Prognostic value of neuron-specific enolase for small cell lung cancer: a systematic review and meta-analysis

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Abstract

Background

Neuron-specific enolase (NSE) has become a widely used and easily attainable laboratory assay of small cell lung cancer (SCLC). However, the prognostic value of NSE for SCLC patients remains controversial. The aim of the study was to evaluate the correlation between elevated serum NSE before therapy and survival of SCLC patients.

Methods

We performed a systematic review and meta-analysis. A systematic literature search was conducted in PubMed, Embase, and the Cochrane Central Register from the inception dates to December 2019. Eligible articles were included according to inclusion and exclusion criteria; then, data extraction and quality assessment were performed. The primary outcome was overall survival (OS), and the secondary endpoint was progression-free survival (PFS).

Results

We identified 18 studies comprising 2981 patients. Pooled results revealed that elevated NSE was associated with worse OS (HR = 1.78, 95% CI 1.55–2.06, p < 0.001) and PFS (HR = 1.50, 95% CI 1.16–1.93, p = 0.002). In subgroup analysis, elevated NSE did not predict worse OS in patients who received only chemotherapy (HR 1.22, 95% CI 0.96–1.55, p = 0.10) or part of whom received surgical resection before chemotherapy and radiotherapy (HR = 2.16, 95% CI 0.82–5.69, p = 0.12).

Conclusion

Elevated serum NSE before any therapy of SCLC patients may be a negative prognostic factor for OS and PFS. The prognostic value of NSE for OS was particularly observed in patients treated by standard management.

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Most cited references 40

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Small-cell lung cancer.

Jan P Van Meerbeeck, Dean Fennell, Dirk De Ruysscher (2011)

The incidence and mortality of small-cell lung cancer worldwide make this disease a notable health-care issue. Diagnosis relies on histology, with the use of immunohistochemical studies to confirm difficult cases. Typical patients are men older than 70 years who are current or past heavy smokers and who have pulmonary and cardiovascular comorbidities. Patients often present with rapid-onset symptoms due to local intrathoracic tumour growth, extrapulmonary distant spread, paraneoplastic syndromes, or a combination of these features. Staging aims ultimately to define disease as metastatic or non-metastatic. Combination chemotherapy, generally platinum-based plus etoposide or irinotecan, is the mainstay first-line treatment for metastatic small-cell lung cancer. For non-metastatic disease, evidence supports early concurrent thoracic radiotherapy. Prophylactic cranial irradiation should be considered for patients with or without metastases whose disease does not progress after induction chemotherapy and radiotherapy. Despite high initial response rates, most patients eventually relapse. Except for topotecan, few treatment options then remain. Signalling pathways have been identified that might yield new drug targets. Copyright © 2011 Elsevier Ltd. All rights reserved.

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Establishment and identification of small cell lung cancer cell lines having classic and variant features.

D N Carney, Richard Zweig, John Minna … (1985)

Using a chemically defined medium containing hydrocortisone, insulin, transferrin, 17 beta-estradiol and selenium, with or without serum supplementation (2.5% v/v), continuous cell lines can be established from 72% of all fresh biopsy specimens of small cell lung cancer (SCLC) containing tumor cells. No differences were observed in the rate of establishing cell lines from newly diagnosed untreated patients, or from patients who have relapsed from prior therapy, or from a variety of different organ sites. Biochemical characterization of 50 SCLC cell lines for the expression of L-dopa decarboxylase; bombesin-like immunoreactivity; neuron-specific enolase, and the brain isozyme of creatine kinase, revealed that SCLC cell lines can be subdivided into two distinct classes: classic SCLC cell lines (35 lines), which express elevated levels of all four biomarkers; and variant SCLC cell lines (15 lines) which have undetectable levels of L-dopa-decarboxylase and bombesin-like immunoreactivity, but continue to express neuron-specific enolase and the brain isozyme of creatine kinase. The presence of the latter two markers distinguishes variant lines fron non-SCLC cell lines. In addition, four distinct classes were identified morphologically. The biomedical differences among established SCLC cell lines may account for the differences in response rates to cytotoxic therapy observed in newly diagnosed SCLC patients. A prospective study of biomarker characterization of SCLC tumors will determine if clinical differences exist between classic and variant SCLC tumors.

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Treatment of small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.

G Kalemkerian, James R. Jett, Steven Schild … (2013)

Small cell lung cancer (SCLC) is a lethal disease for which there have been only small advances in diagnosis and treatment in the past decade. Our goal was to revise the evidence-based guidelines on staging and best available treatment options. A comprehensive literature search covering 2004 to 2011 was conducted in MEDLINE, Embase, and five Cochrane databases using SCLC terms. This was cross-checked with the authors' own literature searches and knowledge of the literature. Results were limited to research in humans and articles written in English. The staging classification should include both the old Veterans Administration staging classification of limited stage (LS) and extensive stage (ES), as well as the new seventh edition American Joint Committee on Cancer/International Union Against Cancer staging by TNM. The use of PET scanning is likely to improve the accuracy of staging. Surgery is indicated for carefully selected stage I SCLC. LS disease should be treated with concurrent chemoradiotherapy in patients with good performance status. Thoracic radiotherapy should be administered early in the course of treatment, preferably beginning with cycle 1 or 2 of chemotherapy. Chemotherapy should consist of four cycles of a platinum agent and etoposide. ES disease should be treated primarily with chemotherapy consisting of a platinum agent plus etoposide or irinotecan. Prophylactic cranial irradiation prolongs survival in those individuals with both LS and ES disease who achieve a complete or partial response to initial therapy. To date, no molecularly targeted therapy agent has demonstrated proven efficacy against SCLC. Evidence-based guidelines are provided for the staging and treatment of SCLC. LS-SCLC is treated with curative intent with 20% to 25% 5-year survival. ES-SCLC is initially responsive to standard treatment, but almost always relapses, with virtually no patients surviving for 5 years. Targeted therapies have no proven efficacy against SCLC.

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Author and article information

Contributors

Guangliang Qiang:

ORCID: http://orcid.org/0000-0002-7809-1892

pkudd@126.com

Journal

Journal ID (nlm-ta): World J Surg Oncol

Journal ID (iso-abbrev): World J Surg Oncol

Title: World Journal of Surgical Oncology

Publisher: BioMed Central (London )

ISSN (Electronic): 1477-7819

Publication date (Electronic): 30 May 2020

Publication date PMC-release: 30 May 2020

Publication date Collection: 2020

Volume: 18

Electronic Location Identifier: 116

Affiliations

GRID grid.415954.8, ISNI 0000 0004 1771 3349, Department of Thoracic Surgery, , China-Japan Friendship Hospital, ; #2 Yinghua East Road, Chaoyang District, Beijing, 100029 China

Author information

Guangliang Qiang http://orcid.org/0000-0002-7809-1892

Article

Publisher ID: 1894

DOI: 10.1186/s12957-020-01894-9

PMC ID: 7261386

PubMed ID: 32473655

SO-VID: afbc11ba-b8bb-4d93-8da8-cfa1ba69d5ab

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 12 February 2020

Date accepted : 21 May 2020

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ScienceOpen disciplines: Surgery

Keywords: neuron-specific enolase,small cell lung cancer,prognosis,meta-analysis

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ScienceOpen disciplines: Surgery

Keywords: neuron-specific enolase, small cell lung cancer, prognosis, meta-analysis

Prognostic value of neuron-specific enolase for small cell lung cancer: a systematic review and meta-analysis

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Karger: Oncology

Most cited references 40

Small-cell lung cancer.

Establishment and identification of small cell lung cancer cell lines having classic and variant features.

Treatment of small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.

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