Biologically Effective Dose (BED) or Radiation Biological Effect (RBEf)?

The current radiosensitive studies are described with linear-quadratic (LQ) cell survival (S) model for one fraction with a dose d. As result of assuming all sublethally damaged cells (SLDCs) are completely repaired during the interfractions, that is, no presence of SLDCs, the survived cells are calculated for a n-fractionated regimen with the LQ S(n,D) model. A mathematically processed subpart of LQS(n,D) is the biologically effective dose (BED) that is used for evaluating a so-called “biological dose.” The interactions of ionizing radiation with a living tissue can produce partial death or sublethal damage from healthy or sublethally damaged cells. The proportions of the killed and sub-lethally damaged cells define the radiation biological effects (RBEfs). Computational simulations using RBEFs for fractionated regimens let calculating tumor control probability. While the derivation of the LQ S(n,D) considers a 100% cell repair, that is, 0% of sublethally damaged cells (SLDCs), the radiobiological simulators take into account the presence of SLDCs, as well as a cell repair <100% during the interfractions and interruption. Given “biological dose” does not exist, but RBEf, there was need for creating the BED. It is shown how some uses of BED, like the derivation of EQ2D expression, can be done directly with the LQ S(n,D)

The use of the normal tissue non-complication probability (NTCP0) methodology as a new alternative of assessing side-effects in brachytherapy treatments

Background: The NTCP methodology evaluating side-effects (S-Es) was initially used in radiotherapy (RT), and later was extended to brachytherapy (BT). The NTCP0 methodology has been recently introduced in RT. Given the advantages, this methodology could replace NTCP. Materials and methods: Revisions of studies related to use of NTCP in the evaluations of S-Es in BT. Development of the first versions of two Matlab applications of the NTCP0 methodology. These applications have three options. Two of them employ the well-known aspects of a phenomenological model, or the probabilistic relationship between NTCP0 and total NTCP (TNTCP) that is the sum(NTCP(xi)) i: ith complication i:1..nc: Number of complications; where NTCP0 = 100% – TNTCP; and the third option assumes a NTCP(xi) discrete probabilistic distribution generated by the binomial distribution, where one of its parameters is automatically obtained from a databased of the Disease locations Vs. Late complications. Results: The NTCP0cal and NTCP0calDr Matlab applications have been developed, and respectively used for fractional continuous low dose-rate BT. Conclusions: NTCP0 is defined as the ratio of the number of patients without acute/late complications and total of them, and also can be obtained using our Matlab applications. NTCP0 works do not disregard the last 10–15 years of NTCP research; but NTCP0 was not considered during these years. A generic example was used for showing the variations of the late complications and NTCP0 for a BT treatment of a constant number of fractions and six different dose per fraction values

Accurate,robust and harmonized implementation of morpho-functional imaging in treatment planning for personalized radiotherapy

In this work we present a methodology able to use harmonized PET/CT imaging in dose painting by number (DPBN) approach by means of a robust and accurate treatment planning system. Image processing and treatment planning were performed by using a Matlab-based platform, called CARMEN, in which a full Monte Carlo simulation is included. Linear programming formulation was developed for a voxel-by-voxel robust optimization and a specific direct aperture optimization was designed for an efficient adaptive radiotherapy implementation. DPBN approach with our methodology was tested to reduce the uncertainties associated with both, the absolute value and the relative value of the information in the functional image. For the same H&N case, a single robust treatment was planned for dose prescription maps corresponding to standardized uptake value distributions from two different image reconstruction protocols: One to fulfill EARL accreditation for harmonization of [18F]FDG PET/CT image, and the other one to use the highest available spatial resolution. Also, a robust treatment was planned to fulfill dose prescription maps corresponding to both approaches, the dose painting by contour based on volumes and our voxel-by-voxel DPBN. Adaptive planning was also carried out to check the suitability of our proposal. Different plans showed robustness to cover a range of scenarios for implementation of harmonizing strategies by using the highest available resolution. Also, robustness associated to discretization level of dose prescription according to the use of contours or numbers was achieved. All plans showed excellent quality index histogram and quality factors below 2%. Efficient solution for adaptive radiotherapy based directly on changes in functional image was obtained. We proved that by using voxel-by-voxel DPBN approach it is possible to overcome typical drawbacks linked to PET/CT images, providing to the clinical specialist confidence enough for routinely implementation of functional imaging for personalized radiotherapy.Junta de Andalucía (FISEVI, reference project CTS 2482)European Regional Development Fund (FEDER

The use of the normal tissue non-complication probability (NTCP0) methodology as a new alternative of assessing side-effects in brachytherapy treatments.

