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The development of alternative therapies for melanoma treatment is of great interest as long-term tumour regression is not achieved with new targeted chemotherapies on selected patients. We previously demonstrated that radioiodinated heteroarylcarboxamide ([131I]ICF01012) induced a strong anti-tumoural effect by inhibiting both primary tumour growth and dissemination process in a B16BL6 melanoma model. In our study, we show that a single injection of [131I]ICF01012 (ranging from 14.8 to 22.2 MBq) was effective and associated with low and transient haematological toxicity. Concerning pigmented organs, cutaneous melanocytes and skin were undamaged. In 30% of treated animals, no histological alteration of retina was observed, and in the remaining 70%, damages were restricted to the optic nerve area. Using the Medical Internal Radiation Dose methodology, we determined that the absorbed dose in major organs is very low (

La directive 97/43/EURATOM du 30 juin 1997 pointe la radiologie interventionnelle comme une des pratiques speciales (Article 9) susceptibles de delivrer des doses elevees, et pour lesquelles il est demande de veiller a ce que les equipements, les procedures, les programmes d’assurance qualite et la formation des operateurs soient particulierement appropriees. En effet, l’utilisation d’un rayonnement X de faible energie lors de procedures allant de quelques secondes a plusieurs heures pour les examens complexes, renvoie inevitablement a des risques stochastiques et deterministes. L’evaluation de la dose maximum a la peau est donc une donnee appreciable dans l’objectif d’un suivi dermatologique du patient. Dans cette etude nous avons choisi d’utiliser comme detecteur les films radiochromiques XR-RV3-Gafchromic ® afin d’obtenir une cartographie de la dose a la peau recue par le patient lors d’une procedure. Les films radiochromiques sont interessants car ils permettent a la fois de visualiser et de quantifier la region de dose maximale. Nous presentons ici les etapes preliminaires a une utilisation sur patient des films, a savoir l’etude des caracteristiques physiques, l’etalonnage en dose, la lecture par scanner plat et l’exploitation des films avec le logiciel de traitement d’images ImageJ. Les resultats obtenus montrent que l’utilisation des films radiochromiques est pertinente pour une evaluation dosimetrique sur patient. Plus particulierement, la reponse des films differe de moins de 3,6 % entre l’etalonnage a 80 kV et 120 kV et l’incertitude globale reste inferieure a 20 % jusqu’a une dose de 12 Gy. L’evolution de la reponse du film dans le temps etant negligeable, la lecture peut etre faite immediatement et l’exploitation du film necessite moins de 15 minutes pour obtenir la cartographie de la dose. L’application de cette technique de mesure in-vivo pour 58 procedures a permis de mettre en evidence une dose maximale a la peau superieure a 3 Gy pour 12 patients. Ces patients ont alors ete orientes vers un suivi dermatologique. Parmi ces patients, l’evaluation de la dose peau a partir des indicateurs dosimetriques fournis par l’installation aurait mene au suivi de seulement 4 patients.

The GATE Monte Carlo simulation platform based on the GEANT4 toolkit has come into widespread use for simulating positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging devices. Here, we explore its use for calculating electron dose distributions in water. Mono-energetic electron dose point kernels and pencil beam kernels in water are calculated for different energies between 15 keV and 20 MeV by means of GATE 6.0, which makes use of the GEANT4 version 9.2 Standard Electromagnetic Physics Package. The results are compared to the well-validated codes EGSnrc and MCNP4C. It is shown that recent improvements made to the GEANT4/GATE software result in significantly better agreement with the other codes. We furthermore illustrate several issues of general interest to GATE and GEANT4 users who wish to perform accurate simulations involving electrons. Provided that the electron step size is sufficiently restricted, GATE 6.0 and EGSnrc dose point kernels are shown to agree to within less than 3% of the maximum dose between 50 keV and 4 MeV, while pencil beam kernels are found to agree to within less than 4% of the maximum dose between 15 keV and 20 MeV.

