scholarly journals Implementing ctDNA Analysis in the Clinic: Challenges and Opportunities in Non-Small Cell Lung Cancer

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3112
Author(s):  
Elisa Gobbini ◽  
Aurélie Swalduz ◽  
Matteo Giaj Levra ◽  
Sandra Ortiz-Cuaran ◽  
Anne-Claire Toffart ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Clinical Relevance ◽  
Residual Disease ◽  
Locally Advanced ◽  
Small Cell ◽  
Small Cell Lung ◽  
Liquid Biopsies ◽  
Ctdna Analysis

Tumor genomic profiling has a dramatic impact on the selection of targeted treatment and for the identification of resistance mechanisms at the time of progression. Solid tissue biopsies are sometimes challenging, and liquid biopsies are used as a non-invasive alternative when tissue is limiting. The clinical relevance of tumor genotyping through analysis of ctDNA is now widely recognized at all steps of the clinical evaluation process in metastatic non-small cell lung cancer (NSCLC) patients. ctDNA analysis through liquid biopsy has recently gained increasing attention as well in the management of early and locally advanced, not oncogene-addicted, NSCLC. Its potential applications in early disease detection and the response evaluation to radical treatments are promising. The aim of this review is to summarize the landscape of liquid biopsies in clinical practice and also to provide an overview of the potential perspectives of development focusing on early detection and screening, the assessment of minimal residual disease, and its potential role in predicting response to immunotherapy. In addition to available studies demonstrating the clinical relevance of liquid biopsies, there is a need for standardization and well-designed clinical trials to demonstrate its clinical utility.

scholarly journals Clinical Relevance of Cd133 Positive Cells in Locally Advanced Non-Small Cell Lung Cancer

2014 ◽  
Vol 25 ◽  
pp. iv422
Author(s):  
E.R. Haspinger ◽  
M. Platania ◽  
G. Bertolini ◽  
R. Caserini ◽  
E. Landoni ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Clinical Relevance ◽  
Locally Advanced ◽  
Small Cell ◽  
Small Cell Lung

ctDNA analysis for personalization of consolidation immunotherapy in localized non-small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2547-2547
Author(s):  
Everett J Moding ◽  
Yufei Liu ◽  
Barzin Nabet ◽  
Jacob J. Chabon ◽  
Aadel Chaudhuri ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Residual Disease ◽  
Small Cell ◽  
Response Monitoring ◽  
Patient Specific ◽  
Small Cell Lung ◽  
Historical Cohort ◽  
Ctdna Analysis

2547 Background: Detection of molecular residual disease via circulating tumor DNA (ctDNA) analysis after chemoradiation (CRT) in localized non-small cell lung cancer (NSCLC) predicts risk of relapse. We explored the hypotheses that (1) patients with undetectable ctDNA after CRT may not require consolidation immunotherapy (CI) and (2) ctDNA analysis could monitor the effectiveness of CI in patients with residual ctDNA after CRT. Methods: We applied CAPP-Seq ctDNA analysis to 88 plasma and matched leukocyte samples collected pre-CRT, post-CRT but pre-CI, and mid-CI in 22 patients with Stage IIB-IIIB NSCLC treated with CRT followed by CI. Identification of patient-specific tumor variants was performed using tumor tissue or pretreatment plasma, and ctDNA was quantified using a tumor mutation-informed bioinformatic strategy. Freedom from progression (FFP) defined radiographically by RECIST 1.1 criteria was compared in patients with ctDNA detected or not detected at pre-CI and mid-CI landmarks. Results: Median follow up from the start of CRT was 11 months. ctDNA detection was associated with inferior rates of FFP when compared to patients with ctDNA not detected both pre-CI (12-month 33% vs. 76%, P = 0.015, HR 7.51, 95% CI 1.47-38.24) and mid-CI (12-month 0% vs. 86%, P < 0.0001, HR 123.3, 95% CI 16.21-937.8). In patients with undetectable ctDNA after CRT, FFP was similar to a historical cohort of patients with undetectable ctDNA after CRT alone (12-month 88% vs. 87%, P = 0.56, HR 0.55, 95% CI 0.07-4.18), suggesting that such patients may not benefit from CI. All patients with detectable ctDNA pre-CI in whom ctDNA increased mid-CI developed progressive disease. Finally, in 2 patients with ctDNA detected after CRT, CI led to elimination of ctDNA at the mid-CI timepoint. One of these patients developed an isolated local recurrence 22 months after CRT and the other patient is currently disease free at 11 months, suggesting clinical benefit from CI. Conclusions: Our results suggest that ctDNA analysis may allow personalization and response monitoring of CI following CRT for NSCLC. Validation in more patients followed by prospective testing in clinical trials will be required to establish clinical utility of such an approach.

Current and future therapeutic approaches in locally advanced (stage III) non[ndash ]small cell lung cancer

2002 ◽  
Vol 29 (3 Suppl 12) ◽  
pp. 10-16 ◽  
Author(s):  
Angela Davies ◽  
David R. Gandara ◽  
Primo Lara ◽  
Zelanna Goldberg ◽  
Peter Roberts ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Locally Advanced ◽  
Small Cell ◽  
Stage Iii ◽  
Advanced Stage ◽  
Therapeutic Approaches ◽  
Small Cell Lung

scholarly journals Polymorphisms in the Gene Encoding Caspase 8 May Predict the Response to First-Line Platinum-Based Chemotherapy in Locally Advanced or Advanced Non-Small-Cell Lung Cancer

2021 ◽  
Vol 10 (5) ◽  
pp. 1126
Author(s):  
Michał Szczyrek ◽  
Radosław Mlak ◽  
Aneta Szudy-Szczyrek ◽  
Karolina Kędziora ◽  
Teresa Małecka-Massalska ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Locally Advanced ◽  
Distant Metastases ◽  
Small Cell ◽  
Caspase 8 ◽  
Small Cell Lung ◽  
Gene Encoding ◽  
Platinum Based Chemotherapy

Caspase 8 is a protein involved in the process of cell apoptosis, which may affect the efficacy of anti-cancer treatment. The aim of our study was to determine the impact of polymorphisms in the CASP-8 gene encoding caspase 8 on the prognosis in non-small-cell lung cancer (NSCLC). The study involved 99 patients with newly diagnosed locally advanced or metastatic NSCLC treated with platinum-based chemotherapy. The presence of the GG genotype was associated with distant metastases, smoking, and a family history of cancer. The higher risk of early progression was associated with weight loss and the CASP-8 genotype (GG vs. AG or AA: 20.51% vs. 2.86%). The higher risk of progression-free survival (PFS) shortening was associated with a higher stage of disease (hazard ratio (HR) = 2.50, 95% CI: 1.61–3.89, p < 0.0001), distant metastases (HR = 2.30, 95% CI: 1.42–3.72, p = 0.0016), and the GG genotype (HR = 1.68, 95% CI: 1.10–2.57, p = 0.0152). The influence of the GG genotype on the PFS was confirmed in a multivariate analysis (HR = 1.80, 95% CI: 1.06–3.05, p = 0.0317). We did not confirm the influence of CASP-8 genotypes on the overall survival (OS).

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