Radiation Medicine Program
University Health Network and Princess Margaret Hospital 
610 University Avenue
Toronto, Ontario, Canada
M5G 2M9

Email: mike.milosevic@rmp.uhn.on.ca
Phone: 416-946-2124Fax: 416-946-6566 

Professional Qualifications:

B.A.Sc. (Engineering and Management), University of Waterloo, Waterloo, Canada

M.D., Queen's University, Kingston, Canada

Fellow of the Royal College of Physicians and Surgeons of Canada (FRCPC) in Radiation Oncology

Appointments:

Clinician Scientist, Radiation Medicine Program, 
Princess Margaret Hospital, Toronto

Director of Research, Radiation Medicine Program,
Princess Margaret Hospital

President-Elect, Canadian Association of Radiation Oncologists (CARO)

Academic and 
Clinical Interests:

My research involves translational biology studies of the tumor microenvironment in patients with cervix or prostate cancer, and the application of engineering principles to cancer biology. I am particularly interested in the abnormal tumor vasculature, and its influence on interstitial fluid dynamics, elevated interstitial fluid pressure (IFP) and hypoxia. Much of my research focuses on the pathophysiologic implications of hypoxia and high IFP with respect to malignant tumor progression, metastasis development and response to radiotherapy, and the use of biologically targeted treatment strategies to improve patient outcome. I am also interested in the implementation of high-precision, image-guided radiotherapy for patients with gynecologic malignancies. 

Current Research Projects:

Hypoxia and IFP in cervix cancer
Biologic imaging of cervix and prostate cancer with dynamic CT and MRI
Inhibition of angiogenesis in cervix cancer
Hypoxia in prostate cancer
The effect of androgen ablation on prostate cancer hypoxia
IMRT for cervix cancer
Internal movement of the cervix and uterus during radiotherapy
Image-guided brachytherapy for cervix cancer
Pelvic lymph node localization for radiotherapy using MRI and ultra-small particles of iron oxide (USPIO)
Spatio-temporal variability in the structure and function of human tumors 

Selected Publications:

1. Milosevic MF, Fyles AW, Wong R, Pintilie M, Kavanagh M-C, Levin W, Manchul LA, Keane TJ, Hill RP. Interstitial fluid pressure in cervix cancer: within-tumor heterogeneity, and relationship to oxygen tension. Cancer 82, 2418-2426, 1998.

2. Fyles A, Milosevic M, Wong R, Kavanagh M-C, Pintilie M, Sun A, Chapman W, Levin W, Manchul L, Keane T, Hill R. Oxygenation predicts radiation response and survival in patients with cervix cancer. Radiother Oncol 48, 149-156, 1998.

3. Fyles AW, Milosevic M, Pintilie M, Hill M. Cervix cancer oxygenation measured following external radiation therapy. Int J Radiat Oncol Biol Phys 42, 751-753, 1998.

4. Milosevic MF, Fyles AW, Hill RP. The relationship between elevated interstitial fluid pressure and tumor blood flow: a bioengineering analysis. Int J Radiat Oncol Biol Phys 43, 1111-1123, 1999.

5. Milosevic M, Voruganti S, Blend R, Alasti H, Warde P, McLean M, Catton P, Catton C, Gospodarowicz M. Magnetic resonance imaging (MRI) for localization of the prostatic apex: comparison to computed tomography (CT) and urethrography. Radiother Oncol 47, 277-284, 1998.

6. Fyles A, Milosevic M, Hedley D, Pintilie M, Levin W, Manchul L, Hill R. Tumor hypoxia has independent predictor impact only in patients with node-negative cervix cancer. J Clin Oncol 20, 610-615, 2002.

7. Fyles A, Voduc D, Syed A, Milosevic M, Pintilie M, Hill R. The effect of smoking on tumour oxygenation and treatment outcome in cervical cancer. Clin Oncol 14, 442-446, 2002.

8. Haugland HK, Vukovic V, Pintilie M, Fyles A, Milosevic M, Hill RP, Hedley D. Expression of hypoxia-inducible factor-1a in cervical carcinomas: correlation with tumor oxygenation. Int J Radiat Oncol Biol Phys 53, 854-861, 2002.

