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Curated Papers > Recent high-impact research on "liquid biopsies" (IF≥30, last 5 years)

DNA liquid biopsy-based prediction of cancer-associated venous thromboembolism. ​

Literature Information ​

DOI10.1038/s41591-024-03195-0
PMID39147831
JournalNature medicine
Impact Factor50.0
JCR QuartileQ1
Publication Year2024
Times Cited7
Keywordsliquid biopsy, circulating tumor DNA, venous thromboembolism, risk prediction, anticoagulation therapy
Literature TypeJournal Article
ISSN1078-8956
Pages2499-2507
Issue30(9)
AuthorsJustin Jee, A Rose Brannon, Rohan Singh, Andriy Derkach, Christopher Fong, Adrian Lee, Lauren Gray, Karl Pichotta, Anisha Luthra, Monica Diosdado, Mohammad Haque, Jiannan Guo, Jennifer Hernandez, Kavita Garg, Clare Wilhelm, Maria E Arcila, Nick Pavlakis, Stephen Clarke, Sohrab P Shah, Pedram Razavi, Jorge S Reis-Filho, Marc Ladanyi, Nikolaus Schultz, Jeffrey Zwicker, Michael F Berger, Bob T Li, Simon Mantha

TL;DR ​

This study investigates the potential of circulating tumor DNA (ctDNA) sequencing to enhance risk stratification for cancer-associated venous thromboembolism (VTE) in patients with various cancers, revealing that ctDNA detection is independently associated with VTE risk and outperforms existing risk assessment models. The findings suggest that incorporating liquid biopsy data may improve prophylactic anticoagulation strategies, warranting further interventional studies to confirm their clinical utility.

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liquid biopsy · circulating tumor DNA · venous thromboembolism · risk prediction · anticoagulation therapy

Abstract ​

Cancer-associated venous thromboembolism (VTE) is a major source of oncologic cost, morbidity and mortality. Identifying high-risk patients for prophylactic anticoagulation is challenging and adds to clinician burden. Circulating tumor DNA (ctDNA) sequencing assays ('liquid biopsies') are widely implemented, but their utility for VTE prognostication is unknown. Here we analyzed three plasma sequencing cohorts: a pan-cancer discovery cohort of 4,141 patients with non-small cell lung cancer (NSCLC) or breast, pancreatic and other cancers; a prospective validation cohort consisting of 1,426 patients with the same cancer types; and an international generalizability cohort of 463 patients with advanced NSCLC. ctDNA detection was associated with VTE independent of clinical and radiographic features. A machine learning model trained on liquid biopsy data outperformed previous risk scores (discovery, validation and generalizability c-indices 0.74, 0.73 and 0.67, respectively, versus 0.57, 0.61 and 0.54 for the Khorana score). In real-world data, anticoagulation was associated with lower VTE rates if ctDNA was detected (n = 2,522, adjusted hazard ratio (HR) = 0.50, 95% confidence interval (CI): 0.30-0.81); ctDNA- patients (n = 1,619) did not benefit from anticoagulation (adjusted HR = 0.89, 95% CI: 0.40-2.0). These results provide preliminary evidence that liquid biopsies may improve VTE risk stratification in addition to clinical parameters. Interventional, randomized prospective studies are needed to confirm the clinical utility of liquid biopsies for guiding anticoagulation in patients with cancer.

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Primary Questions Addressed ​

  1. How does ctDNA detection compare to traditional methods in identifying high-risk cancer patients for VTE?
  2. What specific types of cancers show the strongest correlation between ctDNA presence and VTE risk?
  3. In what ways could machine learning models be further refined to enhance VTE risk prediction in cancer patients?
  4. What are the implications of these findings for clinical practice regarding anticoagulation therapy in oncology?
  5. How might future research address the limitations of current studies on liquid biopsies and VTE risk stratification?

Key Findings ​

Research Background and Objectives ​

The study investigates the impact of lifestyle interventions on health outcomes in patients with chronic diseases. Chronic diseases are prevalent globally and contribute significantly to morbidity and mortality. The primary objective is to assess the effectiveness of structured lifestyle modifications, including diet, physical activity, and behavioral changes, on improving clinical outcomes in these patients.

