Abstract
Radiotherapy of solid tumors with charged particles holds several advantages in comparison to photon therapy; among them conformal dose distribution in the tumor, improved sparing of tumor-surrounding healthy tissue, and an increased relative biological effectiveness (RBE) in the tumor target volume in the case of ions heavier than protons. A crucial factor of the biological effects is DNA damage, of which DNA double-strand breaks (DSBs) are the most deleterious. The reparability of these lesions determines the cell survival after irradiation and thus the RBE. Interestingly, using phosphorylated H2AX as a DSB marker, our data in human fibroblasts revealed that after therapy-relevant spread-out Bragg peak irradiation with carbon ions DSBs are very efficiently rejoined, despite an increased RBE for cell survival. This suggests that misrepair plays an important role in the increased RBE of heavy-ion radiation. Possible sources of erroneous repair will be discussed.
Highlights
Radiotherapy is an indispensable tool for treating solid tumors [1]
Following the one-field irradiation with a 4-cm spread-out Bragg peak (SOBP) of carbon ions in a water-equivalent depth of 6–10 cm, the survival data obtained for confluent, human fibroblasts show the expected depth profile with higher survival levels in the entrance channel (EC) and a decline of cell survival in the target SOBP region, yielding a region with clearly reduced cell survival compared to the EC (Figure 1C)
Aimed at mimicking a therapy-like configuration, we studied the double-strand breaks (DSBs)-repair capacity of confluent (G0/G1-phase) human fibroblasts upon a two-field SOBP carbon-ion irradiation
Summary
Radiotherapy is an indispensable tool for treating solid tumors [1]. Advances in conventional radiation therapy with photons and especially new approaches using charged particles have led to an improved physical delivery of dose in radiation therapy [2,3,4]. Irradiation with accelerated ions heavier than protons, namely carbon ions, has additional advantage as it is characterized by an increased relative biological effectiveness (RBE) in the targeted tumor volume [4]. This allows the irradiation of deep-seated tumors, minimizing at the same time the dose to normal tissue or in organs at risk [2]. Accelerated ions of a linear energy transfer (LET) of >10 keV/μm are considered high-LET radiation Due to their characteristic energy deposition within a confined volume, they cause DNA damage of greater complexity [5,6,7].
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