Integrated Biomarkers for the Management of Indeterminate Pulmonary Nodules.


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

  • Antic SL
  • Atwater T
  • Balagurunathan Y
  • Balar AB
  • Barad U
  • Barón AE
  • Bauza J
  • Billatos E
  • Bornhop DJ
  • Chen H
  • Chen SC
  • Deppen SA
  • Diergaarde B
  • Feser WJ
  • Gillies RJ
  • Grogan EL
  • Helmey S
  • Hirsch E
  • Kaizer A
  • Kammer MN
  • Kussrow AK
  • Lakhani DA
  • Landman B
  • Mahapatra S
  • Maldonado F
  • Massion PP
  • Miller YE
  • New M
  • Qian J
  • Rioth M
  • Rowe DJ
  • Sandler K
  • Schabath MB
  • Shah C
  • Spira A
  • Strong J
  • Walker RC
  • Webster RL
  • Wilson DO
PubMed ID
Appears In
Am J Respir Crit Care Med, 2021, 204 (11)