Prognostic and Theragnostic Applications of Circulating Tumor DNA (CtDNA) in Metastatic Castrate- resistant Prostatic Carcinoma in Veterans: A Novel Promise in Precision Oncology

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S144-S144
Author(s):  
S Dalal ◽  
D Jhala
Keyword(s):  
General Population ◽  
Minimally Invasive ◽  
Liquid Biopsy ◽  
Patient Population ◽  
Prostatic Carcinoma ◽  
Precision Oncology ◽  
Disease Course ◽  
Liquid Biopsies ◽  
Castrate Resistant

Abstract Introduction/Objective Utility of CtDNA in peripheral blood through liquid biopsies serves as a robust biomarker for precision oncology. Prostate cancer is most common cancer diagnosed in veterans, more commonly presenting at advanced stage with increased incidence of metastatic castrate-resistant prostatic carcinoma (MCRPC). Minimally invasive liquid biopsy is not limited by tumor site, type, tumor heterogeneity, and most importantly enables real time disease monitoring for best therapy decisions in MCRPC. The literature is sparse depicting the role of CtDNA in MCRPC in veteran patient population with distinct demographics/frequency of Tp53 mutations. We herein aim to study role of CtDNA in liquid biopsies for prognosis, treatment decisions and outcome in veterans with MCRPC. Methods QA documents from Foundation One (Cambridge MA, NGS) on liquid biopsies performed for the Corporal Michael J. Crescenz Veteran Affairs Medical Center (CMCVAMC) from May 2019 to April 15, 2020 were reviewed. All liquid biopsies were performed on MCRPC with evidence of tumor progression. Statistical data for adequacy, type of mutations either altering therapy, disease course or outcome was noted. Results A total of 23 liquid biopsies were performed. 21/23 (91.3%) biopsies were adequate, 19/21 (90.4%) showed signature mutations for resistance to therapy, predicting prognosis, or suggesting poor outcome with decreased overall survival. 4/21 (19%) showed androgen receptor amplification (ARV7 mutation) that helped in making treatment decisions. Increased frequency of Tp53 mutations were noted (12/21 (57.1%) compared to general population (30- 40%)) indicating worse prognosis/aggressive disease course with decreased survival. Conclusion Combined exposure of herbicide agent orange and smoking may be a fertile soil for observed differences in type and frequency of genomic alterations in veteran patient population with MCRPC. Comprehensive genomic profiling on CtDNA through minimally invasive liquid biopsy is feasible and can be successfully implemented in veterans with multiple co-morbidities. Although ARV7 mutation is much more common in general population, veterans with advanced hormone resistant prostatic carcinoma may benefit from aggressive approach in developing targeted therapy focused on DNA repair genes, especially Tp53.

scholarly journals Precision Detection Technology: Equipping Precision Oncology with Wings

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Rilan Bai ◽  
Zheng Lv ◽  
Xiao Chen ◽  
Hanfei Guo ◽  
Ling Bai ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
New Drugs ◽  
Therapeutic Effects ◽  
Precision Oncology ◽  
Detection Techniques ◽  
Detection Technology ◽  
Future Challenges ◽  
Rare Gene ◽  
The Many

In recent years, precision medical detection techniques experienced a rapid transformation from low-throughput to high-throughput genomic sequencing, from multicell promiscuous detection to single-cell precision sequencing. The emergence of liquid biopsy technology has compensated for the many limitations of tissue biopsy, leading to a tremendous transformation in precision detection. Precision detection techniques contribute to monitoring disease development more closely, evaluating therapeutic effects more scientifically, and developing new targets and new drugs. In the future, the role of precision detection and the joint detection in epigenetics, rare gene detection, individualized targeted therapy, and multigene targeted drug combination therapy should be extensively explored. This article reviews the changes in precision medical detection technology in the era of precision medicine, as well as the development, clinical application, and future challenges of liquid biopsy.

