scholarly journals Detecting an ALK Rearrangement via Liquid Biopsy Enabled a Targeted Therapy-based Approach for Treating a Patient with Advanced Non-small Cell Lung Cancer

2018 ◽  
Vol 14 (1) ◽  
pp. 38 ◽  
Author(s):  
Alejandro R Calvo ◽  
Gabriel H Ibarra ◽  
Cecile Rose T Vibat ◽  
Veena M Singh
Keyword(s):  
Liquid Biopsy ◽  
Clinical Utility ◽  
Tumor Tissue ◽  
Molecular Testing ◽  
Tissue Analysis ◽  
Alk Rearrangement ◽  
Blood Draw ◽  
Diagnostic Biopsy

Initial diagnostic biopsy procedures often yield insufficient tissue for molecular testing, and invasive surgical biopsies can be associated with significant cost as well as risk to the patient. Liquid biopsy offers an alternative and economical means for molecular characterization of tumors via a simple peripheral blood draw. This case report describes the ability of liquid biopsy to detect an ALK translocation where tissue analysis by fluorescence in situ hybridization was negative for the genetic alteration. Identification of an ALK rearrangement in circulating tumor cells from a blood specimen led to sequential targeted therapies that included crizotinib followed by alectinib. The patient demonstrated outstanding clinical response during treatment with each of the prescribed ALK inhibitors. This case demonstrates the clinical utility of Biocept’s liquid biopsy to detect actionable biomarkers by surveying the systemic landscape of a patient’s disease where identification of the same genetic drivers may be missed in analyses of heterogeneous tumor tissue.

scholarly journals Technical and Regulatory Considerations for Taking Liquid Biopsy to the Clinic: Validation of the JAX PlasmaMonitorTM Assay

2019 ◽  
Vol 14 ◽  
pp. 117727191982654 ◽  
Author(s):  
Bridgette A Sisson ◽  
Jasmina Uvalic ◽  
Kevin Kelly ◽  
Pavalan Selvam ◽  
Andrew N Hesse ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Clinical Utility ◽  
Tumor Tissue ◽  
New Technology ◽  
Invasive Procedure ◽  
Standard Of Care ◽  
Liquid Biopsies ◽  
Blood Draw ◽  
Analytical Test ◽  
The Many

The standard of care in oncology has been genomic profiling of tumor tissue biopsies for the treatment and management of disease, which can prove to be quite challenging in terms of cost, invasiveness of procedure, and potential risk for the patient. As the number of available drugs in oncology continues to increase, so too does the demand for technologies and testing applications that can identify genomic alterations targetable by these new therapies. Liquid biopsies that use a blood draw from the diseased patient may offset the many disadvantages of the invasive procedure. However, as with any new technology or finding in the clinical field, the clinical utility of an analytical test such as that of the liquid biopsy has to be established. Here, we review the clinical testing space for liquid biopsy offerings and elucidate the technical and regulatory considerations to develop such an assay, using our recently validated PlasmaMonitorTM test.

scholarly journals The Translational Status of Cancer Liquid Biopsies

2019 ◽  
Author(s):  
Sinisa Bratulic ◽  
Francesco Gatto ◽  
Jens Nielsen
Keyword(s):  
Treatment Outcomes ◽  
Liquid Biopsy ◽  
Tumor Tissue ◽  
Body Fluids ◽  
Precision Oncology ◽  
Liquid Biopsies ◽  
Non Invasive ◽  
Biomarker Research ◽  
Successes And Challenges

