantial increased risks of earlier death. Pathological lymph node involvement (pN) was not significant overall (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.056\u003c/em\u003e), but pN1 (HR\u0026thinsp;=\u0026thinsp;1.889, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.029\u003c/em\u003e) and pN2 (HR\u0026thinsp;=\u0026thinsp;2.701, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.011\u003c/em\u003e) were significant.\u003c/p\u003e\n\u003cp\u003eFurthermore, the ROC curve analysis was conducted to assess the predictive value of various biomarkers for OS in patients with AEG. The AUC for fibrinogen was determined to be 0.738, (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; 95% CI [0.627 to 0.849]) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003ea). Conversely, albumin (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eb) exhibited an AUC of 0.378, with a \u003cem\u003ep\u003c/em\u003e-value of 0.047 and a 95% CI spanning from 0.267 to 0.488. The AUC for the FAR was 0.744 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001, 95% CI 0.637\u0026ndash;0.851) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cstrong\u003e)\u003c/strong\u003e, indicating superior predictive performance compared to both albumin and fibrinogen alone. Consequently, FAR emerges as a better predictor of OS in patients with AEG.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study investigated the clinical impact of the FAR in patients who underwent primarily resection of AEG. Our findings showed that higher FAR values were significantly (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) associated with lower survival rates in these patients, suggesting the potential of FAR as an independent prognostic parameter. Moreover, FAR outperformed albumin and fibrinogen in predicting patient outcomes, highlighting its enhanced predictive value for AEG patients.\u003c/p\u003e \u003cp\u003eThe response of the immunes system inflammation, and initiation of the coagulation cascade play important roles in tumor development, with fibrinogen being primarily responsible for platelet aggregation during hemostasis. As an essential hemostatic factor, it is involved in various mechanisms that hinder antitumor immunity and therefore promoting tumor progression (Mosesson, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2005\u003c/span\u003e). For instance, it may inhibit macrophage migration and disrupt fibrinogen-leukocyte interactions by modifying the leukocyte integrin binding motif and compromising the ability of the host to mount an effective immune response against tumors (Silva et al., \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Additionally, fibrinogen can inhibit the clearance of tumor cells by natural killer (NK) cells, facilitating immune evasion and metastasis (Palumbo et al., \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2005\u003c/span\u003e). Moreover, fibrinogen has been shown to promote epithelial-mesenchymal transition (EMT) through the AKT-mTOR pathway in ESCC, contributing to tumor aggressiveness prognosis (Zhang et al., \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). Therefore aiming a decrease of fibrinogen could be an approach for minimizing poor prognosis (Deng et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSimilarly, there is consensus in the literature regarding the poor prognosis associated with low albumin concentrations in cancer patients (Gupta and Lis, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2010\u003c/span\u003e), reflecting the nutritional status of patients. Malnutrition and inflammatory processes suppress albumin synthesis over time, contributing to tumor cachexia (Ballmer et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e1994\u003c/span\u003e). The prognostic relevance of albumin levels in esophageal carcinomas has been well documented (Otowa et al., \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2017\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWhile previous studies have explored the role of fibrinogen in various malignancies, including esophageal tumors, the specific prognostic value of the FAR in patients with AEG has not been investigated yet, highlighting the significance of our study. Several studies and meta-analyses have demonstrated the negative impact of high FAR values on OS in various cancers including gastrointestinal cancers (Zhang and Xiao, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Our study aligns with these findings, revealing significant results for several prognostic factors, including fibrinogen, albumin and FAR. Furthermore, the results of ROC curve analysis suggest that both fibrinogen and FAR outperform albumin in terms of predicting prognosis, underscoring the potential relevance of these parameters. However, further research is warranted to fully evaluate the prognostic impact of FAR in AEG and other malignancies.\u003c/p\u003e \u003cp\u003eThe findings of our study emphasize the importance of considering FAR, especially in clinical practice for AEG patients. Patients with high preoperative FAR values may benefit from closer monitoring and tailored therapeutic interventions to address potential complications or infections.\u003c/p\u003e \u003cp\u003eFinally, our study highlights the underexplored prognostic significance of systemic inflammatory parameters in large western cohorts with AEG. The optimal inflammatory parameter for predicting overall survival remains uncertain (Puhr et al., \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). However, our findings contribute valuable insights by identifying the FAR as a promising prognostic indicator for estimating OS in a sizable and representative European cohort of AEG patients.\u003c/p\u003e"},{"header":"Limitations","content":"\u003cp\u003eThe main limitation of this study was the retrospective design of our study which introduces inherent biases, notably selection bias, compounded by partial accessibility to pretherapeutic laboratory data. Additionally, being conducted solely at one center may limit the broader applicability of our findings. Furthermore, our study's modest sample size and extended duration could impact result reliability. To substantiate the clinical relevance of FAR, further investigations involving larger and more diverse patient cohorts are needed to validate this finding.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, elevated FAR values are linked to decreased OS in AEG patients undergoing primary surgery. Our study suggests that preoperative FAR serves as an independent prognostic factor in AEG patients, indicating that lower FAR levels may improve OS in this population.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eAuthor contributions:\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe manuscript has been read and approved by all authors. All authors contributed to the preparation of the manuscript significantly and agree with the content of the manuscript. All authors confirm that the manuscript has not been submitted elsewhere.\u0026nbsp;Study concepts: G.J., S.F.S.; Study design: G.J., S.F.S.; Data acquisition: G.J., W.Y., D.K., I.K., H.P.; Quality control of data and algorithms: D.W., A.I-M., R.A., S.F.S.; Data analysis and interpretation: G.J., D.W., A.I-M., R.A., S.F.S.; Statistical analysis: G.J., D.W.; Manuscript preparation: G.J.; Manuscript editing: \u0026nbsp;G.J.; Manuscript review: A.I-M., R.A., S.F.S.