Integrated Biomarkers for the Management of Indeterminate Pulmonary Nodules.
Michael N Kammer, Dhairya A Lakhani, Aneri B Balar, Sanja L Antic, Amanda K Kussrow, Rebekah L Webster, Shayan Mahapatra, Udaykamal Barad, Chirayu Shah, Thomas Atwater, Brenda Diergaarde, Jun Qian, Alexander Kaizer, Melissa New, Erin Hirsch, William J Feser, Jolene Strong, Matthew Rioth, York E Miller, Yoganand Balagurunathan, Dianna J Rowe, Sherif Helmey, Sheau-Chiann Chen, Joseph Bauza, Stephen A Deppen, Kim Sandler, Fabien Maldonado, Avrum Spira, Ehab Billatos, Matthew B Schabath, Robert J Gillies, David O Wilson, Ronald C Walker, Bennett Landman, Heidi Chen, Eric L Grogan, Anna E Bar��n, Darryl J Bornhop, Pierre P Massion
Author Information
Michael N Kammer: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine. ORCID
Dhairya A Lakhani: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine. ORCID
Aneri B Balar: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
Sanja L Antic: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
Amanda K Kussrow: Department of Chemistry, and.
Rebekah L Webster: Department of Chemistry, and.
Shayan Mahapatra: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine. ORCID
Udaykamal Barad: Division of Radiology, and.
Chirayu Shah: Division of Radiology, and.
Thomas Atwater: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
Brenda Diergaarde: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh and UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania. ORCID
Jun Qian: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
Alexander Kaizer: Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado. ORCID
Melissa New: Pulmonary Sciences and Critical Care.
Erin Hirsch: Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
William J Feser: Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Jolene Strong: Biomedical Informatics and Personalized Medicine, and.
Matthew Rioth: Medical Oncology and Biomedical Informatics and Personalized Medicine, School of Medicine, University of Colorado, Aurora, Colorado.
York E Miller: Pulmonary Sciences and Critical Care.
Yoganand Balagurunathan: H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. ORCID
Dianna J Rowe: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
Sherif Helmey: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
Sheau-Chiann Chen: Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee. ORCID
Joseph Bauza: American College of Radiology, Philadelphia, Pennsylvania.
Stephen A Deppen: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine. ORCID
Kim Sandler: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
Fabien Maldonado: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
Avrum Spira: Department of Medicine, Boston University, Boston, Massachusetts. ORCID
Ehab Billatos: Department of Medicine, Boston University, Boston, Massachusetts. ORCID
Matthew B Schabath: H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. ORCID
Robert J Gillies: H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. ORCID
David O Wilson: Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; and.
Ronald C Walker: Division of Radiology, and. ORCID
Bennett Landman: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine. ORCID
Heidi Chen: American College of Radiology, Philadelphia, Pennsylvania.
Eric L Grogan: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine. ORCID
Anna E Bar��n: Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Darryl J Bornhop: Department of Chemistry, and.
Pierre P Massion: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
patients with Indeterminate Pulmonary Nodules (IPNs) at risk of cancer undergo high rates of invasive, costly, and morbid procedures. To train and externally validate a risk prediction model that combined clinical, blood, and imaging biomarkers to improve the noninvasive management of IPNs. In this prospectively collected, retrospective blinded evaluation study, probability of cancer was calculated for 456 patient nodules using the Mayo Clinic model, and patients were categorized into low-, intermediate-, and high-risk groups. A combined biomarker model (CBM) including clinical variables, serum high sensitivity CYFRA 21-1 level, and a radiomic signature was trained in cohort 1 (���=���170) and validated in cohorts 2-4 (total ���=���286). All patients were pooled to recalibrate the model for clinical implementation. The clinical utility of the CBM compared with current clinical care was evaluated in 2 cohorts. The CBM provided improved diagnostic accuracy over the Mayo Clinic model with an improvement in area under the curve of 0.124 (95% bootstrap confidence interval, 0.091-0.156; ���<���2��������10). Applying 10% and 70% risk thresholds resulted in a bias-corrected clinical reclassification index for cases and control subjects of 0.15 and 0.12, respectively. A clinical utility analysis of patient medical records estimated that a CBM-guided strategy would have reduced invasive procedures from 62.9% to 50.6% in the intermediate-risk benign population and shortened the median time to diagnosis of cancer from 60 to 21 days in intermediate-risk cancers. Integration of clinical, blood, and image biomarkers improves noninvasive diagnosis of patients with IPNs, potentially reducing the rate of unnecessary invasive procedures while shortening the time to diagnosis.
