Internal dosimetry through GATE simulations of preclinical radiotherapy using a melanin-targeting ligand.

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.

Comparison of GATE/GEANT4 with EGSnrc and MCNP for electron dose calculations at energies between 15 keV and 20 MeV.

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.

HOPE, an open platform for medical data management on the grid.

The paper describes a platform developed for the secure management and analysis of medical data and images in a grid environment. Designed for telemedicine and built upon the EGEE gLite middleware and particularly the metadata catalogue AMGA as well as the GridSphere web portal, the platform provides to healthcare professionals the capacity to upload and query medical information stored over distributed servers. A job submission environment is also available for data analysis. Security features include authentication and authorization by grid certificates, anonymization of medical data and image encryption. The platform is currently deployed on several sites in Europe and Asia and is being customized for applications in the field of telemedicine and medical physics.

Validation of a dose deposited by low-energy photons using GATE/GEANT4.

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.

GATE: a simulation toolkit for PET and SPECT.

Monte Carlo simulation is an essential tool in emission tomography that can assist in the design of new medical imaging devices, the optimization of acquisition protocols and the development or assessment of image reconstruction algorithms and correction techniques. GATE, the Geant4 Application for Tomographic Emission, encapsulates the Geant4 libraries to achieve a modular, versatile, scripted simulation toolkit adapted to the field of nuclear medicine. In particular, GATE allows the description of time-dependent phenomena such as source or detector movement, and source decay kinetics. This feature makes it possible to simulate time curves under realistic acquisition conditions and to test dynamic reconstruction algorithms. This paper gives a detailed description of the design and development of GATE by the OpenGATE collaboration, whose continuing objective is to improve, document and validate GATE by simulating commercially available imaging systems for PET and SPECT. Large effort is also invested in the ability and the flexibility to model novel detection systems or systems still under design. A public release of GATE licensed under the GNU Lesser General Public License can be downloaded at http:/www-lphe.epfl.ch/GATE/. Two benchmarks developed for PET and SPECT to test the installation of GATE and to serve as a tutorial for the users are presented. Extensive validation of the GATE simulation platform has been started, comparing simulations and measurements on commercially available acquisition systems. References to those results are listed. The future prospects towards the gridification of GATE and its extension to other domains such as dosimetry are also discussed.

[Late metastases of malignant choroidal melanoma after curietherapy: two case reports]. / Métastases tardives après curiethérapie efficace de mélanome malin de la choroïde. A propos de deux cas.

PURPOSE: The technical advancements now provide conservative treatment of choroidal melanoma. The course of the disease remains marked by the metastases that usually set in within 3 years. The aim of this paper is to report two unusual cases of hepatic metastases of choroidal melanoma that set in 11 and 18 Years after curietherapy. METHODS: A 40-year-old woman and a 50-year-old man presented with T2 and T3 choroidal melanomas and were treated by cobalt plaque. The tumors decreased within the year and the patients were monitored every 3 months for 5 years. RESULTS: Metastases set in, respectively, 11 and 18 years after treatment. DISCUSSION AND CONCLUSION: These two observations show that the metastases had already spread at the moment of diagnosis and that the cell doubling time of the melanoma was very long. These findings indicate the difficulties in monitoring patients with choroidal melanoma.

Validation of the GATE Monte Carlo simulation platform for modelling a CsI(Tl) scintillation camera dedicated to small-animal imaging.

Monte Carlo simulations are increasingly used in scintigraphic imaging to model imaging systems and to develop and assess tomographic reconstruction algorithms and correction methods for improved image quantitation. GATE (GEANT4 application for tomographic emission) is a new Monte Carlo simulation platform based on GEANT4 dedicated to nuclear imaging applications. This paper describes the GATE simulation of a prototype of scintillation camera dedicated to small-animal imaging and consisting of a CsI(Tl) crystal array coupled to a position-sensitive photomultiplier tube. The relevance of GATE to model the camera prototype was assessed by comparing simulated 99mTc point spread functions, energy spectra, sensitivities, scatter fractions and image of a capillary phantom with the corresponding experimental measurements. Results showed an excellent agreement between simulated and experimental data: experimental spatial resolutions were predicted with an error less than 100 microns. The difference between experimental and simulated system sensitivities for different source-to-collimator distances was within 2%. Simulated and experimental scatter fractions in a [98-182 keV] energy window differed by less than 2% for sources located in water. Simulated and experimental energy spectra agreed very well between 40 and 180 keV. These results demonstrate the ability and flexibility of GATE for simulating original detector designs. The main weakness of GATE concerns the long computation time it requires: this issue is currently under investigation by the GEANT4 and the GATE collaborations.

[Treatment of conjunctival epithelial tumors: brachytherapy with ruthenium-106]. / Traitement des tumeurs épithéliales de la conjonctive: intérêt de la curiethérapie au ruthénium-106.

