scholarly journals Diagnosis of Non-Small Cell Lung Cancer via Liquid Biopsy Highlighting a Fluorescence-in-situ-Hybridization Circulating Tumor Cell Approach

2021 ◽  
Author(s):  
Xin Ye ◽  
Xiao Zheng Yang ◽  
Roberta Carbone ◽  
Iris Barshack ◽  
Ruth L. Katz

Lung cancer (LC), is the most common and lethal cancer worldwide. It affects both sexes and in its early stages is clinically silent, until it reaches a more advanced stage, when it becomes highly incurable. In order to improve the high mortality associated with LC there has been an urgent need for screening high risk patients by low dose CT scan (LDCT) for the early detection of small resectable malignant tumors. However, while highly sensitive to detect small lung nodules, LDCT is non-specific, resulting in a compelling need for a complementary diagnostic tool. For example, a non-invasive blood test or liquid biopsy, (LB), could prove quite useful to confirm a diagnosis of malignancy prior to definitive therapy. With the advent of LB becoming increasingly clinically accepted in the diagnosis and management of LC, there has been an explosion of publications highlighting new technologies for the isolation of and detection of circulating tumor cells (CTCs) and cell free tumor DNA (cfDNA). The enormous potential for LB to play an important role in the diagnosis and management of LC to obtain valuable diagnostic information via an approach that may yield equivalent information to a surgical biopsy, regarding the presence of cancer and its molecular landscape is described.

2016 ◽  
Vol 140 (8) ◽  
pp. 825-829 ◽  
Author(s):  
Lynette M. Sholl ◽  
Dara L. Aisner ◽  
Timothy Craig Allen ◽  
Mary Beth Beasley ◽  
Philip T. Cagle ◽  
...  

Liquid biopsy has received extensive media coverage and has been called the holy grail of cancer detection. Attempts at circulating tumor cell and genetic material capture have been progressing for several years, and recent financially and technically feasible improvements of cell capture devices, plasma isolation techniques, and highly sensitive polymerase chain reaction– and sequencing-based methods have advanced the possibility of liquid biopsy of solid tumors. Although practical use of circulating RNA-based testing has been hindered by the need to fractionate blood to enrich for RNAs, the detection of circulating tumor cells has profited from advances in cell capture technology. In fact, the US Food and Drug Administration has approved one circulating tumor cell selection platform, the CellSearch System. Although the use of liquid biopsy in a patient population with a genomically defined solid tumor may potentially be clinically useful, it currently does not supersede conventional pretreatment tissue diagnosis of lung cancer. Liquid biopsy has not been validated for lung cancer diagnosis, and its lower sensitivity could lead to significant diagnostic delay if liquid biopsy were to be used in lieu of tissue biopsy. Ultimately, notwithstanding the enthusiasm encompassing liquid biopsy, its clinical utility remains unproven.


2020 ◽  
Vol 12 (11) ◽  
pp. 7048-7056
Author(s):  
Matthew J. Cecchini ◽  
Eunhee S. Yi

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23036-e23036
Author(s):  
Veena M. Singh ◽  
Edgar V. Sales ◽  
Lan Huynh ◽  
Cecile Rose T. Vibat ◽  
Anna E Barón ◽  
...  

e23036 Background: Liquid biopsy is a minimally invasive and cost effective way to assess cancer biomarkers without the risk of surgical biopsy complications. Circulating tumor cell (CTC) analysis from body fluids can provide critical information towards early detection, prognosis and treatment decisions. Accurate CTC evaluations require optimal cell preservation. Cell lysis, DNA degradation, or membrane alterations compromise CTC analyses and accurate diagnoses. This work compares Biocept’s proprietary CEE-Sure BCT and Saccomanno's Cytology Fixative largely used for sputum collection. Methods: One million BT474 (HER2 amplified) or H3112 (ALK re-arranged) cells were spiked into 500 µl medium; 500 µl of CEE-Sure or Saccomanno fixative was added. Tubes were stored at 4°C for 1 day, 1 week, or 1 month. Cells were centrifuged, resuspended, and counted (Celigo). Around 150 cells in 15 µl of RPMI medium were flowed into Biocept's microfludic system for cell capture; recovery (%) was calculated. Captured cells were subjected to fluorescent in situ hybridization (FISH) analyses for qualitative signal evaluation. Results: As similar results were observed for both cell lines and all time points, combined data will be shown. Median cell recovery after CEE-Sure incubation was 14.1% (range 1.7–44%, n = 12) vs 5.4% (range 0.07–26.9%, n = 12) in Saccomanno's fixative. Median cell capture of ~150 cells fed into Biocept’s microchannel was 96% (range 72-98%) for CEE-Sure vs 82% (range 21-96%) for Saccomanno. Paired t-tests showed significant differences for both recovery and capture. FISH signals from CEE-Sure samples were qualitatively rated Fair to Good, while Saccomanno samples had Poor to Fair, grainy, non-specific signals. Conclusions: This preliminary work shows consistently higher cell recovery, better cell membrane maintenance, and higher quality FISH signals for samples stored in Biocept's CEE-Sure vs Saccomano’s fixative. With liquid biopsy testing gaining rapid traction, maximal cell stability during the transport and storage are crucial. Additional fixative comparison is ongoing in various patient specimen types. These results support expansion of molecular analyses in sputum samples enriched for lung epithelial cells.


2018 ◽  
Vol 64 (3) ◽  
pp. 331-334
Author(s):  
Fedor Moiseenko ◽  
Vladislav Tyurin ◽  
Nikita Levchenko ◽  
Yevgeniy Levchenko ◽  
Aglaya Ievleva ◽  
...  

A patient with lung cancer carrying ROS1 translocation was treated by crizotinib and then subjected to surgery. Morphological analysis revealed pathologic complete response in surgically removed tissues, while PCR test provided convincing evidence for the presence of residual tumor cells. PCR analysis of lung cancer specific gene translocations allows carrying out highly sensitive and reliable monitoring of tumor disease during the course of treatment.


2019 ◽  
Vol 14 (7) ◽  
pp. 658-666
Author(s):  
Kai-jian Xia ◽  
Jian-qiang Wang ◽  
Jian Cai

Background: Lung cancer is one of the common malignant tumors. The successful diagnosis of lung cancer depends on the accuracy of the image obtained from medical imaging modalities. Objective: The fusion of CT and PET is combining the complimentary and redundant information both images and can increase the ease of perception. Since the existing fusion method sare not perfect enough, and the fusion effect remains to be improved, the paper proposes a novel method called adaptive PET/CT fusion for lung cancer in Piella framework. Methods: This algorithm firstly adopted the DTCWT to decompose the PET and CT images into different components, respectively. In accordance with the characteristics of low-frequency and high-frequency components and the features of PET and CT image, 5 membership functions are used as a combination method so as to determine the fusion weight for low-frequency components. In order to fuse different high-frequency components, we select the energy difference of decomposition coefficients as the match measure, and the local energy as the activity measure; in addition, the decision factor is also determined for the high-frequency components. Results: The proposed method is compared with some of the pixel-level spatial domain image fusion algorithms. The experimental results show that our proposed algorithm is feasible and effective. Conclusion: Our proposed algorithm can better retain and protrude the lesions edge information and the texture information of lesions in the image fusion.


Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2265
Author(s):  
Elio Gregory Pizzutilo ◽  
Martino Pedrani ◽  
Alessio Amatu ◽  
Lorenzo Ruggieri ◽  
Calogero Lauricella ◽  
...  

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.


Author(s):  
Atocha Romero ◽  
Roberto Serna-Blasco ◽  
Virginia Calvo ◽  
Mariano Provencio

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