TY - JOUR
T1 - Development and validation of a prognostic model using blood biomarker information for prediction of survival of non-small-cell lung cancer patients treated with combined chemotherapy and radiation or radiotherapy alone (NCT00181519, NCT00573040, and NCT00572325)
AU - Dehing-Oberije, Cary
AU - Aerts, Hugo
AU - Yu, Shipeng
AU - De Ruysscher, Dirk
AU - Menheere, Paul
AU - Hilvo, Mika
AU - van der Weide, Hiska
AU - Rao, Bharat
AU - Lambin, Philippe
N1 - Copyright © 2011 Elsevier Inc. All rights reserved.
PY - 2011/10/1
Y1 - 2011/10/1
N2 - PURPOSE: Currently, prediction of survival for non-small-cell lung cancer patients treated with (chemo)radiotherapy is mainly based on clinical factors. The hypothesis of this prospective study was that blood biomarkers related to hypoxia, inflammation, and tumor load would have an added prognostic value for predicting survival.METHODS AND MATERIALS: Clinical data and blood samples were collected prospectively (NCT00181519, NCT00573040, and NCT00572325) from 106 inoperable non-small-cell lung cancer patients (Stages I-IIIB), treated with curative intent with radiotherapy alone or combined with chemotherapy. Blood biomarkers, including lactate dehydrogenase, C-reactive protein, osteopontin, carbonic anhydrase IX, interleukin (IL) 6, IL-8, carcinoembryonic antigen (CEA), and cytokeratin fragment 21-1, were measured. A multivariate model, built on a large patient population (N = 322) and externally validated, was used as a baseline model. An extended model was created by selecting additional biomarkers. The model's performance was expressed as the area under the curve (AUC) of the receiver operating characteristic and assessed by use of leave-one-out cross validation as well as a validation cohort (n = 52).RESULTS: The baseline model consisted of gender, World Health Organization performance status, forced expiratory volume, number of positive lymph node stations, and gross tumor volume and yielded an AUC of 0.72. The extended model included two additional blood biomarkers (CEA and IL-6) and resulted in a leave-one-out AUC of 0.81. The performance of the extended model was significantly better than the clinical model (p = 0.004). The AUC on the validation cohort was 0.66 and 0.76, respectively.CONCLUSIONS: The performance of the prognostic model for survival improved markedly by adding two blood biomarkers: CEA and IL-6.
AB - PURPOSE: Currently, prediction of survival for non-small-cell lung cancer patients treated with (chemo)radiotherapy is mainly based on clinical factors. The hypothesis of this prospective study was that blood biomarkers related to hypoxia, inflammation, and tumor load would have an added prognostic value for predicting survival.METHODS AND MATERIALS: Clinical data and blood samples were collected prospectively (NCT00181519, NCT00573040, and NCT00572325) from 106 inoperable non-small-cell lung cancer patients (Stages I-IIIB), treated with curative intent with radiotherapy alone or combined with chemotherapy. Blood biomarkers, including lactate dehydrogenase, C-reactive protein, osteopontin, carbonic anhydrase IX, interleukin (IL) 6, IL-8, carcinoembryonic antigen (CEA), and cytokeratin fragment 21-1, were measured. A multivariate model, built on a large patient population (N = 322) and externally validated, was used as a baseline model. An extended model was created by selecting additional biomarkers. The model's performance was expressed as the area under the curve (AUC) of the receiver operating characteristic and assessed by use of leave-one-out cross validation as well as a validation cohort (n = 52).RESULTS: The baseline model consisted of gender, World Health Organization performance status, forced expiratory volume, number of positive lymph node stations, and gross tumor volume and yielded an AUC of 0.72. The extended model included two additional blood biomarkers (CEA and IL-6) and resulted in a leave-one-out AUC of 0.81. The performance of the extended model was significantly better than the clinical model (p = 0.004). The AUC on the validation cohort was 0.66 and 0.76, respectively.CONCLUSIONS: The performance of the prognostic model for survival improved markedly by adding two blood biomarkers: CEA and IL-6.
KW - Aged
KW - Antigens, Neoplasm/blood
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Area Under Curve
KW - Biomarkers, Tumor/blood
KW - C-Reactive Protein/analysis
KW - Carbonic Anhydrases/blood
KW - Carcinoembryonic Antigen/blood
KW - Carcinoma, Non-Small-Cell Lung/blood
KW - Combined Modality Therapy/methods
KW - Female
KW - Humans
KW - Inflammation/blood
KW - Interleukin-6/blood
KW - Interleukin-8/blood
KW - Keratin-19/blood
KW - L-Lactate Dehydrogenase/blood
KW - Lung Neoplasms/blood
KW - Male
KW - Models, Statistical
KW - Neoplasm Staging/methods
KW - Osteopontin/blood
KW - Prognosis
KW - Prospective Studies
KW - Tumor Burden
U2 - 10.1016/j.ijrobp.2010.06.011
DO - 10.1016/j.ijrobp.2010.06.011
M3 - Article
C2 - 20888135
SN - 0360-3016
VL - 81
SP - 360
EP - 368
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 2
ER -