scholarly journals Integrating Liquid Biopsy and Radiomics to Monitor Clonal Heterogeneity of EGFR-Positive Non-Small Cell Lung Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Federico Cucchiara ◽  
Marzia Del Re ◽  
Simona Valleggi ◽  
Chiara Romei ◽  
Iacopo Petrini ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Target Therapy ◽  
Case Series ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Clonal Heterogeneity

BackgroundEGFR-positive Non-small Cell Lung Cancer (NSCLC) is a dynamic entity and tumor progression and resistance to tyrosine kinase inhibitors (TKIs) arise from the accumulation, over time and across different disease sites, of subclonal genetic mutations. For instance, the occurrence of EGFR T790M is associated with resistance to gefitinib, erlotinib, and afatinib, while EGFR C797S causes osimertinib to lose activity. Sensitive technologies as radiomics and liquid biopsy have great potential to monitor tumor heterogeneity since they are both minimally invasive, easy to perform, and can be repeated over patient’s follow-up, enabling the extraction of valuable information. Yet, to date, there are no reported cases associating liquid biopsy and radiomics during treatment.Case presentationIn this case series, seven patients with metastatic EGFR-positive NSCLC have been monitored during target therapy. Plasma-derived cell free DNA (cfDNA) was analyzed by a digital droplet PCR (ddPCR), while radiomic analyses were performed using the validated LifeX® software on computed tomography (CT)-images. The dynamics of EGFR mutations in cfDNA was compared with that of radiomic features. Then, for each EGFR mutation, a radiomic signature was defines as the sum of the most predictive features, weighted by their corresponding regression coefficients for the least absolute shrinkage and selection operator (LASSO) model. The receiver operating characteristic (ROC) curves were computed to estimate their diagnostic performance. The signatures achieved promising performance on predicting the presence of EGFR mutations (R2 = 0.447, p <0.001 EGFR activating mutations R2 = 0.301, p = 0.003 for T790M; and R2 = 0.354, p = 0.001 for activating plus resistance mutations), confirmed by ROC analysis.ConclusionTo our knowledge, these are the first cases to highlight a potentially promising strategy to detect clonal heterogeneity and ultimately identify patients at risk of progression during treatment. Together, radiomics and liquid biopsy could detect the appearance of new mutations and therefore suggest new therapeutic management.

Liquid biopsy for EGFR mutations in non-small cell lung cancer cases by RT-PCR

2018 ◽  
Author(s):  
Altug Koc ◽  
Tuncay Goksel ◽  
Berna Komurcuoglu ◽  
Ozge Ozer Kaya ◽  
Berk Ozyilmaz ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Small Cell ◽  
Egfr Mutations ◽  
Rt Pcr ◽  
Small Cell Lung

scholarly journals EGFR Mutations Status For Non-Small-Cell Lung Cancer Patients

2016 ◽  
Vol 26 (5) ◽  
pp. 36-39
Author(s):  
Ieva Mirskytė ◽  
Jūratė Kasnauskienė ◽  
Alvydas Česas ◽  
Loreta Radvinskienė
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Small Cell ◽  
Small Cells ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Tk Inhibitors

With the advent of the molecular-targeted therapy, rapid progress has been made in the treatment of advanced or recurrent non-small-cell lung cancer (NSCLC). EGFR mutations detection in tumor is important to determine an appropriate treatment of EGFR TK inhibitors. We investigated EGFR mutation status for patients with non-small cells lung carcinoma (NSCLC) patients’ tumorous cells from FFPE material in Klaipeda University Hospital, Lithuania (mutation test for the qualitative detection and identification of mutations in exons 18, 19, 20 and 21 of the EGFR gene) and T790M mutation in cfDNA (Liquid biopsy). Mutations of EGFR from FFPE were detected in 24 of the 119 patients (20%). EGFR mutations were more frequently found in women (13 of 36, 36%). cfDNA (Liquid biopsy) testing results show one of the patients had EGFR 20 exon T790M mutation detected which is resistance determining factor for the first and second generation EGFR TK Inhibitors treatment and a predicting marker for the third generation EGFR TK Inhibitors treatment.

RET fusion in first/third-generation EGFR-TKIs resistance in advanced non-small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20634-e20634 ◽  
Author(s):  
Yu Yao ◽  
Min Zhang ◽  
Xiuju Liu ◽  
Jun Zhao ◽  
Xiangyang Cheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Target Therapy ◽  
Small Cell ◽  
Egfr Mutations ◽  
Third Generation ◽  
Small Cell Lung ◽  
Single Nucleotide Variants ◽  
Egfr Tkis

