TY - JOUR
T1 - Blood-Based Biomarker Panel for Personalized Lung Cancer Risk Assessment
AU - Fahrmann, Johannes F.
AU - Marsh, Tracey
AU - Irajizad, Ehsan
AU - Patel, Nikul
AU - Murage, Eunice
AU - Vykoukal, Jody
AU - Dennison, Jennifer B.
AU - Do, Kim Anh
AU - Ostrin, Edwin
AU - Spitz, Margaret R.
AU - Lam, Stephen
AU - Shete, Sanjay
AU - Meza, Rafael
AU - Tammemägi, Martin C.
AU - Feng, Ziding
AU - Hanash, Samir M.
N1 - Funding Information:
Supported by NIH Grant Nos. U01CA194733 (S.H., Z.F., and M.C.T.), U01CA213285 (S.H., Z.F., and M.C.T.), and NCI EDRN U01 CA200468 (S.H.), and U24CA086368 (S.H., Z.F., and M.C.T.) and Cancer Prevention & Research Institute of Texas (CPRIT; RP180505; S.H.) and the generous philanthropic contributions to The University of Texas MD Anderson Cancer Center Moon Shots Program and the Lyda Hill Foundation. We thank the National Cancer Institute for access to their data and specimens collected by the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO). We thank the PLCO screening center investigators and staff members, as well as the staff of Information Management Services Inc and Westat Inc. We thank the trial participants for their contributions that made this study possible. The statements contained herein are solely those of the authors and do not represent or imply concurrence or endorsement by the National Cancer Institute.
Funding Information:
Supported by NIH Grant Nos. U01CA194733 (S.H., Z.F., and M.C.T.), U01CA213285 (S.H., Z.F., and M.C.T.), and NCI EDRN U01 CA200468 (S.H.), and U24CA086368 (S.H., Z.F., and M.C.T.) and Cancer Prevention & Research Institute of Texas (CPRIT; RP180505; S.H.) and the generous philanthropic contributions to The University of Texas MD
Publisher Copyright:
Copyright © 2022 American Society of Clinical Oncology. All rights reserved.
PY - 2022/3/10
Y1 - 2022/3/10
N2 - PURPOSE To investigate whether a panel of circulating protein biomarkers would improve risk assessment for lung cancer screening in combination with a risk model on the basis of participant characteristics. METHODS A blinded validation study was performed using prostate lung colorectal ovarian (PLCO) Cancer Screening Trial data and biospecimens to evaluate the performance of a four-marker protein panel (4MP) consisting of the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and cytokeratin-19 fragment in combination with a lung cancer risk prediction model (PLCOm2012) compared with current US Preventive Services Task Force (USPSTF) screening criteria. The 4MP was assayed in 1,299 sera collected preceding lung cancer diagnosis and 8,709 noncase sera. RESULTS The 4MP alone yielded an area under the receiver operating characteristic curve of 0.79 (95% CI, 0.77 to 0.82) for case sera collected within 1-year preceding diagnosis and 0.74 (95% CI, 0.72 to 0.76) among the entire specimen set. The combined 4MP 1 PLCOm2012 model yielded an area under the receiver operating characteristic curve of 0.85 (95% CI, 0.82 to 0.88) for case sera collected within 1 year preceding diagnosis. The benefit of the 4MP in the combined model resulted from improvement in sensitivity at high specificity. Compared with the USPSTF2021 criteria, the combined 4MP 1 PLCOm2012 model exhibited statistically significant improvements in sensitivity and specificity. Among PLCO participants with $ 10 smoking pack-years, the 4MP 1 PLCOm2012 model would have identified for annual screening 9.2% more lung cancer cases and would have reduced referral by 13.7% among noncases compared with USPSTF2021 criteria. CONCLUSION A blood-based biomarker panel in combination with PLCOm2012 significantly improves lung cancer risk assessment for lung cancer screening.
AB - PURPOSE To investigate whether a panel of circulating protein biomarkers would improve risk assessment for lung cancer screening in combination with a risk model on the basis of participant characteristics. METHODS A blinded validation study was performed using prostate lung colorectal ovarian (PLCO) Cancer Screening Trial data and biospecimens to evaluate the performance of a four-marker protein panel (4MP) consisting of the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and cytokeratin-19 fragment in combination with a lung cancer risk prediction model (PLCOm2012) compared with current US Preventive Services Task Force (USPSTF) screening criteria. The 4MP was assayed in 1,299 sera collected preceding lung cancer diagnosis and 8,709 noncase sera. RESULTS The 4MP alone yielded an area under the receiver operating characteristic curve of 0.79 (95% CI, 0.77 to 0.82) for case sera collected within 1-year preceding diagnosis and 0.74 (95% CI, 0.72 to 0.76) among the entire specimen set. The combined 4MP 1 PLCOm2012 model yielded an area under the receiver operating characteristic curve of 0.85 (95% CI, 0.82 to 0.88) for case sera collected within 1 year preceding diagnosis. The benefit of the 4MP in the combined model resulted from improvement in sensitivity at high specificity. Compared with the USPSTF2021 criteria, the combined 4MP 1 PLCOm2012 model exhibited statistically significant improvements in sensitivity and specificity. Among PLCO participants with $ 10 smoking pack-years, the 4MP 1 PLCOm2012 model would have identified for annual screening 9.2% more lung cancer cases and would have reduced referral by 13.7% among noncases compared with USPSTF2021 criteria. CONCLUSION A blood-based biomarker panel in combination with PLCOm2012 significantly improves lung cancer risk assessment for lung cancer screening.
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U2 - 10.1200/JCO.21.01460
DO - 10.1200/JCO.21.01460
M3 - Article
C2 - 34995129
AN - SCOPUS:85125964671
SN - 0732-183X
VL - 40
SP - 876
EP - 883
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 8
ER -