Radiobiological evaluation and correlation with the local effect model (LEM) of carbon ion radiation therapy and temozolomide in glioblastoma cell lines.

PURPOSE: To investigate the cytotoxic effect of high linear-energy transfer (LET) carbon irradiation on glioblastoma cells lines in combination with temozolomide (TMZ). METHODS AND MATERIALS: The cell lines U87-MG expressing wild-type p53 and LN229 expressing both mutant and wild-type p53 were irradiated with monoenergetic carbon ion beams (LET 172 keV/microm) or an extended Bragg peak (LET 103 keV/microm) after treatment with 10 microM or 20 microM TMZ. Cytotoxicity was measured by a clonogenic survival assay, and cell growth as well as cell cycle progression, were examined. RESULTS: The p53 mutant was more sensitive to X-ray irradiation than the p53 wild type cell line, which was also expressed in a shorter G2 block. High LET carbon ions show an increased biological effectiveness in both cell lines, which is consistent with the predictive calculations by the Local Effect Model (LEM) introduced by Scholz et al. The cell line LN229 was more sensitive to TMZ treatment than the U87MG cell line expressing wild-type p53 only. The combination of TMZ and irradiation showed an additive effect in both cell lines. CONCLUSION: High LET carbon ion irradiation is significantly more effective for glioblastoma cell lines compared to photon irradiation. An additional treatment with TMZ may offer a great chance especially for several tumor types.

Quantification of the relative biological effectiveness for ion beam radiotherapy: direct experimental comparison of proton and carbon ion beams and a novel approach for treatment planning.

PURPOSE: To present the first direct experimental in vitro comparison of the biological effectiveness of range-equivalent protons and carbon ion beams for Chinese hamster ovary cells exposed in a three-dimensional phantom using a pencil beam scanning technique and to compare the experimental data with a novel biophysical model. METHODS AND MATERIALS: Cell survival was measured in the phantom after irradiation with two opposing fields, thus mimicking the typical patient treatment scenario. The novel biophysical model represents a substantial extension of the local effect model, previously used for treatment planning in carbon ion therapy for more than 400 patients, and potentially can be used to predict effectiveness of all ion species relevant for radiotherapy. A key feature of the new approach is the more sophisticated consideration of spatially correlated damage induced by ion irradiation. RESULTS: The experimental data obtained for Chinese hamster ovary cells clearly demonstrate that higher cell killing is achieved in the target region with carbon ions as compared with protons when the effects in the entrance channel are comparable. The model predictions demonstrate agreement with these experimental data and with data obtained with helium ions under similar conditions. Good agreement is also achieved with relative biological effectiveness values reported in the literature for other cell lines for monoenergetic proton, helium, and carbon ions. CONCLUSION: Both the experimental data and the new modeling approach are supportive of the advantages of carbon ions as compared with protons for treatment-like field configurations. Because the model predicts the effectiveness for several ion species with similar accuracy, it represents a powerful tool for further optimization and utilization of the potential of ion beams in tumor therapy.

Neoplastic transformation induced by carbon ions.

PURPOSE: The objective of this experiment was to compare the oncogenic potential of carbon ion beams and conventional photon beams for use in radiotherapy. METHODS AND MATERIALS: The HeLa X human skin fibroblast cell line CGL1 was irradiated with carbon ions of three different energies (270, 100, and 11.4 MeV/u). Inactivation and transformation data were compared with those for 15 MeV photons. RESULTS: Inactivation and transformation frequencies for the 270 MeV/u carbon ions were similar to those for 15-MeV photons. The maximal relative biologic effectiveness (RBE(alpha)) values for 100MeV/u and 11.4 MeV/u carbon ions, respectively, were as follows: inactivation, 1.6 +/- 0.2 and 6.7 +/- 0.7; and transformation per surviving cell, 2.5 +/- 0.6 and 12 +/- 3. The curve for dose-transformation per cell at risk exhibited a maximum that was shifted toward lower doses at lower energies. CONCLUSIONS: Transformation induction per cell at risk for carbon ions in the entrance channel was comparable to that for photons, whereas for the lower energies, 100 MeV/u and 11 MeV/u, which are representative of the energies delivered to the tumor margins and volume, respectively, the probability of transformation in a single cell was greater than it was for photons. In addition, at isoeffective doses with respect to cell killing, the 11.4-MeV/u beam was more oncogenic than were photons.