e20634 Background: EGFR-TKIs is the standard first/second-line treatment for EGFR-mutant advanced non-small-cell lung cancer (NSCLC). The mechanisms of EGFR-TKIs resistance are still under exploration. Acquired fusion have been reported contribute to EGFR-TKIs resistance. Here we focus on RET fusion in first/third-generation EGFR-TKIs resistant NSCLC. Methods: We retrospectively reviewed 3600 cases of EGFR-TKIs resistant NSCLC samples from 2016 to 2018 in our institute. Tumor biopsy, ctDNA or pleural effusion samples were analyzed using hybridization capture-based NGS ER-seq method, which enables simultaneously assess single-nucleotide variants (SNV), insertions/deletions (indel), rearrangements and somatic copy-number(CNV) variation at least 59 genes (range 59-1021 genes). Results: Seven cases with RET fusion were identified (7/3600, 0.2%), with co-occurring EGFR mutations. All were adenocarcinoma, median diagnosis age was 55 years old (range 38-84), four male and three female. Most common RET fusion subtype was CCDC6-RET (5/7, 71%), the other was NCOA4-RET (2/7, 29%). The primary EGFR mutation include four EX19del and three L858R. Six patients received prior first and third-generation EGFR-TKIs treatment. The seventh patient had received only gefitinib treatment, EGFR L858R + T790M + NCOA4-RET were discovered in his plasma when disease progression. Interestingly, one patient had EGFR EX19del + T790M + C797S (cis) + CCDC6-RET in plasma after osimertinib resistance. One patient who had EGFR L858R and NCOA4-RET chose lenvatinib, a RET inhibitor, and had a progression free survival of seven months. Conclusions: Broad NGS panel test suggests that RET fusion could be a rare mechanism of EGFR-TKIs resistance, include first and third-generation. There is no currently target treatment strategy available for these patients, and further investigations, like change target therapy drug or combined target therapy are needed.

scholarly journals Liquid Biopsy for Small Cell Lung Cancer either De Novo or Transformed: Systematic Review of Different Applications and Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2265
Author(s):  
Elio Gregory Pizzutilo ◽  
Martino Pedrani ◽  
Alessio Amatu ◽  
Lorenzo Ruggieri ◽  
Calogero Lauricella ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Liquid Biopsy ◽  
De Novo ◽  
Meta Analysis ◽  
Small Cell ◽  
Genomic Profiling ◽  
Small Cell Lung

Background: The potential added value of liquid biopsy (LB) is not well determined in the case of small cell lung cancer (SCLC), an aggressive tumor that can occur either de novo or from the histologic transformation of non-small cell lung cancer (NSCLC). Methods: A systematic review of studies adopting LB in patients with SCLC have been performed to assess the clinical utility of circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs). Results: After a screening of 728 records, 62 studies (32 evaluating CTCs, 27 ctDNA, and 3 both) met predetermined eligibility criteria. Only four studies evaluated LB in the diagnostic setting for SCLC, while its prognostic significance was evaluated in 38 studies and prominently supported by both ctDNA and CTCs. A meta-analysis of 11 studies as for CTCs enumeration showed an HR for overall survival of 2.63 (1.71–4.05), with a potential publication bias. The feasibility of tumor genomic profiling and the predictive role of LB in terms of response/resistance to chemotherapy was assessed in 11 and 24 studies, respectively, with greater consistency for those regarding ctDNA. Intriguingly, several case reports suggest that LB can indirectly capture the transition to SCLC in NSCLC treated with EGFR tyrosine kinase inhibitors. Conclusions: While dedicated trials are needed, LB holds potential clinical roles in both de novo and transformed SCLC. CtDNA analysis appears the most valuable and practicable tool for both disease monitoring and genomic profiling.

Use of Liquid Biopsy in the Care of Patients with Non-Small Cell Lung Cancer

2021 ◽  
Vol 22 (10) ◽  
Author(s):  
Atocha Romero ◽  
Roberto Serna-Blasco ◽  
Virginia Calvo ◽  
Mariano Provencio
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Current Status and Future Perspectives of Liquid Biopsy in Small Cell Lung Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 48
Author(s):  
Patricia Mondelo-Macía ◽  
Jorge García-González ◽  
Luis León-Mateos ◽  
Adrián Castillo-García ◽  
Rafael López-López ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Small Cell ◽  
New Drugs ◽  
Current Status ◽  
Small Cell Lung ◽  
Tumor Biopsy ◽  
Future Utility

Approximately 19% of all cancer-related deaths are due to lung cancer, which is the leading cause of mortality worldwide. Small cell lung cancer (SCLC) affects approximately 15% of patients diagnosed with lung cancer. SCLC is characterized by aggressiveness; the majority of SCLC patients present with metastatic disease, and less than 5% of patients are alive at 5 years. The gold standard of SCLC treatment is platinum and etoposide-based chemotherapy; however, its effects are short. In recent years, treatment for SCLC has changed; new drugs have been approved, and new biomarkers are needed for treatment selection. Liquid biopsy is a non-invasive, rapid, repeated and alternative tool to the traditional tumor biopsy that could allow the most personalized medicine into the management of SCLC patients. Circulating tumor cells (CTCs) and cell-free DNA (cfDNA) are the most commonly used liquid biopsy biomarkers. Some studies have reported the prognostic factors of CTCs and cfDNA in SCLC patients, independent of the stage. In this review, we summarize the recent SCLC studies of CTCs, cfDNA and other liquid biopsy biomarkers, and we discuss the future utility of liquid biopsy in the clinical management of SCLC.

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