Background/Aim: Immune checkpoint inhibitors (ICI) are a novel medication for non-small cell lung cancer (NSCLC). Recent reports indicated that baseline tumor size (BTS) relates to the efficacy of ICI therapy for melanoma, but no study exists for NSCLC. This study aimed to evaluate the utility of BTS for ICI therapy. Patients and Methods: Data from 58 patients diagnosed with NSCLC who underwent ICI monotherapy, were retrospectively analyzed. Patients were divided into two groups according to BTS (below 101 mm, above 101 mm). The primary endpoint was progression-free survival (PFS) and the secondary endpoint was overall survival (OS). Results: PFS of patients with a large BTS was significantly shorter than that of those with a small BTS (median; 2.07 [95% confidence interval [CI]=0.99-6.77] months versus 6.39 [95%CI=4.17-11.50] months) (p=0.044). OS of patients with large BTS was also significantly shorter (p<0.01). Conclusion: BTS is a predictive and prognostic negative factor of ICI therapy for NSCLC. Lung cancer is one of the leading causes of cancer-related death worldwide (1). Advanced non-small cell lung cancer (NSCLC) is treated using systemic therapies, including chemotherapy, epidermal growth factor receptor-tyrosine kinase inhibitor (TKI), anaplastic lymphoma kinase-TKI, c-ros oncogene 1 inhibitor, a combination of BRAF/MET inhibitor, and an immune checkpoint inhibitor (ICI) (2). The immune system protects the host against cancer cells via seven steps termed the cancer-immunity cycle (3). The seven steps include 'priming and activation' and 'recognition of cancer by T cells' (3). These processes are regulated and activated by various molecules and cytokines, including programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1), which suppress the cancer-immune cycle (3, 4). Cancer cells can express PD-L1 on their surfaces, facilitating recognition by PD-1, which is expressed on the surface of T-cells and acts as a PD-L1 receptor. Binding of PD-L1 to T cells has a profound inhibitory effect on immune functions such as cytokine secretion, growth, and cytotoxicity. Hence, PD-1 and PD-L1 are thought to be important target molecules for the control of cancer. ICI is a novel and promising medication for NSCLC. Nivolumab, a fully human IgG4 anti-PD-1 receptor-blocking monoclonal antibody (5), was the first ICI available for treatment of NSCLC in Japan. The Checkmate 017 and Checkmate 057 studies indicated the superiority of nivolumab over docetaxel for patient progression-free survival (PFS) and overall survival (OS) (6, 7). In addition to nivolumab, various other ICIs are now available, including pembrolizumab (an anti-PD-1 blocking antibody), atezolizumab and durvalumab (anti-PD-L1 blocking antibodies). Use of these ICIs has also been shown to lead to superior PFS and OS (8-10). Previous studies (Checkmate 017, 057, and Keynote-010) showed that the effects of ICI differed according to PD-L1 expression. As ICI is more effective against NSCLC expressing a higher tumor proportion score (TPS) of PD-L1 (6, 7),...

Mutated epidermal growth factor receptor (EGFR) and signaling pathways were associated with multiple brain and intra-pulmonary metastases, oncogenic progression and metastasis. However, features of metastasis to other organs and the independent prognostic influence of metastatic lesions were not elucidated in patients with lung cancer harboring EGFR mutations. Between January 2007 and April 2012, we treated 277 patients diagnosed with stage IV lung adenocarcinoma. Studied were 246 patients with available tumor EGFR mutation data who also underwent radiographic evaluation of lung, abdominal, brain, and bone metastases. The EGFR mutated group (N = 98) had significantly more metastatic lesions in the brain and bone than the wild-type group (N = 148): brain, 3 (1-93) versus 2 (1-32) median (range), P = 0.023; bone, 3 (1-43) versus 2 (1-27), P = 0.035, respectively. In addition, EGFR mutations were significantly more frequent in patients with multiple than non-multiple lung metastases (24/40 vs. 12/42, P = 0.004). Multivariate analysis showed that bone metastasis was a significant independent negative predictive factor of overall survival (OS) in patients with mutated [hazard ratio (HR) 2.04; 95 % confidence interval (CI) 1.17-3.64; P = 0.011] and wild-type EGFR (HR 2.09; 95 % CI 1.37-3.20; P < 0.001). In conclusion, patients with mutated EGFR had more lung, brain, and bone metastases, and bone metastasis was an independent negative predictor of OS.

The addition of bevacizumab to paclitaxel and carboplatin may provide an effective and safe treatment option for patients with advanced nonsquamous NSCLC with ILD.

Immune checkpoint inhibitors (ICIs) have drastically changed the clinical care of cancer. Although cancer immunotherapy has shown promise in various types of malignancies, thus far, the proportion of patients who can benefit from ICIs is relatively small. Immune-related adverse events and high cost are unavoidable problems. Therefore, biomarkers defining patients that are most likely to benefit from ICIs are urgently needed. The expression of programmed cell death-ligand 1 (PD-L1) is a logical biomarker for the prediction of response to anti-PD1/PD-L1 immunotherapies. However, its usefulness is currently debatable because of its varied definition, threshold, and spatial/temporal heterogeneity. Recently, it was reported that the tumor mutational burden, expression of neoantigens, mismatch repair status, and specific gene mutations may be markers for the success of treatment with ICIs. Moreover, it was suggested that the fecal microbiota prior to immunotherapy may play an important role in predicting the efficacy of ICIs. In this review, we focused on these potential biomarkers for cancer immunotherapy reported in recent clinical articles. Further studies are warranted to develop a predictive model using these biomarkers, with the aim of practicing precision medicine in cancer immunotherapy.

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Patients with a high CYFRA 21-1 level have significantly shorter PFS. CYFRA 21-1 is not a prognostic but a predictive marker of EGFR-TKI treatment in EGFR-mutated NSCLC patients.

In the human intestinal tract, there are more than 100 trillion symbiotic bacteria, which form the gut microbiota. Approximately 70% of the human immune system is in the intestinal tract, which prevents infection by pathogenic bacteria. When the intestinal microbiota is disturbed, causing dysbiosis, it can lead to obesity, diabetes mellitus, inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, autism spectrum disorder and cancer. Recent metabolomics analyses have also made the association between the microbiota and carcinogenesis clear. Here, we review the current evidence on the association between the microbiota and gastric, bladder, hepatobiliary, pancreatic, lung and colorectal cancer. Moreover, several animal studies have revealed that probiotics seem to be effective for the prevention of carcinogenesis to some extent. In this review, we focused on this relationship between the microbiota and cancer, and considered how to prevent cancer using strategies involving the gut microbiota.

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