Serum neuron-specific enolase (S-NSE) and the prognosis in small-cell lung cancer (SCLC): a combined multivariable analysis on data from nine centres

Jørgensen, Lone; Østerlind, Kell; Genollá, J; Gomm, S. A.; Hernández, Jesús Rodríguez; Johnson, Paul W.; Løber, J.; Splinter, T. A. W.; Szturmowicz, M

doi:10.1038/bjc.1996.383

Cited by 85 publications

(52 citation statements)

References 16 publications

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“…22 LDH is the most commonly used prognostic factor for SCLC in clinical trials although NSE may be superior. 23 The results from this study suggest additional prognostic information from the measurement of M65 over LDH alone. Although potentially counterintuitive, it is well recognized that increased tumor apoptosis and necrosis are associated with increased proliferation and higher grade and may be regarded as adverse biological factors.…”

Section: Discussionmentioning

confidence: 66%

Evaluation of Circulating Tumor Cells and Serological Cell Death Biomarkers in Small Cell Lung Cancer Patients Undergoing Chemotherapy

Hou

Greystoke

Lancashire

et al. 2009

The American Journal of Pathology

212

186

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Serological cell death biomarkers and circulating tumor cells (CTCs) have potential uses as tools for pharmacodynamic blood-based assays and their subsequent application to early clinical trials. In this study, we evaluated both the expression and clinical significance of CTCs and serological cell death biomarkers in patients with small cell lung cancer. Blood samples from 88 patients were assayed using enzyme-linked immunosorbent assays for various cytokeratin 18 products (eg, M65, cell death, M30, and apoptosis) as well as nucleosomal DNA. CTCs (per 7.5 ml of blood) were quantified using Veridex CellSearch technology. Before therapeutic treatment, cell death biomarkers were elevated in patients compared with controls. CTCs were detected in 86% of patients; additionally, CD56 was detectable in CTCs, confirming their neoplastic origin. M30 levels correlated with the percentage of apoptotic CTCs. M30 , M65 , lactate dehydrogenase , and CTC number were prognostic for patient survival as determined by univariate analysis. Using multivariate analysis , both lactate dehydrogenase and M65 levels remained significant. CTC number fell following chemotherapy , whereas levels of serological cell death biomarkers peaked at 48 hours and fell by day 22 , mirroring the tumor response. A 48-hour rise in nucleosomal DNA and M30 levels was associated with early response and severe toxicity , respectively. Our results provide a rationale to include the use of serological biomark- Small cell lung cancer (SCLC) is initially chemosensitive but invariably relapses with a chemoresistant phenotype.1 A number of molecularly targeted therapies have been evaluated attempting to improve outcome, but none have succeeded to date.2 Ideally, early clinical trials should incorporate validated pharmacodynamic biomarkers, conducted to good clinical laboratory practice, that demonstrate both proof of mechanism (drug hits target) and proof of concept (tumor responds to drug).3 Although possible, serial biopsies are rare in SCLC, and the tissue obtained often insufficient for extensive molecular profiling. Thus, there is a pressing need for blood-based biomarkers that report therapeutic response.Assays of drug-induced cell death are potential proof of concept biomarkers for multiple therapeutics. 4 The M30 Apoptosense and M65 assays (Peviva, Bromma, Sweden) detect cytokeratin (CK) 18, expressed in epithelial but not hematopoietic cells, and released into the blood following cytoskeletal disassembly and degradation during apoptotic and/or necrotic cell death. 5 The M30 antibody recognizes a caspase-cleaved neoepitope of CK18 that is only revealed during apoptosis, whereas the M65 assay detects full length and cleaved forms of CK18 reporting apoptosis and necrosis.6 Nucleosomal DNA (nDNA) results from cleavage of chromatin by apoptotic endonucleases into membrane bound DNA fragments that are phagocytosed by macrophages and sub-

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Section: Discussionmentioning

confidence: 66%

Evaluation of Circulating Tumor Cells and Serological Cell Death Biomarkers in Small Cell Lung Cancer Patients Undergoing Chemotherapy

Hou

Greystoke

Lancashire

et al. 2009

The American Journal of Pathology

212

186

View full text Add to dashboard Cite

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“…NSE was considered to be the representative tumor marker for small cell lung cancer (SCLC). None of these markers are ideal (11)(12)(13)(14)(15)(16)(17)(18). In this study, the levels of these tumor markers simultaneously increased in 2 patients, which indicates poor performance of these tumor markers in the diagnosis of SMPLC.…”

