Sci-Thur AM: Planning - 02: Validation of XiO's eMC module using Gafchromic EBT3 films and triple channel dosimetry.

The aim of this study is to validate the electron Monte Carlo module implemented in XiO, a treatment planning system commercialized by Elekta CMS inc. Two types of phantoms were investigated: homogeneous water phantoms with irregular surfaces and phantoms containing slab and 3D heterogeneities. The phantoms were CT scanned, and dose to water calculations were performed in the eMC module using 2 ×2 × 2 mm2 voxels and a mean relative statistical uncertainty of 0.5%. Concurrently, Gafchromic EBT3 film measurements were performed in the same phantoms. To obtain reliable absolute dose readings from the films, a new method using triple channel dosimetry in the Film QA Pro software was developed. The accuracy of the proposed method was determined empirically and an uncertainty of ±1.5% was found over the range [75, 800] cGy. Dose comparisons between film and simulations were done using an in-house MATLAB program. XiO's eMC module provides accurate dose distributions in the presence of surface irregularities and slab heterogeneities for 12 MeV beams. In the presence of 3D heterogeneities, the percent dose difference comparisons highlighted the need to perform 3D gamma comparisons. In conclusion, the electron Monte Carlo module offered in the XiO treatment planning system is promising and could greatly improve the accuracy of clinical dose calculations. The validation of the software is ongoing, notably concerning more complex phantom geometries. Small field calculations, oblique incidences and cutout factors will also be investigated.

Poster - Thur Eve - 52: Clinical use of nanoDots: In-vivo dosimetry and treatment validation for stereotactic targets with VMAT techniques.

A newly acquired nanoDot In-Light system was compared with TLD-100 dosimeters to confirm the treatment dose in the multiple cases: an electron eye treatment, H&N IMRT and VMAT validation for small targets. Eye tumour treatment with 9 MeV electrons A dose of 1.8 Gy per fraction was prescribed to the 85% isodose. The average dose measured by three TLDs and three Dots was 1.90 and 1.97 Gy. Both detectors overestimated dose, by 2.9% and 6.7% respectively. H&N IMRT treatment of skin cancer with 6 MV photons Dose per fraction is 2.5 Gy. The average doses measured by two TLDs and two Dots were 2.48 and 2.56 Gy, which represent errors of -0.8% and 2.2%, respectively. VMAT validation for small targets using an Agarose phantom, dose 15 Gy A single-tumour brain treatment was delivered using two coplanar arcs to an Agarise phantom containing a large plastic insert holding 3 nanoDots and 4 TLDs. The difference between the average Pinnacle dose and the average dose of the corresponding detectors was -0.6% for Dots and -1.7% for TLDs. A two-tumour brain treatment was delivered using three non-coplanar arcs. Small and large plastic inserts separated by 5 cm were used to validate the dose. The difference between the average Pinnacle dose and the average dose of the corresponding detectors was the following; small phantom 0.7% for Dots and 0.3% for TLDs, large phantom-1.9% for Dots and -0.6% for TLDs. In conclusion, nanoDot detectors are suitable for in-vivo dosimetry with photon and electron beams.

Evidence for a repertoire of functional untolerized CD4+ T cells specific for melanoma-associated antigens.

Active vaccination against melanoma requires tolerance break as melanoma-associated antigens (MAA) used in vaccine formula are mostly self-antigens. While tolerance to MAA in the CD8(+) T cell compartment is well characterized, it is still not the case for the CD4(+) T cell compartment. Here, we analysed CD4(+) T cell tolerance to such antigens in mice genetically engineered to express ovalbumin (OVA) in melanocytes (Tyr-OVA mice). When we crossed Tyr-OVA mice with DO11.10 and OT-II mice transgenic for an OVA-specific TCR restricted by MHC class II, we observed different tolerization levels. Central tolerance was complete for high avidity DO11.10 CD4(+) T cells, but absent for low avidity OT-II CD4(+) T cells. OT-II CD4(+) T cells also ignored OVA in the periphery of Tyr-OVA mice, albeit being potently reactive to vaccination. OVA challenge in single transgenic Tyr-OVA mice confirmed the existence of OVA-reactive CD4(+) T cells with the induction of efficient T helper cells for antibody production and anti-tumour T cell response. In total, our study demonstrates the existence of low avidity MAA-specific CD4(+) T cells escaping by ignorance central and peripheral tolerance, but valuable in the context of vaccination against melanoma.

Interferon-beta induces brain-derived neurotrophic factor in peripheral blood mononuclear cells of multiple sclerosis patients.

Interferon-beta (IFN-beta) achieves its beneficial effect on multiple sclerosis (MS) via anti-inflammatory properties. In this study, we assessed the expression of the brain-derived neurotrophic factor (BDNF) in peripheral blood mononuclear cells (PBMC) from relapsing-remitting multiple sclerosis (RRMS) patients treated or not with IFN-beta. Intracellular BDNF was measured by Western blot and ELISA and compared with serum BDNF. We found higher levels of BDNF in PBMC of IFN-beta-treated versus non-treated patients, whereas serum levels of BDNF were similar. We hypothesize that the increased intracellular BDNF secondary to IFN-beta is not released in the periphery. This release is probably not tissue specific but in MS patients, BDNF could be specifically delivered by PBMC at the site of re-activation, i.e. within the central nervous system.

Sci-Sat AM(2): Brachy-07: Tomosynthesis-based seed reconstruction in LDR prostate brachytherapy: A clinical study.

To develop a tomosynthesis-based dose assessment procedure that can be performed after an I-125 prostate seed implantation, while the patient is still under anaesthesia on the treatment table. Our seed detection procedure involves the reconstruction of a volume of interest based on the backprojection of 7 seed-only binary images acquired over an angle of 60° with an isocentric imaging system. A binary seed-only volume is generated by a simple thresholding of the volume of interest. Seeds positions are extracted from this volume with a 3D connected component analysis and a statistical classifier that determines the number of seeds in each cluster of connected voxels. A graphical user interface (GUI) allows to visualize the result and to introduce corrections, if needed. A phantom and a clinical study (24 patients) were carried out to validate the technique. A phantom study demonstrated a very good localization accuracy of (0.4+/-0.4) mm when compared to CT-based reconstruction. This leads to dosimetric error on D90 and V100 of respectively 0.5% and 0.1%. In a patient study with an average of 56 seeds per implant, the automatic tomosynthesis-based reconstruction yields a detection rate of 96% of the seeds and less than 1.5% of false-positives. With the help of the GUI, the user can achieve a 100% detection rate in an average of 3 minutes. This technique would allow to identify possible underdosage and to correct it by potentially reimplanting additional seeds. A more uniform dose coverage could then be achieved in LDR prostate brachytherapy.

Inhibition of naive Th1 CD4+ T cells by glatiramer acetate in multiple sclerosis.

We investigated whether glatiramer acetate (GA) treatment may affect Th1 differentiation at various T-cell maturation stages. Specifically, we analyzed the effect of in vivo GA treatment on intracellular synthesis of IL-2 and TNF-alpha by naive, memory and effector CD4(+) and CD8(+) T cells by five-colour flow cytometry. Our data indicate that GA treatment downregulates/normalizes an accelerated Th1 differentiation of CD4(+) T cells in RRMS patients at all stages of T-cell maturation. Most notably, we conclude that, by altering naive, unprimed CD4(+) T cells, GA treatment appears to affect T-cell differentiation, at least in part, in an antigen-independent manner.