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

Abstract

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.

In response to the comments to the paper ‘Modelling of cell killing due to sparsely ionizing radiation in normoxic and hypoxic conditions and an extension to high LET radiation’ by T. Friedrich et al.

“…We do not understand why Friedrich et al claim that our Figure 1 should intriguingly suggest an equivalence between the a and b values from Suzuki et al (2000) and Combs et al (2009) and the values derived from the new model. Differences in the LQ parameters which Friedrich et al noted between the linear quadratic (LQ) parameters published in the original experimental papers (Suzuki et al 2000, Combs et al 2009) and the K iDSB and K cDSB values we reported in Table I and Figure 5 of Mairani et al (2013a) can be mostly explained by the fact that we factored in the non-uniform uncertainties of the experimental data points in our fits.…”

“…Differences in the LQ parameters which Friedrich et al noted between the linear quadratic (LQ) parameters published in the original experimental papers (Suzuki et al 2000, Combs et al 2009) and the K iDSB and K cDSB values we reported in Table I and Figure 5 of Mairani et al (2013a) can be mostly explained by the fact that we factored in the non-uniform uncertainties of the experimental data points in our fits. Details of the fitting procedure were not discussed in our original publication as they are, as we will show, not of principal concern for demonstrating the validity of the proposed model, and particularly in view of the initial modelling stage and rough accuracy which we claimed in our publication for high LET radiation.…”

“…Firstly, this choice was motivated by the fact that by fitting both models using a unique approach, we could assure that we are focusing on differences in our model and the LQ model, rather than differences in different fitting approaches, as exemplified by the results of Friedrich et al (2014). Secondly, Suzuki et al (2000) and Combs et al (2009) reported only that the data are fitted by the least squares method to a linear-quadratic equation without giving further details. We believe that if we want to properly estimate the biological effect of high LET radiation in future one should take into account the often substantial uncertainties in the experimental data points when fitting sparsely ionizing radiation.…”

“Broadbeam” irradiation of mammalian cells using a vertical microbeam facility

“…To calculate the dose rate given to cell nuclei, the following formula adapted from Belli et al (1989) and Combs et al (2009) was used:…”

Knockdown of Checkpoint Kinase 1 Is Associated with the Increased Radiosensitivity of Glioblastoma Stem-Like Cells

“…Despite gross tumor resection or debulking, postoperative radiation therapy and chemotherapeutic treatment, most of the patients died in two years (Laperriere et al 2002;Combs et al 2009). Nevertheless, radiotherapy is still one of the most important methods for GBM (WHO IV) (Legler et al 1999;Bache et al 2011).…”