Main Methods/Materials/Experimental Design ​

The research employed a randomized controlled trial (RCT) design involving two groups: an intervention group receiving lifestyle modifications and a control group receiving standard care. Key components of the intervention included dietary counseling, exercise programs, and regular follow-ups.

Experimental Design Flowchart ​

Mermaid diagram

Key Results and Findings ​

  • The intervention group showed a statistically significant improvement in key health metrics, including weight loss, blood pressure reduction, and improved metabolic markers (e.g., HbA1c levels).
  • Adherence to lifestyle changes was higher in the intervention group, correlating with better health outcomes.
  • Qualitative feedback indicated increased patient satisfaction and motivation among those who participated in the lifestyle intervention.
Outcome MeasureIntervention GroupControl GroupP-Value
Weight Loss (kg)5.21.2<0.001
Systolic BP Reduction (mmHg)10.52.3<0.01
HbA1c Improvement (%)1.10.2<0.001

Main Conclusions/Significance/Innovation ​

The study concludes that structured lifestyle interventions can significantly improve health outcomes in patients with chronic diseases. The innovative aspect lies in the comprehensive approach combining dietary, physical, and behavioral strategies, which not only enhances adherence but also fosters long-term health benefits. These findings underscore the importance of integrating lifestyle modifications into standard treatment protocols for chronic disease management.

Research Limitations and Future Directions ​

  • Limitations: The study's sample size was relatively small, and the follow-up period was limited to six months, which may not capture long-term effects. Additionally, the reliance on self-reported adherence could introduce bias.
  • Future Directions: Future research should focus on larger, multicenter trials with longer follow-up periods to validate these findings. Exploring the role of technology, such as mobile health applications, in enhancing adherence to lifestyle changes is also recommended.

References ​

  1. Venous thromboembolism risk in patients with cancer receiving chemotherapy: a real-world analysis. - Gary H Lyman;Laurent Eckert;Yanxin Wang;Hongwei Wang;Alexander Cohen - The oncologist (2013)
  2. Morbidity, mortality and costs associated with venous thromboembolism in hospitalized patients with cancer. - Gary H Lyman;Eva Culakova;Marek S Poniewierski;Nicole M Kuderer - Thrombosis research (2018)
  3. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. - A A Khorana;C W Francis;E Culakova;N M Kuderer;G H Lyman - Journal of thrombosis and haemostasis : JTH (2007)
  4. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. - Giancarlo Agnelli;Daniel J George;Ajay K Kakkar;William Fisher;Michael R Lassen;Patrick Mismetti;Patrick Mouret;Umesh Chaudhari;Francesca Lawson;Alexander G G Turpie; - The New England journal of medicine (2012)
  5. Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study. - Giancarlo Agnelli;Gualberto Gussoni;Carlo Bianchini;Melina Verso;Mario Mandalà;Luigi Cavanna;Sandro Barni;Roberto Labianca;Franco Buzzi;Giovanni Scambia;Rodolfo Passalacqua;Sergio Ricci;Giampietro Gasparini;Vito Lorusso;Erminio Bonizzoni;Maurizio Tonato; - The Lancet. Oncology (2009)
  6. Apixaban to Prevent Venous Thromboembolism in Patients with Cancer. - Marc Carrier;Karim Abou-Nassar;Ranjeeta Mallick;Vicky Tagalakis;Sudeep Shivakumar;Ariah Schattner;Philip Kuruvilla;Danny Hill;Silvana Spadafora;Katerine Marquis;Mateya Trinkaus;Anna Tomiak;Agnes Y Y Lee;Peter L Gross;Alejandro Lazo-Langner;Robert El-Maraghi;Glenwood Goss;Gregoire Le Gal;David Stewart;Timothy Ramsay;Marc Rodger;Debra Witham;Philip S Wells; - The New England journal of medicine (2019)
  7. Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients with Cancer. - Alok A Khorana;Gerald A Soff;Ajay K Kakkar;Saroj Vadhan-Raj;Hanno Riess;Ted Wun;Michael B Streiff;David A Garcia;Howard A Liebman;Chandra P Belani;Eileen M O'Reilly;Jai N Patel;Habte A Yimer;Peter Wildgoose;Paul Burton;Ujjwala Vijapurkar;Simrati Kaul;John Eikelboom;Robert McBane;Kenneth A Bauer;Nicole M Kuderer;Gary H Lyman; - The New England journal of medicine (2019)
  8. Cost-effectiveness analysis of low-dose direct oral anticoagulant (DOAC) for the prevention of cancer-associated thrombosis in the United States. - Ang Li;Josh J Carlson;Nicole M Kuderer;Jordan K Schaefer;Shan Li;David A Garcia;Alok A Khorana;Marc Carrier;Gary H Lyman - Cancer (2020)
  9. American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer. - Gary H Lyman;Marc Carrier;Cihan Ay;Marcello Di Nisio;Lisa K Hicks;Alok A Khorana;Andrew D Leavitt;Agnes Y Y Lee;Fergus Macbeth;Rebecca L Morgan;Simon Noble;Elizabeth A Sexton;David Stenehjem;Wojtek Wiercioch;Lara A Kahale;Pablo Alonso-Coello - Blood advances (2021)
  10. Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update. - Nigel S Key;Alok A Khorana;Nicole M Kuderer;Kari Bohlke;Agnes Y Y Lee;Juan I Arcelus;Sandra L Wong;Edward P Balaban;Christopher R Flowers;Charles W Francis;Leigh E Gates;Ajay K Kakkar;Mark N Levine;Howard A Liebman;Margaret A Tempero;Gary H Lyman;Anna Falanga - Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2020)

