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      Log odds of positive lymph nodes is prognostically equivalent to lymph node ratio in non-metastatic colon cancer

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          Abstract

          Background

          Globally, colorectal cancer (CRC) is the third and second leading cancer in men and women respectively with 600,000 deaths per year. Traditionally, clinicians have relied solely on nodal disease involvement, and measurements such as lymph node ratio (LNR; the ratio of metastatic/positive lymph nodes to total number of lymph nodes examined), when determining patient prognosis in CRC. The log odds of positive lymph nodes (LODDS) is a logistic transformation formula that uses pathologic lymph node data to stratify survival differences among patients within a single stage of disease. This formula allows clinicians to identify whether patients with clinically aggressive tumours fall into higher-risk groups regardless of nodal positivity and can potentially guide adjuvant treatment modalities. The aim of this study was to investigate whether LODDS in colon cancer provides better prognostication compared to LNR.

          Methods

          A retrospective study of patients on the prospectively maintained Cabrini Monash University Department of Surgery colorectal neoplasia database, incorporating data from hospitals in Melbourne Australia, identified patients entered between January 2010 and March 2016. Association of LODDS and LNR with clinical variables were analysed. Disease-free (DFS) and overall (OS) survival were investigated with Cox regression and Kaplan–Meier survival analyses.

          Results

          There were 862 treatment episodes identified in the database (402 male, 47%). The median patient age was 73 (range 22–100 years). There were 799 colonic cancers and 63 rectosigmoid cancers. The lymph node yield (LNY) was suboptimal (< 12) in 168 patients (19.5%) ( p = 0.05). The 5-year OS for the different LNR groups were 86, 91 and 61% ( p < 0.001) for LNR 0 (655 episodes), LNR 1 (128 episodes) and LNR 2 (78 episodes), respectively. For LODDS, they were 85, 91 and 61% ( p < 0.001) in LODDS 0 (569 episodes), LODDS 1 (217 episodes) and LODDS 2 (75 episodes) groups ( p < 0.001). Overall survival rates were comparable between the LNR and LODDS group and for LNY < 12 and stage III patients when each were sub-grouped by LODDS and LNR.

          Conclusion

          This study has shown for that the prognostic impact of LODDS is comparable to LNR for colon cancer patients. Accordingly, LNR is recommended for prognostication given its ease of calculation.

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          Most cited references22

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          Prognostic value of the lymph node ratio in stage III colorectal cancer: a systematic review.

          Although nodal invasion represents one of the most powerful prognostic indicators in colorectal cancer, marked heterogeneity exists within stage III patients. Recently, the lymph node ratio (LNR), defined as the ratio of the number of positive nodes over the total number of examined nodes, was proposed to stratify outcome in stage III patients. A systematic search was performed for studies examining the prognostic significance of the LNR in colon or rectal cancer. Individual studies were assessed for methodological quality and summary data extracted. Hazard ratios from multivariate analyses were entered in a fixed-effects meta-analysis model. In total, 16 studies were identified including 33,984 patients with stage III colon or rectal cancer. In all identified studies, the LNR was identified as an independent prognostic factor in patients with stage III cancer of the colon or rectum. The prognostic separation obtained by the LNR was superior to that of the number of positive nodes (N stage). The pooled hazard ratios for overall and disease-free survival were 2.36 (95% confidence interval, 2.14-2.61) and 3.71 (95% confidence interval, 2.56-5.38), respectively. The LNR allows superior prognostic stratification in stage III colorectal cancer and should be validated in prospective studies.
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            The prognostic superiority of log odds of positive lymph nodes in stage III colon cancer.

