• 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 Barón, Darryl J Bornhop, and Pierre P Massion.
• Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
• Am. J. Respir. Crit. Care Med. 2021 Dec 1; 204 (11): 130613161306-1316.

AbstractRationale: Patients with indeterminate pulmonary nodules (IPNs) at risk of cancer undergo high rates of invasive, costly, and morbid procedures. Objectives: To train and externally validate a risk prediction model that combined clinical, blood, and imaging biomarkers to improve the noninvasive management of IPNs. Methods: 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 (n = 170) and validated in cohorts 2-4 (total n = 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. Measurements and Main Results: 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; P < 2 × 10-16). 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. Conclusions: 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.

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