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConflicts of interest\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAIM declares following general COIs which are not directly related to the content of the manuscript: Participation in advisory boards organized by MSD, Servier, Daiichi Sankyo, BMS and Astellas, lecture honoraria from Eli Lilly, Servier, BMS, MSD, Astellas, Astra Zeneca and Daiichi Sankyo, consulting for Astellas, MSD, Amgen, Astra Zeneca and BeiGene, travel support from BMS, Roche, Eli Lilly, Daiichi Sankyo and BeiGene.\u003c/p\u003e\n\u003cp\u003eThe other authors declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent to participate\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAccording to its retrospective nature and in line with the ethics committees approval, written patient consent was not applicable to this study.\u0026nbsp;This is in line with local ethical standards and was approved\u0026nbsp;based on the ethical principles of the World Medical Association Declaration of Helsinki by the Ethics Committee of the Medical University of Vienna with the ethics vote 1132/2023. 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Cancer Manag Res 11:3381\u0026ndash;3393. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2147/CMAR.S198419\u003c/span\u003e\u003cspan address=\"10.2147/CMAR.S198419\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eAssociation of the FAR with clinicopathologic parameters.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHigh FAR\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e(%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eLow FAR\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e(%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emean Age\u003c/p\u003e\n \u003cp\u003e(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.2\u003c/p\u003e\n \u003cp\u003e(10.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64.84\u003c/p\u003e\n \u003cp\u003e(8.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.053\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.021\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ecT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ecN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.026\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.077)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003epT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.022\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003epN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.120\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAdjuvant therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.020\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eASA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.438\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eECOG PS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.828\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003eAbbreviations: \u003cem\u003eSD\u003c/em\u003e standard deviation, \u003cem\u003ec\u003c/em\u003e clinical staging, \u003cem\u003ep\u003c/em\u003e pathological staging, \u003cem\u003eASA\u003c/em\u003e American society of anesthesiologists classification, \u003cem\u003eECOG\u003c/em\u003e Eastern Cooperative Oncology Group Performance Status, HR hazard ratio,\u0026nbsp;\u003cem\u003eCI\u003c/em\u003e confidential interval;\u003cbr\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab2\" style=\"width: 1003.04px;\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable\u0026nbsp;2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eClinical staging model - univariate and multivariate Cox regression analyses estimating the influence of the FAR and clinicopathologic parameters on OS in patients with primarily resected AEG\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"left\"\u003e\n \u003cp\u003eUnivariate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"left\"\u003e\n \u003cp\u003eMultivariate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"left\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"left\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-Value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"left\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"left\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-Value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"char\"\u003e\n \u003cp\u003e1.013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e0.992\u0026ndash;1.034\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e0.222\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\n \u003cp\u003eNI\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003eSEX (ref. male)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"char\"\u003e\n \u003cp\u003e1.202\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e0.757\u0026ndash;1.909\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e0.437\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"char\"\u003e\n \u003cp\u003e0.671\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e0.408\u0026ndash;1.106\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\n \u003cp\u003e0.118\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003eG (ref. G3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.010\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003e1 vs. 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"char\"\u003e\n \u003cp\u003e0.421\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e0.151\u0026ndash;1.174\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e0.098\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"char\"\u003e\n \u003cp\u003e2.471\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e0.792\u0026ndash;7.377\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\n \u003cp\u003e0.121\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003e2 vs. 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"char\"\u003e\n \u003cp\u003e0.501\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e0.336\u0026ndash;0.747\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"char\"\u003e\n \u003cp\u003e4.309\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e1.334\u0026ndash;13.915\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.015\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003ecT (ref. cT3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"char\"\u003e\n \u003cp\u003e2.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e1.522\u0026ndash;2.640\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026gt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"char\"\u003e\n \u003cp\u003e1.748\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e1.292\u0026ndash;2.363\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003ecN (ref. cN0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"char\"\u003e\n \u003cp\u003e1.840\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e1.406\u0026ndash;2.408\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"char\"\u003e\n \u003cp\u003e1.391\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e1.040\u0026ndash;1.860\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.026\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003epT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\n \u003cp\u003eNI\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003e1 vs. 