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Background: Serum-based tumor biomarkers are used to monitor cancer treatment, while clear guidance on the clinical usage is often lacking. We describe a graphical presentation to support diagnostic accuracy studies and clinical interpretation of longitudinal biomarker data., Methods: A biomarker response characteristic (BReC) plot was designed. To allow demonstration of the BReC plot application, software was developed that supported 1) dynamic generation of BReC plots, and 2) diagnostic accuracy studies of biomarker response-based medical tests. The BReC plot application was demonstrated using serial carcinoembryonic antigen (CEA) and Cyfra 21.1 results from 216 patients with metastasized non-small cell lung cancer, treated with Nivolumab in routine clinical practice., Results: The developed software supported the generation of BReC plots and diagnostic validation of biomarker response-based medical tests by generating the sensitivity, specificity and predictive values. Obtained BReC plots showed a clear relationship between clinical outcome and CEA and Cyfra 21.1 responses. Furthermore, using BReC plots, CEA and Cyfra 21.1 based medical tests were designed with a sensitivity for detection of treatment failure of 0.34 and 0.35 and a specificity of 0.96., Conclusions: The BReC plot appears to support diagnostic validation studies and the interpretation of longitudinal biomarkers though further validation is warranted., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In squamous cell carcinoma, squamous cell carcinoma antigen levels are often elevated. This multi-center study evaluated the technical performance of a new Elecsys ® squamous cell carcinoma assay, which measures serum squamous cell carcinoma antigen 1 and 2 levels in an equimolar manner, and investigated the potential of squamous cell carcinoma antigen for differential diagnosis of cervical, lung, and head and neck squamous cell carcinoma.Assay precision and method comparison experiments were performed across three European sites. Reference ranges for reportedly healthy individuals were determined using samples from banked European and Chinese populations. Differential diagnosis experiments determined whether cervical, lung, or head and neck cancer could be differentiated from apparently healthy, benign, or other malignant cohorts using squamous cell carcinoma antigen levels alone. Squamous cell carcinoma antigen cut-off levels were calculated based on squamous cell carcinoma antigen levels at 95% specificity. Repeatability coefficients of variation across nine analyte concentrations were ≤5.3%, and intermediate precision coefficients of variation were ≤10.3%. Method comparisons showed good correlations with Architect and Kryptor systems (slopes of 1.1 and 1.5, respectively). Reference ranges for 95th percentiles for apparently healthy individuals were 2.3 ng/mL (95% confidence interval: 1.9-3.8; European cohort, n = 153) and 2.7 ng/mL (95% confidence interval: 2.2-3.3; Chinese cohort, n = 146). Strongest differential diagnosis results were observed for cervical squamous cell carcinoma: receiver operating characteristic analysis showed that squamous cell carcinoma antigen levels (2.9 ng/mL cut-off) differentiate cervical squamous cell carcinoma (n = 127) from apparently healthy females (n = 286; area under the curve: 86.2%; 95% confidence interval: 81.8-90.6; sensitivity: 61.4%; specificity: 95.6%), benign diseases (n = 187; area under the curve: 86.3%; 95% confidence interval: 81.2-91.3; sensitivity: 61.4%; specificity: 95.0%), and other cervical cancers (n = 157; area under the curve: 78.9%; 95% confidence interval: 70.8-87.1; sensitivity: 61.4%; specificity: 86.7%). Squamous cell carcinoma may also aid in the differential diagnosis of lung cancer. The Elecsys squamous cell carcinoma assay exhibited good technical performance and is suitable for differential diagnosis of cervical squamous cell carcinoma in clinical practice.

Objective: The aim of this study was to determine whether lymph node metastases or prognosis can be predicted by initial serum Cyfra 21-1, tissue polypeptide antigen (TPA), and squamous cell carcinoma antigen (SCC-Ag) levels in squamous cell cervical cancer., Methods: Pretreatment serum levels of 92 patients were correlated with clinicopathologic parameters and prognostic data. The clinical performance of the tests was evaluated by their receiver operating characteristic curves. The prognostic power of the variables was assessed using Cox regression analysis., Results: Serum levels of each marker were significantly related to tumor stage, size, and depth of infiltration. The clinical performance of each marker in predicting lymph node metastases or parametrial involvement was poor. In the stepwise Cox regression analysis, regarding patients with early stage cervical cancer (stage Ib/IIa, n = 63), tumor size (P = 0.0005) was the only independent prognostic factor for disease-free interval. Lymph node status (P = 0.0014), tumor size (P = 0.004), and parametrial involvement (P = 0.025) were independent risk factors for survival. Considering all patients with stages Ia through IVb disease, tumor size (P = 0.0001) and TPA level (P = 0. 026) were independent risk factors for disease-free interval, whereas tumor size (P = 0.0001) and parametrial involvement (P = 0. 0002) were risk factors for survival., Conclusions: Pretreatment Cyfra 21-1, TPA, and SCC-Ag levels were strongly related to tumor burden, but insufficiently reliable for identifying patients at risk of the presence of lymph node metastases or parametrial involvement. Serum levels of each marker showed no independent prognostic value in early stage cervical cancer., (Copyright 2000 Academic Press.)

