First proton minibeam radiation therapy treatment plan evaluation.

Proton minibeam radiation therapy (pMBRT) is a novel dose delivery method based on spatial dose fractionation. pMBRT has been shown to be promising in terms of reduced side effects and superior tumour control in high-grade glioma-bearing rats compared to standard irradiation. These findings, together with the recent optimized implementation of pMBRT in a clinical pencil beam scanning system, have triggered reflection on the possible application to patient treatments. In this context, the present study was designed to conduct a first theoretical investigation of the clinical potential of this technique. For this purpose, a dedicated dose engine was developed and used to evaluate two clinically relevant patient treatment plans (high-grade glioma and meningioma). Treatment plans were compared with standard proton therapy plans assessed by means of a commercial treatment planning system (ECLIPSE-Varian Medical systems) and Monte Carlo simulations. A multislit brass collimator consisting of 0.4 mm wide slits separated by a centre-to-centre distance of 4 or 6 mm was placed between the nozzle and the patient to shape the planar minibeams. For each plan, spread-out Bragg peaks and homogeneous dose distributions (±7% dose variations) can be obtained in target volumes. The Peak-to-Valley Dose Ratios (PVDR) were evaluated between 9.2 and 12.8 at a depth of 20 mm for meningioma and glioma, respectively. Dose volume histograms (DVHs) for target volumes and organs at risk were quantitatively compared, resulting in a slightly better target homogeneity with standard PT than with pMBRT plans, but similar DVHs for deep-seated organs-at-risk and lower average dose for shallow organs. The proposed delivery method evaluated in this work opens the way to an effective treatment for radioresistant tumours and will support the design of future clinical research.

Monte Carlo modelling of the treatment line of the Proton Therapy Center in Orsay.

This paper presents the main results of a Monte Carlo simulation describing the Orsay Proton Therapy Center (CPO) beam line. The project aimed to obtain a prediction of the dose distribution in a water phantom within 2% accuracy in the dose value and a 2 mm of range. The simulation tool used was MCNPX, version 2.5.0, and included all the elements of the CPO beam line. A new algorithm of multiple Coulomb scattering has been incorporated in MCNPX, resulting in a better prediction of the spatial dose distribution and absolute values of the deposited energy. The simulations of 3D dose profiles in water show a very good agreement with measured data to within 2%. We first performed a comparative analysis of the dosimetry in heterogeneous phantoms between the pencil beam algorithm and MCNPX. The simulations give a better agreement with experimental data compared to the pencil beam approach. In a second phase, we simulated the patient-dependent fields along with the spatial dose distributions in a water phantom. The simulated response of a Pixel chamber located 2 m upstream of the water phantom revealed a good agreement with the measured data to within 1%. The results presented herein support the applicability of Monte Carlo models for absolute dosimetry and for design purposes regarding existing and new beam lines at CPO. This work completes a series of publications reporting the progress in the development of a Monte Carlo simulation tool for the CPO beam line dedicated for the treatment of head and neck tumours.

Spatial fractionation of the dose in proton therapy: Proton minibeam radiation therapy.

In radiation therapy, a renewed interest is emerging for the study of spatially fractionated irradiation. In this article, a few applications using spatial fractionation of the dose will be discussed with a focus on proton minibeam radiation therapy. Examples of calculated dose (1D profiles and 2D dose distributions) and biological evidence obtained so far will be presented for various spatially fractionated techniques GRID, micro- and minibeam radiation therapy. Recent results demonstrating that proton minibeam radiation therapy leads to an increase in normal tissues sparing will be discussed, which opens the door to a dose escalation in the tumour and a possibly efficient treatment of very radioresistant tumours.

Three-year results after radiotherapy for locally advanced sinonasal adenoid cystic carcinoma, using highly conformational radiotherapy techniques proton therapy and/or Tomotherapy.

PURPOSE: We report the patient outcomes of a treatment combining proton therapy and Tomotherapy in sinonasal adenoid cystic carcinoma involving skull base. MATERIALS AND METHODS: We included patients treated at Curie Institute, Paris, France, between March 2010 and February 2014 for an advanced adenoid cystic carcinoma involving skull base. Patients received Tomotherapy, proton therapy or both. We evaluated treatment toxicity (according to CTCAE V4), local control, distant metastasis-free survival and overall survival. RESULTS: Thirteen patients were included, with a median follow-up of 34 months. Radiation therapy followed surgery for 77% of the patients and margins were positive in all those cases. Median dose was 73.8Gy. Local control, distant metastasis-free survival and overall survival at 3 years were respectively 60%, 48% and 60%. One-sided grade 3 hearing impairment occurred in 46% of the patients. CONCLUSION: Combining high-dose proton therapy and Tomotherapy is effective and has moderate toxicity in the treatment of T4 sinonasal adenoid cystic carcinoma involving skull base.

