Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer.

Jeanne Tie, M.D., Joshua D. Cohen, M.Phil., Kamel Lahouel, Ph.D., Serigne N. Lo, Ph.D., Yuxuan Wang, M.D., Ph.D., Suzanne Kosmider, M.B., B.S., Rachel Wong, M.B., B.S., Jeremy Shapiro, M.B., B.S., Margaret Lee, M.B., B.S., Sam Harris, M.B., B.S., Adnan Khattak, M.B., B.S., Matthew Burge, M.B., B.S., Marion Harris, M.B., B.S., James Lynam, M.B., B.S., Louise Nott, M.B., B.S., Fiona Day, Ph.D., Theresa Hayes, M.B., B.S., Sue-Anne McLachlan, M.B., B.S., Belinda Lee, M.B., B.S., Janine Ptak, M.S., Natalie Silliman, B.S., Lisa Dobbyn, B.A., Maria Popoli, M.S., Ralph Hruban, M.D., Anne Marie Lennon, M.D., Ph.D., Nicholas Papadopoulos, Ph.D., Kenneth W. Kinzler, Ph.D., Bert Vogelstein, M.D., Cristian Tomasetti, Ph.D., and Peter Gibbs, M.D. for the DYNAMIC Investigators*

The role of adjuvant chemotherapy in stage II colon cancer continues to be debated. The presence of circulating tumor DNA (ctDNA) after surgery predicts very poor recurrence-free survival, whereas its absence predicts a low risk of recurrence. The benefit of adjuvant chemotherapy for ctDNA-positive patients is not well understood.

Evaluating the Impact of Multi-Cancer Early Detection Testing on Health and Economic Outcomes: Toward a Decision Modeling Strategy. Cancer, in press.

Joseph Lipscomb Ph.D., Susan Horton Ph.D., Albert Kuo B.S., Cristian Tomasetti Ph.D.

Emerging data provide initial support for the concept that a single, minimally invasive liquid biopsy test, performed in conjunction with confirmatory radiologic or other diagnostic testing, when indicated, could be deployed on a broad scale to screen individuals for multiple types of cancer.

Circulating tumor DNA dynamics and recurrence risk in patients undergoing curative intent resection of colorectal cancer liver metastases: a prospective cohort study. Special Issue on Early detection and Minimal Residual Disease. PLoS Medicine 2021, in press.​

Jeanne Tie , Yuxuan Wang , Joshua Cohen, Lu Li,Wei Hong, Michael Christie, Hui Li Wong, Suzanne Kosmider, Rachel Wong, Benjamin Thomson, Julian Choi, Adrian Fox, Kathryn Field, Matthew Burge, Jenny Shannon, Dusan Kotasek, Niall C. Tebbutt, Christos Karapetis, Craig Underhill, Andrew Haydon, Joy Schaeffer, Janine Ptak, Cristian Tomasetti, Nicholas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein , Peter Gibbs

In patients with resectable colorectal liver metastases (CRLM), the role of pre- and postoperative systemic therapy continues to be debated. Previous studies have shown that circulating tumor DNA (ctDNA) analysis, as a marker of minimal residual disease, is a powerful prognostic factor in patients with nonmetastatic colorectal cancer (CRC). Serial analysis of ctDNA in patients with resectable CRLM could inform the optimal use of perioperative chemotherapy. Here, we performed a validation study to confirm the prognostic impact of postoperative ctDNA in resectable CRLM observed in a previous discovery study.

Revisiting the tumorigenesis timeline with a data-driven generative model | PNAS

Kamel Lahouel, Laurent Younes ,Ludmila Danilova, , Francis M. Giardiello, Ralph H. Hruban, John Groopman, Kenneth W. Kinzler, Bert Vogelstein, Donald Geman ,Cristian Tomasetti

Recently, investigators have shown that only a few driver gene mutational events appear to be needed for cancer to occur. However, the reason that some mutational events precede others in the same cancer and the explanation for tissue-specific differences in this timing, remain mysterious. We here combine mathematical modeling with epidemiologic studies and sequencing data to address these questions. We suggest that the first driver event in cancers generally occurred at early ages and provide estimates for the fitness of different types of drivers during tumor evolution, showing how they vary with the tissue of origin.

Supervised mutational signatures for obesity and other tissue-specific etiological factors in cancer. eLife 2021, 10:e61082.

Bahman Afsari, Albert Kuo, YiFan Zhang, Lu Li, Kamel Lahouel, Ludmila Danilova, Alexander Favorov, Thomas A Rosenquist, Arthur P Grollman, Ken W Kinzler, Leslie Cope, Bert Vogelstein, Cristian Tomasetti

Determining the etiologic basis of the mutations that are responsible for cancer is one of the fundamental challenges in modern cancer research. Different mutational processes induce different types of DNA mutations, providing ‘mutational signatures’ that have led to key insights into cancer etiology. 

Non-steroidal anti-inflammatory drugs, intravenous fluids, pancreatic stents, or their combinations for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a systematic review and network meta-analysis. The Lancet Gastroenterology & Hepatology 2021, 6(9):733-742.

Venkata S Akshintala , Christina J Sperna Weiland , Furqan A Bhullar , Ayesha Kamal , Kavin Kanthasamy , Albert Kuo , Cristian Tomasetti , Merve Gurakar , Joost P H Drenth , Dhiraj Yadav , B Joseph Elmunzer , D Nageshwar Reddy , Mahesh K Goenka , Rakesh Kochhar , Anthony N Kalloo , Mouen A Khashab , Erwin J M van Geenen , Vikesh K Singh

Non-steroidal anti-inflammatory drugs (NSAIDs), intravenous fluid, pancreatic stents, or combinations of these have been evaluated in randomised controlled trials (RCTs) for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, but the comparative efficacy of these treatments remains unclear. Our aim…

Prognostic Significance of Post-Surgery Circulating Tumor DNA in Non-Metastatic Colorectal Cancer: Individual Patient Pooled Analysis of Three Cohort Studies. Int J Cancer 2020, DOI: 10.1002/ijc.33312.

Jeanne Tie , Joshua D Cohen , Serigne N Lo, Yuxuan Wang, Lu Li, Michael Christie, Margaret Lee, Rachel Wong , Suzanne Kosmider, Iain Skinner , Hui Li Wong, Belinda Lee, Matthew E Burge, Desmond Yip , Christos S Karapetis , Timothy J Price , Niall C Tebbutt , Andrew M Haydon , Janine Ptak , Mary J Schaeffer , Natalie Silliman , Lisa Dobbyn , Maria Popoli, Cristian Tomasetti, Nickolas Papadopoulos, Kenneth W Kinzler, Bert Vogelstein, Peter Gibbs

Studies in multiple solid tumor types have demonstrated the prognostic significance of ctDNA analysis after curative intent surgery. A combined analysis of data across completed studies could further our understanding of circulating tumor DNA (ctDNA) as a prognostic marker and inform future trial design.

Division of Mathematics for Cancer Evolution and Early Detection, Department of Computational and Quantitative Medicine, Beckman Research Institute, City of Hope

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ctomasetti@coh.org
ctomasetti@tgen.org