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      Comparative study of clinicopathological characteristics and prognosis between combined and pure small cell lung cancer (SCLC) after surgical resection

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          Abstract

          Background

          Histologically, SCLC are classified as pure (P‐SCLC) and combined subtypes (C‐SCLC). Currently, few studies compare the clinicopathological characteristics and explore the treatment strategies applied to them.

          Methods

          Between July 2005 and April 2016, the clinical records of 297 postoperative patients with pathologically confirmed SCLC were retrospectively analyzed. Kaplan‐Meier method and Cox regression model were separately used for stratified univariate and multivariate survival analysis.

          Results

          A total of 46 cases (15.5%) of C‐SCLCs and 251 cases (85.5%) of pure SCLCs (P‐SCLCs) were included in this study. The average age of C‐SCLCs was a little higher than that of P‐SCLCs (59.65 ± 8.72 vs. 56.56 ± 10.12; P = 0.053). More patients had a history of smoking in C‐SCLC (78.3% vs. 63.3%; P = 0.074). The five‐year overall survival (OS) rate for P‐SCLCs and C‐SCLCs was 65.1% and 56.7%, respectively ( P = 0.683). For P‐SCLC, stage and an intervention of prophylactic cranial irradiation (PCI) were independent factors that affected OS. In C‐SCLCs cases, performing sublobectomy was an independent risk factor for poor prognosis.

          Conclusions

          We identified no significant difference in clinical characteristics and outcome between C‐SCLCs and P‐SCLCs. However, the factors affecting the prognosis of the two subtypes were slightly inconsistent. For C‐SCLCs, the extent of resection had a greater impact on survival, and lobectomy combined with systemic lymph node dissection should therefore be performed as extensively as possible. In addition, PCI was beneficial in improving the SCLC OS rate.

          Key points

          • This study demonstrated the prognosis of C‐SCLCs did not significantly differ from that of P‐SCLCs, but was more susceptible to the extent of resection. Patients with C‐SCLC who underwent limited resection had a significantly increased risk of shorter OS.

          • This study highlighted the importance of performing lobectomy for resectable C‐SCLC patients. This study also proved the benefit of PCI in improving the OS rate for both P‐SCLC and C‐SCLC patients.

          Abstract

          We performed a retrospective study to compare the clinicopathological characteristics and explore treatment strategies of pure and combined SCLC and found the prognosis of C‐SCLCs were more susceptible to extent of resection than P‐SCLCs. Patients with C‐SCLC who underwent limited resection had a significantly increased risk of shorter overall survival. Based on these results, we recommend a lobectomy should be performed, especially in resectable C‐SCLC patients.

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          Most cited references15

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          The new World Health Organization classification of lung tumours.

          Tumour classification systems provide the foundation for tumour diagnosis and patient therapy and a critical basis for epidemiological and clinical studies. This updated classification was developed with the aim to adhere to the principles of reproducibility, clinical significance, and simplicity in order to minimize the number of unclassifiable lesions. Major changes in the revised classification as compared to the previous one (WHO 1981) include the addition of two pre-invasive lesions to squamous dysplasia and carcinoma in situ; atypical adenomatous hyperplasia and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. Another change is the subclassification of adenocarcinoma: the definition of bronchioalveolar carcinoma has been restricted to noninvasive tumours. There has been substantial evolution of concepts in neuroendocrine lung tumour classification. Large cell neuroendocrine carcinoma (LCNEC) is now recognized as a histologically high grade non small cell carcinoma showing histopathological features of neuroendocrine differentiation as well as immunohistochemical neuroendocrine markers. The large cell carcinoma class has been enriched with several variants, including the LCNEC and the basaloid carcinoma, both with a dismal prognosis. Finally, a new class was defined called carcinoma with pleomorphic, sarcomatoid, or sarcomatous elements, which brings together a number of proliferations characterized by a spectrum of epithelial to mesenchymal differentiation. Immunohistochemistry and electron microscopy are invaluable techniques for diagnosis and subclassification, but our intention was to render the classification simple and practical to every surgical laboratory, so that most lung tumours could be classified by light microscopic criteria.
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            Staging small cell lung cancer: Veterans Administration Lung Study Group versus International Association for the Study of Lung Cancer--what limits limited disease?

            Small cell lung cancer (SCLC) is usually classified into a two-stage system, limited (LD) and extensive disease (ED). However, the criteria for these two categories remain controversial. The widely used Veterans Administration Lung Study Group (VALG) definition of LD includes patients with primary tumor and nodal involvement limited to one hemithorax. In contrast, the International Association for the Study of Lung Cancer (IASLC) recommends that LD should additionally include all patients without distant metastasis. As a consequence, since treatment modalities for LD and ED could be different, individual clinical outcome of SCLC patients may be influenced by the staging system chosen. Among 109 consecutive SCLC patients treated in our clinic between 1989 and 1999 (mean age 68+/-9.1 years, 81% male) 23 patients (21%) could be either classified as LD or ED (LD-ED), depending on the staging system used. The prognosis of this overlapping group (LD-ED: median survival 291 days) was not statistically different from patients with limited disease defined by VALG criteria (LD-VALG: 385 days, log-rank test P = 0.42). On the other hand the survival difference between LD-ED patients and the ED-IASLC population was relevant (ED-IASLC: 208 days, P = 0.05), indicating that LD-ED patients should rather be included in the LD category. This is further supported by the results of a multivariate Cox regression analysis with all clinically relevant data. Only stage as defined by IASLC criteria was an independent prognostic factor in the likelihood-ratio-forward (hazard ratio = 1.94, CI = 1.26-2.99; P = 0.005) and backward model (hazard ratio = 1.76, CI: 1.12-2.76; P = 0.012), confirming the higher discriminatory power of the IASLC definition. In conclusion, the IASLC staging criteria for SCLC patients have a higher prognostic impact and are therefore preferable in clinical practice and future therapeutic trials. Copyright 2002 Elsevier Science Ireland Ltd.
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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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                Author and article information

                Contributors
                lijunling@cicams.ac.cn
                Journal
                Thorac Cancer
                10.1111/(ISSN)1759-7714
                TCA
                Thoracic Cancer
                John Wiley & Sons Australia, Ltd (Melbourne )
                1759-7706
                1759-7714
                11 August 2020
                October 2020
                : 11
                : 10 ( doiID: 10.1111/tca.v11.10 )
                : 2782-2792
                Affiliations
                [ 1 ] Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
                [ 2 ] Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
                [ 3 ] Department of Medical Oncology Cancer Hospital of HuanXing Beijing China
                Author notes
                [*] [* ] Correspondence

                Junling Li, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

                Tel: +86 13801178891

                Fax: +86 10 8011 5555 566 181

                Email: lijunling@ 123456cicams.ac.cn

                Author information
                https://orcid.org/0000-0002-9506-5901
                https://orcid.org/0000-0002-9678-9653
                https://orcid.org/0000-0003-2781-0962
                https://orcid.org/0000-0002-7361-325X
                Article
                TCA13591
                10.1111/1759-7714.13591
                7529571
                32779385
                7ae9c7a3-4636-4186-a9fd-d16d18ba6619
                © 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 02 May 2020
                : 05 July 2020
                : 08 July 2020
                Page count
                Figures: 4, Tables: 3, Pages: 11, Words: 6173
                Funding
                Funded by: China Cancer Foundation Marathon Fund Project
                Award ID: LC2017A20
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                October 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.1 mode:remove_FC converted:01.10.2020

                combined small cell lung cancer,prognosis,small cell lung cancer,survival analysis,treatment

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