SCK•CEN

Dosimetry study

In the history of radiation therapy there are many examples of how cure rates have been increased through improvements in physical dose distribution and the resulting increase in feasible tumor dose. In many cases, however, an exact fit of the irradiated volume to the target volume is impossible due to the physical characteristics of the gamma rays or electron-bremsstrahlung used in therapy. After a short buildup, the dose progressively decreases at greater depth.

Beams of charged particles (protons or ions) produce a much more favorable dose distribution.

For protons and ions, the delivered dose increases at greater depth, and then declines abruptly beyond a sharply defined maximum known as the Bragg peak. The location of this maximum in the patient’s body can be precisely determined by the energy of the particles. In addition, protons and ions exhibit a small lateral and range scattering, which is another prerequisite for achieving a tumor conform treatment. These physical properties of charged-particle beams make it possible to substantially increase the tumor dose while at the same time reducing the integral dose in healthy tissues.

In addition to the favorable physical dose distribution, a specific high-LET effect becomes effective in the case of ions as distinct from protons. This manifests itself by an increase of the relative biological effectiveness (RBE) that in turn allows higher curative success rates for well defined indications. Amongst these indications are hypoxic tumors, slowly growing tumors, and tumors being less or almost non-responsive to conventional photon therapy.

Conclusion

As a result of its high precision and the specific high-LET effect, radiation therapy with ions is recognized as the treatment of choice for slowgrowing, inoperable, radiation resistant tumors (e.g., chordomas and chondrosarcomas), especially in the vicinity of high-risk organs like the brain stem, optic nerve or spinal chord.

Biological study

Minimizing uncertainty on healthy tissue response to protons and carbon ions is necessary to expand the applications of hadrontherapy in curing cancer. It is planned to compare the biological effects of protons and carbon ions with X-rays in different normal versus cancer tissue cells (central nervous system, lung, gastrointestinal, haemotopoietic) using in vitro models and to transfer the experimental results in mathematical models used in the treatment planning for protons and carbon ions. In vitro experiments are necessary to understand the biological mechanisms involved in the effects of protons and carbon ions.

Within the Radiobiology Unit, in vitro experiments (using normal and cancer cells) are performed to assess the biological advantages of hadrontherapy over conventional radiotherapy with photons. Fundamental research can contribute in gaining more insight into clinical effects including individual sensitivity, toxicity of normal tissues, induction of secondary malignancies and metastasis.

The Radiobiology Unit performs research on three different topics related to hadrontherapy.

  • Project 1: A contribution to the biological study of the response of prostate and colon cells to carbon ion irradiation. The main objective of this project is to investigate differences in the in vitro biological response of prostate and colon cells (normal and cancer cells), exposed to charged particles and conventional X-rays, in order to decipher potential quantitative and qualitative differences. Emphasis is placed on changes in gene expression, DNA damage, cell survival and cell cycle changes.
  • Project 2: Toxicity of normal tissues. Within this project the potential differences in toxicity of normal tissues (human endothelial cells lining the blood vessels) after exposure to different radiation qualities is studied. A focus is placed on DNA damage and apoptosis (cell death), cell cycle effects, and high-throughput gene expression.
  • Project 3: Identification of biomarkers for exposure and for predicting individual sensitivity to charged particles radiation. Identification of robust and reliable radiation biomarkers is one of the main concerns of current radiobiological research. This project aims at identifying new biomarkers for radiation exposure to low- and high-LET radiation. A focus is placed on the use of gene, exon and/or cytokine expression signatures in human white blood cells. These data will be integrated with those from DNA damage/repair kinetics in order to identify biomarkers of individual radiosensitivity.

In order to perform experiments with accelerated charged particles, all three radiobiological projects are dependent on beam time provided by the available accelerator facilities in Belgium (FUNDP, Namur) as well as Europe including GSI (Germany) and GANIL (France). To compare the effects between high-LET and low-LET, similar experiments with X-rays (250 keV maximal energy, 15 mA) are performed at SCK•CEN or, when possible, on site of the accelerator facility.