Abstract Precision oncology aims to tailor clinical decisions specifically to patients with the objective of improving treatment outcomes. This can be achieved by leveraging omics information for accurate molecular characterization of tumors. Tumor tissue biopsies are currently the main source of information for molecular profiling. However, biopsies are invasive and limited in resolving spatiotemporal heterogeneity in tumor tissues. Alternative non-invasive liquid biopsies can exploit patient’s body fluids to access multiple layers of tumor-specific biological information (genomes, epigenomes, transcriptomes, proteomes, metabolomes, circulating tumor cells, and exosomes). Analysis and integration of these large and diverse datasets using statistical and machine learning approaches can yield important insights into tumor biology and lead to discovery of new diagnostic, predictive, and prognostic biomarkers. Translation of these new diagnostic tools into standard clinical practice could transform oncology, as demonstrated by a number of liquid biopsy assays already entering clinical use. In this review, we highlight successes and challenges facing the rapidly evolving field of cancer biomarker research. Lay Summary Precision oncology aims to tailor clinical decisions specifically to patients with the objective of improving treatment outcomes. The discovery of biomarkers for precision oncology has been accelerated by high-throughput experimental and computational methods, which can inform fine-grained characterization of tumors for clinical decision-making. Moreover, advances in the liquid biopsy field allow non-invasive sampling of patient’s body fluids with the aim of analyzing circulating biomarkers, obviating the need for invasive tumor tissue biopsies. In this review, we highlight successes and challenges facing the rapidly evolving field of liquid biopsy cancer biomarker research.

Multi-analyte liquid biopsies based treatment in advanced refractory cancers.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15623-e15623
Author(s):  
Sewanti Limaye ◽  
Darshana Patil ◽  
Dadasaheb B Akolkar ◽  
Timothy Crook ◽  
Anantbhushan Ranade ◽  
...  
Keyword(s):  
Treatment Response ◽  
Liquid Biopsy ◽  
Tumor Tissue ◽  
Single Gene ◽  
Objective Response ◽  
Specific Treatment ◽  
Patient Specific ◽  
Solid Organ ◽  
Liquid Biopsies ◽  
Blood Draw

e15623 Background: Tumor tissue profiling following invasive biopsies is presently the standard approach for indication-based therapy management in solid organ cancers. However, challenges in biopsy are traditionally described due to proximity to vital organs, or patients’ co-morbidities or unwillingness for an invasive procedure. Liquid biopsies for evaluation of cancers are also largely restricted to single gene testing for selection of targeted therapy agents. We developed a comprehensive liquid biopsy based multi-analyte (molecular and functional) investigation of the cancer (eLBx: Encyclopedic Liquid Biopsy) for selection and management of individualised treatments in a cohort of advanced refractory cancers. Methods: We obtained 20 mL blood from 65 patients with solid organ cancers where the disease had progressed following failure of at least two lines of systemic therapies and where biopsy to obtain tumor tissue for molecular profiling of tumor was unviable. Cell free tumor DNA (ctDNA) was interrogated for mutations, while exosomal mRNA was profiled for gene expression. Viable circulating tumor associated cells (C-TACs) were tested in vitro for chemoresistance and used to determine expression of cell surface signalling receptors by immunocytochemistry (ICC). The findings were integrated to generate patient-specific treatment regimens. In patients who received treatment, response was determined radiologically. Results: Fifty-one patients received eLBx-guided personalized treatments with combinations of cytotoxic, targeted and endocrine agents. No two patients received the same treatment regimen. Forty-three patients were evaluable for treatment response per protocol among whom Partial Response (PR) was observed in 14 patients yielding an Objective Response Rate (ORR) of 32.6%. Additionally, 23 patients showed Stable Disease thus yielding an overall Disease Control rate of 86.1%. Median Progression Free Survival (PFS) was 108 days. There were no Grade IV therapy related Adverse Events or therapy related deaths. Conclusions: The ability to make informed treatment choices from a convenient blood draw implies a reduced dependence on invasive biopsies for disease management. We demonstrate successful management of advanced refractory solid tumor malignancies using an integrational non-invasive multi-analyte liquid biopsy approach. Clinical trial information: CTRI/2019/02/017548.

