Comprehensive analysis of genomic alterations detected by next-generation sequencing-based tissue and circulating tumor DNA assays in Chinese patients with non-small cell lung cancer.

While tumor genotyping is the standard treatment for patients with non-small cell lung cancer (NSCLC), spatial and temporal tumor heterogeneity and insufficient specimens can lead to limitations in the use of tissue-based sequencing. Circulating tumor DNA (ctDNA) fully encompasses tumor-specific sequence alterations and offers an alternative to tissue sample biopsies. However, few studies have evaluated whether the frequency of multiple genomic alterations observed following ctDNA sequencing is similar to that observed following tissue sequencing in NSCLC. Therefore, in the present study, targeted next-generation sequencing (NGS) was performed on tissue and plasma ctDNA samples in 99 patients with NSCLC. Overall, the frequencies of genetic alterations detected in ctDNA were positively correlated with those detected via tissue profiling (r=0.812; P=0.022). Genomic data revealed significant mutual exclusivity between alterations in epidermal growth factor receptor (EGFR) and tumor protein 53 (TP53; P=0.020), and between alterations in EGFR and KRAS (P=0.008), as well as potential mutual exclusivity between alterations in EGFR and Erb-B2 receptor tyrosine kinase 2 (P=0.059). Furthermore, the EGFR mutant allele frequency (MAF) was positively correlated with the TP53 MAF in individual tumors (r=0.773; P=0.005), and there was a marked difference in the EGFR MAF between patients with and without the TP53 mutation (P=0.001). Levels of the tumor serum marker CA242 in patients with ctDNA-detectable mutations were higher compared with those in patients without ctDNA-detectable mutations. The data from the present study highlight the importance of tissue and plasma ctDNA screening by NGS to guide personalized therapy and promote the clinical management of patients with NSCLC.

[Therapeutic efficacy of chemotherapy combined with radiotherapy in 527 patients with stage III and IV non-small cell lung cancer].

BACKGROUND: Chemotherapy is very important in treatment of advanced non-small cell lung cancer (NSCLC), and the third-generation cisplatin-based chemotherapy regimens have been the standard treatment for advanced NSCLC. The aim of this study is to compare the efficacy and toxicity among four different chemotherapeutic regimens combined with radiotherapy in patients with stage III/IV NSCLC. METHODS: A total of 527 patients with stage III/IV NSCLC were enrolled, among whom there were 243 patients received cisplatin/vinorelbine (NP group), 163 patients for cisplatin/paclitaxel (TP group), 65 patients for cisplatin/gemcitabine (GP group) and 56 patients for cisplatin/docetaxel (DP group). The efficacy, side effects, median time to progression (TTP), median survival time (MST), 1- and 2-year survival rate were compared. RESULTS: The response rate was 46.9% in the NP arm, 44.8% in the TP arm, 47.7% in the GP arm and 42.9% in the DP arm (P > 0.05). The response rate of patients with radiochemotherapy was 69.9%, and 40.8% for those with chemotherapy alone (P < 0.05). In group NP, TP, GP and DP, median TTP was 5.7, 5.3, 5.9 and 5.5 months (P > 0.05) respectively, MST was 10.4, 10.6, 11.5 and 10.4 months (P > 0.05) respectively, 1-year survival rate was 41.9%, 41.1%, 43.1% and 42.9% (P > 0.05) respectively, and 2-year survival rate was 21.3%, 19.4%, 23.1% and 23.2% (P > 0.05) respectively. CONCLUSIONS: The third-generation cisplatin-based chemotherapy regimens may be the standard treatment for advanced NSCLC, and their combination with radiotherapy may improve the therapeutic efficacy and prolong the survival of patients.