The NTCP methodology evaluating side-effects (S-Es) was initially used in radiotherapy (RT), and later was extended to brachytherapy (BT). The NTCP0 methodology has been recently introduced in RT. Given the advantages, this methodology could replace NTCP. Revisions of studies related to use of NTCP in the evaluations of S-Es in BT. Development of the first versions of two Matlab applications of the NTCP0 methodology. These applications have three options. Two of them employ the well-known aspects of a phenomenological model, or the probabilistic relationship between NTCP0 and total NTCP (TNTCP) that is the sum(NTCP(xi)) i: ithcomplication i:1..nc: Number of complications; where NTCP0 = 100% - TNTCP; and the third option assumes a NTCP(xi) discrete probabilistic distribution generated by the binomial distribution, where one of its parameters is automatically obtained from a databased of the Disease locations Vs. Late complications. The NTCP0cal and NTCP0calDr Matlab applications have been developed, and respectively used for fractional continuous low dose-rate BT. NTCP0 is defined as the ratio of the number of patients without acute/late complications and total of them, and also can be obtained using our Matlab applications. NTCP0 works do not disregard the last 10-15 years of NTCP research; but NTCP0 was not considered during these years. A generic example was used for showing the variations of the late complications and NTCP0 for a BT treatment of a constant number of fractions and six different dose per fraction values

Implications of the Harmonization of [18F]FDG-PET/CT Imaging for Response Assessment of Treatment in Radiotherapy Planning

The purpose of this work is to present useful recommendations for the use of [F]FDG-PET/CT imaging in radiotherapy planning and monitoring under different versions of EARL accreditation for harmonization of PET devices. A proof-of-concept experiment designed on an an-thropomorphic phantom was carried out to establish the most suitable interpolation methods of the PET images in the different steps of the planning procedure. Based on PET/CT images obtained by using these optimal interpolations for the old EARL accreditation (EARL1) and for the new one (EARL2), the treatment plannings of representative actual clinical cases were calculated, and the clinical implications of the resulting differences were analyzed. As expected, EARL2 provided smaller volumes with higher resolution than EARL1. The increase in the size of the reconstructed volumes with EARL1 accreditation caused high doses in the organs at risk and in the regions adjacent to the target volumes. EARL2 accreditation allowed an improvement in the accuracy of the PET imaging precision, allowing more personalized radiotherapy. This work provides recommendations for those centers that intend to benefit from the new accreditation, EARL2, and can help build confidence of those that must continue working under the EARL1 accreditation.Project P20_01053 funded by the European Union and the Junta de Andalucía through the European Regional Development Fund (FEDER)

A robust Monte Carlo treatment planning optimization algorithm for dose painting clinical implementation

[Purpose] In order to start accurate clinical trials based on treatments more aggressive than traditional margin approaches, a robust optimization algorithm has been developed for dose calculation full Monte Carlo-based. Specifically, the algorithm is presented here to manage uncertainties on dose painting from PET/CT image data. [Material and Methods] CARMEN platform was updated to allow heterogeneous dose prescription by means the recurrent both approaches. For the approach considered as true dose painting by number (tDPBN) where the restriction of dose to volumes makes no sense, it was necessary to develop a novel algorithm including an optimization method at the voxel level under Lineal Programming (LP) formulation. For the approach based on the discretization of functional information into several clusterings (DPBN), instead of a recurrent equidistant isolevel, we implemented several algorithms able to reflect the diffuse and multifocal nature of the uptake regions. For this study, the affinity propagation proposed by Foster in order to reduce random errors due to the PET images registration process. Full Monte Carlo simulations were performed for pre-optimization and final dose calculation for taking into account the interactions of particles by means an explicit transport along the beam modifiers in the linac head. Axesse/Synergy linacs of Elekta were modellized with the EGSnrc/BEAMnrc code. The dose calculation in patient was carried out with the BEAMDOSE code, a modified version of DOSXYZnr for calculate the specific beamlet dose contribution on each voxel. A grid calculation consisting on 256 × 256 voxels per slice was used from the interpolation of PET/CT images reconstructed by keeping a compromise with EARL (ResEARch4Life®) accreditation requirements. Linear Programming formulation at voxel level allowed stablishing a tractable robustness of the uncertainties related to the heterogeneous dose prescription, imposing lower and upper-bound constraints to each voxel in accordance to the clustering volume to which they belong. For tDPBN, an inverse planning schema was previously developed. For DPBN by clusterings approach, a specific direct aperture optimization (BIOMAP) based on the sequencing of biophysical maps has been modified to generate apertures with Boolean combinations of the clustering projections. [Results] DPBN by means inverse planning showed excellent QVHs, although they were achieved by means of solutions with high MUs (around 2000 MU/fraction with more than 350 segments). Secondary contribution from MLC meant a high dose spillage to the body, so cannot be directly assumed for clinical implementation. The robust solutions for DPBN by means BIOMAP allow the accurate clinical implementation (around 750 MU/fraction with less than 200 segments) with Q index (planned_dose_matrix/true_prescribed_dose_matrix) over 95%.Peer reviewe