Abstract 5388: RNA in situ detection and characterization of ALK rearrangement in NSCLC FFPE tissues

2018 ◽  
Author(s):  
Na Li ◽  
Shafei Wu ◽  
Mindy Wang ◽  
Hongzhe Sun ◽  
Zhifu Zhang ◽  
...  
Keyword(s):  
Alk Rearrangement ◽  
Ffpe Tissues ◽  
In Situ Detection

scholarly journals Liquid biopsy for patients with IBD-associated neoplasia

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hideaki Kinugasa ◽  
Sakiko Hiraoka ◽  
Kazuhiro Nouso ◽  
Shumpei Yamamoto ◽  
Mami Hirai ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Target Genes ◽  
Tumor Tissue ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Tissue Samples ◽  
Non Invasive ◽  
Tumor Tissues ◽  
Inflammatory Bowel

Abstract Background It is often difficult to diagnose inflammatory bowel disease (IBD)-associated neoplasia endoscopically due to background inflammation. In addition, due to the absence of sensitive tumor biomarkers, countermeasures against IBD-associated neoplasia are crucial. The purpose of this study is to develop a new diagnostic method through the application of liquid biopsy. Methods Ten patients with IBD-associated cancers and high-grade dysplasia (HGD) with preserved tumor tissue and blood were included. Tumor and non-tumor tissues were analyzed for 48 cancer-related genes using next-generation sequencing. Simultaneously, circulating tumor DNA (ctDNA) was analyzed for mutations in the target genes using digital PCR. Results Out of 10 patients, seven had IBD-related cancer and three had IBD-related HGD. Two patients had carcinoma in situ; moreover, three had stageII and two had stage III. To avoid false positives, the mutation rate cutoff was set at 5% based on the control results; seven of 10 (70%) tumor tissue samples were mutation-positive. Mutation frequencies for each gene were as follows: TP53 (20.9%; R136H), TP53 (25.0%; C110W), TP53 (8.5%; H140Q), TP53 (31.1%; R150W), TP53 (12.8%; R141H), KRAS (40.0%; G12V), and PIK3CA (34.1%; R 88Q). The same mutations were detected in the blood of these seven patients. However, no mutations were detected in the blood of the remaining three patients with no tumor tissue mutations. The concordance rate between tumor tissue DNA and blood ctDNA was 100%. Conclusion Blood liquid biopsy has the potential to be a new method for non-invasive diagnosis of IBD-associated neoplasia.

A multi-gene colorectal cancer liquid biopsy with >90% accuracy in diagnosis and assessment of disease status.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16079-e16079
Author(s):  
Irvin Mark Modlin ◽  
Mark S. Kidd ◽  
Alexandra Kitz ◽  
Ignat A. Drozdov ◽  
Anna Malczewska ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Colon Cancer ◽  
Surgical Resection ◽  
Cell Lines ◽  
Stable Disease ◽  
Liquid Biopsy ◽  
Clinical Utility ◽  
Tumor Tissue ◽  
Blood Gene Expression

e16079 Background: There are few blood-based biomarkers for colorectal cancer (CRC). We report a 13-gene colon cancer circulating-free mRNA to diagnose CRC. Clinical utility was assessed in surgical and chemotherapy patients. Methods: Gene identification/validation: Publicly available colon cancer transcriptomes (E-MTAB-57) to identify candidate markers using gene co-expression network enrichment, differential expression and functional enrichment analyses. Cell line/tumor tissue gene expression: Candidate gene expression was evaluated in 3 CRC cell-lines (LOVO, LS-180 and COLO320DM) and surgical resection samples (CRC adenocarcinomas: n= 33) and biomarkers validated in the TCGA-COAD database ( n= 261 adenocarcinomas, 41 mucinous adenocarcinomas). Blood gene expression: CRC set (cancers: n= 312, controls n= 117) and a CRC artificial intelligence model constructed. Normalized gene expression algorithmically scored (0-100). Matched tumor/ blood samples were available in 33 patients. RECIST criteria Clinical score assessment: Score utility was assessed in surgical and treated cohorts: Surgical: n= 37, follow>7 days. Chemotherapy: n= 75; stable disease (SD): n= 20, progressive disease (PD): n= 55). The relationship to CEA and CA-19-9 were assessed. Statistics: Non-parametric (Mann-Whitney), Pearson-correlation, Fisher’s and AUROC analyses (Mean±SEM). Results: Transcriptomic analysis: Thirteen candidate CRC genes blood were identified. Cell lines and tumor tissue: Expression levels were significantly elevated ( p< 0.001, 20-100-fold) in cell lines and CRC tumors. All 13 markers were confirmed in TCGA-COAD samples (average TPM ranged from 692-4405). Blood gene expression: All 13 CRC marker genes were identified in CRC blood. Levels were 54.4±1.5 ( p< 0.0001) compared to controls (9.5±1.7); AUROC:0.91±0.02, accuracy 90.5% (sensitivity 93.1%, specificity 81.2%). The matched tissue/blood correlation was r = 0.80 ( p= 0.002). Clinical Utility: In the surgical cohort, accuracy was 100% vs CEA (35%) or CA-19-9 (17%) (both p< 0.0001). Resection (R0–92%) significantly decreased levels (47±2) at follow-up ( p< 0.006). In the treated cohort, levels were elevated in PD (63±4.1) vs SD (30±3.2, p< 0.0001). Conclusions: A CRC gene marker panel in blood identified colon cancer with a diagnostic accuracy of 91%. This was significantly greater than CEA or CA-19 in CRCs. Surgical resection decreased levels. CRC score was elevated in progressive vs stable disease. A colorectal cancer liquid biopsy will facilitate image-based management.

