Exploratory analysis of introducing next-generation sequencing-based method to treatment-naive lung cancer patients

Abstract

Background: The utilization of cancer-linked genetic alterations for categorizing patients against optimal treatment is becoming increasingly popular, especially in non-small cell lung cancer (NSCLC). However, disadvantages of the conventional techniques, such as the low throughput and limited detectable alteration types, lead to the demand of large-scale parallel sequencing for different forms of genetic variants. Methods: We evaluated the potential of performing next-generation sequencing (NGS)-based methods in a cohort of 61 treatment-naive NSCLC patients to profile their driver mutations, using a panel consisting of 8 well-established driver genes of lung cancer. Results: Our data revealed that 80% of patients harbored driver mutations. Moreover, our data revealed a few rare mutations, such as BRAF K601E and EGFR exon 20 insertion, which cannot be detected using commercially available single gene testing kits of conventional methods. We detected one patient with dual driver mutations. Next, correlations between driver mutations and clinical characteristics were interrogated in this cohort. Our results revealed that EGFR alterations were positively correlated with early stage, adenocarcinoma, alveolar and papillary component, TTF1 expression, and negatively correlated with P40 and Ki67 expression. ERBB2 alterations were associated with younger age and micro-invasive feature of tumor. Rearrangements of ALK indicated tumor relapse. Conclusions: Our study highlights the potential of NGS-based methods in treatment-naive patients, thus paving its way for routine clinical use. Investigation of clinical correlation of driver mutations might be helpful for clinicians in cancer diagnosis and has implications for seeking patients with specific gene alteration in clinical studies.

The Influence of KDR Genetic Variation on the Efficacy and Safety of Patients With Advanced NSCLC Receiving First-Line Bevacizumab Plus Chemotherapy Regimen

“… 5 Unfortunately, approximately 40% of patients were still lack of clear driver targets and became a research hotspot currently. 6 Amazingly, the anti-angiogenic drug bevacizumab combined with chemotherapy as first-line treatment achieved superior progression-free survival (PFS) and improved the survival of patients in the BEYOND and ECOG 4599 clinical trial. 7 , 8 Given that the objective response rate (ORR) of first-line platinum-based chemotherapy regimens ranged from 15%-26%, 9 addition of bevacizumab improved the ORR to approximately 50%.…”

The characteristics and nomogram for primary lung papillary adenocarcinoma

“…Nevertheless, our nomogram did not include other clinical information, including pivotal clinical symptoms, imaging presentations, and comprehensive laboratory indicators such as serum tumor markers [15]. More importantly, accumulating clinical studies revealed the identification of such tumors with alterations in genes such as ALK [21], epidermal growth factor receptor (EGFR) [22][23][24][25], which was momentous to guide tyrosine kinase inhibitors (TKIs) therapy. As an example, approximately 71% of Asiatic patients with PPA harbored EGFR mutation [26] and EGFR-TKIs was used to lengthen progressionfree survival in patients with an EGFR gene mutation and was introduced as first-line therapy in these patients [27].…”

“…As an example, approximately 71% of Asiatic patients with PPA harbored EGFR mutation [26] and EGFR-TKIs was used to lengthen progressionfree survival in patients with an EGFR gene mutation and was introduced as first-line therapy in these patients [27]. Moreover, rearrangements of ALK highlighted disease recurrence [23]. With the advent of immune checkpoint inhibitors, PD-L1 protein expression was considered as a well-characterized predictive biomarker for immunotherapy of PPA patients [28].…”

Next Generation Sequencing for Gene Fusion Analysis in Lung Cancer: A Literature Review

“…Other smaller DNA-targeted panels have been evaluated on FFPE clinical samples: a good concordance with gold standard methods and a good sensitivity and specificity was observed, the overall amount of DNA input required is usually equal to 50–250 ng [ 47 , 48 , 49 , 50 , 51 , 52 ]. Moreover, this approach has also been specifically tested on critical clinical samples like Endobronchial Ultrasound Guided Transbronchial Needle Aspiration (EBUS).…”