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.

scholarly journals Rational Development of Liquid Biopsy Analysis in Renal Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5825
Author(s):  
Kate I. Glennon ◽  
Mahafarin Maralani ◽  
Narges Abdian ◽  
Antoine Paccard ◽  
Laura Montermini ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Liquid Biopsy ◽  
Renal Cell ◽  
Somatic Mutations ◽  
Circulating Tumor Dna ◽  
Precision Oncology ◽  
Liquid Biopsies ◽  
Disease Evolution ◽  
Ctdna Analysis

Renal cell carcinoma (RCC) is known for its variable clinical behavior and outcome, including heterogeneity in developing relapse or metastasis. Recent data highlighted the potential of somatic mutations as promising biomarkers for risk stratification in RCC. Likewise, the analysis of circulating tumor DNA (ctDNA) for such informative somatic mutations (liquid biopsy) is considered an important advance for precision oncology in RCC, allowing to monitor molecular disease evolution in real time. However, our knowledge about the utility of ctDNA analysis in RCC is limited, in part due to the lack of RCC-appropriate assays for ctDNA analysis. Here, by interrogating different blood compartments in xenograft models, we identified plasma cell-free (cf) DNA and extracellular vesicles (ev) DNA enriched for RCC-associated ctDNA. Additionally, we developed sensitive targeted sequencing and bioinformatics workflows capable of detecting somatic mutations in RCC-relevant genes with allele frequencies ≥ 0.5%. Applying this assay to patient-matched tumor and liquid biopsies, we captured tumor mutations in cf- and ev-DNA fractions isolated from the blood, highlighting the potentials of both fractions for ctDNA analysis. Overall, our study presents an RCC-appropriate sequencing assay and workflow for ctDNA analysis and provides a proof of principle as to the feasibility of detecting tumor-specific mutations in liquid biopsy in RCC patients.

Incidence of Androgen Receptor and DNA Repair Gene Mutations in Advanced Solid Malignancies: Clinical Impact of Liquid Biopsy at Veteran Affairs Medical Center

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S145-S146
Author(s):  
S Dalal ◽  
D Jhala
Keyword(s):  
Dna Repair ◽  
Liquid Biopsy ◽  
Medical Center ◽  
Gene Mutations ◽  
Genetic Mutations ◽  
Precision Oncology ◽  
Liquid Biopsies ◽  
Repair Gene ◽  
Solid Malignancies ◽  
Dna Repair Gene

Abstract Introduction/Objective The advent of Liquid biopsy targeting genetic mutations in solid tumors is a major milestone in field of precision oncology. This minimally invasive, novel revolutionary technique analyses circulating tumor cells (CTC) in peripheral blood and detects signature genomic alterations. DNA repair gene (DDR) mutations have been reported in 25-40% of prostatic cancers and >50% of non-small cell lung cancers (NSCLC), being more common in late-stage and hormone refractory prostate cancers. One of the DDR, especially Tp53 has been found to be associated with poor prognosis and increased germline mutations. We herein present a quality assurance study to determine feasibility of liquid biopsy for personalized management in veterans for advanced solid malignancies and its clinical impact. Methods Quality assurance documentation from Foundation One (Cambridge MA, NGS) on liquid biopsies performed for the Corporal Michael J. Crescenz Veteran Affairs Medical Center (CMCVAMC) from May 2019 to April 15, 2020 were reviewed. Statistical data for adequacy, cases with notable mutations, frequency and type of mutations of AR, DNA damage repair (DDR) gene and Tp53 were noted. Results A total of 31 liquid biopsies were performed over this time period, of which 29/31 (93.50%) were adequate for evaluation. 23/29 (79.30%) showed notable mutations, in 4/23 (17.39%) guided treatment decisions based on androgen receptor (AR) amplification, and 7/29 (24.1%) of all cases showed DDR gene mutations indicating poor outcome and resistance to the current therapy. Greater than 50% (16/29 (55.7%)) of the veterans with advanced cancers harbored Tp53 mutation, which instills hope and future insight for patient tailored oncologic therapy. Conclusion The minimally invasive liquid biopsy shows a great promise as a diagnostic and prognostic tool in the personalized clinical management of advanced prostate and NSCLC in veteran patient population with unique demographic characteristics. Difference in frequency of the genetic mutations (DDR, TP53, AR) in this cohort provides valuable information for disease progression, lack of response, mechanism of resistance to the implemented therapy and clinical decision making. Precision oncology can be further tailored for this cohort by focusing on DNA repair genes and Tp53 in future for personalized targeted therapy.

scholarly journals Tandem microfluidic chip isolation of prostate and breast cancer cells from simulated liquid biopsies using CD71 as an affinity ligand

RSC Advances ◽  
2020 ◽  
Vol 10 (54) ◽  
pp. 32628-32637
Author(s):  
Bhagya Wickramaratne ◽  
Dimitri Pappas
Keyword(s):  
Breast Cancer ◽  
Minimally Invasive ◽  
Cancer Cells ◽  
Microfluidic Chip ◽  
Liquid Biopsy ◽  
Breast Cancer Cells ◽  
Patient Monitoring ◽  
Liquid Biopsies ◽  
Affinity Ligand

The use of blood as a liquid biopsy provides a minimally invasive and less traumatic approach for initial cancer screens as well as patient monitoring.

