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  1. Article: Case report: Real-world experience using a personalized cancer-specific circulating tumor DNA assay in different metastatic melanoma scenarios.

    Khaddour, Karam / Zhou, Alice / Butt, Omar H / Budde, Griffin / Malashevich, Allyson Koyen / Ansstas, George

    Frontiers in oncology

    2022  Volume 12, Page(s) 978996

    Abstract: Circulating-tumor DNA (ctDNA) has emerged as an important biomarker for monitoring disease status in cancer patients. Different ctDNA testing platforms have shown promising results in the early detection of disease, monitoring response to treatment, and ... ...

    Abstract Circulating-tumor DNA (ctDNA) has emerged as an important biomarker for monitoring disease status in cancer patients. Different ctDNA testing platforms have shown promising results in the early detection of disease, monitoring response to treatment, and prognostication in metastatic melanoma. However, several challenges exist, including the reduced shedding of ctDNA into the bloodstream in the metastatic setting, differences in sensitivity among various ctDNA assays, and the inherent inability to distinguish tumor-specific mutations from other mutations that are not related to the cancer of interest. Using a ctDNA assay that is designed to detect multiple single-nucleotide variants (SNVs) that are specific to the tumor itself may allow for more accurate monitoring of disease status in metastatic melanoma. In this case series, we describe a real-world experience using a personalized, tumor-informed ctDNA assay to monitor the clinical trajectories of four patients with metastatic melanoma. Our report highlights potential benefits and limitations using ctDNA in this setting to inform clinical decision-making. This report provides a proof of concept of the technique using an mPCR-NGS-based ctDNA assay (Signatera
    Language English
    Publishing date 2022-11-17
    Publishing country Switzerland
    Document type Case Reports
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.978996
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: ctDNA Clearance and Radiographic Resolution of Disease in Response to Dual Checkpoint Inhibition in Metastatic Microsatellite Stable Colorectal Cancer with a High Tumor Mutation Burden.

    Schneider, Charles J / Krainock, Michael / Malashevich, Allyson Koyen / Malhotra, Meenakshi / Olshan, Perry / Billings, Paul R / Aleshin, Alexey

    Case reports in oncology

    2021  Volume 14, Issue 2, Page(s) 849–853

    Abstract: Immunotherapy (IO) has increasingly been demonstrated to provide therapeutic benefit to patients with metastatic colorectal cancer (mCRC). However, only a subset of mCRC tumors respond to IO. Monitoring response with tumor biomarkers like ... ...

    Abstract Immunotherapy (IO) has increasingly been demonstrated to provide therapeutic benefit to patients with metastatic colorectal cancer (mCRC). However, only a subset of mCRC tumors respond to IO. Monitoring response with tumor biomarkers like carcinoembryonic antigen (CEA) has been challenging in patients with microsatellite stable (MSS) mCRC due to low expression of CEA (CEA/lo). Noninvasive blood-based biomarkers such as circulating tumor DNA (ctDNA) can inform early treatment response and augment radiographic monitoring. We describe a case study of a patient with chemotherapy-refractory CEA/lo MSS mCRC, with metastatic disease present in a cardiophrenic lymph node. The patient was given 2 cycles of combination IO (ipilimumab/nivolumab). Response was monitored by ctDNA using a multiplex PCR next-generation sequencing assay, CEA, and CT scan. After IO administration, ctDNA levels rapidly declined, becoming undetectable. This was concurrent with radiographic resolution of the lymph node metastasis. Serial monitoring of CEA during this same period was uninformative, with no significant changes observed. Significant decline in ctDNA identified metastatic response to IO in a patient with CEA/lo, MSS mCRC and was concurrently validated by CT scan. This case study provides evidence that ctDNA can be used as a prospective surrogate for radiographic tumor response.
    Language English
    Publishing date 2021-06-11
    Publishing country Switzerland
    Document type Case Reports
    ZDB-ID 2458961-5
    ISSN 1662-6575
    ISSN 1662-6575
    DOI 10.1159/000516190
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Correlation between variant allele frequency and mean tumor molecules with tumor burden in patients with solid tumors.