But Les progres techniques autorisent maintenant les traitements conservateurs des melanomes malins de la choroide. L’evolution de la maladie reste dominee par la crainte de metastases, survenant en moyenne apres trois ans. Le but de ce travail est de rapporter deux cas inhabituels de metastases hepatiques de melanome malin de la choroide survenues 11 et 18 ans apres curietherapie. Materiel et methodes Une femme de 40 ans et un homme de 50 ans ont presente un melanome malin de la choroide du pole posterieur de taille T2 et T3. Ils ont ete traites par disque de cobalt. Dans l’annee qui a suivi, les deux tumeurs ont completement regresse. Les patients ont ete suivis regulierement tous les trois mois pendant cinq ans. Resultats Les metastases hepatiques sont apparues respectivement 11 ans et 18 ans plus tard. Discussion et conclusion Ces deux observations semblent indiquer que la dissemination metastatique etait deja presente au moment du diagnostic et que le temps de doublement cellulaire du melanome uveal etait particulierement long. Elles posent le probleme de la duree du melanome uveal et du depistage infraclinique des metastases.

International audience; The GATE Monte Carlo simulation platform based on the Geant4 toolkit is in constant improvement for dosimetric calculations. In this paper, we present the integration of Geant4-DNA processes into the GATE 7.0 platform in the objective to perform multi-scale simulations (from macroscopic to nanometer scale). We simulated three types of clinical and preclinical beams: a 6 MeV electron clinical beam, a X-ray irradiator beam and a clinical proton beam for which we validated depth dose distributions against measurements in water. Frequencies of energy depositions and DNA damage were evaluated using a specific algorithm in charge of allocating energy depositions to atoms constituting DNA molecules represented by their PDB (Protein Data Bank) description.

Resume Objectif de l'etude Analyse retrospective des resultats de la radiotherapie de l'adenocarcinome non metastatique de la prostate a l'exclusion des complications. Patients et methodes Les 610 cas de stade T1-T2 repertories ont ete traites par irradiation externe dans 19 instituts, entre janvier 1983 et janvier 1988. Le recul moyen etait de 10,4 ans, la moyenne d'âge au debut du traitement de 68,5 ans. Resultats Un controle local a 10 ans a ete obtenu pour 86 % des cancers classes T1-T2 (81,4 % dans le cas des T2). Le taux de rechute metastatique etait a 5 et 10 ans respectivement de 25,3 et 30 % (29 et 38,1 % pour les T2). A 10 ans, 62,4 % des tumeurs de stade T1-T2 n'avaient pas recidive; par ailleurs, le taux de survie globale etait de 45,8 % et celui de survie specifique de 70,5 %; 29,9 % des patients etaient vivants sans signe de recidive. Il y avait une correlation entre le stade (TNM), le grade, le statut ganglionnaire pelvien, le controle tumoral local, la presence d'une obstruction ureterale, et la survie. L'irradiation pelvienne, la dose, l'etalement, le traitement hormonal neoadjuvant et la resection transuretrale n'avaient pas d'influence sur le pronostic. Conclusion Il n'y a pas de difference entre les deux etudes francaises (1975–1982 et 1983–1988) sur le plan du recrutement et du pronostic. Les resultats releves dans la litterature sont voisins des notres. Cette etude souligne l'importance des facteurs de pronostic inherents a la tumeur et au malade.

Beta Irradiation (106Ru/106Rh) versus Gamma Irradiation (125I): A Comparative Study on the Normal Rabbit Eye. We compared beta irradiation (106Ru/106Rh) to gamma irradiation (125I) on the normal rabbit eye, using ophthalmic plaques to deliver doses similar to those recommended in man for choroidal melanoma treatment. A detailed dosimetry was performed and the animals were followed up by clinical and histological examinations during 1 year. The mean total doses were either comparable, or larger with iodine-125, but the globes treated with ruthenium-106 exhibited more damaging effects: total destruction of the chorioretina on the plaque site, abnormalities of the retinal vessels and of the close nerve fiber layers, cavernous atrophy of the optic nerve. In the eyes treated with iodine-125, only the external retinal layers were destroyed.

International audience; The GATE Monte Carlo simulation platform based on the Geant4 toolkit is under constant improvement for dosimetric calculations. In this study, we explore its use for the dosimetry of the preclinical targeted radiotherapy of melanoma using a new specific melanin-targeting radiotracer labeled with iodine 131. Calculated absorbed fractions and S values for spheres and murine models (digital and CT-scan-based mouse phantoms) are compared between GATE and EGSnrc Monte Carlo codes considering monoenergetic electrons and the detailed energy spectrum of iodine 131. The behavior of Geant4 standard and low energy models is also tested. Following the different authors' guidelines concerning the parameterization of electron physics models, this study demonstrates an agreement of 1.2% and 1.5% with EGSnrc, respectively, for the calculation of S values for small spheres and mouse phantoms. S values calculated with GATE are then used to compute the dose distribution in organs of interest using the activity distribution in mouse phantoms. This study gives the dosimetric data required for the translation of the new treatment to the clinic.