            Literature showed that lymph node ratio (LNR) and total number of lymph nodes (TNODS) are independent prognostic factors in node-positive colon cancer. Our study assesses the prognostic superiority of the log odds of positive lymph nodes (LODDS) in the same patient population. A total of 24,477 stage III colon cancer cases from the SEER registry were reviewed. Patients were categorized based on LNR into LNR1 to LNR4, according to cutoff points 0.07, 0.25, and 0.50, and based on LODDS into LODDS1 to LODDS5, according to cutoff points -2.2, -1.1, 0, and 1.1. The relative risk (RR), and 95% confidence interval (CI) were evaluated using the method of Kaplan-Meier and Cox model. Patients with LNR4 could be classified into LODDS4 (61.4%) and LODDS5 (38.4%). The survival in these two groups was significantly different (5-year survival, 33.5% vs. 23.3%, p < 0.0001). Univariate analysis showed that the higher LNR (RR = 3.45, 95% CI = 3.26-3.66) or low TNODS (RR = 0.99, 95% CI = 0.986-0.99) was significantly associated with poor survival. However, after adjusting for LODDS status, the association did not appear to be significant (LNR, RR = 0.90, 95% CI = 0.65-1.24, p = 0.52; TNODS, RR = 1.001, 95% CI = 0.997-1.005, p = 0.54). Colon cancer patients with LNR4 disease represent a heterogeneous group. The previously reported prognostic association of TNODS and LNR and outcome of stage III disease were confounded by LODDS.
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              Ratios of involved nodes in early breast cancer

              Introduction The number of lymph nodes found to be involved in an axillary dissection is among the most powerful prognostic factors in breast cancer, but it is confounded by the number of lymph nodes that have been examined. We investigate an idea that has surfaced recently in the literature (since 1999), namely that the proportion of node-positive lymph nodes (or a function thereof) is a much better predictor of survival than the number of excised and node-positive lymph nodes, alone or together. Methods The data were abstracted from 83,686 cases registered in the Surveillance, Epidemiology, and End Results (SEER) program of women diagnosed with nonmetastatic T1–T2 primary breast carcinoma between 1988 and 1997, in whom axillary node dissection was performed. The end-point was death from breast cancer. Cox models based on different expressions of nodal involvement were compared using the Nagelkerke R2 index (R2 N). Ratios were modeled as percentage and as log odds of involved nodes. Log odds were estimated in a way that avoids singularities (zero values) by using the empirical logistic transform. Results In node-negative cases both the number of nodes excised and the log odds were significant, with hazard ratios of 0.991 (95% confidence interval 0.986–0.997) and 1.150 (1.058–1.249), respectively, but without improving R2 N. In node-positive cases the hazard ratios were 1.003–1.088 for the number of involved nodes, 0.966–1.005 for the number of excised nodes, 1.015–1.017 for the percentage, and 1.344–1.381 for the log odds. R2 N improved from 0.067 (no nodal covariate) to 0.102 (models based on counts only) and to 0.108 (models based on ratios). Discussion Ratios are simple optimal predictors, in that they provide at least the same prognostic value as the more traditional staging based on counting of involved nodes, without replacing them with a needlessly complicated alternative. They can be viewed as a per patient standardization in which the number of involved nodes is standardized to the number of nodes excised. In an extension to the study, ratios were validated in a comparison with categorized staging measures using blinded data from the San Jose–Monterey cancer registry. A ratio based prognostic index was also derived. It improved the Nottingham Prognostic Index without compromising on simplicity.
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                Author and article information

                Contributors
                simonwilkins@cabrini.com.au
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                14 August 2020
                14 August 2020
                2020
                : 20
                : 762
                Affiliations
                [1 ]GRID grid.1002.3, ISNI 0000 0004 1936 7857, Department of Surgery, Cabrini Hospital, , Cabrini Monash University, ; Malvern, VIC 3144 Australia
                [2 ]GRID grid.1002.3, ISNI 0000 0004 1936 7857, Department of Epidemiology and Preventive Medicine, , Monash University, ; Melbourne, VIC 3004 Australia
                [3 ]GRID grid.440111.1, ISNI 0000 0004 0430 5514, Cabrini Institute, Cabrini Hospital, ; Malvern, VIC 3144 Australia
                Author information
                https://orcid.org/0000-0001-7712-4114
                Article
                7260
                10.1186/s12885-020-07260-y
                7427861
                32795292
                ac6cde31-4079-4686-9dac-6f0e24a171e6
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.

                History
                : 21 May 2020
                : 4 August 2020
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Oncology & Radiotherapy
                colon cancer,lymph nodes,patient outcomes
                Oncology & Radiotherapy
                colon cancer, lymph nodes, patient outcomes

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