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      Unusual metachronous lung adenocarcinomas harboring EGFR L858R/T790M mutations: A case report

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          Multiple primary lung cancer (MPLC) is defined as two or more primary lung cancers occurring in the same patient and can be classified as synchronous multiple primary lung cancer (sMPLC) and metachronous multiple primary lung cancer (mMPLC). Due to various clinicopathological characteristics and genetic features, MPLC is increasingly encountered in clinical practice. The distinction between MPLC and intrapulmonary metastasis (IM) is of great importance to clinical treatment and prognosis. However, there are currently no golden diagnostic criteria for MPLC due to tumor heterogeneity. Here, we report the case of a patient with four lung cancers (tumor 1, named T1, in the right middle lobe seven years earlier; tumor 2, named T2, in the left lower lobe; tumor 3 and tumor 4, named T3 and T4, in the left upper lobe) and two tumors (T1 and T2) which shared the mutation in epidermal growth factor receptor (EGFR) L858R/T790M based on targeted multigene sequencing, which indicate that these two tumors might have originated from a common ancestor. However, based on previously published guidelines, these three tumors (T2T4) were diagnosed as mMPLC.


          This is the first case of metachronous lung adenocarcinoma harboring EGFR L858R/T790M mutations in a treatment‐naïve non‐small lung cancer patient. Comprehensive clinical and molecular analysis could be helpful in differentiating multiple primary lung cancer from intrapulmonary metastasis.

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          Most cited references 19

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          The novel histologic International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification system of lung adenocarcinoma is a stage-independent predictor of survival.

          Our aim was to analyze and validate the prognostic impact of the novel International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) proposal for an architectural classification of invasive pulmonary adenocarcinomas (ADCs) across all tumor stages. The architectural pattern of a large cohort of 500 patients with resected ADCs (stages I to IV) was retrospectively analyzed in 5% increments and classified according to their predominant architecture (lepidic, acinar, solid, papillary, or micropapillary), as proposed by the IASLC/ATS/ERS. Subsequently, histomorphologic data were correlated with clinical data, adjuvant therapy, and patient outcome. Overall survival differed significantly between lepidic (78.5 months), acinar (67.3 months), solid (58.1 months), papillary (48.9 months), and micropapillary (44.9 months) predominant ADCs (P = .007). When patterns were lumped into groups, this resulted in even more pronounced differences in survival (pattern group 1, 78.5 months; group 2, 67.3 months; group 3, 57.2 months; P = .001). Comparable differences were observed for overall, disease-specific, and disease-free survival. Pattern and pattern groups were stage- and therapy-independent prognosticators for all three survival parameters. Survival differences according to patterns were influenced by adjuvant chemoradiotherapy; in particular, solid-predominant tumors had an improved prognosis with adjuvant radiotherapy. The predominant pattern was tightly linked to the risk of developing nodal metastases (P < .001). Besides all recent molecular progress, architectural grading of pulmonary ADCs according to the novel IASLC/ATS/ERS scheme is a rapid, straightforward, and efficient discriminator for patient prognosis and may support patient stratification for adjuvant chemoradiotherapy. It should be part of an integrated clinical, morphologic, and molecular subtyping to further improve ADC treatment.
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            Multiple primary lung cancers.

             N. Martini,  M Melamed (1975)
            Data on 50 patients with multiple separate primary carcinomas of the lung are presented. Eighteen had synchronous tumors and 32 had metachronous tumors, the intervals between diagnoses varying from 4 months to 16 years. Histologic patterns in the two different carcinomas were the same in 31 patients, most commonly epidermoid, and they were different in 19 patients. The problems involved in establishing the diagnosis of multiple primary lung cancers, the choice of treatment, and the expectation for survival are discussed.
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              Next-generation sequencing reveals high concordance of recurrent somatic alterations between primary tumor and metastases from patients with non-small-cell lung cancer.

              Characterization of the genomic changes that drive an individual patient's disease is critical in management of many cancers. In patients with non-small-cell lung cancer (NSCLC), obtaining tumor samples of sufficient size for genomic profiling on recurrence is often challenging. We undertook this study to compare genomic alterations identified in archived primary tumors from patients with NSCLC with those identified in metachronous or synchronous metastases. Primary and matched metastatic tumor pairs from 15 patients were analyzed by using a targeted next-generation sequencing assay in a Clinical Laboratory Improvement Amendments laboratory. Genomic libraries were captured for 3,230 exons in 182 cancer-related genes plus 37 introns from 14 genes often rearranged in cancer and sequenced to high coverage. Among 30 tumors, 311 genomic alterations were identified of which 63 were known recurrent (32 in primary tumor, 31 in metastasis) and 248 were nonrecurrent (likely passenger). TP53 mutations were the most frequently observed recurrent alterations (12 patients). Tumors harbored two or more (maximum four) recurrent alterations in 10 patients. Comparative analysis of recurrent alterations between primary tumor and matched metastasis revealed a concordance rate of 94% compared with 63% for likely passenger alterations. This high concordance suggests that for the purposes of genomic profiling, use of archived primary tumor can identify the key recurrent somatic alterations present in matched NSCLC metastases and may provide much of the relevant genomic information required to guide treatment on recurrence.

                Author and article information

                Thorac Cancer
                Thoracic Cancer
                John Wiley & Sons Australia, Ltd (Melbourne )
                12 August 2020
                October 2020
                : 11
                : 10 ( doiID: 10.1111/tca.v11.10 )
                : 3020-3023
                [ 1 ] Department of Thoracic Surgery, Beijing Haidian Hospital Haidian Section of Peking University Third Hospital Beijing China
                [ 2 ] Acornmed Biotechnology Co., Ltd Beijing China
                Author notes
                [* ] Correspondence

                Yuqing Huang, Department of Thoracic Surgery, Beijing Haidian Hospital (Haidian Section of Peking University Third Hospital), No 29, Zhongguancun Street, Haidian District, Beijing, 100080, China. Tel: +86 8269 3152; Fax: +86 10 6264 6336;

                Email: huangyuqing555@ ;

                © 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 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                Page count
                Figures: 3, Tables: 0, Pages: 4, Words: 2150
                Case Report
                Case Reports
                Custom metadata
                October 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.1 mode:remove_FC converted:01.10.2020


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