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      The pretreatment Controlling Nutritional Status (CONUT) score is an independent prognostic factor in patients with resectable thoracic esophageal squamous cell carcinoma: results from a retrospective study


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          The purpose of this study was to investigate the impact of the Controlling Nutritional Status (CONUT) score on survival compared with the platelet to lymphocyte ratio (PLR), the neutrophil to lymphocyte ratio (NLR), and the Glasgow Prognostic Score (GPS) in patients with resectable thoracic esophageal squamous cell carcinoma (ESCC).


          One hundred eighty-five consecutive patients who underwent subtotal esophagectomy with curative intent for resectable thoracic ESCC were retrospectively reviewed. Time-dependent receiver operating characteristic curve analyses for 3-year overall survival (OS) as the endpoint were performed, and the maximal Youden indices were calculated to assess discrimination ability and to determine the appropriate cut-off values of CONUT, PLR, and NLR. The patients were then classified into high and low groups based on these cut-off values. Correlations between CONUT and other clinicopathological characteristics were analyzed. Prognostic factors predicting overall survival (OS) and relapse-free survival (RFS) were analyzed using Cox proportional hazards models.


          The areas under the curve predicting 3-year OS were 0.603 for CONUT, 0.561 for PLR, 0.564 for NLR, and 0.563 for GPS. The optimal cut-off values were two for the CONUT score, 193 for PLR, and 3.612 for NLR. The high-CONUT group was significantly associated with lower BMI, high-PLR, high-NLR, and GPS1/2 groups. On univariate analysis, high-CONUT, high-PLR, high-NLR, and GPS 1/2 groups were significantly associated with poorer OS and RFS. Of these factors, multivariate analysis revealed that only the CONUT score was an independent prognostic factor for OS (HR 2.303, 95 % CI 1.191–4.455; p = 0.013) and RFS (HR 2.163, 95 % CI 1.139–4.109; p = 0.018).


          The CONUT score was an independent predictor of OS and RFS before treatment and was superior to PLR, NLR, and GPS in terms of predictive ability for prognosis in patients with resectable thoracic ESCC.

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          Time-dependent ROC curves for censored survival data and a diagnostic marker.

          ROC curves are a popular method for displaying sensitivity and specificity of a continuous diagnostic marker, X, for a binary disease variable, D. However, many disease outcomes are time dependent, D(t), and ROC curves that vary as a function of time may be more appropriate. A common example of a time-dependent variable is vital status, where D(t) = 1 if a patient has died prior to time t and zero otherwise. We propose summarizing the discrimination potential of a marker X, measured at baseline (t = 0), by calculating ROC curves for cumulative disease or death incidence by time t, which we denote as ROC(t). A typical complexity with survival data is that observations may be censored. Two ROC curve estimators are proposed that can accommodate censored data. A simple estimator is based on using the Kaplan-Meier estimator for each possible subset X > c. However, this estimator does not guarantee the necessary condition that sensitivity and specificity are monotone in X. An alternative estimator that does guarantee monotonicity is based on a nearest neighbor estimator for the bivariate distribution function of (X, T), where T represents survival time (Akritas, M. J., 1994, Annals of Statistics 22, 1299-1327). We present an example where ROC(t) is used to compare a standard and a modified flow cytometry measurement for predicting survival after detection of breast cancer and an example where the ROC(t) curve displays the impact of modifying eligibility criteria for sample size and power in HIV prevention trials.
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            A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907).

            Patients with esophageal carcinoma receiving postoperative chemotherapy showed superior disease-free survival than those receiving surgery alone in a Japan Clinical Oncology Group trial (JCOG9204). The purpose of this study was to evaluate optimal perioperative timing-that is, before or after surgery-for providing chemotherapy in patients with locally advanced esophageal squamous cell carcinoma. Eligible patients with clinical stage II or III, excluding T4, squamous cell carcinoma were randomized to undergo surgery followed (group 1) or preceded (group 2) by chemotherapy consisting of two courses of cisplatin plus 5-fluorouracil. The primary end point was progression-free survival. We randomized 330 patients, with 166 assigned to group 1 and 164 to group 2, between May 2000 and May 2006. The planned interim analysis was conducted after completion of patient accrual. Progression-free survival did not reach the stopping boundary, but overall survival in group 2 was superior to that of group 1 (P = 0.01). Therefore, the Data and Safety Monitoring Committee recommended early publication. Updated analyses showed the 5-year overall survival to be 43% in group 1 and 55% in group 2 (hazard ratio 0.73, 95% confidence interval 0.54-0.99, P = 0.04), where the median follow-up of censored patients was 61.6 months. Concerning operative morbidity, renal dysfunction after surgery in group 2 was slightly higher than in group 1. Preoperative chemotherapy with cisplatin plus 5-fluorouracil can be regarded as standard treatment for patients with stage II/III squamous cell carcinoma.
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              Elevated preoperative neutrophil:lymphocyte ratio as a predictor of postoperative disease recurrence in esophageal cancer.

              The prognosis for patients with esophageal cancer is poor, even among those who undergo potentially curative esophagectomy. The neutrophil:lymphocyte ratio (NLR) is hypothesized to reflect the systemic inflammatory response created by a tumor and is possibly predictive of tumor aggressiveness and propensity for metastasis. We performed a single-center retrospective analysis of esophageal cancer patients who underwent attempted curative esophagectomy at Weill Cornell Medical Center between 1996 and 2009. We collected data on patient demographics, clinical characteristics, and receipt of neoadjuvant treatment. Preoperative blood tests were used to calculate NLR. Elevated NLR was defined a priori as ≥5.0. Logistic regression modeling was performed to analyze characteristics associated with elevated NLR. We conducted Kaplan-Meier analyses and Cox regression modeling to determine estimates and predictors of disease-free and overall survival. We identified a total of 295 patients who underwent esophagectomy. The median duration of follow-up was 31 months (interquartile range [IQR] 13-61). There were 56 patients (18.9%) who had elevated NLR preoperatively. Receipt of neoadjuvant therapy was independently associated with high NLR (odds ratio [OR] 2.14, 95% confidence interval [95% CI] 1.02-4.51). In multivariable analyses, elevated NLR was associated with significantly worse disease-free (hazard ratio [HR] 2.26, 95% CI 1.43-3.55) and overall survival (HR 2.31, 95% CI 1.53-3.50). Preoperative NLR is a potential prognostic marker for recurrence and death after esophagectomy. It is unclear whether NLR reflects the degree of inflammatory response to the primary tumor or other patient-specific or tumor characteristics that predispose to recurrence. Further investigation is warranted to clarify the mechanisms explaining the observed associations between elevated NLR and poor outcomes in esophageal cancer.

                Author and article information

                +8666453838 , t-toyokawa@med.osaka-cu.ac.jp
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                6 September 2016
                6 September 2016
                : 16
                : 1
                : 722
                [1 ]Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585 Japan
                [2 ]Department of Gastroenterological Surgery, Osaka City General Hospital, 2-13-22, Miyakojimahondohri, Miyakojima-ku, Osaka, 534-0021 Japan
                Author information
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                : 10 June 2016
                : 7 August 2016
                Research Article
                Custom metadata
                © The Author(s) 2016

                Oncology & Radiotherapy
                esophageal cancer,esophagectomy,prognostic factor,nutrition,controlling nutritional status


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