Liquid Biopsies in Castrate-Resistant Prostate Cancer: Future Prospects in Radiation Oncology

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Carlos Galvis ◽  
María Caicedo Martinez
Keyword(s):  
Prostate Cancer ◽  
Radiation Oncology ◽  
Liquid Biopsies ◽  
Castrate Resistant Prostate Cancer ◽  
Pre Treatment ◽  
Castrate Resistant ◽  
Molecular Patterns ◽  
Available Information

The use of liquid biopsies, based on circulating tumor cells and tumoral DNA, provides information on the molecular patterns and genomics of Castrate-Resistant Prostate Cancer. There is evidence on the role of the androgen receptor variant 7 as a prognostic and as a follow-up tool, especially as a follow-up to treatment response and resistance with Enzalutamide and Abiraterone. Little is known about the genomics of Castrate Resistant Prostate Cancer and its relationship to radiation therapy’s sensibility. This is particularly relevant for patients with oligometastatic disease, who could obtain a long control of the disease with radiation. In this narrative review, we summarize the available information on liquid biopsies and Castrate Resistant Prostate Cancer. As radiation oncology evolves towards Genomically Adapted Radiation Dose, the role of liquid biopsies as a possible pre-treatment assessment is a future target. Nonetheless, models have been modeled after other malignancies. This highlights the need for further studies to assess the use of personalized medicine in these patients. Keywords: Radiotherapy; Prostate Cancer; Receptors Androgen; Liquid Biopsy; Precision Medicine;

The role of liquid biopsies in prostate cancer management

Lab on a Chip ◽  
2021 ◽  
Author(s):  
Chi-Ju Kim ◽  
Liang Dong ◽  
Sarah Amend ◽  
Yoon-Kyoung Cho ◽  
Kenneth Pienta
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Diagnosis ◽  
Liquid Biopsy ◽  
Liquid Biopsies ◽  
Cancer Management ◽  
The Common ◽  
Prostate Cancer Management

Liquid biopsy has emerged as a complement to invasive tissue biopsy to guide cancer diagnosis and treatment. The common liquid biopsy biomarkers are circulating tumor cells (CTCs), extracellular vesicles (EVs),...

Utility Of Ebus-Tbna In Diagnosis And Staging Of Lung Nodules In The Setting Of Known Second Malignancy In Veterans - A Quality Assurance Study

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S162-S163
Author(s):  
S Dalal ◽  
D Jhala
Keyword(s):  
Minimally Invasive ◽  
Lymph Nodes ◽  
Patient Population ◽  
Predictive Marker ◽  
Endobronchial Ultrasound ◽  
Lung Nodules ◽  
Molecular Testing ◽  
Precision Oncology ◽  
Second Malignancy ◽  
Cervical Lymph Nodes

Abstract Introduction/Objective Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) is minimally invasive procedure for diagnosis/staging/restaging of lung nodules, recommended by the National Comprehensive Cancer Network (NCCN) 2017 Clinical Practice Guidelines. Veteran patients are an elderly patient cohort with multiple comorbidities and many have existing known 2nd malignancy. It will be crucial to diagnose and appropriately stage lung nodules. Our primary aim was to assess the efficacy of EBUS-TBNA in diagnosis/nodal staging in elderly patients with known 2nd malignancy. Our secondary aim was to evaluate the safety of this procedure for veterans. Methods A retrospective search for cases of EBUS-TBNA in patients with known second malignancy was carried out in Vista/Fileman at the Corporal Michael J Crescenz VA Medical Center between the period of June 2019 to January 2020. Sites included lung, cervical lymph nodes, mediastinum and hilar region. Results Of total 93 EBUS-TBNA procedures performed; EBUS-TBNA targeted both the lung and lymph node (62 cases), lymph nodes alone (28 cases) and only lung (3 cases). Total 53 were diagnosed malignant; with primary being lung (39 cases) and pleura (2 cases); and diagnosis of new metastatic carcinomas to lung was made in (12 cases). The metastatic neoplasms included 2 urothelial carcinoma, 7 squamous carcinoma, 2 metastatic adenocarcinoma, and 1 prostatic adenocarcinoma. 32/53 (60.3%) had the history of prior extrapulmonary second malignancy. Immunohistochemical studies was able to be performed in 50/53 (94%) of malignant cases, predictive marker PD-L1 on 50/53 (94%) cases, molecular testing on 23/53(43.3%) cases and Foundation One testing (Cambridge, MA, NGS) on 11/53(20.7%) cases. In all 93 cases, there were no complications (0/93) (0%) of the procedure. Conclusion EBUS-TBNA is an efficient, cost effective and minimally invasive modality in elderly veteran patient population with multiple co-morbidities. EBUS-TBNA is successful in procuring adequate material for diagnosis, molecular and predictive marker studies; thus, it can play a crucial role in precision oncology. EBUS-TBNA plays a pivotal role diagnosing and ruling out metastatic nodal disease in veteran patient population which has a high incidence of known 2nd extrapulmonary malignancy. EBUS-TBNA is deemed safe in veterans.