Although cancer of the penis is a rare disease, we have collected 506 cases through a multicentric study. In the present study we analyse the results obtained from 259 patients treated by interstitial brachytherapy from 1959 to 1989. Among the 259 patients, 184 males had exclusive brachytherapy (group A) while 75 received a combination of surgery and brachytherapy and/or external beam irradiation (EBI) (group B). Five- and 10-year survival rates are, respectively: overall survival, 66 and 52%; cause-specific survival, 88 and 88%; disease-free survival, 78 and 67%. One hundred and forty-three patients in group A (78%) and 48 (64%) in group B avoided mutilation of the penis while late side effects occurred in 137/259 patients (53%). Survival depends on the volume of the tumor and the presence of involved nodes; systematic groin dissection does not however seem advisable.

The GATE Monte Carlo simulation platform based on the Geant4 toolkit has now become a diffused tool for simulating PET and SPECT imaging devices. In this paper, we explore its relevance for dosimetry of low-energy 125I photon brachytherapy sources used to treat prostate cancers. To that end, three 125-iodine sources widely used in prostate cancer brachytherapy treatment have been modelled. GATE simulations reproducing dosimetric reference observables such as radial dose function g(r), anisotropy function F(r, theta) and dose-rate constant (Lambda) were performed in liquid water. The calculations were splitted on the EGEE grid infrastructure to reduce the computing time of the simulations. The results were compared to other relevant Monte Carlo results and to measurements published and fixed as recommended values by the AAPM Task Group 43. GATE results agree with consensus values published by AAPM Task Group 43 with an accuracy better than 2%, demonstrating that GATE is a relevant tool for the study of the dose induced by low-energy photons.

Purpose: In this study, we validate the accuracy of the new GATE 6.0 Monte Carlo platform (using GEANT4 9.2 Standard Electromagnetic Physics Package) to model accurate treatment plans in radiation therapy using 18 MV photon beams. Furthermore, we investigate how the specifications of the particle transport management, physic processes and geometry influence the dosimetric accuracy of the results to propose recommendations on the usage of GATE 6.0. Methods: 3D conformational plans were simulated for a lung irradiation using 18MV photon beams from a Varian Clinac 2100C accelerator. The patient volume was derived from CT images and converted into specific format in order to use different voxel sizes. Treatment plans were computed using GATE 6.0 and EGSnrc. Treatment plans obtained with both of the codes were compared using a gamma index evaluation (acceptance criteria 3%/3mm). Investigations on the influence of simulation parameters related to physics or algorithm were examined by qualitative comparisons of DVHs in several regions of interest: PTV and OARs. Results: At first, GATE 6.0 is able to reproduce complex dosimetry in agreement with the well validated Monte Carlo code EGSnrc. Nevertheless, the choice of specific simulation parameters such as cuts, particle production threshold or stepping algorithm showed differences on treatment plans. Users have to fix parameters according to the geometry simulated to ensure a good tracking of particles by taking into account the computation time efficiency. Conclusions: GATE 6.0 provides convivial tools for realistic treatment planning and give comparable results with EGSnrc while the parameters of the simulation are well fixed. These investigations highlight several issues of general interest to users of GATE 6.0 who wish to calculate accurate treatment plans. We wish to thank the GEANT4 collaboration and the OpenGATE collaboration to their scientific and technical suuport. This work was partly supported by grants from the European Commission (through the EGI inititative project), by the French National Grid Inititative (France Grilles), and regional authorites (Conseil General de l'Allier and Conseil Regional d'Auvergne).

Purpose: By calibratingbrachytherapy (BT) sources to the TG‐43U1 reference position at 1cm in water, named the nominal absorbed dose‐rate to water, Ḋ w ,1, accuracy and precision for patient treatment will be increased. Traceability must be provided to Ḋ w ,1 ‐primary‐standards; which soon become available. Methods and Materials: Efforts have been made in discussions with fellow scientists from many countries, by reviewing concerned literature, and similarities are drawn from documents (e.g. extending TG‐43U1). Results: From the study of primary photon interaction mechanisms, a need was recognized to classify BT‐photon radiation qualities as: high‐energy >100keV, medium energy 40keV to 100keV, and low energy

International audience