Circulating endothelial cells and tumor blood volume as predictors in lung cancer

The current criteria for evaluating antiangiogenic efficacy is insufficient as tumor shrinkage occurs after blood perfusion decreases. Tumor blood volume (BV) in computed tomography perfusion imaging and circulating endothelial cells (CEC) might predict the status of angiogenesis. The present study aimed to validate their representation as feasible predictors in non‐small‐cell lung carcinoma (NSCLC). A total of 74 patients was categorized randomly into two arms undergoing regimens of vinorelbine and cisplatin (Navelbine and platinum [NP]) with rh‐endostatin or single NP. The response rate, perfusion imaging indexes and activated CEC (aCEC) during treatment were recorded. Progression‐free survival (PFS) was determined through follow up. Correlations among the above indicators, response and PFS were analyzed: aCEC increased significantly in cases of progressive disease after single NP chemotherapy (P = 0.024). Tumor BV decreased significantly in cases with a clinical benefit in the combined arm (P = 0.026), whereas inverse correlations existed between ∆aCEC (post‐therapeutic value minus the pre‐therapeutic value) and PFS (P = 0.005) and between ∆BV and PFS (P = 0.044); a positive correlation existed between ∆aCEC and ∆BV. Therefore, both aCEC and tumor BV can serve as predictors, and detection of both indicators can help evaluate the chemo‐antiangiogenic efficacy in NSCLC more accurately.

[1]  B. Han,et al.  Can Determination of Circulating Endothelial Cells and Serum Caspase-Cleaved CK18 Predict for Response and Survival in Patients with Advanced Non–Small-Cell Lung Cancer Receiving Endostatin and Paclitaxel–Carboplatin Chemotherapy? A Retrospective Study , 2012, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[2]  C. Staton,et al.  Anti-angiogenic drug discovery: lessons from the past and thoughts for the future , 2012, Expert opinion on drug discovery.

[3]  J. Chen,et al.  A randomized phase II study of recombinant human endostatin plus gemcitabine/cisplatin compared with gemcitabine/cisplatin alone as first-line therapy in advanced non-small-cell lung cancer , 2012, Investigational New Drugs.

[4]  O. Casanovas Cancer: Limitations of therapies exposed , 2012, Nature.

[5]  P. Woll,et al.  Analysis of circulating angiogenic biomarkers from patients in two phase III trials in lung cancer of chemotherapy alone or chemotherapy and thalidomide , 2012, British Journal of Cancer.

[6]  M. Toi,et al.  Determining circulating endothelial cells using CellSearch system during preoperative systemic chemotherapy in breast cancer patients. , 2011, European journal of cancer.

[7]  M. Gnant,et al.  Discrimination between circulating endothelial cells and blood cell populations with overlapping phenotype reveals distinct regulation and predictive potential in cancer therapy. , 2011, Neoplasia.

[8]  Mauro Biffoni,et al.  Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells , 2011, Nature.

[9]  S. Erzurum,et al.  Pro-angiogenic hematopoietic progenitor cells and endothelial colony-forming cells in pathological angiogenesis of bronchial and pulmonary circulation , 2011, Angiogenesis.

[10]  Yang Zhang,et al.  A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of Paclitaxel-Carboplatin Alone or with Endostar for Advanced Non-small Cell Lung Cancer , 2011, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[11]  D. Richel,et al.  Vascular Endothelial Growth Factor in the Circulation in Cancer Patients May Not Be a Relevant Biomarker , 2011, PloS one.

[12]  X. Pivot,et al.  Clinical value of circulating endothelial cells and circulating tumor cells in metastatic breast cancer patients treated first line with bevacizumab and chemotherapy. , 2010, Annals of oncology : official journal of the European Society for Medical Oncology.

[13]  Gilles Chatellier,et al.  Metastatic renal carcinoma: evaluation of antiangiogenic therapy with dynamic contrast-enhanced CT. , 2010, Radiology.

[14]  Z. Yang,et al.  First-pass perfusion imaging of solitary pulmonary nodules with 64-detector row CT: comparison of perfusion parameters of malignant and benign lesions. , 2010, The British journal of radiology.

[15]  P. Hegde,et al.  Circulating vascular endothelial growth factor (VEGF) as a biomarker for bevacizumab-based therapy in metastatic colorectal, non-small cell lung, and renal cell cancers: Analysis of phase III studies. , 2010 .

[16]  M. Bellomi,et al.  Perfusion CT in solid body-tumours part II. Clinical applications and future development , 2010, La radiologia medica.

[17]  T. Mok,et al.  Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. , 2009, The New England journal of medicine.

[18]  Y. Ohe,et al.  Circulating Endothelial Cells in Non-small Cell Lung Cancer Patients Treated with Carboplatin and Paclitaxel , 2009, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[19]  Xi-yin Wei,et al.  Changes of activated circulating endothelial cells and survivin in patients with non-small cell lung cancer after antiangiogenesis therapy. , 2008, Chinese medical journal.

