New insights into the impact of primary lung adenocarcinoma location on metastatic sites and sequence: A multicenter cohort study
New insights into the impact of primary lung adenocarcinoma location on metastatic sites and sequence: A multicenter cohort study
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DOI：
10.1016/j.lungcan.2018.11.004
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发表时间：
2018-12-01
期刊：
影响因子：
5.3
通讯作者：
Moldvay, Judit
中科院分区：
文献类型：
--
作者：
Klikovits, Thomas;Lohinai, Zoltan;Moldvay, Judit
简介：器官转移的存在是肺腺癌（LADC）预后不良的主要因素。然而，原发肿瘤位置对转移部位和顺序的影响尚未得到广泛分析。方法：我们进行了一项多中心队列研究，评估了 1126 名白种人 LADC 患者的临床病理数据，重点关注疾病进展过程中原发肿瘤和转移部位的不同位置。结果：发生肺转移（p < 0.001）、胸膜转移（p < 0.001）和肾上腺转移（p < 0.001）疾病进展早期和中心原发肿瘤与早期转移相关（OR 1.43，p = 0.02）。在二次探索性分析中，我们发现中心性肿瘤患者骨转移更常见（OR 1.86，p = 0.017），而周围肿瘤患者肺转移更常见（OR 1.35，p = 0.015）。在单变量（HR 2.075，p = 0.001）和多变量（HR 1.558，p < 0.001）分析中，中央原发性 LADC 与中位总生存期下降（与周围肿瘤相比，10.2 个月与 22 个月）相关，且与分期和 T 因子无关。通过随后的分析，我们发现，如果转移事件独立发生，骨转移往往与肾上腺和肝转移一起出现，肾上腺与皮肤转移、胸膜转移与心包转移一起出现的频率比预期更高。结论：这项全面的大队列分析表明，LADC 患者存在转移部位和序列特异性变异。中央 LADC 与早期转移性疾病、骨受累以及因此导致的生存率降低有关。
Introduction: The presence of organ metastases is a major factor for unfavorable prognosis in lung adenocarcinoma (LADC). However, the influence of primary tumor location on metastatic sites and sequence has not been extensively analyzed.Methods: We performed a multicenter cohort study, evaluating clinicopathological data of 1126 Caucasian LADC patients, focusing on the distinct location of primary tumors and metastatic sites during disease progression.Results: Metastases to the lung (p < 0.001), pleura (p < 0.001) and adrenal glands (p < 0.001) occurred earlier during disease progression and central primary tumors were associated with early metastases (OR 1.43, p = 0.02). In secondary exploratory analysis we found that bone metastases were more frequent in patients with central tumors (OR 1.86, p = 0.017), whereas lung metastases in those with peripheral tumors (OR 1.35, p = 0.015). Central primary LADCs were associated with decreased median overall survival (vs. peripheral tumors, 10.2 vs. 22 months) both in univariate (HR 2.075, p = 0.001) and in multivariate (HR 1.558, p < 0.001) analyses and independent from stage and T factor. By subsequent analysis, we found that bone metastases tend to appear together with adrenal and liver metastases, and adrenal with skin, and pleural with pericardial metastases more frequently than expected if metastatic events occurred independently.Conclusion: This comprehensive large cohort analysis demonstrates metastatic site- and sequence-specific variations in patients with LADC. Central LADC is associated with early metastatic disease, bone involvement and, consequently, decreased survival.