Merih TEPEOĞLU, Hüseyin BORA, Eda YİRMİBEŞOĞLU ERKAL, Müge AKMANSU

Role of Vascular Endothelial Growth Factor in Clinically Localized Prostate Cancer Treated with Radiation Therapy

Background:Anti-vascular endothelial growth factor (Anti-VEGF) agents area promising approach to increase theefficacy of treatment for treatment-resistant prostate cancer.Aims:Tocorrelate vascular endothelial growth factor (VEGF) ex-pression andoutcome following radiation therapy in thetreatment of clinically localized prostate cancer.Study Design: Retrospective observational study.Methods:Forty-one patients andclinically localized disease that were treated withradiation therapy were analyzed. ForVEGF ex-pression, immunoreactivity scores (IRS) were calculated using per-centscores andintensity scores. Twenty-four patients wereclassified ashaving low(0to 4 IRS)and17patients wereclassified ashaving high (5 to 8 IRS) VEGF expression.Results:Themedian agewas71years, median follow-up was5.4 years andmedian radiation therapy dosewas70Gy.VEGF expres-sionwascalculated aslowin24patients andhighin17patients. Higher VEGF expression wasobserved in6/26 patients with a lowGleason score versus 11/15 patients witha highGleason score (p=0.02). Biochemical failure (BF) wasobserved in2/24patients withlowVEGF expression versus 7/17patients withhighVEGF expression (p=0.01). Inunivariate analysis, having a higher Glea-sonscore (p