scholarly journals Liquid Biopsies in Solid Cancers: Implementation in a Nordic Healthcare System

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1861
Author(s):  
Oddmund Nordgård ◽  
Rakel Brendsdal Forthun ◽  
Morten Lapin ◽  
Bjørn Henning Grønberg ◽  
Karl Henning Kalland ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Cancer Biology ◽  
Growth Factor Receptor ◽  
Relevant Information ◽  
Circulating Tumor Dna ◽  
Cancer Diagnostics ◽  
Current Evidence ◽  
Liquid Biopsies ◽  
Clinical Role

Liquid biopsies have emerged as a potential new diagnostic tool, providing detailed information relevant for characterization and treatment of solid cancers. We here present an overview of current evidence supporting the clinical relevance of liquid biopsy assessments. We also discuss the implementation of liquid biopsies in clinical studies and their current and future clinical role, with a special reference to the Nordic healthcare systems. Our considerations are restricted to the most established liquid biopsy specimens: circulating tumor DNA (ctDNA) and circulating tumor cells (CTC). Both ctDNA and CTCs have been used for prognostic stratification, treatment choices, and treatment monitoring in solid cancers. Several recent publications also support the role of ctDNA in early cancer detection. ctDNA seems to provide more robust clinically relevant information in general, whereas CTCs have the potential to answer more basic questions related to cancer biology and metastasis. Epidermal growth factor receptor-directed treatment of non-small-cell lung cancer represents a clinical setting where ctDNA already has entered the clinic. The role of liquid biopsies in treatment decisions, standardization of methods, diagnostic performance and the need for further research, as well as cost and regulatory issues were identified as factors that influence further integration in the clinic. In conclusion, substantial evidence supports the clinical utility of liquid biopsies in cancer diagnostics, but further research is still required for a more general application in clinical practice.

scholarly journals Epigenetic Landscape of Liquid Biopsy in Colorectal Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Aitor Rodriguez-Casanova ◽  
Nicolás Costa-Fraga ◽  
Aida Bao-Caamano ◽  
Rafael López-López ◽  
Laura Muinelo-Romay ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Liquid Biopsy ◽  
Current Knowledge ◽  
Monitoring And Evaluation ◽  
Precision Oncology ◽  
Epigenetic Mechanisms ◽  
Epigenetic Alterations ◽  
Liquid Biopsies ◽  
Dna And Rna

Colorectal cancer (CRC) is one of the most common malignancies and is a major cause of cancer-related deaths worldwide. Thus, there is a clinical need to improve early detection of CRC and personalize therapy for patients with this disease. In the era of precision oncology, liquid biopsy has emerged as a major approach to characterize the circulating tumor elements present in body fluids, including cell-free DNA and RNA, circulating tumor cells, and extracellular vesicles. This non-invasive tool has allowed the identification of relevant molecular alterations in CRC patients, including some indicating the disruption of epigenetic mechanisms. Epigenetic alterations found in solid and liquid biopsies have shown great utility as biomarkers for early detection, prognosis, monitoring, and evaluation of therapeutic response in CRC patients. Here, we summarize current knowledge of the most relevant epigenetic mechanisms associated with cancer development and progression, and the implications of their deregulation in cancer cells and liquid biopsy of CRC patients. In particular, we describe the methodologies used to analyze these epigenetic alterations in circulating tumor material, and we focus on the clinical utility of epigenetic marks in liquid biopsy as tumor biomarkers for CRC patients. We also discuss the great challenges and emerging opportunities of this field for the diagnosis and personalized management of CRC patients.

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