@article{6ebdb073ff864744ba16b0090bf36dc4,
title = "Dynamic Risk Profiling Using Serial Tumor Biomarkers for Personalized Outcome Prediction",
abstract = "Accurate prediction of long-term outcomes remains a challenge in the care of cancer patients. Due to the difficulty of serial tumor sampling, previous prediction tools have focused on pretreatment factors. However, emerging non-invasive diagnostics have increased opportunities for serial tumor assessments. We describe the Continuous Individualized Risk Index (CIRI), a method to dynamically determine outcome probabilities for individual patients utilizing risk predictors acquired over time. Similar to “win probability” models in other fields, CIRI provides a real-time probability by integrating risk assessments throughout a patient's course. Applying CIRI to patients with diffuse large B cell lymphoma, we demonstrate improved outcome prediction compared to conventional risk models. We demonstrate CIRI's broader utility in analogous models of chronic lymphocytic leukemia and breast adenocarcinoma and perform a proof-of-concept analysis demonstrating how CIRI could be used to develop predictive biomarkers for therapy selection. We envision that dynamic risk assessment will facilitate personalized medicine and enable innovative therapeutic paradigms.",
keywords = "biomarkers, cancer, liquid biopsy, personalized medicine, predictive modeling",
author = "Kurtz, {David M.} and Esfahani, {Mohammad S.} and Florian Scherer and Joanne Soo and Jin, {Michael C.} and Liu, {Chih Long} and Newman, {Aaron M.} and Ulrich D{\"u}hrsen and Andreas H{\"u}ttmann and Olivier Casasnovas and Westin, {Jason R.} and Matthais Ritgen and Sebastian B{\"o}ttcher and Langerak, {Anton W.} and Mark Roschewski and Wilson, {Wyndham H.} and Gianluca Gaidano and Davide Rossi and Jasmin Bahlo and Michael Hallek and Robert Tibshirani and Maximilian Diehn and Alizadeh, {Ash A.}",
note = "Funding Information: This work was supported by the National Cancer Institute (R01CA188298 and R01CA233975 to M.D. and A.A.A. R01CA229766 and U01CA194389 to A.A.A. and training grant R25CA180993 to M.S.E.), the Damon Runyon Cancer Research Foundation (DR-CI#71-14 to A.A.A. and PST#09-16 to D.M.K.), American Society of Hematology Scholar Award (to A.A.A.), Leukemia and Lymphoma Society Scholar Award (to A.A.A.), V Foundation for Cancer Research Abeloff Scholar Award (to A.A.A.), Conquer Cancer Foundation of the American Society of Clinical Oncology Young Investigator Award (to D.M.K.), the Emerson Collective Cancer Research Fund (to A.A.A.), the Stinehart/Reed Award (to A.A.A.), the Shanahan Family Fund (to A.A.A.), the NIH Director's New Innovator Award Program (1-DP2-CA186569), and the Ludwig Institute for Cancer Research. Conceptualization, D.M.K. M.S.E. F.S. M.D. and A.A.A.; Methodology, D.M.K. M.S.E. A.M.N. and R.T.; Investigation, D.M.K. M.S.E. F.S. J.S. and M.C.J.; Software, D.M.K. M.S.E. and C.L.L.; Resources, U.D. A.H. O.C. J.R.W. M.R. S.B. A.W.L. M.R. W.H.W. G.G. D.R. J.B. and M.H.; Writing ? Original Draft, D.M.K. and M.S.E.; Writing ? Review & Editing, all authors. O.C. served as a consultant for Roche, Takeda, Gilead, BMS, MSD, Janssen, and received research support from Roche, Gilead, and Takeda. A.W.L. is a member of the AbbVie advisory board and received research support from Roche-Genentech and Gilead. M.R. is a member of the Roche advisory board. S.B. received research support and personal fees from AbbVie, Janssen, and F Hoffman-La Roche; research support from Celgene and Genentech; and personal fees from Becton Dickinson and Novartis. D.R. received research support from Gilead, Janssen, Roche, and AbbVie. M.H. received research support from Roche, Gilead, Mundipharma, Janssen, Celgene, Pharmacyclics, and AbbVie. M.D. served as a consultant for Roche, AstraZeneca, Novartis, BioNTech, and Quanticell, and received research support from Varian Medical Systems. A.A.A. served as a consultant for Roche, Genentech, Janssen, Pharmacyclics, Gilead, Celgene, and Chugai, and received research support from Pfizer. He is also a shareholder in FortySeven. A.A.A. M.D. and A.M.N. are co-founders of CiberMed. Funding Information: O.C. served as a consultant for Roche, Takeda, Gilead, BMS, MSD, Janssen, and received research support from Roche, Gilead, and Takeda. A.W.L. is a member of the AbbVie advisory board and received research support from Roche-Genentech and Gilead. M.R. is a member of the Roche advisory board. S.B. received research support and personal fees from AbbVie, Janssen, and F Hoffman-La Roche; research support from Celgene and Genentech; and personal fees from Becton Dickinson and Novartis. D.R. received research support from Gilead, Janssen, Roche, and AbbVie. M.H. received research support from Roche, Gilead, Mundipharma, Janssen, Celgene, Pharmacyclics, and AbbVie. M.D. served as a consultant for Roche, AstraZeneca, Novartis, BioNTech, and Quanticell, and received research support from Varian Medical Systems. A.A.A. served as a consultant for Roche, Genentech, Janssen, Pharmacyclics, Gilead, Celgene, and Chugai, and received research support from Pfizer. He is also a shareholder in FortySeven. A.A.A., M.D., and A.M.N. are co-founders of CiberMed. Funding Information: This work was supported by the National Cancer Institute ( R01CA188298 and R01CA233975 to M.D. and A.A.A., R01CA229766 and U01CA194389 to A.A.A., and training grant R25CA180993 to M.S.E.), the Damon Runyon Cancer Research Foundation ( DR-CI#71-14 to A.A.A. and PST#09-16 to D.M.K.), American Society of Hematology Scholar Award (to A.A.A.), Leukemia and Lymphoma Society Scholar Award (to A.A.A.), V Foundation for Cancer Research Abeloff Scholar Award (to A.A.A.), Conquer Cancer Foundation of the American Society of Clinical Oncology Young Investigator Award (to D.M.K.), the Emerson Collective Cancer Research Fund (to A.A.A.), the Stinehart/Reed Award (to A.A.A.), the Shanahan Family Fund (to A.A.A.), the NIH Director{\textquoteright}s New Innovator Award Program ( 1-DP2-CA186569 ), and the Ludwig Institute for Cancer Research . Publisher Copyright: {\textcopyright} 2019",
year = "2019",
month = jul,
day = "25",
doi = "10.1016/j.cell.2019.06.011",
language = "English (US)",
volume = "178",
pages = "699--713.e19",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "3",
}