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      Overall Survival of Stage III Colon Cancer with Only One Lymph Node Metastasis Is Independently Predicted by Preoperative Carcinoembryonic Antigen Level and Lymph Node Sampling Status

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          Abstract

          Background

          This study identified predictors of favorable overall survival (OS) for stage III colon cancer patients who had only one lymph node (LN) metastasis (N1a).

          Methods

          Variables, including preoperative carcinoembryonic antigen (CEA) level, LN sampling status, and the choices of postoperative adjuvant chemotherapy, were recorded. Prognostic significance was determined using the log-rank test and multivariate Cox regression analysis.

          Results

          The median 42-month follow-up period included 363 eligible patients. Among them, 230 (63.3%) received only 5-flurouracil (5-FU) adjuvant chemotherapy; 76 (20.9%) underwent oxaliplatin-based regimens; and 57 (15.7%) chose surgery alone. The 5-year survival rate of these evaluated patients was 75%, 63%, and 77%, respectively (P = 0.823). Multivariate analysis revealed that normal preoperative CEA level (≦5 ng/mL) and adequate LN sampling (LN ≧ 12) were significant predictors for higher 5-year OS (P < 0.001; P = 0.007, respectively). However, the use of postoperative adjuvant chemotherapy in these N1a colon cancer patients did not significantly affect their 5-year OS.

          Conclusions

          A preoperative CEA level of less than or equal to 5 ng/mL, and curative surgery with an adequate lymphadenectomy determined a favorable OS outcome in stage III colon cancer with only one LN metastasis.

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          Most cited references 18

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          Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial.

          PURPOSE Three-year disease-free survival (DFS) was significantly improved in patients who had undergone resection with curative intent for stage II or III colon cancer who received bolus plus continuous-infusion fluorouracil plus leucovorin (LV5FU2) with the addition of oxaliplatin (FOLFOX4). Final results of the study, including 6-year overall survival (OS) and 5-year updated DFS, are reported. PATIENTS AND METHODS A total of 2,246 patients were randomly assigned to receive LV5FU2 or FOLFOX4 for 6 months. The primary end point was DFS. Secondary end points were OS and safety. Results Five-year DFS rates were 73.3% and 67.4% in the FOLFOX4 and LV5FU2 groups, respectively (hazard ratio [HR] = 0.80; 95% CI, 0.68 to 0.93; P = .003). Six-year OS rates were 78.5% and 76.0% in the FOLFOX4 and LV5FU2 groups, respectively (HR = 0.84; 95% CI, 0.71 to 1.00; P = .046); corresponding 6-year OS rates for patients with stage III disease were 72.9% and 68.7%, respectively (HR = 0.80; 95% CI, 0.65 to 0.97; P = .023). No difference in OS was seen in the stage II population. The incidence of second noncolorectal cancers was 5.5% and 6.1% in the FOLFOX4 and LV5FU2 groups, respectively. Among patients receiving oxaliplatin, the frequency of grade 3 peripheral sensory neuropathy was 1.3% 12 months after treatment and 0.7% at 48 months. CONCLUSION Adding oxaliplatin to LV5FU2 significantly improved 5-year DFS and 6-year OS in the adjuvant treatment of stage II or III colon cancer and should be considered after surgery for patients with stage III disease.
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            Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging.

            The recently revised American Joint Committee on Cancer (AJCC) sixth edition cancer staging system increased the stratification within colon cancer stages II and III defined by the AJCC fifth edition system. Using nationally representative Surveillance, Epidemiology, and End Results (SEER) data, we compared survival rates associated with colon cancer stages defined according to both AJCC systems. Using SEER data (from January 1, 1991, through December 31, 2000), we identified 119,363 patients with colon adenocarcinoma and included all patients in two analyses by stages defined by AJCC fifth and sixth edition systems. Tumors were stratified by SEER's "extent of disease" and "number of positive [lymph] nodes" coding schemes. Kaplan-Meier analyses were used to compare overall and stage-specific 5-year survival. All statistical tests were two-sided. Overall 5-year survival was 65.2%. According to stages defined by the AJCC fifth edition system, 5-year stage-specific survivals were 93.2% for stage I, 82.5% for stage II, 59.5% for stage III, and 8.1% for stage IV. According to stages defined by the AJCC sixth edition system, 5-year stage-specific survivals were 93.2% for stage I, 84.7% for stage IIa, 72.2% for stage IIb, 83.4% for stage IIIa, 64.1% for stage IIIb, 44.3% for stage IIIc, and 8.1% for stage IV. Under the sixth edition system, 5-year survival was statistically significantly better for patients with stage IIIa colon cancer (83.4%) than for patients with stage IIb disease (72.2%) (P<.001). The AJCC sixth edition system for colon cancer stratifies survival more distinctly than the fifth edition system by providing more substages. The association of stage IIIa colon cancer with statistically significantly better survival than stage IIb in the new system may reflect current clinical practice, in which stage III patients receive chemotherapy but stage II patients generally do not.
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              Cancer statistics, 2009

               A Jemal,  A. JEMAL,  R. SIegel (2009)
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                18 September 2015
                2015
                : 10
                : 9
                Affiliations
                [1 ]Division of Colorectal Surgery, Department of Surgery, National Taiwan University Hospital and College of Medicine, No. 7, Chung-Shan South Road, Taipei, Taiwan, ROC
                [2 ]Department of Oncology, National Taiwan University Hospital and College of Medicine, No. 7, Chung-Shan South Road, Taipei, Taiwan, ROC
                University of Florida, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: BRL YLL HSL PHL KJC JTL. Performed the experiments: BRL YLL. Analyzed the data: BRL YLL. Contributed reagents/materials/analysis tools: BRL YLL HSL PHL KJC JTL. Wrote the paper: BRL YLL.

                PONE-D-14-35222
                10.1371/journal.pone.0137053
                4575069
                26381396

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

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                Figures: 3, Tables: 3, Pages: 10
                Product
                Funding
                This study was funded by National Research Program for Biopharmaceuticals (NRPB) at the Ministry of science and Technology of Taiwan; MOST 103-2325-B-002-033.
                Categories
                Research Article
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                All relevant data are included within the Supporting Information files.

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