Calibration of imaging plate detectors to mono-energetic protons in the range 1-200 MeV.

Responses of Fuji Imaging Plates (IPs) to proton have been measured in the range 1-200 MeV. Mono-energetic protons were produced with the 15 MV ALTO-Tandem accelerator of the Institute of Nuclear Physics (Orsay, France) and, at higher energies, with the 200-MeV isochronous cyclotron of the Institut Curie-Centre de Protonthérapie d'Orsay (Orsay, France). The experimental setups are described and the measured photo-stimulated luminescence responses for MS, SR, and TR IPs are presented and compared to existing data. For the interpretation of the results, a sensitivity model based on the Monte Carlo GEANT4 code has been developed. It enables the calculation of the response functions in a large energy range, from 0.1 to 200 MeV. Finally, we show that our model reproduces accurately the response of more complex detectors, i.e., stack of high-Z filters and IPs, which could be of great interest for diagnostics of Petawatt laser accelerated particles.

Mechanisms of phosphene generation in ocular proton therapy as related to space radiation exposure.

Particle therapy provides an opportunity to study the human response to space radiation in ground-based facilities. On this basis, a study of light flashes analogous to astronauts' phosphenes reported by patients undergoing ocular proton therapy has been undertaken. The influence of treatment parameters on phosphene generation was investigated for 430 patients treated for a choroidal melanoma at the proton therapy centre of the Institut Curie (ICPO) in Orsay, France, between 2008 and 2011. 60% of them report light flashes, which are predominantly (74%) blue. An analysis of variables describing the patient's physiology, properties of the tumour and dose distribution shows that two groups of tumour and beam variables are correlated with phosphene occurrence. Physiology is found to have no influence on flash triggering. Detailed correlation study eventually suggests a possible twofold mechanism of phosphene generation based on (i) indirect Cerenkov light in the bulk of the eye due to nuclear interactions and radioactive decay and (ii) direct excitation of the nerve fibres in the back of the eye and/or radical excess near the retina.

An empirical model for calculation of the collimator contamination dose in therapeutic proton beams.

Collimators are used as lateral beam shaping devices in proton therapy with passive scattering beam lines. The dose contamination due to collimator scattering can be as high as 10% of the maximum dose and influences calculation of the output factor or monitor units (MU). To date, commercial treatment planning systems generally use a zero-thickness collimator approximation ignoring edge scattering in the aperture collimator and few analytical models have been proposed to take scattering effects into account, mainly limited to the inner collimator face component. The aim of this study was to characterize and model aperture contamination by means of a fast and accurate analytical model. The entrance face collimator scatter distribution was modeled as a 3D secondary dose source. Predicted dose contaminations were compared to measurements and Monte Carlo simulations. Measurements were performed on two different proton beam lines (a fixed horizontal beam line and a gantry beam line) with divergent apertures and for several field sizes and energies. Discrepancies between analytical algorithm dose prediction and measurements were decreased from 10% to 2% using the proposed model. Gamma-index (2%/1 mm) was respected for more than 90% of pixels. The proposed analytical algorithm increases the accuracy of analytical dose calculations with reasonable computation times.

Dosimetric characteristics of four PTW microDiamond detectors in high-energy proton beams.

Small diamond detectors are useful for the dosimetry of high-energy proton beams. However, linear energy transfer (LET) dependence has been observed in the literature with such solid state detectors. A novel synthetic diamond detector has recently become commercially available from the manufacturer PTW-Freiburg (PTW microDiamond type 60019). This study was designed to thoroughly characterize four microDiamond detectors in clinical proton beams, in order to investigate their response and their reproducibility in high LET regions. Very good dosimetric characteristics were observed for two of them, with good stability of their response (deviation less than 0.4% after a pre-irradiation dose of approximately 12 Gy), good repeatability (coefficient of variation of 0.06%) and a sensitivity of approximately 0.85 nC Gy(-1). A negligible dose rate dependence was also observed for these two microDiamonds with a deviation of the sensitivity less than 0.7% with respect to the one measured at the reference dose rate of 2.17 Gy min(-1), in the investigated dose rate range from 1.01 Gy min(-1) to 5.52 Gy min(-1). Lateral dose profile measurements showed the high spatial resolution of the microDiamond oriented with its stem perpendicular to the beam axis and with its small sensitive thickness of about 1 µm in the scanning profile direction. Finally, no significant LET dependence was found with these two diamond dosimeters in comparison to a reference ionization chamber (model IBA PPC05). These good results were in accordance to the literature. However, this study showed also a non reproducibility between the devices in terms of stability, sensitivity and LET dependence, since the two other microDiamonds characterized in this work showed different dosimetric characteristics making them not suitable for proton beam dosimetry with a maximum difference of the peak-to-plateau ratio of 6.7% relative to the reference ionization chamber in a clinical 138 MeV proton beam.