In malignant mesothelioma, survival is claimed to be related to age, duration of symptoms, performance status, histological subtype, stage and platelet count. However the exact prognostic value of these factors is still a matter of debate. We studied the two cytokeratin markers, Cyfra 21-1 and Tissue polypeptide antigen (TPA) for their significance in predicting survival retrospectively in 52 patients. Cyfra 21-1 and TPA were elevated in 26 (50%) and 30 (58%) patients, respectively, and were highly correlated (r = 0.98). Univariate analysis of data from 51 patients, showed a relation with survival for performance status (P = 0.010), thoracic pain (P = 0.014), platelet count (P = 0.027), Cyfra 21-1 (P = 0.002) and TPA (P = 0.003). Multivariate analysis identified independent prognostic significance for performance status, platelet count and Cyfra 21-1. In addition to performance status ( < 80 vs. > 80) the cytokeratin markers identified patients with good prognosis in a log rank test. Values of Cyfra 21-1 and TPA are significantly correlated.

Background: Serum concentrations of CEA and Cyfra were compared in patients with mesothelioma., Materials and Methods: Serum levels of patients were analysed for prognosis of survival and follow up of disease., Results: Cyfra 21-1 and TPA have significant prognostic value for survival., Conclusion: Assays measuring CK19 fragments seem to be good markers in the management of patients with malignant mesothelioma.

Background: The value of serum Cyfra 21-1 level was compared with tissue polypeptide antigen (TPA), and squamous cell carcinoma antigen (SCC-Ag) in squamous cell cervical cancer., Materials and Methods: Pre- and post-treatment serum levels of patients were compared with lymph node status, parametrial involvement, and prognostic data., Results: Pretreatment serum levels of each marker were significantly related to tumor stage, tumor size and the presence of either lymph node metastases or parametrial involvement. The clinical performance of each marker in predicting extracervical disease at initial diagnosis appeared to be similar. None of these tests achieved the conditions of a perfect test. Pretreatment serum levels of each marker showed prognostic value in the univariate analysis. The clinical performance of post-treatment SCC-Ag levels in predicting complete remission versus the presence of tumor during follow-up was better than Cyfra 21-1 or TPA., Conclusion: SCC-Ag appears to be more useful than Cyfra 21-1 for monitoring patients with cervical cancer.

Cyfra 21-1, measuring serum fragments of cytokeratin 19, has been found to be related to tumor stage and tumour size in patients with cervical cancer and suggested to be a promising marker in squamous lung cancer. We compared the value of this new marker with tissue polypeptide antigen (TPA) and squamous cell carcinoma antigen (SCC-Ag) in monitoring 30 patients with squamous cell cervical cancer. Serum levels of each marker were studied in relation to tumour stage and clinical status of patient. The clinical performance of the various assays to separate those patients with complete remission from those patients with the presence of tumour (i.e., partial remission, stable disease, or progressive disease) was assessed by their receiver operating characteristic (ROC) curves. We found that tumour stage was a prognostic factor for survival (p = 0.02). Pretreatment serum Cyfra 21-1, TPA, and SCC-Ag levels were not related to stage of disease and were not found to be predictive of survival. In contrast, an elevated post-treatment serum SCC-Ag level was associated with a poor survival rate (p = 0.03). Such a relation was not found for Cyfra 21-1 or TPA. The clinical performance of post-treatment serum SCC-Ag levels in predicting the presence of tumour was better than the Cyfra 21-1 or TPA assays. This is shown by the left uppermost position of the ROC curve for SCC-Ag. We concluded that SCC-Ag appeared to be a better parameter than Cyfra 21-1 and TPA in predicting the presence of tumour during follow-up and survival of patients with cervical cancer.

Background: The clinical value of pretreatment serum concentrations of cytokeratin 19 fragments, measured by Cyfra 21-1, was compared with tissue polypeptide antigen (TPA) and squamous cell carcinoma antigen (SCC-Ag) in 78 patients with squamous cell cervical cancer., Methods: Serum levels were compared with tumor stage, size, lymph node status, parametrial involvement, and prognostic data. The clinical performance of the different tests was evaluated by their receiver operating characteristic (ROC) curves., Results: Serum levels of all markers were related significantly to tumor stage and size. Elevated serum levels of these markers were not found to be predictive for the presence of lymph node metastases. In contrast, a positive relation was found between quantitative serum Cyfra 21-1, TPA, and SCC-Ag levels and the presence of either lymph node metastases or parametrial involvement (i.e., extracervical disease). An elevated, i.e. positive, serum Cyfra 21-1 level was related significantly to the presence of extracervical disease (P = 0.020). The clinical performance of each serum marker in predicting lymph node metastases or parametrial involvement appeared to be similar as expressed by their ROC curves. In the univariate analysis, Cyfra 21-1, TPA, and SCC-Ag showed prognostic value with respect to disease free interval and survival. Elevated serum levels were associated with a poor prognosis. However, after adjusting for tumor stage and size, none of these markers remained statistically significant., Conclusions: Cyfra 21-1 may be of additional value in assessing stage of disease, tumor size, and the presence of extracervical disease in patients with cervical cancer. Determining its value during follow-up warrants further study.