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"char\"\u003e\n \u003cp\u003e0.099\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e0.036\u0026ndash;0.272\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003e2 vs. 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"char\"\u003e\n \u003cp\u003e0.325\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e0.125\u0026ndash;0.843\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.021\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003e3 vs. 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"char\"\u003e\n \u003cp\u003e0.595\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e0.232\u0026ndash;1.523\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e0.279\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003epN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\n \u003cp\u003eNI\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003e1 vs. 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"char\"\u003e\n \u003cp\u003e0.157\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e0.075\u0026ndash;0.328\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003e2 vs. 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"char\"\u003e\n \u003cp\u003e0.517\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e0.257\u0026ndash;1.040\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e0.064\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003e3 vs. 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"char\"\u003e\n \u003cp\u003e0.998\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e0.451\u0026ndash;2.208\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e0.996\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003eAdjuvant therapy (ref. yes)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"char\"\u003e\n \u003cp\u003e0.239\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e0.157\u0026ndash;0.364\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003eASA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e0.507\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\n \u003cp\u003e0.550\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003eI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"char\"\u003e\n \u003cp\u003e1.088\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e0.610\u0026ndash;1.940\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e0.776\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"char\"\u003e\n \u003cp\u003e1.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e0.515\u0026ndash;1.949\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\n \u003cp\u003e0.997\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"char\"\u003e\n \u003cp\u003e1.651\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e0.765\u0026ndash;5.651\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e0.202\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"char\"\u003e\n \u003cp\u003e0.689\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e0.265\u0026ndash;1.789\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\n \u003cp\u003e0.444\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"char\"\u003e\n \u003cp\u003e0.739\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e0.097\u0026ndash;5.651\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e0.770\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"char\"\u003e\n \u003cp\u003e0.261\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e0.029\u0026ndash;2.348\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\n \u003cp\u003e0.231\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003eECOG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003eECOG 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"char\"\u003e\n \u003cp\u003e0.950\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e0.627\u0026ndash;1.438\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e0.808\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"char\"\u003e\n \u003cp\u003e0.711\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e0.457\u0026ndash;1.106\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\n \u003cp\u003e0.130\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003eECOG 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"char\"\u003e\n \u003cp\u003e1.063\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e0.578\u0026ndash;1.956\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e0.844\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"char\"\u003e\n \u003cp\u003e0.831\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e0.402\u0026ndash;1.716\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\n \u003cp\u003e0.616\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003eECOG 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"char\"\u003e\n \u003cp\u003e39.862\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e7.050-225.383\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"char\"\u003e\n \u003cp\u003e23.421\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e3.602-152.297\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003eFibrinogen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"char\"\u003e\n \u003cp\u003e1.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e1.000-1.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.013\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eSee suppl. Table\u0026nbsp;1\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003eAlbumin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"char\"\u003e\n \u003cp\u003e0.969\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e0.939-1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e0.053\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eSee suppl. Table\u0026nbsp;2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 603px;\" align=\"left\"\u003e\n \u003cp\u003eFAR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\" align=\"char\"\u003e\n \u003cp\u003e0.1082\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e1.030\u0026ndash;1.136\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\" align=\"char\"\u003e\n \u003cp\u003e1.102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\" align=\"char\"\u003e\n \u003cp\u003e1.040\u0026ndash;1.168\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"char\"\u003e\u0026nbsp;\u003cp\u003eAbbreviations: \u003cem\u003eNI\u003c/em\u003e not included, \u003cem\u003ec\u003c/em\u003e clinical staging, \u003cem\u003ep\u003c/em\u003e pathological staging, \u003cem\u003eOP\u003c/em\u003e operation, \u003cem\u003eHR\u003c/em\u003e hazard ratio, \u003cem\u003eCI\u003c/em\u003e confidence interval, \u003cem\u003eASA\u003c/em\u003e American society of anesthesiologists classification, \u003cem\u003eECOG\u003c/em\u003e Eastern Cooperative Oncology Group\u003c/p\u003e\n \u003cp\u003eBold values indicate statistical significance\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"char\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"char\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"char\"\u003e\u003cstrong\u003eTable 3:\u0026nbsp;\u003c/strong\u003e Pathological staging model - univariate and multivariate Cox regression analyses estimating the FAR and clinicopathologic parameters on OS in patients with primarily resected