br Interstitial lung disease br Histology br Driver mutation

Interstitial lung disease
Histology
Driver mutations
M factor
No. of metastatic organs
Metastasis within the chest cavity
Bone metastasis
Brain metastasis
Liver metastasis
Adrenal gland metastasis
Lymph node metastasis
Muscle metastasis
Skin metastasis
CI: confidence interval, ECOG: Eastern Cooperative Oncology Group, HR: hazard ratio, NSCLC: non-small cell lung cancer, OS: overall survival,
SCLC: small cell lung cancer.
4.9 metastatic organs, respectively), whereas the average number of metastatic organs in patients without muscle or skin Cell Counting Kit-8 was approximately 1.8. In patients with liver metastasis, the number of metastatic organs was 2.9.
This study included patients who had received the best supportive care without chemotherapy or molecular-targeted therapy. Patients with a high number of metastatic organs
might have less opportunity to receive first-line therapy because of their lower performance status. Therefore, to determine whether the specific metastatic organ site influ-enced the first-line therapeutic effect, we assessed the response rate (Fig. 3B) and PFS (Table 3) in patients who had received first-line therapy. Interestingly, a lower response rate was observed in patients with muscle and skin metastases
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
Fig. 2 e KaplaneMeier curves of overall survival (OS) based on the status of metastases in the (A) liver and (B) muscle.
than in those without (14.3% vs. 49.4% in patients with vs. without muscle metastasis, p¼0.0122; 11.1% vs. 48.9% in pa-tients with vs. without skin metastasis, p¼0.038). No signifi-cant difference was observed regarding liver metastasis (response rate of 40.6% vs. 49.6% in patients with vs. without liver metastasis) or other metastatic conditions. When the analysis was limited to patients with NSCLC treated using chemotherapy, similar results were observed (Fig. 3C).
However, tyrosine kinase inhibitors (TKIs) resulted in a high response rate even in patients with muscle and skin metas-tases, even though the number of patients was very small (Fig. 3D).
Fig. 3 e (A) Number of total metastatic organs based on each metastatic status. (BeD) Response rates to first-line therapy based on each metastatic status. (B) All patients. (C) Non-small cell lung cancer (NSCLC) treated with chemotherapy. (D) NSCLC treated with tyrosine kinase inhibitors (TKIs). “Chest cavity” includes pulmonary metastasis, pleural effusion, and pericardial effusion. “Lymph node” means extraregional lymph node. *p<0.05 compared to the absence of each metastasis.
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
Table 3 e Influence of metastatic organs on PFS.
Metastatic organs
All patients
Patients treated with TKIs
n Median Univariate analysis
Multivariate analysis
n Median Univariate analysis
PFS (days)
PFS (days)
p-value
p-value
Chest cavity
Bone
Brain
Liver
Adrenal gland
Lymph node
Muscle
Skin
CI: confidence interval, HR: hazard ratio, PFS: progression-free survival, TKIs: tyrosine kinase inhibitors.
in patients with 3 vs. 2 metastatic organs, respectively). In contrast, the univariate analysis showed that liver, muscle, and skin metastases were associated with shorter PFS (Table 3). The multivariate analysis showed that liver and muscle metastases were independently associated with shorter PFS. Patients with muscle metastasis showed far shorter PFS (median, 53 days). In patients treated with TKIs, no associa-tion was found between the metastatic sites and PFS.
4. Discussion
This retrospective analysis of 400 patients with advanced lung cancer demonstrated that (1) a higher number of metastatic organs was associated with shorter OS; (2) both muscle and liver metastases were independent poor prognostic factors for OS and PFS; and (3) muscle and skin metastases were associ-ated with a lower response rate to first-line therapy.
Our findings indicate that the number of metastatic organs is a very important prognostic factor, thus expanding on the findings of previous related studies [2e4]. The prognosis significantly worsened in a stepwise manner from only one organ to two or more organs, from two or fewer to three or more organs, and from three or fewer to four or more organs. This finding may indicate that a detailed assessment of the number of metastatic organs is necessary to predict the prognosis of patients in the M1c category.