scholarly journals The biology and clinical potential of circulating tumor cells

2019 ◽  
Vol 53 (2) ◽  
pp. 131-147 ◽  
Author(s):  
Taja Lozar ◽  
Klara Gersak ◽  
Maja Cemazar ◽  
Cvetka Grasic Kuhar ◽  
Tanja Jesenko
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Liquid Biopsy ◽  
Clinical Utility ◽  
Cancer Metastasis ◽  
Predictive Biomarkers ◽  
Cell Types ◽  
Biological Properties ◽  
Great Promise ◽  
Blood Draw

Abstract Background Tumor cells can shed from the tumor, enter the circulation and travel to distant organs, where they can seed metastases. These cells are called circulating tumor cells (CTCs). The ability of CTCs to populate distant tissues and organs has led us to believe they are the primary cause of cancer metastasis. The biological properties and interaction of CTCs with other cell types during intravasation, circulation in the bloodstream, extravasation and colonization are multifaceted and include changes of CTC phenotypes that are regulated by many signaling molecules, including cytokines and chemokines. Considering a sample is readily accessible by a simple blood draw, monitoring CTC levels in the blood has exceptional implications in oncology field. A method called the liquid biopsy allows the extraction of not only CTC, but also CTC products, such as cell free DNA (cfDNA), cell free RNA (cfRNA), microRNA (miRNA) and exosomes. Conclusions The clinical utility of CTCs and their products is increasing with advances in liquid biopsy technology. Clinical applications of liquid biopsy to detect CTCs and their products are numerous and could be used for screening of the presence of the cancer in the general population, as well as for prognostic and predictive biomarkers in cancer patients. With the development of better CTC isolation technologies and clinical testing in large prospective trials, increasing clinical utility of CTCs can be expected. The understanding of their biology and interactions with other cell types, particularly with those of the immune system and the rise of immunotherapy also hold great promise for novel therapeutic possibilities.

scholarly journals Sinonasal Papillomas and Carcinomas: A Contemporary Update With Review of an Emerging Molecular Classification

2019 ◽  
Vol 143 (11) ◽  
pp. 1304-1316 ◽  
Author(s):  
Steven C. Weindorf ◽  
Noah A. Brown ◽  
Jonathan B. McHugh ◽  
Aaron M. Udager
Keyword(s):  
Molecular Basis ◽  
Clinical Utility ◽  
Molecular Classification ◽  
Accurate Diagnosis ◽  
Molecular Testing ◽  
Diagnostic Challenge ◽  
Pertinent Literature ◽  
Molecular Features ◽  
Relative Rarity

