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Factors predicting organ-specific distant metastasis in patients with completely resected lung adenocarcinoma.

ABSTRACT: The aim of the study is to demonstrate the relationship between clinicopathological variables and organ sites of metastasis in resected lung adenocarcinoma. The clinicopathological characteristics of 748 patients of resected lung adenocarcinoma at Taipei Veterans General Hospital between 2004 and 2012 were retrospectively reviewed. The prognostic value of clinicopathological variables for specific organ site metastasis-free survival was demonstrated. Among the 182 patients with distant metastasis, 93 (51.1%) patients developed contralateral lung metastasis, 81 (44.5%) had brain metastasis, 71 (39.0%) had bone metastasis, and 18 (8.9%) had liver metastasis during follow-up. Acinar predominant (Hazard ratio [HR], 0.468; 95% confidence interval [CI]: 0.250 to 0.877; P = 0.018) was significantly associated with less contralateral lung metastasis in multivariate analysis. Micropapillary predominant (HR, 2.686; 95% CI, 1.270 to 5.683; P = 0.010) was significantly associated with brain metastasis. Acinar predominant (HR, 0.461; 95% CI, 0.216 to 0.986; P = 0.046) was a significant prognostic factor for better contralateral lung metastasis-free survival in multivariate analysis. Micropapillary predominant (HR, 2.186; 95% CI, 1.148 to 4.163; P = 0.017) and solid predominant (HR, 4.093; 95% CI, 1.340 to 12.504; P = 0.013) were significant prognostic factors for worse brain metastasis-free survival and liver metastasis free-survival, respectively. There are significant differences in metastatic behavior between predominant pathological subtypes of lung adenocarcinoma. This information is important for patient follow-up strategy and identification of organ-specific distant metastasis. Prospective multi-institutional studies are mandatory for further validation.

SUBMITTER: Hung JJ

PROVIDER: S-EPMC5295429 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Factors predicting organ-specific distant metastasis in patients with completely resected lung adenocarcinoma.

Hung Jung-Jyh JJ Jeng Wen-Juei WJ Wu Yu-Chung YC Chou Teh-Ying TY Hsu Wen-Hu WH

Oncotarget 20160901 36

The aim of the study is to demonstrate the relationship between clinicopathological variables and organ sites of metastasis in resected lung adenocarcinoma. The clinicopathological characteristics of 748 patients of resected lung adenocarcinoma at Taipei Veterans General Hospital between 2004 and 2012 were retrospectively reviewed. The prognostic value of clinicopathological variables for specific organ site metastasis-free survival was demonstrated. Among the 182 patients with distant metastasi ...[more]

PMID: 27542223

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Project description:Background Lymph node involvement is one of the important prognostic factors for early-stage lung cancer. However, in lymph node-negative (N0) lung cancer the recurrent rate may be as high as 30%. We aimed to study potential prognostic factors including clinicopathological factors and epidermal growth factor receptor (EGFR) mutation status in this lung cancer population. Methods We retrospectively reviewed the medical records and pathological examinations of patients with completely resected N0 pulmonary adenocarcinoma treated in our institute between 2009 and 2016. We used Cobas® test to determine EGFR mutation status. Recurrence-free survival (RFS) was analyzed by univariable and multivariable Cox regression analyses. Results We recruited 220 patients with median duration of follow up 5 years. Majority of these patients were in stage I (80%) and did not receive adjuvant therapy (86%). There were 53% with EGFR mutations which comprised of exon 19 deletion 51% and L858R 43%. Recurrence occurred in 64 out of 220 patients (29%). The median time to recurrence was 2.1 years. Statistically significant prognostic factors in both univariate and multivariate analyses included tumor size ≥4 centimeter (cm) (HR: 1.94; 95% CI: 1.03–3.67), visceral pleural invasion (HR: 2.53; 95% CI: 1.34–4.79), tumor necrosis (HR: 2.45; 95% CI: 1.13–5.31) and bronchial resection margin <2 cm (HR: 1.96; 95% CI: 1.10–3.51). However, presence of sensitizing EGFR mutation was not found to be a significant prognostic factor (HR: 1.20; 95% CI: 0.66–2.18; P=0.56). Conclusions In N0 surgically resected lung adenocarcinoma, there were significant pathological prognostic factors including tumor 4 cm or more, visceral pleural invasion, tumor necrosis and bronchial resection margin less than 2 cm. Mutation of EGFR is not a significant prognostic factor to determine the risk of recurrence in this population and their risks shall be determined by the other poor prognostic factors.

Project description:BackgroundThe genomic features of cancer cells may confer the metastatic ability of lung adenocarcinoma (LUAD) to metastasize to specific organs. We aimed to identify the differences in genomic alterations between patients with primary LUAD with and without metastases and to elucidate the metastatic biology that may help developing biomarker-directed therapies for advanced or metastatic disease.MethodsA retrospective cohort of 497 patients with LUAD including 388 primary tumors (PR), 53 bone metastases (MT-bone), 30 liver metastases (MT-liver), and 26 brain metastases (MT-brain) was tested for genomic alterations by a next-generation sequencing assay.ResultsThe EGFR, TP53, TERT, LRP1B, CDKN2A, ERBB2, ALK, and KMT2C genes had a high frequency of mutations, and the mutations were shared by PR and metastases groups. TP53 and EGFR were the most common mutated genes. In comparison with PR, KRAS, STK11, ATM, NPM1, and ROS1 were significantly mutated in MT-brain, and TP53, MYC, RSPO2, CDKN2a, and CDKN2B were significantly mutated in MT-liver. The frequencies of TP53, CDKN2A, MTAP, PRKCI, and APC mutations were higher in MT-bone than that in PR. The ERBB, phosphoinositide-3-kinase/protein kinase B (PI3K-AKT), cell cycle, Fibroblast growth factor (FGF), and homologous recombination deficiency signaling pathways were affected in both PR and metastases, and there is higher frequency of mutations in metastases. Moreover, the co-mutations in patients with PR and metastasis were respectively analyzed. In addition, the programmed death ligand 1 (PD-L1) level was obviously related to tumor stage and tumor metastases, and the tumor mutational burden was correlated to clinicopathological features including age, gender, pathological stages, and tumor metastases. FGFR1, KAT6A, MYC, RAD21, TP53, and DAXX were also dramatically correlated to the tumor mutational burden.ConclusionMetastases are the most devastating stage of tumors and the main cause of cancer-related deaths. Our results provided a clinically relevant view of the tumor-intrinsic mutational landscape of patients with metastatic LUAD.

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Factors predicting organ-specific distant metastasis in patients with completely resected lung adenocarcinoma.

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Factors predicting organ-specific distant metastasis in patients with completely resected lung adenocarcinoma.

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