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BACKGROUND: To clarify the rate of concordance between the results of concurrent sequencing of circulating tumor DNA (ctDNA) and tumor tissue samples based in clinic settings, and to explore potential factors influencing consistency. METHODS: A retrospective analysis of 27 patients with lung cancer who underwent gene sequencing at the Department of Biotherapy of Tianjin Medical University Cancer Hospital from February 2016 to April 2019, was conducted by synchronous sequencing of tumor and plasma DNA samples and the concordance of mutations in nine known driver genes was calculated. RESULTS: The overall concordance, sensitivity, and specificity for sequencing driver genes in plasma samples, were 85.2%, 87.0%, and 75%, respectively, relative to tumor samples. Concordance was 100% in patients with bone metastases, while the rate in those without bone metastases was 69.2%. Moreover, in patients where both the driver gene and TP53 mutations in plasma were detected, the findings of plasma sequencing of the driver gene were identical to those of tumor sequencing (concordance: 100%). CONCLUSIONS: Overall, our data show that circulating tumor DNA (ctDNA) was able to identify 75% of the identical information in driver genes, with higher rates of concordance in lung cancer patients with bone metastases or TP53 mutation-positive plasma samples.

PD-L1 and tumor mutation burden (TMB) are the most widely used immunotherapy biomarkers to identify populations who would attain clinical benefit, with the higher values predicting better therapeutic efficacy. This review addresses the predictive values and unresolved challenges of these two biomarkers. PD-1 and PD-L1 inhibitors have induced durable and effective responses in patients with advanced non-small cell lung cancer, confirmed by multiple clinical trials and real-world studies. Different clinical trials, involving both PD-1/PD-L1 inhibitors alone and combination regimens, adopted either PD-L1 or TMB to stratify the patients, although the predictive capabilities of these two biomarkers are different. In the first-line setting, PD-L1 of 50% or more as a cut-off value can help select candidates for pembrolizumab or atezolizumab monotherapy; however, these two biomarkers poorly predict the efficacy of immunotherapy combination regimens as first-line treatments. In the second-line setting, although patients can benefit from nivolumab regardless of PD-L1 expression, both PD-L1 and blood TMB can be used as biomarkers to find patients suitable for atezolizumab. Except for inaccurate predictiveness, there are many unresolved problems with regard to the two biomarkers, such as the lack of standard detection methods, and their susceptibilities to other dynamic changes. The predictive values of TMB and PD-L1 were low in most circumstances; however, PD-L1 expression greater than ≥ 50% can help select appropriate patients for pembrolizumab and atezolizumab, respectively, as first-line monotherapies. Higher PD-L1 or TMB was associated with greater efficacy for atezolizumab as a second-line monotherapy.

BACKGROUND: To investigate the roles of gastrin-releasing peptide (ProGRP) in the diagnosis of small cell lung cancer (SCLC). METHODS: We retrospectively analyzed data from 11,206 patients with clinical suspicion of lung cancer from January 1, 2015 to May 31, 2018. ProGRP and neuron-specific enolase (NSE) were detected in peripheral blood, and receiver operating characteristic curve (ROC) was used for analysis. RESULTS: ROC indicated that the cutoff values of ProGRP and NSE were 66 ng/L and 18 µg/L respectively, and the diagnosis efficacy of ProGRP was greater than that of NSE (sensitivity: 86.5% vs. 78.8%; specificity: 96.5% vs. 86.3%, respectively) in the diagnosis of SCLC. Moreover, the median level of ProGRP in SCLC increased with the accompanying stages (P