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Lung Cancer. 2019 Apr;130:194-200. doi: 10.1016/j.lungcan.2019.02.017. Epub 2019 Feb 19.

Potential for the blood-based biomarkers cytokeratin 19 fragment (CYFRA 21-1) and human epididymal protein 4 (HE4) to detect recurrence during monitoring after surgical resection of adenocarcinoma of the lung.

Author information

1
Translational Research Unit, Thoraxklinik at University Hospital Heidelberg, Germany; Translational Lung Research Center (TLRC) Heidelberg, Member of the German Center for Lung Research (DZL), Germany. Electronic address: thomas.muley@med.uni-heidelberg.de.
2
Roche Diagnostics GmbH, Penzberg, Germany. Electronic address: ying.he@roche.com.
3
Roche Diagnostics GmbH, Penzberg, Germany. Electronic address: vinzent.rolny@roche.com.
4
Roche Diagnostics GmbH, Penzberg, Germany. Electronic address: birgit.wehnl@roche.com.
5
Roche Diagnostics International Ltd, Rotkreuz, Switzerland. Electronic address: achim.escherich@roche.com.
6
Translational Lung Research Center (TLRC) Heidelberg, Member of the German Center for Lung Research (DZL), Germany; Pathological Institute, University of Heidelberg, Heidelberg, Germany. Electronic address: arne.warth@med.uni-heidelberg.de.
7
Translational Research Unit, Thoraxklinik at University Hospital Heidelberg, Germany. Electronic address: Christa.stolp@med.uni-heidelberg.de.
8
Translational Research Unit, Thoraxklinik at University Hospital Heidelberg, Germany; Translational Lung Research Center (TLRC) Heidelberg, Member of the German Center for Lung Research (DZL), Germany. Electronic address: Marc.schneider@med.uni-heidelberg.de.
9
Translational Research Unit, Thoraxklinik at University Hospital Heidelberg, Germany; Translational Lung Research Center (TLRC) Heidelberg, Member of the German Center for Lung Research (DZL), Germany. Electronic address: Michael.Meister@med.uni-heidelberg.de.
10
Translational Lung Research Center (TLRC) Heidelberg, Member of the German Center for Lung Research (DZL), Germany; Department of Pneumology and Critical Care Medicine, Thoraxklinik at University Hospital Heidelberg, Germany. Electronic address: fdayyani@uci.edu.
11
Roche Diagnostics International Ltd, Rotkreuz, Switzerland. Electronic address: felix.herth@med.uni-heidelberg.de.

Abstract

OBJECTIVES:

The biomarkers cytokeratin 19 fragment (CYFRA 21-1) and human epididymis protein 4 (HE4) are useful in the diagnosis, prognosis, and monitoring of non-small cell lung cancer (NSCLC), but their combination has not been investigated yet. The objective of this analysis was to evaluate the ability of CYFRA 21-1 and HE4 to predict recurrence as part of follow-up monitoring in patients with adenocarcinoma (ADC) of the lung.

MATERIALS AND METHODS:

Serum samples were collected from patients with stage I-IIIA ADC preoperatively and during follow-up at 3, 6, 12, 18, and 24 months and then every 6-12 months up to 5 years post-R0 resection. Samples were analyzed for CYFRA 21-1 and HE4 via electrochemiluminescence immunoassay. All cases of disease recurrence were verified by imaging. The diagnostic performance of CYFRA 21-1, HE4, and their combination to predict recurrence was assessed by Receiver Operating Characteristic (ROC) and corresponding area under the curve (AUC).

RESULTS:

115 patients with ADC were included (N = 612 biomarker measurements); median age was 63 years; most had stage I-II disease (n = 97; 84.3%). All patients underwent surgical resection; 44 patients (38%) also received adjuvant chemotherapy and 16 (14%) received radiation therapy. At the median timepoint for the last blood sample collection (37 months), 31 patients (27%) had experienced recurrence. Both CYFRA 21-1 and HE4 were able to detect recurrence (AUC and 95% confidence interval [CI]): 75.9% (66.0-85.8%) and 75.4% (65.9-84.8%), respectively, but this increased with the combination (78.8% [69.0-88.6%]). At a sensitivity of 80%, the respective specificities (95% CI) for CYFRA 21-1, HE4, and the combination were 57.1% (53.0-61.2%), 57.1% (53.0-61.2%), and 69.7% (65.8-73.4%).

CONCLUSION:

Serial measurements of serum CYFRA 21-1 and HE4 levels could provide a valuable method for follow-up monitoring of patients with ADC to detect recurrence.

KEYWORDS:

Adenocarcinoma; CYFRA 21-1; HE4; NSCLC; Recurrence

PMID:
30885344
DOI:
10.1016/j.lungcan.2019.02.017
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