Context.— Sinonasal papillomas and carcinomas are uncommon head and neck neoplasms that comprise a broad clinicopathologic and morphologic spectrum, and thus frequently represent a diagnostic challenge for surgical pathologists. Recent molecular interrogation of these tumors has delineated a number of recurrent alterations that correspond to distinct entities with potential diagnostic and/or therapeutic clinical utility. Objective.— To summarize the salient clinicopathologic, morphologic, and molecular features of sinonasal papillomas and carcinomas. Data Sources.— Review of pertinent literature regarding sinonasal papillomas and sinonasal carcinomas. Conclusions.— Despite their relative rarity in many surgical pathology practices, sinonasal papillomas and carcinomas frequently demonstrate characteristic morphologic features that are important for accurate diagnosis. Given our emerging understanding of the molecular basis for these tumors, judicious use of available ancillary tools—including immunohistochemistry and in situ hybridization—may be helpful in subsets of cases, whereas additional molecular testing may be useful for diagnostically challenging and/or clinically aggressive sinonasal tumors.

scholarly journals Blood-Based Liquid Biopsy for Comprehensive Cancer Genomic Profiling Using Next-Generation Sequencing: An Emerging Paradigm for Non-invasive Cancer Detection and Management in Dogs

2021 ◽  
Vol 8 ◽  
Author(s):  
Kristina M. Kruglyak ◽  
Jason Chibuk ◽  
Lisa McLennan ◽  
Prachi Nakashe ◽  
Gilberto E. Hernandez ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Liquid Biopsy ◽  
Tumor Tissue ◽  
Genomic Profiling ◽  
Next Generation ◽  
Blood Draw ◽  
Genomic Alterations ◽  
Tissue Samples ◽  
Non Invasive ◽  
Generation Sequencing

This proof-of-concept study demonstrates that blood-based liquid biopsy using next generation sequencing of cell-free DNA can non-invasively detect multiple classes of genomic alterations in dogs with cancer, including alterations that originate from spatially separated tumor sites. Eleven dogs with a variety of confirmed cancer diagnoses (including localized and disseminated disease) who were scheduled for surgical resection, and five presumably cancer-free dogs, were enrolled. Blood was collected from each subject, and multiple spatially separated tumor tissue samples were collected during surgery from 9 of the cancer subjects. All samples were analyzed using an advanced prototype of a novel liquid biopsy test designed to non-invasively interrogate multiple classes of genomic alterations for the detection, characterization, and management of cancer in dogs. In five of the nine cancer patients with matched tumor and plasma samples, pre-surgical liquid biopsy testing identified genomic alterations, including single nucleotide variants and copy number variants, that matched alterations independently detected in corresponding tumor tissue samples. Importantly, the pre-surgical liquid biopsy test detected alterations observed in spatially separated tissue samples from the same subject, demonstrating the potential of blood-based testing for comprehensive genomic profiling of heterogeneous tumors. Among the three patients with post-surgical blood samples, genomic alterations remained detectable in one patient with incomplete tumor resection, suggesting utility for non-invasive detection of minimal residual disease following curative-intent treatment. Liquid biopsy allows for non-invasive profiling of cancer-associated genomic alterations with a simple blood draw and has potential to overcome the limitations of tissue-based testing posed by tissue-level genomic heterogeneity.

The Use of Advanced Analytical Techniques for Characterization of the Chemical, Physical, and Crystallographic Nature of a Surface

1973 ◽  
Vol 31 ◽  
pp. 132-133 ◽  
Author(s):  
R. E. Herfert
Keyword(s):  
Surface Characterization ◽  
Analytical Techniques ◽  
X Ray Diffraction ◽  
Depth Of Penetration ◽  
X Ray ◽  
The Past ◽  
Transmission Electron ◽  
Scanning Electron

Studies of the nature of a surface, either metallic or nonmetallic, in the past, have been limited to the instrumentation available for these measurements. In the past, optical microscopy, replica transmission electron microscopy, electron or X-ray diffraction and optical or X-ray spectroscopy have provided the means of surface characterization. Actually, some of these techniques are not purely surface; the depth of penetration may be a few thousands of an inch. Within the last five years, instrumentation has been made available which now makes it practical for use to study the outer few 100A of layers and characterize it completely from a chemical, physical, and crystallographic standpoint. The scanning electron microscope (SEM) provides a means of viewing the surface of a material in situ to magnifications as high as 250,000X.

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