Distinction of ALK fusion gene- and EGFR mutation-positive lung cancer with tumor markers.

BACKGROUND: It is difficult to predict gene mutations individually based on clinical background alone. Tumor markers may help to predict each gene mutation. Identifying tumor markers that can predict gene mutation will facilitate timely genetic testing and intervention. METHODS: We selected 134 cases of advanced or recurrent ALK-positive and 172 cases of advanced or recurrent EGFR-positive lung cancer from our clinical database. The cutoff values for the tumor markers were defined as 5.0 ng/mL or higher for carcinoembryonic antigen (CEA) and 3.5 ng/mL or higher for soluble fragment of cytokeratin 19 (CYFRA21-1) in accordance with the institutional standards. A positive CYFRA21-1:CEA ratio was defined as 0.7 or higher. RESULTS: The CEA-positivity rate was 49% for ALK-positive lung cancers and 73% for EGFR-positive lung cancers, which was significantly different (p < 0.001). The CYFRA21-1 positivity rate was significantly higher in ALK-positive lung cancer (36%) compared with EGFR-positive lung cancer (23%) (p = 0.034). The median CYFRA21-1:CEA ratio was 0.395 for the ALK group, which was significantly higher compared with 0.098 for the EGFR group (p < 0.001). These trends were similar when excluding histology other than adenocarcinoma. The median time-to-treatment failure (TTF) for initial tyrosine kinase inhibitor (TKI) therapy was 308 days for the high CYFRA21-1:CEA ratio group and 617 days for the low CYFRA21-1:CEA ratio group for ALK-positive lung cancer (p = 0.100). CONCLUSIONS: A higher proportion of patients with ALK-positive lung cancer were CYFRA21-1 positive and had higher CYFRA21-1:CEA ratios compared with EGFR-positive lung cancer patients.

Clinical characteristics of patients with KRAS mutation detected by liquid biopsy.

BACKGROUND: KRAS mutation positive lung cancer is known to be clinically characterized by older age, males, and smokers. It is reported to be more common in mucinous adenocarcinoma, but all reports are based on analysis of tissue samples. Recently, blood samples have become available for analysis, suggesting a low detection rate of circulating tumor DNA in histological types, especially mucinous adenocarcinoma. In this study, we investigated the clinical characteristics of KRAS mutation-positive cases in the analysis of blood specimens, as these remain unclear. METHODS: The clinical background of patients with KRAS mutation among those who underwent next-generation sequencing (NGS) analysis using blood samples was evaluated. RESULTS: NGS analysis was performed on 214 blood samples. KRAS mutations were detected in blood samples in 33 cases (15.4%), of which 31 cases (14.5%) had a histological pathology diagnosis. Mucinous adenocarcinoma accounted for 28.6% of cases with positive blood and tissue specimens, 10.0% of cases with positive blood specimens only, and 57.1% of cases with positive tissue specimens only. Mucinous adenocarcinoma tended to be less common in cases with positive blood specimens. In KRAS-positive patients with lung metastasis only, only one nonmucinous adenocarcinoma had a positive blood sample, and the others all had mucinous adenocarcinomas with positive tissue samples only. CONCLUSION: The results showed that the detection rate of KRAS-positive lung cancers detected by blood and tissue samples differs, and that the detection rate of blood samples may be poor, especially in the case of mucinous adenocarcinoma with lung metastases only.

Real-World Outcome Analysis of Patients With Stage IV NSCLC Treated With Tyrosine Kinase and Immune Checkpoint Inhibitors.

Introduction: Only a few reports have determined whether recently advanced anticancer drugs, particularly next-generation tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), prolong the survival of patients with NSCLC in the real world. Methods: To evaluate the association between recently advanced drugs and patient survival, survival data of 2078 patients with stage IV NSCLC from 1995 to 2022 were analyzed in the present study. The patients were classified into the following six groups in terms of the date of diagnosis: period A, 1995 to 1999; period B, 2000 to 2004; period C, 2005 to 2009; period D, 2010 to 2014; period E, 2015 to 2019; and period F, 2000 to 2022. They were further grouped in terms of EGFR mutation and ALK fusion. Results: The median overall survival (mOS) times were 8.9, 11.0, 13.6, 17.9, and 25.2 months in periods A to E, respectively, and the mOS time was not reached in period F. This time was significantly longer in period E than in period D (25.2 versus 17.9 mo, p < 0.005). Moreover, the mOS times of patients with EGFR mutation, those with ALK fusion, and those without both alterations were significantly longer in period E than in period D (46.0 versus 32.0 mo, p < 0.005; not reached versus 36.2 mo, p = 0.018; 14.6 versus 11.7 mo, p < 0.005). The history of treatment with next-generation TKIs and ICIs was found to be associated with overall survival. Conclusions: The survival of patients with NSCLC was improved from period D to period E, regardless of the presence of driver gene alteration. We found that next-generation TKIs and ICIs may be associated with improvements in overall survival.