[20]  R. Kerbel,et al.  Rapid chemotherapy-induced acute endothelial progenitor cell mobilization: implications for antiangiogenic drugs as chemosensitizing agents. , 2008, Cancer cell.

[21]  Hai-wei Zhang,et al.  Endostar Suppresses Invasion Through Downregulating the Expression of Matrix Metalloproteinase-2/9 in MDA-MB-435 Human Breast Cancer Cells , 2008, Experimental biology and medicine.

[22]  Gabriele Bergers,et al.  Modes of resistance to anti-angiogenic therapy , 2008, Nature Reviews Cancer.

[23]  T. Roberts,et al.  Computed Tomography Perfusion Using First Pass Methods for Lung Nodule Characterization , 2008, Investigative radiology.

[24]  W. Figg,et al.  Circulating endothelial cells as a therapeutic marker for thalidomide in combined therapy with chemotherapy drugs in a human prostate cancer model , 2008, BJU international.

[25]  A. Jemal,et al.  Cancer Statistics, 2008 , 2008, CA: a cancer journal for clinicians.

[26]  Massimo Bellomi,et al.  CT perfusion for the monitoring of neoadjuvant chemotherapy and radiation therapy in rectal carcinoma: initial experience. , 2007, Radiology.

[27]  J. Manola,et al.  Blood-Based Biomarkers of SU11248 Activity and Clinical Outcome in Patients with Metastatic Imatinib-Resistant Gastrointestinal Stromal Tumor , 2007, Clinical Cancer Research.

[28]  S. Sleijfer,et al.  Cells meeting our immunophenotypic criteria of endothelial cells are large platelets , 2007, Cytometry. Part B, Clinical cytometry.

[29]  C. Rao,et al.  Endothelial cells in peripheral blood of healthy subjects and patients with metastatic carcinomas , 2007, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[30]  Robert Gray,et al.  Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. , 2006, The New England journal of medicine.

[31]  B. Thürlimann,et al.  Circulating endothelial cells and angiogenic serum factors during neoadjuvant chemotherapy of primary breast cancer , 2006, British Journal of Cancer.

[32]  Qinghua Zhou,et al.  [Results of randomized, multicenter, double-blind phase III trial of rh-endostatin (YH-16) in treatment of advanced non-small cell lung cancer patients]. , 2005, Zhongguo fei ai za zhi = Chinese journal of lung cancer.

[33]  J. Folkman,et al.  Differential Effects of Vascular Endothelial Growth Factor Receptor-2 Inhibitor ZD6474 on Circulating Endothelial Progenitors and Mature Circulating Endothelial Cells: Implications for Use as a Surrogate Marker of Antiangiogenic Activity , 2005, Clinical Cancer Research.

[34]  J. Zwaginga,et al.  Circulating endothelial (progenitor) cells reflect the state of the endothelium: vascular injury, repair and neovascularization , 2005, Vox sanguinis.

[35]  Rakesh K. Jain,et al.  Vascular Normalization by Vascular Endothelial Growth Factor Receptor 2 Blockade Induces a Pressure Gradient Across the Vasculature and Improves Drug Penetration in Tumors , 2004, Cancer Research.

[36]  R. Kerbel,et al.  Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells. , 2003, Cancer research.

[37]  L. Ellis,et al.  Phase I study of recombinant human endostatin in patients with advanced solid tumors. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[38]  A. Goldhirsch,et al.  Resting and activated endothelial cells are increased in the peripheral blood of cancer patients. , 2001, Blood.

[39]  J. Isner,et al.  VEGF contributes to postnatal neovascularization by mobilizing bone marrow‐derived endothelial progenitor cells , 1999, The EMBO journal.

[40]  J. Folkman What is the evidence that tumors are angiogenesis dependent? , 1990, Journal of the National Cancer Institute.

[41]  S. Kumar,et al.  Purified tumour angiogenesis factor enhances proliferation of capillary, but not aortic, endothelial cells in vitro. , 1982, Journal of cell science.

[42]  J. Folkman,et al.  TUMOR ANGIOGENESIS , 1972, The Journal of cell biology.

[43]  J. Folkman Tumor angiogenesis: therapeutic implications. , 1971, The New England journal of medicine.

[44]  E. Hannan,et al.  Invited commentary. , 2015, The Annals of thoracic surgery.

[45]  L. Ricci-Vitiani,et al.  Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells , 2011, Nature.

[46]  E. Voest,et al.  Late release of circulating endothelial cells and endothelial progenitor cells after chemotherapy predicts response and survival in cancer patients. , 2010, Neoplasia.

[47]  L. Schwartz,et al.  New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). , 2009, European journal of cancer.

[48]  A. Fortier,et al.  Zinc ligand-disrupted recombinant human Endostatin: Potent inhibition of tumor growth, safety and pharmacokinetic profile , 2004, Angiogenesis.

[49]  J. Eastwood,et al.  Perfusion CT with iodinated contrast material. , 2003, AJR. American journal of roentgenology.

[50]  TUMOR ANGIOGENESIS Rapid Induction of Endothelial Mitoses Demonstrated by Autoradiography , 2003 .