    Kalashnikova, Ekaterina / Aushev, Vasily N / Malashevich, Allyson Koyen / Tin, Antony / Krinshpun, Shifra / Salari, Raheleh / Scalise, Carly Bess / Ram, Rosalyn / Malhotra, Meenakshi / Ravi, Harini / Sethi, Himanshu / Sanchez, Stephanie / Hagelstrom, Robert Tanner / Brevnov, Maxim / Rabinowitz, Matthew / Moshkevich, Solomon / Zimmermann, Bernhard G / Liu, Minetta C / Aleshin, Alexey

    Molecular oncology

    2023  

    Abstract: Several studies have demonstrated the prognostic value of circulating tumor DNA (ctDNA); however, the correlation of mean tumor molecules (MTM)/ml of plasma and mean variant allele frequency (mVAF; %) with clinical parameters is yet to be understood. In ... ...

    Abstract Several studies have demonstrated the prognostic value of circulating tumor DNA (ctDNA); however, the correlation of mean tumor molecules (MTM)/ml of plasma and mean variant allele frequency (mVAF; %) with clinical parameters is yet to be understood. In this study, we analyzed ctDNA data in a pan-cancer cohort of 23 543 patients who had ctDNA testing performed using a personalized, tumor-informed assay (Signatera™, mPCR-NGS assay). For ctDNA-positive patients, the correlation between MTM/ml and mVAF was examined. Two subanalyses were performed: (a) to establish the association of ctDNA with tumor volume and (b) to assess the correlation between ctDNA dynamics and patient outcomes. On a global cohort, a positive correlation between MTM/ml and mVAF was observed. Among 18 426 patients with longitudinal ctDNA measurements, 13.3% had discordant trajectories between MTM/ml and mVAF at subsequent time points. In metastatic patients receiving immunotherapy (N = 51), changes in ctDNA levels expressed both in MTM/ml and mVAF showed a statistically significant association with progression-free survival; however, the correlation with MTM/ml was numerically stronger.
    Language English
    Publishing date 2023-12-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2415106-3
    ISSN 1878-0261 ; 1574-7891
    ISSN (online) 1878-0261
    ISSN 1574-7891
    DOI 10.1002/1878-0261.13557
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6637: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  4. Article: Treatment Response Monitoring Using a Tumor-Informed Circulating Tumor DNA Test in an Advanced Triple-Negative Breast Cancer Patient: A Case Report.

    Azzi, Georges / Krinshpun, Shifra / Tin, Antony / Maninder, Minu / Malashevich, Allyson Koyen / Malhotra, Meenakshi / Vega, Ruben Ruiz / Billings, Paul R / Rodriguez, Angel / Aleshin, Alexey

    Case reports in oncology

    2022  Volume 15, Issue 2, Page(s) 473–479

    Abstract: Triple-negative breast cancer (TNBC) is highly aggressive disease that is often refractory to surgery and multiple lines of therapy. Although the repertoire of FDA-approved treatments has expanded, there is an unmet need for biomarkers that can aid in ... ...

    Abstract Triple-negative breast cancer (TNBC) is highly aggressive disease that is often refractory to surgery and multiple lines of therapy. Although the repertoire of FDA-approved treatments has expanded, there is an unmet need for biomarkers that can aid in appropriate selection and timing of therapy. We present a case of highly aggressive treatment-resistant TNBC that employed a comprehensive genomic profiling (CGP)-based assay to identify therapeutic targets, followed by longitudinal circulating tumor DNA (ctDNA) testing. For this, a tumor-naïve next-generation sequencing-based targeted panel was used to aid in therapy selection, along with longitudinal personalized and tumor-informed ctDNA testing to monitor tumor response to treatment. Longitudinal ctDNA testing using the tumor-informed assay detected post-surgical molecular residual disease, and rise in ctDNA levels during the surveillance period provided rationale for switching between four lines of therapy. Overall, the combined use of CGP assay with longitudinal ctDNA testing resulted in a potential prolonged survival in this highly aggressive case of TNBC.
    Language English
    Publishing date 2022-05-02
    Publishing country Switzerland
    Document type Case Reports
    ZDB-ID 2458961-5
    ISSN 1662-6575
    ISSN 1662-6575
    DOI 10.1159/000524324
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: The Utility of Circulating Tumor DNA (ctDNA) Monitoring in Cancer Patients Who Are Pregnant or Planning to Become Pregnant.

