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      Further understanding of an uncommon disease of combined small cell lung cancer: clinical features and prognostic factors of 114 cases

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          Abstract

          Objective

          Combined small cell lung cancer (C-SCLC) is an uncommon subgroup of small cell lung cancer (SCLC) and few clinical data can be referred. Our study is to investigate the clinical features and prognostic factors of C-SCLC, as well as the role of multimodality treatment.

          Methods

          Between January 2004 and December 2012, patients with histologically diagnosed C-SCLC were retrospectively analyzed. The survivals were evaluated with the Kaplan-Meier method. Univariate and multivariate analyses were used to evaluate potential prognostic factors.

          Results

          One hundred and fourteen patients were enrolled, with a median age of 59 (range: 20−79) years old. The most common combined component was squamous cell carcinoma (52.6%). Among these patients, the disease was stage I, II, III and IV in 9.6%, 19.3%, 46.5% and 24.6% of the patients, respectively. Eighty patients (70.2%) received at least two of the three modalities containing chemotherapy, radiotherapy and surgery. The median follow-up was 32.5 months. The median time of overall survival (OS) was 26.2 months. On univariate analysis, smoking (P=0.029), Karnofsky performance score (KPS) <80 (P=0.000), advanced TNM stage (P=0.000), no surgery (P=0.010), positive resection margin (P=0.000), positive lymph nodes ≥4 (P=0.000), positive lymph node ratio >10% (P=0.000) and non-multimodality treatment (P=0.004) were associated with poor OS. Multivariate analysis confirmed that smoking, advanced TNM stage, positive resection margin and positive lymph nodes ratio >10% were poor prognostic features.

          Conclusions

          C-SCLC has a relatively early stage and good prognosis, which may due to the underestimated diagnosis in non-surgical patients. Multimodality therapy is recommended, especially for limited disease. Smoking, advanced TNM stage, positive resection margin and positive lymph nodes ratio >10% are poor prognostic factors.

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          Most cited references17

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          Pleomorphic (spindle/giant cell) carcinoma of the lung. A clinicopathologic correlation of 78 cases.

          The authors undertook this study to define the clinical and histologic characteristics of spindle and giant cell carcinomas of the lung and the survival and prognostic features of these tumors. Seventy-eight cases of pleomorphic (spindle and/or giant cell) carcinoma of the lung were studied by light microscopy and immunohistochemistry to establish clinical, gross, and histologic parameters. Follow-up information was obtained from contributing physicians and analyzed by statistical means to determine prognostically significant parameters. The patient population consisted of 57 men and 21 women (male to female ratio, 2.7 to 1) between the ages of 35 and 83 years (mean, 62 years). Clinically, 58 patients (80%) presented with symptoms including thoracic pain, cough, and hemoptysis, whereas 14 (18%) were asymptomatic. At the time of diagnosis, 41% of the patients had clinical Stage I lesions, 6% Stage II lesions, 39% Stage III lesions, and 12% Stage IV lesions. Histologically, foci of squamous cell carcinoma were present in 8% of the tumors, large cell carcinoma in 25%, and adenocarcinoma in 45%. The remaining 22% of neoplasms were completely spindle and/or giant cell carcinomas. Spindle and giant cell carcinomas were found together in 38% of the patients. In the 69 patients for whom follow-up information was obtained, 53 (77%) died within 7 days to 6 years after diagnosis, with a 23-month mean survival (median, 10 months) (Kaplan-Meier method). There was a significant shortening of survival for patients with tumor size greater than 5 cm, clinical stage greater than 1, and lymph node involvement. The presence of nodal metastases was the most significant single prognostic factor, whereas the presence of squamous or adenocarcinomatous differentiation did not have an impact on length of survival. The frequency with which spindle and giant cell carcinomas are found together, their frequent association with other histologic subtypes of lung carcinoma, and the similar clinicopathologic features of these tumors suggest that they are best regarded as one type of lung cancer called pleomorphic carcinoma.
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            Small cell lung carcinoma (SCLC): a clinicopathologic study of 100 cases with surgical specimens.