INTRODUCTION: Treatment of conjunctival epithelial tumors is not standardized because it is difficult to compare large series in this rare disease. Surgical excision is usual, but the recurrence rate has led several authors to propose alternative therapies. PATIENTS AND METHODS: During the past 20 years, brachytherapy using ophthalmic applicators has been developed and the results of different studies have confirmed the usefulness of this therapy. We report a retrospective study of 13 patients presenting with a conjunctival epithelial tumor treated with ruthenium106 applicators and followed up in our department since 1987. RESULTS AND CONCLUSION: There was no recurrence during a mean follow-up of 48 months. Complications depended on the size of the area treated and the dose of radiation.

Effects of low-dose neutrons applied at reduced dose rate on human melanoma cells.

Human melanoma cells that are resistant to gamma rays were irradiated with 14 MeV neutrons given at low doses ranging from 5 cGy to 1.12 Gy at a very low dose rate of 0.8 mGy min(-1) or a moderate dose rate of 40 mGy min(-1). The biological effects of neutrons were studied by two different methods: a cell survival assay after a 14-day incubation and an analysis of chromosomal aberrations in metaphases collected 20 h after irradiation. Unusual features of the survival curve at very low dose rate were a marked increase in cell killing at 5 cGy followed by a plateau for survival from 10 to 32.5 cGy. The levels of induced chromosomal aberrations showed a similar increase for both dose rates at 7.5 cGy and the existence of a plateau at the very low dose rate from 15 to 30 cGy. The existence of a plateau suggests that a repair process after low-dose neutrons might be induced after a threshold dose of 5-7.5 cGy which compensates for induced damage from doses as high as 32.5 cGy. These findings may be of interest for understanding the relative biological effectiveness of neutrons and the effects of environmental low-dose irradiation.

[Long-term results of cobalt 60 curietherapy for uveal melanoma]. / Résultats à long terme de la curiethérapie par le cobalt 60 des mélanomes de l'uvée.

PURPOSE: To analyze 65 patients with uveal melanomas treated with cobalt plaque therapy with regards to mortality, visual results and complications. PATIENTS AND METHODS: Most of the melanomas were large (T3: 52.5%), with a mean largest dimension of the base of 11 mm, and a mean thickness of 6 mm. Most of the tumors were located in the choroid (95%), with an anterior margin behind the equator (65%), and a posterior margin at less than 3 mm of the disc and/or of the macula (69%). The plaque radiotherapy delivered a mean dose of 95 Gy to the tumor apex, either with a cobalt plaque alone (51 cases), or in association with a ruthenium plaque (14 cases). The mean follow up period was over 8 years. RESULTS: The local control was achieved initially in 86% of the eyes. The estimated melanoma specific survival rate was 83% after 5 years and 74% after 10 years. The main parameter associated with the metastases was the largest dimension of the base (p < 0.01). The eye was retained in 83% of the cases. The probability of keeping a vision better than or equal to 0,1 was 39% after 5 years and 27% after 10 years. The main parameter associated with the visual loss was the tumor size (p < 0.01). The complications included cataract (39%), radiation retinopathy (34%), with maculopathy (19%) and/or papillopathy (13.5%), vitreous hemorrhages (22%), neovascular glaucoma (15%) and retinal detachment (12%). CONCLUSION: These results supported the value of cobalt plaque radiotherapy in the management of uveal melanomas.

[Comparative study of beta irradiation (106Ru/106Rh) and gamma irradiation (125I) on the rabbit eye]. / Etude comparative de l'irradiation bêta (106Ru/106Rh) et de l'irradiation gamma (125I) sur l'oeil du lapin.

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.

[Radiotherapy of stage T1-T2 M0 prostatic adenocarcinoma. Analysis of the carcinologic results of a multicenter study of 610 patients. Groupe Radiothérapie de la Commission de Coopération Médicale Intercentres (CCMI)]. / Radiothérapie de l'adénocarcinome prostatique de stade T1-T2 M0. Analyse des résultats carcinologiques d'une étude multicentrique de 610 patients. Groupe Radiothérapie de la Commission de Coopération Médicale Intercentres (CCMI).

PURPOSE: Retrospective analysis of the results of radiotherapy in localized prostatic adenocarcinoma. Complications were excluded. PATIENTS AND METHODS: Six-hundred-and-ten T1-T2 adenocarcinomas of the prostate were treated with continuous courses of external beam radiation therapy in 19 participating Institutes between January 1983 and January 1988. The mean follow-up was 10.4 years; the mean age of patients at the beginning of radiotherapy was 68.5 years. RESULTS: A 10-year, local control had been achieved in 86% of T1-T2 (81.4% for T2). The 5- and 10-year metastatic relapse rates were 25.3% and 30% (29% and 38.1% for T2), respectively. At 10 years, 62.4% of T1-T2 were recurrence-free; overall survival rate was 45.8% and cause-specific survival rate was 70.5%; 29.9% of T1-T2 patients were alive and disease-free. T category (TNM), pathologic grade, pelvic lymph node status, local tumor control, and obstructive ureteral symptoms were correlated with survival. The influence of pelvic nodes radiation, dose, overall treatment time, previous endocrine treatment, and transuretral resection was not significant for disease-free survival (alive and disease-free) and other endpoints. CONCLUSION: There was no difference between the French series (1975-1982 and 1983-1988). The results of the literature are comparable to ours. As far as prognostic factors are concerned, this report provides evidence that the explainable variables which influence survival depend on the tumor and patient status.