9. Doll CM, Milosevic M, Pintilie M, Hill RP, Fyles AW. Estimating hypoxic status in human tumours: a simulation using Eppendorf oxygen probe data in cervix cancer patients. Int J Radiat Oncol Biol Phys 55, 1239-1246, 2003.

10. Tsang RW, Juvet S, Pintilie M, Milosevic M, Hill R, Wong CS, Chapman W, Fyles AW. Pretreatment proliferation parameters do not predict clinical outcome in cervical cancer treated with definitive radiation therapy. Clin Cancer Res 9, 4387-4395, 2003.

11. Hill RP, Fyles A, Milosevic M, Pintilie M, Tsang R. Is there a relationship between repopulation and hypoxia/reoxygenation? Results from human carcinoma of the cervix. Int J Radiat Biol, 79, 487-494, 2003.

12. Henderson E, Milosevic M, Haider M, Yeung IWT. Functional CT imaging of prostate cancer. Phys Med Biol, 48, 3085-3100, 2003.

13. Hedley D, Pintilie M, Woo J, Morrison A, Birle D, Fyles M, Milosevic M, Hill RP. Carbonic anhydrase IX expression, hypoxia and prognosis in patients with invasive uterine cervical carcinomas. Clin Cancer Res, 15 (Nov), 5666-5674, 2003.

14. Parker C, Milosevic M, Toi A, Sweet J, Panzarella T, Bristow R, Catton C, Catton P, Crook J, Gospodarowicz M, Maclean M, Warde P, Hill R. A polarographic electrode study of tumor oxygenation in localized prostate cancer. Int J Radiat Oncol Biol Phys, 58 (Mar), 750-757, 2004.

15. Hedley DH, Pintilie M, Woo J, Nicklee, T, Morrison A, Birle D, Fyles A, Milosevic M, Hill RP. Upregulation of the redox mediators thioredoxin and APE/Ref-1 in hypoxic Microregions of invasive cervical carcinomas, mapped using multispectral, wide field fluorescence image analysis. Am J Pathol, 164 (Feb), 557-565, 2004.

16. Chan P, Milosevic M, Fyles A, Carson J, Pintilie M, Rauth M, Thomas G. A phase III randomized study of misonidazole vs. radiation alone for cervix cancer. Radiother Oncol, 70 (Mar), 295-299, 2004.

17. Milosevic M, Fyles A, Hedley D, Hill R. The human tumor microenvironment: invasive (needle) measurement of oxygen and interstitial fluid pressure (IFP). Sem Radiat Oncol, 14(3), 249-258, 2004.

18. Khosravani H, Chugh B, Milosevic M, Norwich K. Time response of interstitial fluid pressure measurements in cervix cancer. Microvasc Res, 68(1), 63-70, 2004.

19. Hedley DW, Nicklee T, Moreno-Merlo, F, Pintilie M, Fyles A, Milosevic M, Hill RP. Relations between non-protein sulfydryl levels in the nucleus and cytoplasm, tumor oxygenation, and clinical outcome of patients with uterine cervical carcinoma. Int J Radiat Oncol Biol Phys. 2005 Jan 1;61(1):137-44.

20. Dinniwell R, Lock M, Pintilie M, Fyles A, Laframboise S, DePetrillo D, Levin W, Manchul L, Murphy J, Oza A, Rosen B, Sturgeon J, Milosevic M. Consolidative abdomino-pelvic radiotherapy (APRT) following surgery and carboplatin/paclitaxel chemotherapy for epithelial ovarian cancer. Int J Radiat Oncol Biol Phys, 64(1), 104-110, 2005.

21. Haider MA, Milosevic M, Fyles A, Sitartchouk I, Yeung I, Henderson E, Roberts TPL, Lockwood G, Lee, TY. Assessment of the tumor microenvironment in cervix cancer using dynamic contrast enhanced CT, interstitial fluid pressure and oxygen measurements. Int J Radiat Oncol Biol Phys, 62(5), 1100-1107, 2005.

22. Bachtiary B, Dewitt A, Pintilie M, Jezioranski J, Ahonen S, Levin W, Manchul L, Yeung I, Milosevic M, Fyles A. Comparison of late toxicity between continuous low-dose-rate and pulsed-dose-rate brachytherapy in cervical cancer patients. Int J Radiat Oncol Biol Phys, In press 2005.