AEG\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"char\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tabb\" border=\"1\"\u003e\n \u003cthead\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003cth style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eUnivariate\u003c/p\u003e\n \u003c/th\u003e\n \u003cth style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eMultivariate\u003c/p\u003e\n \u003c/th\u003e\n \u003cth style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-Value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-Value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e1.013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.992\u0026ndash;1.034\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.222\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eNI\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eSEX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e1.202\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.757\u0026ndash;1.909\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.437\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.734\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.434\u0026ndash;1.242\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e0.249\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eG (ref. 3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e0.162\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e1 vs. 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.421\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.151\u0026ndash;1.174\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.098\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e1.370\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.474\u0026ndash;3.959\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e0.561\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e2 vs. 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.501\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.336\u0026ndash;0.747\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e2.087\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.696\u0026ndash;6.258\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.015\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003ecT (ref. cT3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e2.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e1.522\u0026ndash;2.640\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026gt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eNI\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003ecN (ref. cN0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e1.840\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e1.406\u0026ndash;2.408\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eNI\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003epT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e1 vs.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.099\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.036\u0026ndash;0.272\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e3.434\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e1.771\u0026ndash;6.657\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e2 vs. 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.325\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.125\u0026ndash;0.843\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.021\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e4.289\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e2.060\u0026ndash;8.926\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e3 vs. 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.595\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.232\u0026ndash;1.523\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.279\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e4.512\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e1.354\u0026ndash;15.039\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e0.072\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003epN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e0.056\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e1 vs. 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.157\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.075\u0026ndash;0.328\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e1.889\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e1.067\u0026ndash;3.345\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e0.290\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e2 vs. 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.517\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.257\u0026ndash;1.040\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.064\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e2.701\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e1.255\u0026ndash;5.424\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.011\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e3 vs. 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.998\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.451\u0026ndash;2.208\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.996\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e2.246\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.930\u0026ndash;5.424\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e0.071\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eAdjuvant therapy (ref. yes)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.239\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.157\u0026ndash;0.364\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eASA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.507\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e0.167\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e1.088\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.610\u0026ndash;1.940\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.776\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.454\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.220\u0026ndash;0.938\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.033\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e1.651\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.765\u0026ndash;5.651\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.202\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.374\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.127-1.100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e0.074\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.739\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.097\u0026ndash;5.651\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.770\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.493\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.051\u0026ndash;4.786\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e0.542\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eECOG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eECOG 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.950\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.627\u0026ndash;1.438\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.808\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.688\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.433\u0026ndash;1.092\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e0.113\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eECOG 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e1.063\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.578\u0026ndash;1.956\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.844\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.785\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.336\u0026ndash;1.835\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e0.576\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eECOG 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e39.862\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e7.050-225.383\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e21.268\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e2.916-155.098\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.003\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eFibrinogen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e1.