PURPOSE: Low-dose computed tomography (LDCT) screening of high-risk patients decreases lung cancer-related mortality. However, high false-positive rates associated with LDCT result in unnecessary interventions. To distinguish non-small-cell lung cancer (NSCLC) from benign nodules, in the present study, we integrated cellular liquid biomarkers in patients with suspicious lung nodules (lung cancer screening reporting and data system [Lung-RADS] 4). METHODS: Prospectively, 7.5 mL of blood was collected from 221 individuals (training set: 90 nonscreened NSCLC patients, 74 high-risk screening patients with no/benign nodules [Lung-RADS 1-3], and 20 never smokers; validation set: 37 patients with suspicious nodules [Lung-RADS 4]). Circulating tumor cells (CTCs), CTC clusters, and tumor-macrophage fusion (TMF) cells were identified by blinded analyses. Screening patients underwent a median of two LDCTs (range, 1-4) with a median surveillance time of 30 (range, 11-50) months. RESULTS: In the validation set of 37 Lung-RADS 4 patients, all circulating cellular biomarker counts (P < .005; Wilcoxon test) and positivity rates were significantly higher in 23 biopsy-proven NSCLC patients (CTCs: 23 of 23 [100%], CTC clusters: 6 of 23 [26.1%], and TMF cells: 15 of 23 [65.2%]) than in 14 patients with biopsy-proven benign nodules (6 of 14 [42.9%], 0 of 14 [0%], and 2 of 14 [14.3%]). On the basis of cutoff values from the training set, logistic regression with receiver operating characteristic and area under the curve analyses demonstrated that CTCs (sensitivity: 0.870, specificity: 1.0, and area under the curve: 0.989) and TMF cells (0.652; 0.880; 0.790) complement LDCT in diagnosing NSCLC in Lung-RADS 4 patients. CONCLUSION: Cellular liquid biomarkers have a potential to complement LDCT interpretation of suspicious Lung-RADS 4 nodules to distinguish NSCLC from benign lung nodules. A future prospective, large-scale, multicenter clinical trial should validate the role of cellular liquid biomarkers in improving diagnostic accuracy in high-risk patients with Lung-RADS 4 nodules.
PURPOSE: Low-dose computed tomography (LDCT) screening of high-risk patients decreases lung cancer-related mortality. However, high false-positive rates associated with LDCT result in unnecessary interventions. To distinguish non-small-cell lung cancer (NSCLC) from benign nodules, in the present study, we integrated cellular liquid biomarkers in patients with suspicious lung nodules (lung cancer screening reporting and data system [Lung-RADS] 4). METHODS: Prospectively, 7.5 mL of blood was collected from 221 individuals (training set: 90 nonscreened NSCLC patients, 74 high-risk screening patients with no/benign nodules [Lung-RADS 1-3], and 20 never smokers; validation set: 37 patients with suspicious nodules [Lung-RADS 4]). Circulating tumor cells (CTCs), CTC clusters, and tumor-macrophage fusion (TMF) cells were identified by blinded analyses. Screening patients underwent a median of two LDCTs (range, 1-4) with a median surveillance time of 30 (range, 11-50) months. RESULTS: In the validation set of 37 Lung-RADS 4 patients, all circulating cellular biomarker counts (P < .005; Wilcoxon test) and positivity rates were significantly higher in 23 biopsy-proven NSCLC patients (CTCs: 23 of 23 [100%], CTC clusters: 6 of 23 [26.1%], and TMF cells: 15 of 23 [65.2%]) than in 14 patients with biopsy-proven benign nodules (6 of 14 [42.9%], 0 of 14 [0%], and 2 of 14 [14.3%]). On the basis of cutoff values from the training set, logistic regression with receiver operating characteristic and area under the curve analyses demonstrated that CTCs (sensitivity: 0.870, specificity: 1.0, and area under the curve: 0.989) and TMF cells (0.652; 0.880; 0.790) complement LDCT in diagnosing NSCLC in Lung-RADS 4 patients. CONCLUSION: Cellular liquid biomarkers have a potential to complement LDCT interpretation of suspicious Lung-RADS 4 nodules to distinguish NSCLC from benign lung nodules. A future prospective, large-scale, multicenter clinical trial should validate the role of cellular liquid biomarkers in improving diagnostic accuracy in high-risk patients with Lung-RADS 4 nodules.
Authors: Mario Giuliano; Anum Shaikh; Hin Ching Lo; Grazia Arpino; Sabino De Placido; Xiang H Zhang; Massimo Cristofanilli; Rachel Schiff; Meghana V Trivedi Journal: Cancer Res Date: 2018-02-02 Impact factor: 12.701
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: Gary A Clawson; Gail L Matters; Ping Xin; Christopher McGovern; Eric Wafula; Claude dePamphilis; Morgan Meckley; Joyce Wong; Luke Stewart; Christopher D'Jamoos; Naomi Altman; Yuka Imamura Kawasawa; Zhen Du; Loren Honaas; Thomas Abraham Journal: PLoS One Date: 2017-09-28 Impact factor: 3.240
Authors: Yariswamy Manjunath; Sathisha V Upparahalli; Diego M Avella; Chelsea B Deroche; Eric T Kimchi; Kevin F Staveley-O'Carroll; Charles J Smith; Guangfu Li; Jussuf T Kaifi Journal: Cancers (Basel) Date: 2019-06-11 Impact factor: 6.639
Authors: Benjamin Berndt; Sonja Haverkampf; Georg Reith; Silvia Keil; Bernd Niggemann; Kurt S Zänker; Thomas Dittmar Journal: PLoS One Date: 2013-05-07 Impact factor: 3.240
Authors: Cha-Mei Tang; Peixuan Zhu; Shuhong Li; Olga V Makarova; Platte T Amstutz; Daniel L Adams Journal: Cytometry A Date: 2018-10-19 Impact factor: 4.355