Rationale: 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.
Rationale: 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.
Authors: Kristin J Lastwika; Julia Kargl; Yuzheng Zhang; Xiaodong Zhu; Edward Lo; David Shelley; Jon J Ladd; Wei Wu; Paul Kinahan; Sudhakar N J Pipavath; Timothy W Randolph; Melissa Shipley; Paul D Lampe; A McGarry Houghton Journal: Am J Respir Crit Care Med Date: 2019-05-15 Impact factor: 21.405
Authors: Denise R Aberle; Amanda M Adams; Christine D Berg; William C Black; Jonathan D Clapp; Richard M Fagerstrom; Ilana F Gareen; Constantine Gatsonis; Pamela M Marcus; JoRean D Sicks Journal: N Engl J Med Date: 2011-06-29 Impact factor: 91.245
Authors: Amelia W Maiga; Stephen A Deppen; Sarah Fletcher Mercaldo; Jeffrey D Blume; Chandler Montgomery; Laszlo T Vaszar; Christina Williamson; James M Isbell; Otis B Rickman; Rhonda Pinkerman; Eric S Lambright; Jonathan C Nesbitt; Eric L Grogan Journal: JAMA Surg Date: 2018-04-01 Impact factor: 14.766
Authors: Michael N Kammer; Dianna J Rowe; Stephen A Deppen; Eric L Grogan; Alexander M Kaizer; Anna E Barón; Fabien Maldonado Journal: Cancer Epidemiol Biomarkers Prev Date: 2022-09-02 Impact factor: 4.090