論文No1907
New insights into the impact of primary lung adenocarcinoma location on metastatic sites and sequence: A multicenter cohort study
Thomas Klikovits, Zoltán Lohinai, Katalin Fábián, Márton Gyulai, Mária Szilasi, Judit Varga, Erika Baranya, Orsolya Pipek, István Csabai, Zoltán Szállási, József Tímár, Mir Alireza Hoda, Viktoria Laszlo, Balázs Hegedűs, Ferenc Renyi-Vamos, Walter Klepetko, Gyula Ostoros, Balázs Döme, Judit Moldvay
Lung Cancer, Volume 126, Pages 139–148, 2018.
＜背景＞
肺腺がん(LADC)において臓器転移は予後不良の主な因子である。
しかし、原発巣の部位と転移の部位との関連、影響についてはよくわかっていない。
＜方法＞
多施設コホート研究で、1126名の白人のLADC患者の臨床病理データを、
原発巣の部位と経過中の転移の部位に焦点をあてて評価した。
＜結果＞
肺転移(p<0.001)、胸膜転移(p<0.001)、副腎転移(p<0.001)は早期に起こり、
中枢性の原発巣では早期の転移と関連していた(OR 1.43, P=0.02)。
探索的解析では、骨転移は中枢性腫瘍でより頻度が高かった(OR 1.86, p=0.017)。
末梢型肺がんでは肺転移が多かった(OR 1.35, p=0.015)。
中枢型LADCでは生存期間中央値が短く(10.2 vs 22 か月)、
これは単変量解析(HR 2.075, p=0.001)でも多変量解析(HR 1.558, p<0.001)でも有意差があり、
ステージやＴ因子に関連しなかった。
さらなる解析で、骨転移や副腎転移や肝臓転移と同時に現れる傾向にあり、
副腎転移は皮膚転移と、胸膜転移は心膜転移と同時期に現れる傾向にあった。
＜感想＞
中枢型の肺腺がんでは転移が早く起こり、予後不良で、骨転移が多かったようです。
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.