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    2020-08-06


    * Corresponding author.
    E-mail address: [email protected] (N. Kanaji).
    Please cite this article as: Kanaji N et al., Association of specific metastatic organs with the prognosis and chemotherapeutic response in patients with advanced lung cancer, Respiratory Investigation, https://doi.org/10.1016/j.resinv.2019.06.004
    1. Introduction
    The International Association for the Study of Lung Cancer proposed the M1a, b, and c categories in the 8th version of the TNM classification for lung cancer staging [1]. A poorer prog-nosis in M1c diseases, which are stage IVB, has been confirmed in several studies [2e4]. Individuals with two or more extrapulmonary metastatic sites (EPMSs) have a worse prognosis than do those with one EPMS [2]. Similarly, a high number of metastatic organs is an independent poor prog-nostic factor in patients with advanced lung adenocarcinoma [5].
    Several research groups have investigated whether specific metastatic organs affect patient survival [2,3,6e10], but their findings have been varied. Bone 2-Guanidinoethylmercaptosuccinic Acid may not affect survival or may be associated with better or poor survival [6,9,10]. Adrenal metastases may also be associated with bet-ter or poor survival [2,7]. Thus, the influences of different metastatic organs on the prognosis and therapeutic effect have not been fully elucidated. We conducted the present study to examine the effects of specific metastatic organs on the prognosis and first-line therapeutic efficacy in patients with advanced lung cancer.
    basis of these radiological modalities. When necessary, the diagnosis of metastasis was confirmed using a histological examination.
    In cases of multiple metastases in a single organ, the organ was counted as one metastatic organ. In cases of multiple metastases within the chest cavity (contralateral pulmonary metastases, pleural effusion/dissemination, and pericardial effusion/dissemination), the organ was again counted as one metastatic organ.
    2.3. Statistical analysis
    Overall survival (OS) was defined as the duration of time from the date of diagnosis to the date of death from any cause. Progression-free survival (PFS) was defined as the duration of time from the start of first-line therapy to the diagnosis of disease progression or death. OS and PFS curves were con-structed using the KaplaneMeier method, and differences in survival were compared using the log-rank test. The c2 test, Fisher’s exact test, and Student’s t-test were used to analyze patient characteristics and the significance of the association of the response rate and metastatic organs. All statistical an-alyses were conducted using Ekuseru-Toukei 2015 (Social Survey Research Information Co., Ltd., Tokyo, Japan).
    2. Patients and Methods
    Patients with pathologically confirmed lung cancer who pre-sented to the Department of Internal Medicine, Kagawa Uni-versity Hospital between January 2007 and December 2017 were retrospectively identified, and relevant clinical and lab-oratory data were collected from their medical records. Pa-tients with clinical stage IV cancer according to the 8th edition of the TNM classification were included in this study. Patients who had undergone surgery with curative intent or had another concomitant active malignancy were excluded. In total, 400 patients were finally included in this study.
    This study was approved by the Research Ethics Commit-tee of Kagawa University on December 21, 2018 (No. H30-162). All procedures performed in the study involving human par-ticipants were in accordance with the 1964 Helsinki Declara-tion and its later amendments covering patient data confidentiality. Informed consent was not obtained from the patients because the study was retrospective and included data from deceased patients. However, our institute officially presented the study design to provide all potential partici-pants the opportunity to evaluate it and reject participation if desired.
    2.2. Counting the metastatic organs
    All patients were determined to have the M factor by using 18F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography-computed tomography (PET-CT) and enhanced CT; enhanced magnetic resonance imaging of the brain was also performed unless a contraindication existed. In most patients, the number of metastatic organs was counted on the
    3. Results
    3.1. Metastatic status of patients with advanced lung cancer
    The patient and tumor characteristics are summarized in Table 1. Of the 400 patients, 288 were male and 300 were current or ex-smokers. Interstitial lung disease (ILD) was identified in 106 patients (26.5%) and was classified as idio-pathic interstitial pneumonia (n¼100), connective tissue disease-related (n¼5), and radiation-induced fibrosis (n¼1). Small cell lung cancer (SCLC) was identified in 69 patients, and the remaining 331 patients were classified as having non-SCLC (NSCLC). Adenocarcinoma was the most frequent type (228 patients) among the NSCLCs.