PDF

___

Bolla M, Van Tienhoven G, Warde P, Dubois JB, Mirimanoff RO, Storme G, et al. External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. Lancet Oncol 2010;11:1066-73. [CrossRef]
Movsas B, Chapman JD, Hanlon AL, Horwitz EM, Greenberg RE, Stobbe C, et al. Hypoxic prostate/muscle pO2 ratio predicts for biochemical failure in patients with prostate cancer: preliminary findings. Urology 2002;60:634-9. [CrossRef]
Nordsmark M, Overgaard M, Overgaard J. Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head and neck. Radiother Oncol 1996;41:31-9. [CrossRef]
Fyles AW, Milosevic M, Wong R, Kavanagh MC, Pintilie M, Sun A, et al. Oxygenation predicts radiation response and survival in patients with cervix cancer. Radiother Oncol 1998;48:149-56. [CrossRef]
Lee CG, Heijn M, di Tomaso E, Griffon-Etienne G, Ancukiewicz M, Koike C, et al. Anti-Vascular endothelial growth factor treatment augments tumor radiation response under normoxic or hypoxic conditions. Cancer Res 2000;60:5565-70.
Geng L, Donnelly E, McMahon G, Lin PC, Sierra-Rivera E, Oshinka H, et al. Inhibition of vascular endothelial growth factor receptor signaling leads to reversal of tumor resistance to radiotherapy. Cancer Res 2001;61:2413-9.
Vergis R, Corbishley CM, Norman AR, Bartlett J, Jhavar S, Borre M, et al. Intrinsic markers of tumour hypoxia and angiogenesis in localised prostate cancer and outcome of radical treatment: a retrospective analysis of two randomised radiotherapy trials and one surgical cohort study. Lancet Oncol 2008;9:342-51. [CrossRef]
D'Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 1998;280:969-74. [CrossRef]
Cvetkovic D, Movsas B, Dicker AP, Hanlon AL, Greenberg RE, Chapman JD, et al. Increased hypoxia correlates with increased expression of the angiogenesis marker vascular endothelial growth factor in human prostate cancer. Urology 2001;57:821-5. [CrossRef]
Cuzick J, Fisher G, Kattan MW, Berney D, Oliver T, Foster CS, et al. Transatlantic Prostate Group. Long-term outcome among men with conservatively treated localised prostate cancer. Br J Cancer 2006;95:1186-94. [CrossRef]
Stephenson AJ, Scardino PT, Eastham JA, Bianco FJ Jr, Dotan ZA, Fearn PA, et al. Preoperative nomogram predicting the 10-year probability of prostate cancer recurrence after radical prostatectomy. J Natl Cancer Inst 2006;98:715-7. [CrossRef]
Folkman J. Anti-angiogenesis: new concept for therapy of solid tumors. Ann Surg 1972;175:409-16. [CrossRef]
Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 2005;23:1011-27. [CrossRef]
Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med 2003;9:677-84. [CrossRef]
Maeda K, Chung YS, Ogawa Y, Takatsuka S, Kang SM, Ogawa M, et al. Prognostic value of vascular endothelial growth factor expression in gastric carcinoma. Cancer 1996;77:858-63. [CrossRef]
Inoue K, Ozeki Y, Suganuma T, Sugiura Y, Tanaka S. Vascular endothelial growth factor expression in primary esophageal squamous cell carcinoma. Association with angiogenesis and tumor progression. Cancer 1997;79:206-13. [CrossRef]
Linderholm B, Tavelin B, Grankvist K, Henriksson R Vascular endothelial growth factor is of high prognostic value in node-negative breast carcinoma. J Clin Oncol 1998;16:3121-8.
Linderholm B, Tavelin B, Grankvist K, Henriksson R. Does vascular endothelial growth factor (VEGF) predict local relapse and survival in radiotherapy-treated node-negative breast cancer? Br J Cancer 1999;81:727-32. [CrossRef]
Linderholm B, Grankvist K, Wilking N, Johansson M, Tavelin B, Henriksson R. Correlation of vascular endothelial growth factor content with recurrences, survival, and first relapse site in primary node-positive breast carcinoma after adjuvant treatment. J Clin Oncol 2000;18:1423-31.
Ishigami SI, Arii S, Furutani M, Niwano M, Harada T, Mizumoto M, et al. Predictive value of vascular endothelial growth factor (VEGF) in metastasis and prognosis of human colorectal cancer. Br J Cancer 1998;78:1379-84. [CrossRef]
Peng Y, Wang L, Du C, Gu J. Expression of vascular endothelial growth factor can predict distant metastasis and disease-free survival for clinical stage III rectal cancer following 30-Gy/10-f preoperative radiotherapy. Int J Colorectal Dis 2012;27:1555-60. [CrossRef]
Loncaster JA, Cooper RA, Logue JP, Davidson SE, Hunter RD, West CM. Vascular endothelial growth factor (VEGF) expression is a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix. Br J Cancer 2000;83:620-5. [CrossRef]
Harper ME, Glynne-Jones E, Goddard L, Thurston VJ, Griffiths K. Vascular endothelial growth factor (VEGF) expression in prostatic tumours and its relationship to neuroendocrine cells. Br J Cancer 1996;74:910-6. [CrossRef]
Peyromaure M, Camparo P, Badoual C, Descazeaud A, Dinh-Xuan AT. The expression of vascular endothelial growth factor is associated with the risk of cancer progression after radical prostatectomy. BJU Int 2007;99:1150-3. [CrossRef]
Green MM, Hiley CT, Shanks JH, Bottomley IC, West CM, Cowan RA, et al. Expression of vascular endothelial growth factor (VEGF) in locally invasive prostate cancer is prognostic for radiotherapy outcome. Int J Radiat Oncol Biol Phys 2007;67:84-90. [CrossRef]
Tong RT, Boucher Y, Kozin SV, Winkler F, Hicklin DJ, Jain RK. Vascular normalization by vascular endothelial growth factor receptor 2 blockade induces a pressure gradient across the vasculature and improves drug penetration in tumors. Cancer Res 2004;64:3731-6. [CrossRef]
Winkler F, Kozin SV, Tong RT, Chae SS, Booth MF, Garkavtsev I, et al. Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell 2004;6:553-63. [CrossRef]
Vuky J, Pham HT, Warren S, Douglass E, Badiozamani K, Madsen B, et al. Phase II study of long-term androgen suppression with bevacizumab and intensity-modulated radiation therapy (IMRT) in high-risk prostate cancer. Int J Radiat Oncol Biol Phys 2012;82:e609-15. [CrossRef]