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      Prognostic Value of Metastatic N1 Lymph Node Ratio and Angiolymphatic Invasion in Patients With Pathologic Stage IIA Non-Small Cell Lung Cancer

      research-article
      , MD, , MD, , MD, , MD, , MD, , MD, , MD
      Medicine
      Wolters Kluwer Health

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          Abstract

          With regard to pathologic stage IIA (pIIA) non-small cell lung cancer (NSCLC), there is a paucity of literature evaluating the risk factors for disease-free survival (DFS) and overall survival (OS). The aim of this study was to identify the prognostic factors of DFS and OS in patients with NSCLC pIIA.

          We performed a retrospective review of 98 stage II patients (7th edition of the American Joint Committee on Cancer) who underwent lung resection from January 2005 to February 2011. Of these, 23 patients were excluded for this study because of loss of follow-up or different substage, and 75 patients with pIIA were included for further univariate and multivariate analysis. Risk factors for DFS and OS were analyzed, including age, gender, smoking history, operation method, histology, differential grade, visceral pleural invasion, angiolymphatic invasion, and metastatic N1 lymph node ratio (LNR).

          Of the 75 patients with pIIA NSCLC who were examined, 29 were female and 46 were male, with a mean age of 61.8 years (range: 34–83 years). The average tumor size was 3.188 cm (range: 1.10–6.0 cm). Under univariate analysis, angiolymphatic invasion and metastatic N1 LNR were risk factors for DFS ( P = 0.011, P = 0.007). Under multivariate analysis, angiolymphatic invasion and metastatic N1 LNR were all independent risk factors for DFS, while adjuvant chemotherapy and higher metastatic N1 LNR were independent prognostic factors for OS.

          For patients with pIIA, higher metastatic N1 LNR and angiolymphatic invasion were related to poor DFS. In addition to DFS, higher metastatic N1 LNR was also a poor prognostic factor for OS rates and adjuvant therapy effectiveness. Clinical physicians should devise different postsurgical follow-up programs depending on these factors, especially for patients with high risk.

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          Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer.

          On the basis of a previous meta-analysis, the International Adjuvant Lung Cancer Trial was designed to evaluate the effect of cisplatin-based adjuvant chemotherapy on survival after complete resection of non-small-cell lung cancer. We randomly assigned patients either to three or four cycles of cisplatin-based chemotherapy or to observation. Before randomization, each center determined the pathological stages to include, its policy for chemotherapy (the dose of cisplatin and the drug to be combined with cisplatin), and its postoperative radiotherapy policy. The main end point was overall survival. A total of 1867 patients underwent randomization; 36.5 percent had pathological stage I disease, 24.2 percent stage II, and 39.3 percent stage III. The drug allocated with cisplatin was etoposide in 56.5 percent of patients, vinorelbine in 26.8 percent, vinblastine in 11.0 percent, and vindesine in 5.8 percent. Of the 932 patients assigned to chemotherapy, 73.8 percent received at least 240 mg of cisplatin per square meter of body-surface area. The median duration of follow-up was 56 months. Patients assigned to chemotherapy had a significantly higher survival rate than those assigned to observation (44.5 percent vs. 40.4 percent at five years [469 deaths vs. 504]; hazard ratio for death, 0.86; 95 percent confidence interval, 0.76 to 0.98; P<0.03). Patients assigned to chemotherapy also had a significantly higher disease-free survival rate than those assigned to observation (39.4 percent vs. 34.3 percent at five years [518 events vs. 577]; hazard ratio, 0.83; 95 percent confidence interval, 0.74 to 0.94; P<0.003). There were no significant interactions with prespecified factors. Seven patients (0.8 percent) died of chemotherapy-induced toxic effects. Cisplatin-based adjuvant chemotherapy improves survival among patients with completely resected non-small-cell lung cancer. Copyright 2004 Massachusetts Medical Society
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            Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer.

