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. 2013 Jun;14(6):469-75.
doi: 10.4161/cbt.24425.

Systemic inflammatory status at baseline predicts bevacizumab benefit in advanced non-small cell lung cancer patients

Cirino Botta  1 , Vito Barbieri, Domenico Ciliberto, Antonio Rossi, Danilo Rocco, Raffaele Addeo, Nicoletta Staropoli, Pierpaolo Pastina, Giulia Marvaso, Ignazio Martellucci, Annamaria Guglielmo, Luigi Pirtoli, Pasquale Sperlongano, Cesare Gridelli, Michele Caraglia, Pierfrancesco Tassone, Pierosandro Tagliaferri, Pierpaolo Correale
Affiliations
Free PMC article

Systemic inflammatory status at baseline predicts bevacizumab benefit in advanced non-small cell lung cancer patients

Cirino Botta et al. Cancer Biol Ther. 2013 Jun.
Free PMC article

Abstract

Bevacizumab is a humanized anti-VEGF monoclonal antibody able to produce clinical benefit in advanced non-squamous non-small-cell lung cancer (NSCLC) patients when combined to chemotherapy. At present, while there is a rising attention to bevacizumab-related adverse events and costs, no clinical or biological markers have been identified and validated for baseline patient selection. Preclinical findings suggest an important role for myeloid-derived inflammatory cells, such as neutrophils and monocytes, in the development of VEGF-independent angiogenesis. We conducted a retrospective analysis to investigate the role of peripheral blood cells count and of an inflammatory index, the neutrophil-to-lymphocyte ratio (NLR), as predictors of clinical outcome in NSCLC patients treated with bevacizumab plus chemotherapy. One hundred and twelve NSCLC patients treated with chemotherapy ± bevacizumab were retrospectively evaluated for the predictive value of clinical or laboratory parameters correlated with inflammatory status. Univariate analysis revealed that a high number of circulating neutrophils and monocytes as well as a high NLR were associated with shorter progression-free survival (PFS) and overall survival (OS) in bevacizumab-treated patients only. We have thus developed a model based on the absence or the presence of at least one of the above-mentioned inflammatory parameters. We found that the absence of all variables strongly correlated with longer PFS and OS (9.0 vs. 7.0 mo, HR: 0.39, p = 0.002; and 20.0 vs. 12.0 mo, HR: 0.29, p < 0.001 respectively) only in NSCLC patients treated with bevacizumab plus chemotherapy. Our results suggest that a baseline systemic inflammatory status is marker of resistance to bevacizumab treatment in NSCLC patients.

Keywords: angiogenesis; bevacizumab; inflammation; lung cancer; monocytes; neutrophil-to-lymphocyte ratio; neutrophils.

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Figures

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Figure 1. Progression free survival estimation of the whole group (A) and according to baseline neutrophil (B) and monocyte (C) count and NLR value (D) in NSCLC patients treated with bevacizumab.
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Figure 2. Progression free survival probability according to the baseline inflammatory status (neutrophil count > 7000 cells/mmc, monocyte count > 600/mmc, NLR > 4; see text) in NSCLC patients treated with (A) or without (B) bevacizumab
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Figure 3. Overall survival estimation according to the baseline inflammatory status (neutrophil count > 7000 cells/mmc, monocyte count > 600/mmc, NLR > 4; see text) in NSCLC patients treated with (A) or without (B) bevacizumab
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