[Clinical research in radiation oncology: how to move from the laboratory to the patient?] / Recherche clinique en oncologie radiothérapie : comment passer du laboratoire au patient ?

Translational research in radiation oncology is undergoing intense development. An increasingly rapid transfer is taking place from the laboratory to the patients, both in the selection of patients who can benefit from radiotherapy and in the development of innovative irradiation strategies or the development of combinations with drugs. Accelerating the passage of discoveries from the laboratory to the clinic represents the ideal of any translational research program but requires taking into account the multiple obstacles that can slow this progress. The ambition of the RadioTransNet network, a project to structure preclinical research in radiation oncology in France, is precisely to promote scientific and clinical interactions at the interface of radiotherapy and radiobiology, in its preclinical positioning, in order to identify priorities for strategic research dedicated to innovation in radiotherapy. The multidisciplinary radiotherapy teams with experts in biology, medicine, medical physics, mathematics and engineering sciences are able to meet these new challenges which will allow these advances to be made available to patients as quickly as possible.

[Combination radiotherapy-immunotherapy in genitourinary cancer]. / Combinaison radiothérapie-immunothérapie en cancérologie génito-urinaire.

Immunotherapy occupies a growing place in urologic oncology, mainly for kidney and bladder cancers. On the basis of encouraging preclinical work, the combination of immunotherapy with radiotherapy aims to increase the tumor response, including in metastatic tumors, which raises many hopes, which this article reviews.

Validation of the analytical irradiator model and Monte Carlo dose engine in the small animal irradiation treatment planning system µ-RayStation 8B.

Dose calculation in preclinical context with a clinical level of accuracy is a challenge due to the small animal scale and the medium photon energy range. In this work, we evaluate the effectiveness and accuracy of an analytical irradiator model combined with Monte Carlo (MC) calculations in the irradiated volume to calculate the dose delivered by a modern small animal irradiator. A model of the XRAD225Cx was created in µ-RayStation 8B, a preclinical treatment planning system, allowing arc and static beams for seven cylindrical collimators. Calculations with the µ-RayStation MC dose engine were compared with EBT3 measurements in water for all static beams and with a validated GATE model in water, heterogeneous media and a mouse CT. The GATE model is a complete MC representation of the XRAD225Cx. In water, µ-RayStation calculations, compared to GATE calculations and EBT3 measurements, agreed within a maximal error of 3.2% (mean absolute error of 0.6% and 0.8% respectively) and maximal distance-to-agreement (DTA) was 0.2 mm at 50% of the central dose. For a 5 mm static beam in heterogeneous media, the maximal absolute error between µ-RayStation and GATE calculations was below 1.3% in each medium and DTA was 0.1 mm at interfaces. For calculations on a mouse CT, µ-RayStation and GATE calculations agreed well for both static and arc beams. The 2D local gamma passing rate was >98.9% for 1%/0.3 mm criteria and >92.9% for 1%/0.2 mm criteria. Moreover, µ-RayStation reduces calculation time significantly comparing with GATE (speed-up factor between 120 and 680). These findings show that the analytical irradiator model presented in this work combined with the µ-RayStation MC dose engine accurately computes dose for the XRAD225Cx irradiator. The improvements in calculation time and availability of functionality and tools for managing, planning and evaluating the irradiation makes this platform very useful for pre-clinical irradiation research.

A new tissue segmentation method to calculate 3D dose in small animal radiation therapy.

BACKGROUND: In pre-clinical animal experiments, radiation delivery is usually delivered with kV photon beams, in contrast to the MV beams used in clinical irradiation, because of the small size of the animals. At this medium energy range, however, the contribution of the photoelectric effect to absorbed dose is significant. Accurate dose calculation therefore requires a more detailed tissue definition because both density (ρ) and elemental composition (Zeff) affect the dose distribution. Moreover, when applied to cone beam CT (CBCT) acquisitions, the stoichiometric calibration of HU becomes inefficient as it is designed for highly collimated fan beam CT acquisitions. In this study, we propose an automatic tissue segmentation method of CBCT imaging that assigns both density (ρ) and elemental composition (Zeff) in small animal dose calculation. METHODS: The method is based on the relationship found between CBCT number and ρ*Zeff product computed from known materials. Monte Carlo calculations were performed to evaluate the impact of ρZeff variation on the absorbed dose in tissues. These results led to the creation of a tissue database composed of artificial tissues interpolated from tissue values published by the ICRU. The ρZeff method was validated by measuring transmitted doses through tissue substitute cylinders and a mouse with EBT3 film. Measurements were compared to the results of the Monte Carlo calculations. RESULTS: The study of the impact of ρZeff variation over the range of materials, from ρZeff = 2 g.cm- 3 (lung) to 27 g.cm- 3 (cortical bone) led to the creation of 125 artificial tissues. For tissue substitute cylinders, the use of ρZeff method led to maximal and average relative differences between the Monte Carlo results and the EBT3 measurements of 3.6% and 1.6%. Equivalent comparison for the mouse gave maximal and average relative differences of 4.4% and 1.2%, inside the 80% isodose area. Gamma analysis led to a 94.9% success rate in the 10% isodose area with 4% and 0.3 mm criteria in dose and distance. CONCLUSIONS: Our new tissue segmentation method was developed for 40kVp CBCT images. Both density and elemental composition are assigned to each voxel by using a relationship between HU and the product ρZeff. The method, validated by comparing measurements and calculations, enables more accurate small animal dose distribution calculated on low energy CBCT images.

Semaphorin, neuropilin and VEGF expression in glial tumours: SEMA3G, a prognostic marker?

Gliomas are characterised by local infiltration, migration of tumour cells across long distances and sustained angiogenesis; therefore, proteins involved in these processes are most likely important. Such candidates are semaphorins involved in axon guidance and cell migration. In addition, semaphorins regulate tumour progression and angiogenesis. For cell signalling, class-4 semaphorins bind directly to plexins, whereas class-3 semaphorins require additional neuropilin (NRP) receptors that also bind VEGF(165). The anti-angiogenic activity of class-3 semaphorins can be explained by competition with VEGF(165) for NRP binding. In this study, we analysed the expressions of seven semaphorins of class-3, SEMA4D, VEGF and the NRP1 and NRP2 receptors in 38 adult glial tumours. In these tumours, SEMA3B, SEMA3G and NRP2 expressions were related to prolonged survival. In addition, SEMA3D expression was reduced in high-grade as compared with low-grade gliomas. In contrast, VEGF correlated with higher grade and poor survival. Thus, our data suggest a function for a subset of class-3 semaphorins as inhibitors of tumour progression, and the prognostic value of the VEGF/SEMA3 balance in adult gliomas. Moreover, in multivariate analysis, SEMA3G was found to be the only significant prognostic marker.