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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / diagnosis*
  • Adenocarcinoma of Lung / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / blood*
  • Biomarkers, Tumor / metabolism*
  • Female
  • Humans
  • Keratin-19 / blood*
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Monitoring, Physiologic
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Pneumonectomy
  • Predictive Value of Tests
  • Prognosis
  • WAP Four-Disulfide Core Domain Protein 2 / metabolism*

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Keratin-19
  • WAP Four-Disulfide Core Domain Protein 2
  • WFDC2 protein, human
  • antigen CYFRA21.1