Prof. Valentin Djonov

Institute of Anatomy, University of Bern

Title: How microbeam technology could change the radiooncology treatment

Abstract

Introduction: Microbeam-Radiation-Therapy (MRT) is a type of spatially fractionated radiation therapy which modulates the radiation dose on a micrometre scale. This unique dose distribution makes MRT highly efficient even for the treatment of radioresistant tumours.

Results: In murine B16-F10 melanoma model, temporally fractionated MRT completely ablated 50% of tumors and prevented organ metastases and local recurrences for 18-months after treatment. In mouse glioblastoma model, MRT in combination with cisplatin reduced tumor volume 6-fold compared with cisplatin alone and 60-fold compared with untreated mice.

The radiation biology underlying the “MRT effect” include novel radiobiological mechanisms: (1) Induction of selective vascular disruption of immature tumor vasculature or transient vascular permeability in a dose-dependent manner (2) Direct cellular damage in the microbeam path that elicits tissue-specific responses. (3) Induction of a unique, tumor-targeted immune response leading to local and systemic anti-tumor immune responses including infiltration of cytotoxic lymphocytes.

Discussion: spatially fractionated MRT demonstrated one best treatment outcome ever achieved in preclinical models. MRT provides a novel mechanism for drug delivery by increasing vascular transpermeability while preserving vessel integrity and in addition is busting the anti-tumor immune response. These unique features support MRT as a novel therapeutic approach for the treatment of inoperable, radioresistant lesions.

Keywords: cancer treatment, spatially fractionated radiotherapy, cell death, micro beams, vascular permeability

Biography

After several years in neuro- and general surgery, in 1992 V. Djonov entered a research position in the Department of Clinical Research at the University of Bern, Switzerland.
In 1996 he became a research assistant in the Division of Developmental Biology within the Institute of Anatomy, Bern. This was followed by his habilitation (assistant professorship) in 2002 followed by associate professor in 2006 at the same institute.
In September 2007, V. Djonov was promoted to full professor and became co-director of the Institute of Anatomy in Fribourg, Switzerland. After a period of 3 years, he returned to Berne where he is currently the director of the Institute of Anatomy and medical advisor at the translational research center SITEM, Switzerland.

The main scientific interest of his group is the radio-biological effects induced by Spatially Fractionated Radiation Therapy (SFRT). SFRT is a novel radiotherapy technique using spatially fractionated X-rays to produce alternating regions of high and low dose deposition in the target tissue. This results in unique radiation/tissue interactions that expands the therapeutic index of radiation therapy by increasing tumor control, including that of radioresistant malignancies, while simultaneously exhibiting remarkable normal tissue sparing even when delivering peak doses of hundreds of Grays. SFRT demonstrated first promising results by treatment of inoperable, radioresistant lesions in human and pet patients.

Valentin Djonov is the author of more than 300 scientific papers with more than 16’000 citations (h-index=65) and numerous patents.