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[en] Purpose. To clarify the radiosensitivity of intratumor total and quiescent (Q) cells in vivo to accelerated carbon ion beams compared with γ-ray irradiation. Materials and methods. SCC VII tumor-bearing mice received a continuous administration of 5-bromo-2'-deoxyuridine (BrdU) to label all intratumor proliferating (P) cells. Then they received 290 MeV/u carbon ions or γ-rays. Immediately or 12 hours after the irradiation, the radiosensitivity of Q cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. That of the total (=P+Q) tumor cells was determined from the BrdU non-treated tumors based on the micronucleus frequency and clonogenic cell survival. Results. The apparent difference in radiosensitivity between total and Q cell populations under γ-ray irradiation was markedly reduced with carbon ion beam, especially with a higher linear energy transfer (LET) value. Clearer repair in Q cells than total cells through delayed assay under ?-ray irradiation was efficiently inhibited with carbon ion beams, especially with a higher LET. Conclusion. In terms of tumor cell-killing effect as a whole, including intratumor Q cells, carbon ion beams, especially with higher LET values, were very useful for suppressing the dependency on the heterogeneity within solid tumors as well as depositing radiation dose precisely
[en] Tumour hypoxia is one of the limiting factors in obtaining tumour control in radiotherapy. The high-LET region of a beam of heavy charged particles such as carbon ions is located in the distal part of the Bragg peak. A modulated or spread out Bragg peak (SOBP) is a weighted function of several Bragg peaks at various energies, which however results in a dilution of the dose-average LET in the target volume. Here, we investigate the possibility to redistribute the LET by dedicated treatment plan optimisation, in order to maximise LET in the target volume. This may be a strategy to potentially overcome hypoxia along with dose escalation or dose painting. The high-LET region can be shaped in very different ways, while maintaining the distribution of the absorbed dose or biological effective dose. Treatment plans involving only carbon ion beams, show very different LET distributions depending on how the fields are arranged. Alternatively, a LET boost can be applied in multi-modal treatment planning, such as combining carbon ions with protons and/or photons. For such mixed radiation modalities, significant 'LET boosts' can be achieved at nearly arbitrary positions within the target volume. Following the general understanding of the relationship between hypoxia, LET and the oxygen enhancement ratio (OER), we conclude, that an additional therapeutic advantage can be achieved by confining the high-LET part of the radiation in hypoxic compartments of the tumour, and applying low-LET radiation to the normoxic tissue. We also anticipate that additional advantages may be achieved by deliberate sparing of normal tissue from high LET regions. Consequently, treatment planning based on simultaneous dose and LET optimisation has a potential to achieve higher tumour control and/or reduced normal tissue control probability (NTCP).
[en] For dose delivery to patients, scanning ion beams are going to be increasingly used in the upcoming ion beam therapy facilities. Especially carbon ion beams are able to produce steep dose gradients. However, the currently used method for patient dose verification, employing ionization chamber arrays, provides a spatial resolution of 1 cm only. As continuous media, EBT films, widely used in photon therapy, are interesting candidates to be used for this purpose. The EBT film is the ancestor of the currently available EBT2 film. In our contribution two dimensional dosimetry and film response quenching in ion beams were investigated. For a real 12C patient plan a good qualitative agreement with the planned dose distribution including a high signal-to-noise ratio and a good resolution in the measured photon-equivalent dose was found. The depth-dose response of EBT films for a 12C ion beam shows response quenching, which rises towards the Bragg peak. It was quantified by the relative efficiency determined at different depths. Furthermore, the relative efficiency was measured in monoenergetic proton and carbon ion beams. All the measured efficiencies show no significant dependency on the dose up to the highest measured doses of 6 Gy. However, differences between proton and carbon ions as well as between carbon ion beams of different energies were observed. The measurements reveal, that the use of EBT films for absolute dose verification measurements requires to take the relative efficiency into account, dependent on the ion type and energy.
[en] New charged particle accelerators for radiotherapy applications are currently being discussed and designed. Thus, the question of which particle beams are optimal for specific clinical applications needs to be investigated. Dose localization plays an important role in treatment. Theoretical considerations based on multiple scattering theories indicate that carbon beams have better dose localization properties than proton beams because heavier charged particles scatter less than lighter ones. We have measured dose distributions produced by narrowly collimated carbon and proton beams using an identical experimental setup thus allowing a direct comparison. 3 figs