Section: Discussionmentioning

confidence: 84%

Early clinical diagnosis of synchronous multiple primary lung cancer

Xue

Wang

et al. 2011

Oncology Letters

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Abstract. The diagnosis of synchronous multiple primary lung cancer (SMPLC) remains a formidable challenge. The aim of the present study was to identify useful clues for the clinical diagnosis of SMPLC, in particular for the early stages. The medical records of 10 patients diagnosed with SMPLC with different histological types were analyzed retrospectively. Chest computed tomography (CT) findings showed two pulmonary lesions in all patients. The two lesions displayed malignant characteristics of primary lung cancer. The levels of a number of tumor markers, including carcinoembryonic antigen, neuron-specific enolase, cytokeratin fragment 21-1, squamous cell carcinoma and CA125 increased in 2 patients. Auxiliary examinations of other physical sites in these patients did not show signs of neoplasm metastasis. Two tumors were separately staged and appropriate treatment was carried out based on the revised stage, which provided more benefits for SMPLC patients. The diagnosis of SMPLC might be delayed or mistaken owing to its similarity to neoplasm metastasis. A high index of awareness is required for the early diagnosis of this disease. The malignant characteristics of primary lung cancer in various lesions may be valuable clues for the diagnosis of SMPLC. Alterations in the levels of tumor markers may be a poor diagnostic tool for the detection of SMPLC. Separate biopsies for different pulmonary masses should be performed for clinical staging as soon as possible and reasonable treatment based on the stage should also be selected.

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“…TNM was not introduced in order to avoid statistical redundancy. For the biological variables, previously published thresholds were used particularly for Cyfra 21-1 (Pujol et al, 1993(Pujol et al, , 2001) and NSE serum levels (Jorgensen et al, 1996;Pujol et al, 2001). …”

Section: Statisticsmentioning

confidence: 99%

A new simplified comorbidity score as a prognostic factor in non-small-cell lung cancer patients: description and comparison with the Charlson's index

et al. 2005

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Treatment of non-small-cell lung cancer (NSCLC) might take into account comorbidities as an important variable. The aim of this study was to generate a new simplified comorbidity score (SCS) and to determine whether or not it improves the possibility of predicting prognosis of NSCLC patients. A two-step methodology was used.Step 1: An SCS was developed and its prognostic value was compared with classical prognostic determinants in the outcome of 735 previously untreated NSCLC patients.Step 2: the SCS reliability as a prognostic determinant was tested in a different population of 136 prospectively accrued NSCLC patients with a formal comparison between SCS and the classical Charlson comorbidity index (CCI). Prognosis was analysed using both univariate and multivariate (Cox model) statistics. The SCS summarised the following variables: tobacco consumption, diabetes mellitus and renal insufficiency (respective weightings 7, 5 and 4), respiratory, neoplastic and cardiovascular comorbidities and alcoholism (weighting ¼ 1 for each item). In step 1, aside from classical variables such as age, stage of the disease and performance status, SCS was a statistically significant prognostic variable in univariate analyses. In the Cox model weight loss, stage grouping, performance status and SCS were independent determinants of a poor outcome. There was a trend towards statistical significance for age (P ¼ 0.08) and leucocytes count (P ¼ 0.06). In Step 2, both SCS and well-known prognostic variables were found as significant determinants in univariate analyses. There was a trend towards a negative prognostic effect for CCI. In multivariate analysis, stage grouping, performance status, histology, leucocytes, lymphocytes, lactate dehydrogenase, CYFRA 21-1 and SCS were independent determinants of a poor prognosis. CCI was removed from the Cox model. In conclusion, the SCS, constructed as an independent prognostic factor in a large NSCLC patient population, is validated in another prospective population and appears more informative than the CCI in predicting NSCLC patient outcome.

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Serum neuron-specific enolase (S-NSE) and the prognosis in small-cell lung cancer (SCLC): a combined multivariable analysis on data from nine centres

Abstract: Serum neuron-specific enolase (S-NSE)

Cited by 85 publications

References 16 publications

Evaluation of Circulating Tumor Cells and Serological Cell Death Biomarkers in Small Cell Lung Cancer Patients Undergoing Chemotherapy

Evaluation of Circulating Tumor Cells and Serological Cell Death Biomarkers in Small Cell Lung Cancer Patients Undergoing Chemotherapy

Early clinical diagnosis of synchronous multiple primary lung cancer

A new simplified comorbidity score as a prognostic factor in non-small-cell lung cancer patients: description and comparison with the Charlson's index

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