Abstract
BackgroundTo evaluate the cytotoxic effect of carbon ion radiotherapy and chemotherapy in glioblastoma cells in vitro.Methods and MaterialsThe human glioblastoma (GBM) cell line U87 was irradiated with photon radiotherapy (RT) doses of 2 Gy, 4 Gy and 6 Gy. Likewise, irradiation with carbon ions was performed with single carbon doses of 0.125, 0.5, 2 and 3 Gy. Four chemotherapeutic substances, camptothecin, gemcitabine, paclitaxel and cisplatinum, were used for single and combination experiments. The assessment of the effect of single and double treatment on cell viability was performed using the clonogenic growth assay representing the radiobiological gold standard.ResultsThe RBE of carbon ions ranges between 3.3 and 3.9 depending on survival level and dose. All chemotherapeutic substances showed a clear does-response relationhips. in their characteristic concentrations. For subsequent combination experiments, two dose levels leading to low and medium reduction of cell survival were chosen. Combination experiments showed additive effects independently of the drugs' mechanisms of action. Paclitaxel and campthothecin demonstrated the most prominent cytotoxic effect in combination with carbon ion radiotherapy.ConclusionIn conclusion, combination of carbon ion radiotherapy with chemotherapies of different mechanisms of action demonstrates additive effects. The most dominant effect was produced by paclitaxel, followed by camptothecin, as espected from previously published work. The present data serve as an important radiobiological basis for further combination experiments, as well as clinical studies on combination treatments.
Highlights
To evaluate the cytotoxic effect of carbon ion radiotherapy and chemotherapy in glioblastoma cells in vitro
The most dominant effect was produced by paclitaxel, followed by camptothecin, as espected from previously published work
The present data serve as an important radiobiological basis for further combination experiments, as well as clinical studies on combination treatments
Summary
To evaluate the cytotoxic effect of carbon ion radiotherapy and chemotherapy in glioblastoma cells in vitro. In spite of extensive research, current outcome after the Particle radiotherapy, such as proton or carbon ion radiation, offers distinct physical characteristics leading to a more conformal dose distribution: Due to the inverted dose profile with low dose deposition in the entry channel of the beam, and high local doses in the so called Bragg Peak, normal tissue surrounding the tumor area can be spared, and the integral dose to the patient can be reduced. Several in vitro studies including our own work have shown that, for GBM, the RBE of carbon ions is between 3 and 5, depending on the cell line and the endpoint [7,8,9]. Comparable to radiochemotherapy with protons, we could show that combination of carbon ions and TMZ lead to an additive effect with respect to cytotoxicity [7]
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