    Cohen, Stacey A / Kasi, Anup / Hook, Nicole / Krainock, Michael / Budde, Griffin / Malashevich, Allyson Koyen / Meltzer, Jeffrey / Jelsema, Russ / Olshan, Perry / Billings, Paul R / Aleshin, Alexey / Poklepovic, Andrew S

    Case reports in obstetrics and gynecology

    2022  Volume 2022, Page(s) 9412201

    Abstract: The number of pregnant women with cancer is on the rise. These patients and their providers encounter complex medical management decisions. Standard-of-care systemic therapy and radiological imaging can impair fetal development and affect viability. ... ...

    Abstract The number of pregnant women with cancer is on the rise. These patients and their providers encounter complex medical management decisions. Standard-of-care systemic therapy and radiological imaging can impair fetal development and affect viability. Conversely, insufficient monitoring and treatment can lead to cancer progression, compromising the health of the patient. Personalized and tumor-informed circulating tumor DNA (ctDNA) testing (Signatera™, bespoke mPCR NGS assay) is a validated, noninvasive blood test that can accurately assess cancer progression and tumor response to treatment ahead of radiological imaging, across solid tumors. In this case series of four patients, we explore the clinical utility of longitudinal ctDNA testing in the medical management of pregnant patients with solid tumors, to aid in informed decision-making for patients and providers.
    Language English
    Publishing date 2022-03-15
    Publishing country United States
    Document type Case Reports
    ZDB-ID 2627654-9
    ISSN 2090-6692 ; 2090-6684
    ISSN (online) 2090-6692
    ISSN 2090-6684
    DOI 10.1155/2022/9412201
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Association Between Total Cell Free DNA and SARS-CoV-2 In Kidney Transplant Patients: A Preliminary Study.

    Reusing, Jose Otto / Yoo, Jongwon / Desai, Amishi / Brossart, Katya / McCormick, Sarah / Malashevich, Allyson Koyen / Bloom, Michelle S / Fehringer, Gordon / White, Roseann / Billings, Paul R / Tabriziani, Hossein / Demko, Zachary P / Gauthier, Philippe / Akkina, Sanjeev K / David-Neto, Elias

    Transplantation proceedings

    2022  Volume 54, Issue 6, Page(s) 1446–1454

    Abstract: Background: Kidney transplant (KT) recipients are at high risk for developing severe COVID-19. Lowering immunosuppression levels in KT recipients with COVID-19 encourages native immune responses but can raise the risk of rejection. Donor-derived cell- ... ...

    Abstract Background: Kidney transplant (KT) recipients are at high risk for developing severe COVID-19. Lowering immunosuppression levels in KT recipients with COVID-19 encourages native immune responses but can raise the risk of rejection. Donor-derived cell-free DNA (dd-cfDNA), reported as a fraction of total cfDNA, is a proven biomarker for KT rejection. Total cfDNA levels are elevated in patients with COVID-19, which may depress dd-cfDNA fractions, potentially leading to missed rejections.
    Methods: A retrospective analysis of 29 KT recipients hospitalized with COVID-19 between April and November 2020 examined total and dd-cfDNA levels. Blood samples were collected after onset of COVID-19, with follow-up samples collected from a subset of patients, when infection had likely subsided.
    Results: After COVID-19 diagnosis, the median total cfDNA level was elevated (7.9 multiples of median [MoM]). A significant decrease in total cfDNA levels was observed between the first and second time points (6.2 MoM, 1.0 MoM; P <001). A significant positive association was identified between total cfDNA levels and COVID-19 severity (P = .02; R
    Conclusions: In this preliminary study, total cfDNA levels were elevated in KT patients with COVID-19, subsiding after resolution of infection. High total cfDNA levels may confound dd-cfDNA results, leading to failure to identify rejection. Considering total cfDNA levels is important in interpretation of dd-cfDNA tests for assessment of rejection in KT patients with COVID-19 or other infection.
    MeSH term(s) Biomarkers ; COVID-19 ; COVID-19 Testing ; Cell-Free Nucleic Acids ; Graft Rejection ; Humans ; Kidney Transplantation/adverse effects ; Retrospective Studies ; SARS-CoV-2 ; Tissue Donors
    Chemical Substances Biomarkers ; Cell-Free Nucleic Acids
    Language English
    Publishing date 2022-03-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 82046-5
    ISSN 1873-2623 ; 0041-1345
    ISSN (online) 1873-2623
    ISSN 0041-1345
    DOI 10.1016/j.transproceed.2022.02.027
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 835: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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