Pleural fluid osteopontin, vascular endothelial growth factor, and urokinase-type plasminogen activator levels as predictors of pleurodesis outcome and prognosticators in patients with malignant pleural effusion: a prospective cohort study

Abstract

BackgroundRapidly growing cancer cells secrete growth-promoting polypeptides and have increased proteolytic activity, contributing to tumor progression and metastasis. Their presentation in malignant pleural effusion (MPE) and their predictive value for the outcome of pleurodesis and survival were studied.MethodsBetween February 2011 and March 2012, MPE samples were prospectively collected from 61 patients. Twenty-five patients with non-malignant pleural effusion in the same period were included as controls. Pleural fluid osteopontin (OPN), vascular endothelial growth factor (VEGF), and urokinase-type plasminogen activator (uPA) concentrations were measured.ResultsPatients with MPE had higher pleural fluid OPN, VEGF, and uPA concentrations than those with non-malignant pleural effusion, but only differences in VEGF were statistically significant (p = 0.045). Patients with distant metastases had significantly elevated pleural fluid VEGF concentrations than those without (p = 0.004). Pleural fluid OPN, VEGF, and uPA concentrations were positively correlated in most patients. However, there was no significant difference in pleural fluid OPN, VEGF, and uPA concentrations between patients with successful pleurodesis and those without. There was also no significant difference in cancer-specific survival between sub-groups with higher and lower pleural fluid OPN, VEGF, or uPA concentrations. Patients with successful pleurodesis had significantly longer cancer-specific survival than those without (p = 0.015).ConclusionsPleural fluid OPN, VEGF, and uPA concentrations are elevated in MPE but are not satisfactory predictors of pleurodesis outcome or survival. Patients with higher pleural fluid VEGF concentration have higher risk of distant metastasis. Evaluating the benefits of therapy targeting the VEGF pathway in these patients warrants further studies.

Estrogen, Estrogen Receptor and Lung Cancer

“…Ikeda et al measured the estrogen concentrations in the noncancerous peripheral lung tissue using liquid chromatography/electrospray tandem mass spectrometry in the postmenopausal female patients with synchronous multiple lung adenocarcinomas, and found a significantly higher level than the control cases with a single lung adenocarcinoma [ 78 ] ( Figure 1 ). Our study of the malignant pleural effusion of lung adenocarcinoma revealed that some postmenopausal women had extraordinarily high pleural fluid estradiol concentrations, and there was no correlation between the pleural fluid concentrations of estradiol and the vascular endothelial growth factor, a marker of pleural vascular hyperpermeability [ 79 ]. In addition, the EGFR wild-type lung adenocarcinoma is probably an estrogen-dependent carcinoma, as a higher expression and potent poor prognosticator of aromatase and the ERβ in the group [ 62 ].…”

Wet M1a non-small cell lung cancer: is it possible to predict recurrence of pleural effusion?

“…Two randomized trials recently analyzed MPE recurrence. The TIME 1 randomized trial reported that pleurodesis through 12 French chest tube is more associated with higher MPE recurrence after 3 months than 24 French chest tube (30% vs. 24% difference, −6%; 1-sided 95% CI, −20% to ∞; P=0.14 for noninferiority) (21 (24). As far as we know, our study is the first to evaluate risk factors for MPE recurrence only in NSCLC patients.…”

The role of VEGF in the diagnosis and treatment of malignant pleural effusion in patients with non‑small cell lung cancer (Review)

“…The results indicated that local pleural administration of bevacizumab plus cisplatin, alongside the systemic administration of paclitaxel, resulted in a much higher ORR (83.3 vs. 50.0%; P<0.05), compared with that in patients who received systemic administration of paclitaxel plus local cisplatin only ( 75 ). Patients in the first group demonstrated a significant reduction in the amount of pleural effusion, accompanied with a markedly improved quality of life, and tolerated the treatment well ( 75 ). Substantial additional clinical studies have all reported that bevacizumab is safe and effective for the treatment of MPE in patients with NSCLC ( Table III ) ( 76 – 82 ).…”

“…Data from two retrospective studies also confirmed that bevacizumab combined with chemotherapy drugs through intravenous injection can effectively control MPE in patients with nonsquamous NSCLC, with a MPE control rate of 92.3% and a MPE release rate of ≤71.4% ( 4 ). The efficacy of bevacizumab combined with platinum through local pleural administration in the treatment of MPE was investigated by Hsu et al ( 75 ). The results indicated that local pleural administration of bevacizumab plus cisplatin, alongside the systemic administration of paclitaxel, resulted in a much higher ORR (83.3 vs. 50.0%; P<0.05), compared with that in patients who received systemic administration of paclitaxel plus local cisplatin only ( 75 ).…”

“…The efficacy of bevacizumab combined with platinum through local pleural administration in the treatment of MPE was investigated by Hsu et al ( 75 ). The results indicated that local pleural administration of bevacizumab plus cisplatin, alongside the systemic administration of paclitaxel, resulted in a much higher ORR (83.3 vs. 50.0%; P<0.05), compared with that in patients who received systemic administration of paclitaxel plus local cisplatin only ( 75 ). Patients in the first group demonstrated a significant reduction in the amount of pleural effusion, accompanied with a markedly improved quality of life, and tolerated the treatment well ( 75 ).…”