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e1.000-1.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.013\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eSee suppl. Table\u0026nbsp;1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eAlbumin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.969\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.939-1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.053\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eSee suppl. Table\u0026nbsp;2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eFAR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.1082\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e1.030\u0026ndash;1.136\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e2.170\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e1.278\u0026ndash;3.683\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003eAbbreviations: \u003cem\u003eNI\u003c/em\u003e not included, \u003cem\u003ec\u003c/em\u003e clinical staging, \u003cem\u003ep\u003c/em\u003e pathological staging, \u003cem\u003eOP\u003c/em\u003e operation, \u003cem\u003eHR\u003c/em\u003e hazard ratio, \u003cem\u003eCI\u003c/em\u003e confidence interval, \u003cem\u003eASA\u003c/em\u003e American society of anesthesiologists classification, \u003cem\u003eECOG\u003c/em\u003e Eastern Cooperative Oncology Group\u003c/p\u003e\n \u003cp\u003eBold values indicate statistical significance\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003c/div\u003e\n\u003c/div\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-cancer-research-and-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jocr","sideBox":"Learn more about [Journal of Cancer Research and Clinical Oncology](https://www.springer.com/journal/432)","snPcode":"432","submissionUrl":"https://submission.nature.com/new-submission/432/3","title":"Journal of Cancer Research and Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"esophageal cancer, fibrinogen to albumin ratio, prognostic parameter, malignant tumor, prognosis","lastPublishedDoi":"10.21203/rs.3.rs-4755706/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4755706/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e\u003cem\u003e:\u003c/em\u003e Serum fibrinogen and albumin play important roles in systemic inflammation and are implicated in tumor progression. The fibrinogen-to-albumin ratio (FAR) has shown a prognostic impact in several malignancies. This study aims to assess the prognostic value of the pretherapeutic FAR in patients with adenocarcinoma of the gastroesophageal junction (AEG) who underwent upfront resection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003cem\u003e \u003c/em\u003eConsecutive patients who underwent surgical resection at the Department of Surgery at the Medical University of Vienna between 1992 and 2014 were included into this study. Optimal cut-off values were determined with the receiver-operating characteristic (ROC) curve, uni- and multivariate analyzes were calculated by the Cox proportional hazard regression model for overall survival (OS).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eAmong 135 included patients, the majority were male (79.26%), with a mean age of 66.53 years. Elevated FAR correlated significantly (\u003cem\u003ep=0.002\u003c/em\u003e) with shorter OS in univariate analysis, also confirmed as independent prognostic factor (\u003cem\u003ep=0.005\u003c/em\u003e) in multivariable analysis. The ROC curve of FAR (AUC=0.744) outperformed fibrinogen (AUC=0.738) and albumin (AUC=0.378) in predicting OS for AEG patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e The FAR serves as an independent prognostic factor for OS in patients undergoing primarily resection for AEG. Given its routine availability and ease of calculation, FAR could help in diagnosis and treatment selection for AEG patients. Further validation studies are warranted to confirm these findings conclusively.\u003c/p\u003e","manuscriptTitle":"Elevated fibrinogen-albumin ratio is an adverse prognostic factor for patients with primarily resected gastroesophageal adenocarcinoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-18 23:46:41","doi":"10.21203/rs.3.rs-4755706/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-08-13T21:22:10+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-13T20:38:53+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-02T02:19:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"336535883877179075083405841236535458775","date":"2024-08-01T09:27:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"301527202498204111479264472763694759715","date":"2024-08-01T05:01:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"94217506087671827222122333354444545168","date":"2024-08-01T02:06:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"31304498123993182259276525553230735849","date":"2024-07-21T23:36:11+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-07-18T14:51:57+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-18T14:22:54+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-18T14:21:01+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Cancer Research and Clinical Oncology","date":"2024-07-17T11:02:15+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-cancer-research-and-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jocr","sideBox":"Learn more about [Journal of Cancer Research and Clinical Oncology](https://www.springer.com/journal/432)","snPcode":"432","submissionUrl":"https://submission.nature.com/new-submission/432/3","title":"Journal of Cancer Research and Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"622a9ca3-5f38-41d2-9dfd-d7f6cb8728b2","owner":[],"postedDate":"August 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-10-21T16:08:17+00:00","versionOfRecord":{"articleIdentity":"rs-4755706","link":"https://doi.org/10.1007/s00432-024-05976-z","journal":{"identity":"journal-of-cancer-research-and-clinical-oncology","isVorOnly":false,"title":"Journal of Cancer Research and Clinical Oncology"},"publishedOn":"2024-10-14 15:56:59","publishedOnDateReadable":"October 14th, 2024"},"versionCreatedAt":"2024-08-18 23:46:41","video":"","vorDoi":"10.1007/s00432-024-05976-z","vorDoiUrl":"https://doi.org/10.1007/s00432-024-05976-z","workflowStages":[]},"version":"v1","identity":"rs-4755706","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4755706","identity":"rs-4755706","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}