TP6 preclinical studies on the effect of heavy ions on normal tissue and hypoxic tumor tissue
Compared to photons, protons and heavy ions show an inverted depth dose profile (Bragg-peak) which is ideal for conformal irradiation of critically situated tumors. Unlike protons, heavy ions show a higher biologic effectiveness at the distal end of their range (peak area) than in their entry zone (plateau area). This can be explained by the rising linear energy transfer (LET) with tissue penetration of heavier ions. This feature of heavy ions can be exploited to increase the biologically effective dose in the tumor relative to normal tissue (α/β). The increased biological effectiveness of heavy ions stems from the lower doses required for the same effect compared to iso-effective doses of photons and thus is referred to as relative biologic effectiveness (RBE).
The RBE is a very complex parameter that depends on ion type, LET, dose, tissue type and the desired biological endpoint. Since treatment planning for heavy ions is calculated with RBE * physical dose (in GyE) it is necessary to calculate doses for clinical applications for every point in the patient using mathematical models. For the raster scan method developed at GSI that we use at the HIT, the RBE calculations are performed with the Local effect Modell (LEM). For passive irradiation techniques as applied in other centers, analogous RBE models are applied.
The aim of this project is to systematically and quantitatively investigate the effect of heavy ions irradiation on normal and tumor tissue. Toward this goal we are addressing the following questions:
- How exact ist the RBE local effect model we use for treatment planning?
- Existiert für Schwerionenbestrahlungen ein klinisch nutzbarer differentieller Effekt zwischen Tumor- und Normalgewebe?
- Is there a differential effect (α/β value) between normal and tumor tissue after irradiation with heavy ions that can be exploited clinically?
- May irradiation with heavy ions overcome radio resistance of hypoxic tumors?
- Was sind die zugrunde liegenden Mechanismen einer hoch-LET- im Vergleich zu einer Photonen-Bestrahlung?
- What are the underlying mechanisms of high-LET irradiation in comparison to photon (low-LET) irradiation?
Saager M, Glowa C, Peschke P, Brons S, Grün R, Scholz M, Huber PE, Debus J, Karger CP. Split dose carbon ion irradiation of the rat spinal cord: Dependence of the relative biological effectiveness on dose and linear energy transfer. Radiother Oncol. 2015 Jul 18
Saager M, Glowa C, Peschke P, Brons S, Scholz M, Huber PE, Debus J, Karger CP. Carbon ion irradiation of the rat spinal cord: dependence of the relative biological effectiveness on linear energy transfer. Int J Radiat Oncol Biol Phys. 2014 Sep 1;90(1):63-70
Karger CP, Scholz M, Huber PE, Debus J, Peschke P. Photon and carbon ion irradiation of a rat prostate carcinoma: does a higher fraction number increase the metastatic rate? Radiat Res. 2014 Jun;181(6):623-8
Karger CP, Peschke P, Scholz M, Huber PE, Debus J. Relative biological effectiveness of carbon ions in a rat prostate carcinoma in vivo: comparison of 1, 2, and 6 fractions. Int J Radiat Oncol Biol Phys. 2013 Jul 1;86(3):450-5
Peschke P, Karger CP, Scholz M, Debus J, Huber PE. Relative biological effectiveness of carbon ions for local tumor control of a radioresistant prostate carcinoma in the rat. Int J Radiat Oncol Biol Phys. 2011 Jan 1;79(1):239-46
Schlampp I, Karger CP, Jäkel O, Scholz M, Didinger B, Nikoghosyan A, Hoess A, Krämer M, Edler L, Debus J, Schulz-Ertner D. Temporal lobe reactions after radiotherapy with carbon ions: incidence and estimation of the relative biological effectiveness by the local effect model. Int J Radiat Oncol Biol Phys. 2011 Jul 1;80(3):815-23