[Proton therapy of occult neovessels in age-related macular degeneration]. / Protonthérapie des néovaisseaux occultes dans la dégénérescence maculaire liée à l'âge.

INTRODUCTION: The interest of radiation therapy in the management of age-related macular degeneration inaccessible to photocoagulation is still controversial. Our purpose was to demonstrate the feasibility and the possible efficacy of a single dose delivered to the macular region using a 65-MeV proton beam. MATERIAL AND METHODS: A phase II trial was set up using the cyclotron in Nice, France. Fifty-eight patients were included after signing an informed consent. All patients presented with occult subfoveal choroidal neovascularization. A single dose of 9.1 Gy (i.e., 10 Gy cobalt equivalent) was delivered to the macular region. RESULTS: The results were analyzed 3, 6, 12 and, 18 months after proton therapy. At 3 months, the visual acuity was stable or enhanced for 86% of patients, at 6 months for 82.3%, at 12 months for 80%, and at 18 months for 61%. For 22 patients at follow-up at 18 months, the reasons for a decrease in visual acuity were a macular hemorrhage for 4 patients and a progression of the neovascular membrane for 3 patients. No secondary effects related to the treatment have been observed. Regarding the lesions visible on the angiographies (i.e., hemorrhage, exudates, subretinal detachment), we observed a stabilization or a decrease in two-thirds of the cases. CONCLUSION: Preliminary results of single-dose proton therapy are at least comparable to those obtained by other teams. A second study is in progress comparing 3 dose levels, looking for a dose-effect relationship. Furthermore, a randomized study comparing a single proton dose to a placebo will be necessary to assess the long-term value of proton treatment.

Results of proton therapy of uveal melanomas treated in Nice.

PURPOSE: To present the first results of uveal melanomas treated with the Medicyc Cyclotron 65 MeV proton beam facility in Nice, analyzing the factors that affect the cause-specific survival (CSS), metastatic rate, and reporting the visual outcome. METHODS AND MATERIALS: This study concerns 538 patients referred by French institutions between June 1991 and December 1996. The eye and tumor parameters were measured using ultrasonography and angiography. Since 1994, CT scans were performed in most patients to help determine the axial length and the shape of the ocular globe. Tantalum clips were inserted around the tumor by the referring ophthalmologist. There were 349 posterior pole tumors (64.9%), 130 equatorial tumors (24.1%), and 59 ciliary body tumors (11%). Two hundred four patients (37.9%) had T1 or T2 tumors, and 334 patients (62.1%) had T3 or T4 tumors. The median tumor diameter was 14.6 mm, and the median tumor height was 5.1 mm. All patients received 52 Gy (57.20 Gy Co-equivalent dose) on 4 consecutive days. The data were analyzed by December 1997. RESULTS: The CSS was 77.4% at 78 months, the overall survival was 73.8% and the local control was 89.0%. The CSS was not influenced by the patient age or the site of the tumor. It was 81.5% for T1 and T2 tumors, versus 75% for T3 and T4 tumors (P = 0.035). It was found that the tumor diameter, rather than the height, was the most important parameter affecting outcome. The metastatic rate was 8%. It depended on the T stage, tumor diameter and thickness, but not the tumor site. Thirty-eight enucleations were performed, most of them due to tumor progression and/or glaucoma. One-third of the patients in whom visual acuity was adequately scored before and after treatment had a stable, if not improved vision, and half the patients retained useful vision after treatment. CONCLUSION: The outcome of patients suffering from uveal melanoma and treated with high-energy protons compares favorably with other techniques of treatment. The tumor dimensions affected CSS and metastatic rate. Even though two-thirds of patients had posterior pole tumors, half of them retained useful vision.

The Nice high-energy neutron facility: dosimetry intercomparisons.

Neutron dosimetry intercomparison studies have been undertaken at the Nice neutrontherapy facility with the staff at Louvain-la-Neuve which has had wide experience in both dosimetric and radiobiological intercomparisons. Tissue equivalent (TE) ionization chambers were first calibrated in 60Co beams and then exposed in the neutron beam at different depths in a water phantom; the largest difference observed in neutron beam measurements with all the chambers tested was 0.89%, and most of them agreed to within less than 0.5%. The gamma component at four depths was derived from measurements with Geiger-Müller counters; the results obtained with the two counters (Nice and Louvain-la-Neuve), expressed as a percentage of the total dose (neutron + gamma), agreed to within less than 0.03% and the value increased from 1.4 to 4.2% between 2 and 20 cm in depth.

Boron neutron capture irradiation: setting up a clinical programme in Nice.

Neutron capture irradiation aims to selectively destroy tumor cells using 10B(n,alpha)7Li nuclear reactions produced within themselves. Following the capture reaction, an alpha particle and a, 7Li ion are emitted. Carrying an energy of 2.79 MeV, they destroy all molecular structures along their path close to 10 microns. These captures, used exclusively with a 'slow' neutron irradiation, provide a neutron capture therapy (BNCT). If they are used in addition to a fast neutron beam irradiation, they provide a neutron capture potentiation (NCP). The Centre Antoine-Lacassagne in Nice is actively involved in the European Demonstration Project for BNCT of grade IV glioblastomas (GBM) after surgical excision and BSH administration. Taking into account the preliminary results obtained in Japan, work on an 'epithermal' neutron target compatible with various cyclotron beams is in progress to facilitate further developments of this technique. For NCP, thermalized neutron yield has been measured in phantoms irradiated in the fast neutron beam of the biomedical cyclotron in Nice. A thermal peak appears after 5 cm depth in the tissues, delayed after the fast neutron peak at 1.8 cm depth. Thus, a physical overdosage of 10% may be obtained if 100 ppm of 10B are assumed in the tissues. Our results using CAL 58 GBM cell line demonstrate a dose modification factor (DMF) of 1.19 when 100 ppm of boric acid are added to the growth medium. Thus for the particles, issued from neutron capture, a biological efficiency at least twice that of fast neutrons can be derived. These results, compared with historical data on fast neutron irradiation of glioblastoma, suggest that a therapeutic window may be obtained for GBM.

Proton therapy in ophthalmology: status report and problems encountered.

The proton therapy facility of the Centre Antoine-Lacassagne in Nice began treatment of ocular tumors in June 1991. Up to October 1995, a total number of 600 patients were treated. An overview of the cases treated during the first 4 years of activity is given and the main problems encountered in the field, possibly interacting with the accuracy and reliability of the dose distribution, are listed.