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. 2020 Aug 11:12:1758835920942378.
doi: 10.1177/1758835920942378. eCollection 2020.

Analysis of systemic inflammatory biomarkers in neuroendocrine carcinomas of the lung: prognostic and predictive significance of NLR, LDH, ALI, and LIPI score

Antonio Galvano  1 , Marta Peri  1 , Aurelia Ada Guarini  1 , Marta Castiglia  1 , Antonino Grassadonia  2 , Michele De Tursi  2 , Luciana Irtelli  2 , Sergio Rizzo  1 , Alessandro Bertani  3 , Valerio Gristina  1 , Nadia Barraco  1 , Antonio Russo  4 , Clara Natoli  2 , Viviana Bazan  5
Affiliations

Analysis of systemic inflammatory biomarkers in neuroendocrine carcinomas of the lung: prognostic and predictive significance of NLR, LDH, ALI, and LIPI score

Antonio Galvano et al. Ther Adv Med Oncol. .

Abstract

Background: Lung neuroendocrine carcinoma (NEC) is characterized by aggressive clinical behavior and lack of treatment advances. We evaluate the prognostic and the predictive roles of systemic inflammatory biomarkers in patient circulating blood: neutrophil-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), advanced lung cancer inflammation index (ALI), and the Lung Immune Prognostic Index (LIPI) score.

Methods: A total of 120 patients with small-cell lung cancer (SCLC) (n = 110) and large cell neuroendocrine carcinoma (LCNEC) (n = 10) were enrolled. Overall survival (OS) was evaluated by Kaplan-Meier estimator and univariate and multivariate Cox proportional hazard analyses were performed to determine prognostic factors associated with OS while χ2 test was used for categorical data.

Results: NLR cutoff value was 1.93. NLR was measured before and after first-line chemotherapy; 25 (21%) patients had higher NLR (delta NLR >1), whereas NLR was lower in 37 (31%). At the univariate analysis, median OS was 12 months: OS for SCLC and LCNEC were 11 months and 14 months, respectively. OS had a prognostic positive value in patients with pre-treatment NLR <1.93 (p = 0.0002), LDH <600 U/L (p = 0,03) and ALI ⩾34 (p = 0,0065). At the multivariate analysis, Eastern Cooperative Oncology Group performance status, LDH levels and response after first-line chemotherapy were independently associated with OS. Median OS for good, intermediate, and poor LIPI was 15 months, 11 months, and 9 months, respectively(p = 0.091). Patients with higher NLR (>1.93) had an increased probability of tumor progression (p = 0.045, χ2 test).

Conclusion: This study demonstrated that systemic inflammatory biomarkers could facilitate the understanding of survival differences in the clinical management of lung NEC patients, underlying the need for prospective biomarker-driven studies in the immune checkpoint inhibitors setting.

Keywords: blood-based biomarker; neuroendocrine tumor; predictive biomarker; prognostic biomarker; small-cell lung cancer (SCLC); systemic inflammatory response.

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Conflict of interest statement

Conflict of interest statement: The authors declare that there is no conflict of interest.

Figures

Figure 1.
Figure 1.
Kaplan–Meier survival curve for overall survival (OS) according to neutrophil–lymphocyte ratio (NLR) values.
Figure 2.
Figure 2.
Kaplan–Meier survival curve for overall survival (OS) according to lactate dehydrogenase (LDH) values.
Figure 3.
Figure 3.
Kaplan–Meier survival curve for overall survival (OS) according to lung cancer inflammation index (ALI) values.
Figure 4.
Figure 4.
Kaplan–Meier survival curve for overall survival (OS) according to Lung Immune Prognostic Index (LIPI) values.
Figure 5.
Figure 5.
Number of patients who reach disease control stratified by neutrophil–lymphocyte ratio (NLR). In the χ2 test patients were divided into two groups (NLR ⩽1.93 and NLR >1.93). Patients in the NLR >1.93 group showed a significantly higher progressive disease rate than patients in the NLR ⩽1.93 group.
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