Interstitial brachytherapy for penile carcinoma: a multicentric survey (259 patients).

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.

Interstitial iridium-192 for bladder cancer (a multicentric survey: 205 patients).

Interstitial irradiation is a technique currently used in the treatment of bladder cancer. We report the data on 205 patients (177 men and 28 women) treated in eight French centers. The patients had received the following treatment: a short course of pre-operative pelvic irradiation, followed by surgery consisting of partial cystectomy or tumor resection, and implantation of plastic tubes filled with inactive lead wires, which were replaced by iridium 192 wires. The tumor characteristics were: transitional cell carcinoma, 88.8%; mean size of the tumor, 29 mm; pathological stages: pTis, 1; pT1, 98; pT2, 66; pT3a, 26; pT3b, 9; pT4, 1; unknown, 4 respectively; surgical lymph node status: N+, 3; N-, 118; no node dissection, 84. The mean follow-up was 51 months. Intravesical failures were seen in 35 patients (17.0%), 25 (71.4%) of them without metastases or regional recurrences. Twenty-one patients (10.2%) presented distant metastases, 2/3 of them suffered no bladder relapse. The 5-year survival, calculated according to the Kaplan-Meier method (all causes of death taken together) was 77.4% for the T1, 62.9% for the T2, and 46.8% for the T3. Fifty-three patients had immediate side-effects and three died from surgical complications. Twenty-nine patients had delayed bladder side-effects (haematuria, fistula, chronic cystitis). Six patients presented an ureteral stenosis. Of the disease-free survivors, 96.1% retained the bladder function. Three factors were significantly predictive of delayed side-effects: partial cystectomy, pre-operative radiotherapy total dose, and linear activity of the wires (p < 0.01). Comparing our results to different authors' series interstitial irradiation is likely to provide a high local and general control of the disease and good quality of life in patients with selected tumors.

[Oncologic and functional results of 57 malignant melanoma of the uvea treated by curietherapy]. / Résultats carcinologiques et fonctionnels de 57 mélanomes malins de l'uvée traités par curiethérapie.

Fifty-seven uveal malignant melanomas (T2: 36.8%; T3: 49.1%) were treated between 1983 and 1989 with Cobalt 60 or/and Ruthenium 106 Rhodium 106 plaques. The mean follow-up was 32 months (from 6 to 69 months). A diminution of tumor size was observed in 88% of the cases, either rapid and marked (57%), or slower and more moderate (31%). A multivariate study showed the radiation dose administered to the tumor edge to be the most significant parameter associated with the tumor control. Seven patients developed metastases, and the probability of survival at 60 months was 83.3%. This probability was identical to that of 59 comparable patients treated, some years before, by enucleation. The most frequent complications were radiation retinopathy (28.1%) and retinal detachment (15.8%). The treated eye was retained in 86% of cases. In 57% of treated eyes, vision remained better or equal to 0.1. The predictive parameters of vision impairment after treatment seemed to be tumor size, tumor site near the macula and the optic nerve, and the radiation dose to the tumor base. The use of Ruthenium 106 Rhodium 106 appeared to be advantageous in controlling the disease as well as in reducing the incidence of complications.

[Treatment of various malignant melanomas of the choroid using a combination of ruthenium 106 and cobalt 60]. / Traitement de certains mélanomes malins de la choroïde par l'association ruthénium 106 et cobalt 60.

The association 106Ru/106Rh and 60Co was used to treat choroidal malignant melanomas with a height of 7 mm above the scleral surface (4 cases) and tumors unsuccessfully treated with a first 60Co plaque therapy (3 cases). The association of both radionuclides allowed a dose of 85 Gy at the apex of the tumor and of 700 Gy at least on the base in every case. All the patients were alive without evidence of metastases with a minimum follow up of one year and the tumor regression was constant and sometimes spectacular.

[Ureteral dosimetry during gynecological curietherapy. Possible effects on the occurrence of postoperative ureteral complications]. / La dosimétrie urétérale en curiethérapie gynécologique. Incidence possible sur la survenue des complications urétérales postopératoires.

The dosage of radiations delivered during gynaecological brachytherapy is usually calculated for the bladder and the rectum. A new technical approach is described in order to known the dose of radiation received by the terminal portion of the ureter. During placement of the Fletcher suit one of the ureters is catheterized by a special stent which appears on the X-rays control used for dosimetry. Data of 16 pre-operative brachytherapies for carcinoma of the cervix were studied. In half of the cases, the dose debit was higher on the ureter than on the bladder and the rectum. In 7 cases, the dose delivered was also higher on the ureter rather than on the bladder and the rectum. And in 3 cases this dose was higher than 50 grays. It is concluded that the ureter is frequently the most irradiated organ in the pelvis during brachytherapy for carcinoma of the cervix. This may be a physiopathologic explanation for some ureterovaginal fistulas occurring after radical hysterectomy.