br Another important finding of the present study is that
Another important finding of the present study is that muscle and skin metastases were associated with a lower response rate to first-line therapy. There are several possible explanations for the lower responsiveness among patients with these metastases. First, the tumor burden may be related to the therapeutic effect. A popular concept in cancer chemotherapy is that smaller tumors are more sensitive to chemotherapy than are larger tumors, as reported in animal studies [22, 23]. Confluence-dependent resistance to a chemotherapeutic agent also supports this “smaller is more sensitive” theory . In addition, the neutrophil and lymphocyte counts can change during tumor progression, which alters the host immunological conditions with respect to tumor resistance and affects the efficacy of
chemotherapy, EGFR-TKIs, and immune-checkpoint in-hibitors [25e29]. The elevated blood cell counts are prog-nostic factors . Second, driver gene mutations were detected less frequently in our patients with metastases in the muscle (2 of 19 patients, 11%) or skin (1 of 13 patients, 8%) than in the total population (90 of 400 patients, 23%), even though this difference was not significant. Driver gene mutation-matched TKIs provided greater antitumor efficacy than did chemotherapy. Whether the lower frequency of driver gene mutations in patients with muscle or skin 50-07-7 is accidental or a necessity should be clarified in future studies. Third, tumors that spread to some specific organs may have distinct tumor characteristics. Pleural dissemination and liver metastasis are associated with a decreased incidence of KRAS mutation . Bone metastases are more frequent in central tumors than in peripheral tu-mors . Differences in tumor characteristics and patients’ prognoses between central and peripheral tumors have also been reported [33,20]. Tumors that are able to use the muscle and skin as appropriate “soil” and develop at those sites may have an originally strong malignant potential.
The limitations of this study are as follows. First, this was a retrospective, single-center study. Some characteristics, such as the frequency of ILD, vary among facilities [34,35]. Second, all patients included in this study were Japanese. Third, the T and N factors were not assessed. They also affect the selection of the therapeutic strategy and prognosis, albeit not in all patients.
In patients with advanced lung cancer, the number and sites of metastatic organs are associated with survival and response to treatment. Liver and muscle metastases in particular are associated with poor outcomes. Oncologists should assess potential treatment strategies while consid-ering the patient’s metastatic status as well as other clinical characteristics.
Conflict of interest
The authors have no conflicts of interest to declare.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors thank Angela Morben, DVM, ELS, from the Edanz Group (www.edanzediting.com/ac), for editing a draft of this manuscript.
Appendix A. Supplementary data
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