            Separation of small cell lung carcinoma (SCLC) from nonsmall cell lung carcinoma (NSCLC) is a critical distinction to be made in the diagnosis of lung cancer. However, the diagnosis of SCLC is most commonly made on small biopsies and cytologic specimens, and practicing pathologists may not be familiar with all its morphologic guises and frequent combination with NSCLC elements, which may be seen in larger specimens. Following the most recent WHO classification of lung tumors and with the hope of identifying prognostic markers, we examined in detail the histology of 100 surgical biopsies or resections with a diagnosis of SCLC from the AFIP and pathology panel of the International Association for the Study of Lung Cancer (IASLC). Multiple clinical and histologic features were studied by Kaplan-Meier analysis. Neuroendocrine architectural patterns, including nested and trabecular growth, with peripheral palisading and rosette formation were common in SCLC. Necrosis and apoptotic debris was prominent in all cases, but crush artifact was infrequent. Cell size in surgical biopsy specimens appears larger than in bronchoscopic biopsy specimens and occasional cells may show prominent nucleoli and vesicular nuclear chromatin, but this does not preclude the diagnosis of SCLC. A high percentage of cases (28%) showed combinations with NSCLC, with large cell carcinoma the most common, followed by adenocarcinoma and squamous cell carcinoma. Because of the frequency of a few scattered large cells in SCLC, we arbitrarily recommend that at least 10% of the tumor show large cell carcinoma before subclassification as combined SC/LC. However, combined SCLC is easily recognized if the additional component consists of other NSCLC subtypes such as adenocarcinoma or squamous cell carcinoma, so no percentage requirement is needed. Stage remained the only predictor of prognosis.
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              Combined SCLC clinical and pathologic characteristics.

              Despite the well characterized clinical course of 'pure' SCLC, there have not been many data on combined SCLC, ie, tumors, which contain both small-cell and non-small-cell components. We analyzed 1628 consecutive cases of lung cancer (1200 NSCLC, 428 SCLC) at our institution over the past decade. We identified 22 patients with C-SCLC. The pathologic and clinical characteristics of these patients were reviewed. Survival analysis was performed and prognostic factors were assessed. These data were compared with the results obtained from our 406 pure SCLC patients who presented during the same time period. The most common pathology was combined small-cell and large-cell with 16 cases followed by combined small- and squamous-cell carcinoma (3 cases), 2 cases of small-cell and nonspecified NSCLC, and 1 case of small cell and adenocarcinoma. Overall survival was significantly higher in C-SCLC patients compared with pure SCLC (median 15 vs. 10.8 months; P = .035). Surgery was significantly more common in this group of patients (45% vs. 3% in the pure small cell group; P < .0001). No difference in overall survival was observed in patients with C-SCLC and patients with pure SCLC, that did not receive surgery (P = .64). Patients with combined SCLC carry a better prognosis than those with pure small-cell variety and are more likely to undergo surgery. Copyright © 2013 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Chin J Cancer Res
                Chin. J. Cancer Res
                CJCR
                Chinese Journal of Cancer Research
                AME Publishing Company
                1000-9604
                1993-0631
                October 2016
                : 28
                : 5
                : 486-494
                Affiliations
                [1 ]Department of Radiation Oncology
                [2 ]Department of Special Medical Services & Department of Radiation Oncology, National Cancer Center/Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China
                Author notes
                Zhouguang Hui, MD. Department of Special Medical Services & Department of Radiation Oncology, National Cancer Center/Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, China. Email: drhuizg@ 123456163.com
                Article
                cjcr-28-5-486
                10.21147/j.issn.1000-9604.2016.05.03
                5101222
                cb260232-5504-4a8d-b87f-aaa390a0c3bc
                Copyright © 2016 Chinese Journal of Cancer Research. All rights reserved.

                This work is licensed under a Creative Commons Attribution-Non Commercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/

                Categories
                Original Article

                combined small cell lung carcinoma,diagnosis,prognosis,multimodality therapy

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