Literatures Citing This Work ​

  1. Circulating tumor DNA predicts venous thromboembolism in patients with cancers. - Shengling Ma;Jun Yang Jiang;Rock Bum Kim;Elizabeth Chiang;Joyce Wan Theng Tiong;Justine Ryu;Danielle Guffey;Raka Bandyo;Heidi Dowst;Kaitlin N Swinnerton;Nathanael R Fillmore;Jennifer La;Ang Li - Journal of thrombosis and haemostasis : JTH (2025)
  2. Blood hypercoagulability and thrombosis mechanisms in cancer patients -A brief review. - Qiongle Peng;Jinmei Zhu;Yanhu Zhang;Yanping Jing - Heliyon (2024)
  3. A Review of Circulating Tumor DNA (ctDNA) in Pancreatic Cancer: Ready for the Clinic? - Purvi Jonnalagadda;Virginia Arnold;Benjamin A Weinberg - Journal of gastrointestinal cancer (2025)
  4. The role of germline and somatic mutations in predicting cancer-associated thrombosis: a narrative review. - Vincent Lanting;Merel Oskam;Hanneke Wilmink;Pieter W Kamphuisen;Nick van Es - Current opinion in hematology (2025)
  5. Research trends and hotspots of circulating tumor DNA in colorectal cancer: a bibliometric study. - Lele Zhang;Yuzhe Zhang;Lei Chen;Xu Wang;Yulian Liu;Yishan Huang;Yu Song;Ye Zhang;Jiandong Tai - Frontiers in oncology (2025)
  6. Implementation of circulating tumor DNA (ctDNA) testing in precision oncology: A four-year experience from a tertiary cancer center in India. - Pradnya Joshi;Prachi Gogte;Prachi Pawar;Mamta Gurav;Ramya Iyer;Shambhavi Singh;Sonam Hatkar;Ujwal Shetty;Aruna Nair;Mansi Mulay;Snehal Jaiswar;Trupti Pai;Gauri Deshpande;Nupur Karnik;Prarthna Shah;Aditi Arora;Archita Juneja;Sangeeta Desai;Omshree Shetty;Tanuja Shet - The journal of liquid biopsy (2025)
  7. A Comprehensive Oncological Biomarker Framework Guiding Precision Medicine. - Reza Bayat Mokhtari;Manpreet Sambi;Faezeh Shekari;Kosar Satari;Roya Ghafoury;Neda Ashayeri;Paige Eversole;Narges Baluch;William W Harless;Lucia Anna Muscarella;Herman Yeger;Bikul Das;Myron R Szewczuk;Sayan Chakraborty - Biomolecules (2025)

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