The Mayo Clinic Florida Microdosimetric Kinetic Model of Clonogenic Survival: Application to Various Repair-Competent Rodent and Human Cell Lines

Abstract

The relative biological effectiveness (RBE) calculations used during the planning of ion therapy treatments are generally based on the microdosimetric kinetic model (MKM) and the local effect model (LEM). The Mayo Clinic Florida MKM (MCF MKM) was recently developed to overcome the limitations of previous MKMs in reproducing the biological data and to eliminate the need for ion-exposed in vitro data as input for the model calculations. Since we are considering to implement the MCF MKM in clinic, this article presents (a) an extensive benchmark of the MCF MKM predictions against corresponding in vitro clonogenic survival data for 4 rodent and 10 cell lines exposed to ions from 1H to 238U, and (b) a systematic comparison with published results of the latest version of the LEM (LEM IV). Additionally, we introduce a novel approach to derive an approximate value of the MCF MKM model parameters by knowing only the animal species and the mean number of chromosomes. The overall good agreement between MCF MKM predictions and in vitro data suggests the MCF MKM can be reliably used for the RBE calculations. In most cases, a reasonable agreement was found between the MCF MKM and the LEM IV.

A methodology to abridge microdosimetric distributions without a significant loss of the spectral information needed for the RBE computation in carbon ion therapy

“…In this work, this was done by processing the obtained distributions with Equation ( 5) using the cell-specific weighting functions shown in Figure 1c.This approach (processing entire microdosimetric distributions with the MCF MKM) was proven to provide accurate RBE predictions for very different exposure conditions and cell lines. [6][7][8] However, its clinical application is hindered by the relatively large amount of data (300 bins) to be stored in each voxel (i.e., 1 × 1 × 1 mm 3 ) for a realistic patient scenario.…”

“…It should be mentioned that, differently from other MKMs, 5 the MCF MKM also includes an expression to describe the decrease of β at high LET. [6][7][8] The MCF MKM relies on novel strategies [6][7] based on morphological and karyotypical measurements to determine a priori the cell-specific values of R n and r d . Consequently, the only in vitro data needed for the ion RBE calculations is the dose-response of the cell after the reference photons.…”

“…These cell lines were chosen for their clinical relevance and their different radiosensitivity. The validated [6][7] MCF MKM parameters are summarized in Table 1.For the NB1RGB cell line, these parameters are meant to be representative of the average radiosensitivity of the cell line over the different published experiments. 7 For consistency between the two cell lines, the α ref values needed for the calculation of RBE α were simulated for the same reference radiation, namely 6 MV x-rays.…”

“…The validated [6][7] MCF MKM parameters are summarized in Table 1.For the NB1RGB cell line, these parameters are meant to be representative of the average radiosensitivity of the cell line over the different published experiments. 7 For consistency between the two cell lines, the α ref values needed for the calculation of RBE α were simulated for the same reference radiation, namely 6 MV x-rays. These α ref values differ from the ones experimentally assessed using other photon qualities (200 kVp for the HSG cell line and different photon qualities for the NB1RGB cell line).…”

“…The fraction of absorbed dose deposited by lineal energy events within the bin j is named Δ bin j and it is calculated with Equation (7).…”