            We undertook to determine whether adjuvant vinorelbine plus cisplatin prolongs overall survival among patients with completely resected early-stage non-small-cell lung cancer. We randomly assigned patients with completely resected stage IB or stage II non-small-cell lung cancer to vinorelbine plus cisplatin or to observation. The primary end point was overall survival; principal secondary end points were recurrence-free survival and the toxicity and safety of the regimen. A total of 482 patients underwent randomization to vinorelbine plus cisplatin (242 patients) or observation (240); 45 percent of the patients had pathological stage IB disease and 55 percent had stage II, and all had an Eastern Cooperative Oncology Group performance status score of 0 or 1. In both groups, the median age was 61 years, 65 percent were men, and 53 percent had adenocarcinomas. Chemotherapy caused neutropenia in 88 percent of patients (including grade 3 febrile neutropenia in 7 percent) and death from toxic effects in two patients (0.8 percent). Nonhematologic toxic effects of chemotherapy were fatigue (81 percent of patients), nausea (80 percent), anorexia (55 percent), vomiting (48 percent), neuropathy (48 percent), and constipation (47 percent), but severe (grade 3 or greater) toxic effects were uncommon (<10 percent). Overall survival was significantly prolonged in the chemotherapy group as compared with the observation group (94 vs. 73 months; hazard ratio for death, 0.69; P=0.04), as was relapse-free survival (not reached vs. 46.7 months; hazard ratio for recurrence, 0.60; P<0.001). Five-year survival rates were 69 percent and 54 percent, respectively (P=0.03). Adjuvant vinorelbine plus cisplatin has an acceptable level of toxicity and prolongs disease-free and overall survival among patients with completely resected early-stage non-small-cell lung cancer. Copyright 2005 Massachusetts Medical Society.
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              Long-term results of the international adjuvant lung cancer trial evaluating adjuvant Cisplatin-based chemotherapy in resected lung cancer.

              PURPOSE Based on 5-year or shorter-term follow-up data in recent randomized trials, adjuvant cisplatin-based chemotherapy is now generally recommended after complete surgical resection for patients with non-small-cell lung cancer (NSCLC). We evaluated the results of the International Adjuvant Lung Cancer Trial study with three additional years of follow-up. PATIENTS AND METHODS Patients with completely resected NSCLC were randomly assigned to three or four cycles of cisplatin-based chemotherapy or to observation. Cox models were used to evaluate treatment effect according to follow-up duration. Results The trial included 1,867 patients with a median follow-up of 7.5 years. Results showed a beneficial effect of adjuvant chemotherapy on overall survival (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.02; P = .10) and on disease-free survival (HR, 0.88; 95% CI, 0.78 to 0.98; P = .02). However, there was a significant difference between the results of overall survival before and after 5 years of follow-up (HR, 0.86; 95% CI, 0.76 to 0.97; P = .01 v HR, 1.45; 95% CI, 1.02 to 2.07; P = .04) with P = .006 for interaction. Similar results were observed for disease-free survival. The analysis of non-lung cancer deaths for the whole period showed an HR of 1.34 (95% CI, 0.99 to 1.81; P = .06). CONCLUSION These results confirm the significant efficacy of adjuvant chemotherapy at 5 years. The difference in results beyond 5 years of follow-up underscores the need for the long-term follow-up of other adjuvant lung cancer trials and for a better identification of patients deriving long-term benefit from adjuvant chemotherapy.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                October 2014
                24 October 2014
                : 93
                : 20
                : e102
                Affiliations
                Division of Thoracic and Cardiovascular Surgery (C-FW, C-YW, Y-HL, M-JH, Y-CW), Department of Surgery; Division of Pulmonary and Critical Care (J-YF), Department of Internal Medicine; and Division of Pathology (C-WW), Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.
                Author notes
                Correspondence: Ching-Yang Wu, MD, Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang GungMemorial Hospital, Chang Gung University, Taoyuan, Taiwan (e-mail address: wu.chingyang@ 123456gmail.com ).
                Article
                00102
                10.1097/MD.0000000000000102
                4616304
                25365403
                bd205272-8ecd-4840-a246-aba039a3658d
                © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

                This is an open access article distributed under the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

                History
                : 30 June 2014
                : 7 August 2014
                : 10 August 2014
                Categories
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                Observational Study
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