[Chordomas of the base of the skull and upper cervical spine. 100 patients irradiated by a 3D conformal technique combining photon and proton beams]. / Les chordomes de la base du crâne et du rachis cervical haut. A propos d'une série de 100 patients irradiés selon une technique conformationnelle 3D par une association de faisceaux de photons et de protons.

OBJECTIVE: To define prognostic factors for local control and survival in 100 consecutive patients treated by fractionated photon and proton radiation for chordoma of the skull base and upper cervical spine. PATIENTS AND METHODS: Between December 1995 and August 2002, 100 patients (median age: 53 years, range: 8-85, M/F sex-ratio: 3/2), were treated by a combination of high-energy photons and protons. The proton component was delivered by the 201 MeV proton beam of the Centre de Protonthérapie d'Orsay (CPO). The median total dose delivered to the gross tumour volume was 67 Cobalt Gray Equivalent (CGE) (range: 60-71). A complete surgery, incomplete surgery or a biopsy was performed before the radiotherapy in 16, 75 and 9 cases, respectively. RESULTS: With a median follow-up of 31 months (range: 1-87), 25 tumours failed locally. The 2 and 4-year local control rates were 86.3% (+/-3.9%) and 53.8% (+/-7.5%), respectively. According to multivariate analysis, less than 95% of the tumour volume encompassed by the 95% isodose line (P=0.048; RR: 3.4 IC95% [1.01-11.8]) and a minimal dose less than 56 CGE (p=0.042; RR: 2.3 IC95% [1.03-5.2]) were independent prognostic factors of local control. Ten patients died. The 2 and 5-year overall survival rates were 94.3% (+/-2.5%) and 80.5% (+/-7.2%). According to multivariate analysis, a controlled tumour (P=0.005; RR: 21 IC95% [2.2-200]) was the lonely independent favourable prognostic factor for overall survival. CONCLUSION: In chordomas of the skull base and upper cervical spine treated by surgical resection followed by high-dose photon and proton irradiation, local control is mainly dependent on the quality of radiation, especially dose-uniformity within the gross tumour volume. Special attention must be paid to minimise underdosed areas due to the close proximity of critical structures and possibly escalate dose-constraints to tumour targets in future studies, in view of the low toxicity observed to date.

Proton minibeam radiation therapy: Experimental dosimetry evaluation.

PURPOSE: Proton minibeam radiation therapy (pMBRT) is a new radiotherapy (RT) approach that allies the inherent physical advantages of protons with the normal tissue preservation observed when irradiated with submillimetric spatially fractionated beams. This dosimetry work aims at demonstrating the feasibility of the technical implementation of pMBRT. This has been performed at the Institut Curie - Proton Therapy Center in Orsay. METHODS: Proton minibeams (400 and 700 µm-width) were generated by means of a brass multislit collimator. Center-to-center distances between consecutive beams of 3200 and 3500 µm, respectively, were employed. The (passive scattered) beam energy was 100 MeV corresponding to a range of 7.7 cm water equivalent. Absolute dosimetry was performed with a thimble ionization chamber (IBA CC13) in a water tank. Relative dosimetry was carried out irradiating radiochromic films interspersed in a IBA RW3 slab phantom. Depth dose curves and lateral profiles at different depths were evaluated. Peak-to-valley dose ratios (PVDR), beam widths, and output factors were also assessed as a function of depth. RESULTS: A pattern of peaks and valleys was maintained in the transverse direction with PVDR values decreasing as a function of depth until 6.7 cm. From that depth, the transverse dose profiles became homogeneous due to multiple Coulomb scattering. Peak-to-valley dose ratio values extended from 8.2 ± 0.5 at the phantom surface to 1.08 ± 0.06 at the Bragg peak. This was the first time that dosimetry in such small proton field sizes was performed. Despite the challenge, a complete set of dosimetric data needed to guide the first biological experiments was achieved. CONCLUSIONS: pMBRT is a novel strategy in order to reduce the side effects of RT. This works provides the experimental proof of concept of this new RT method: clinical proton beams might allow depositing a (high) uniform dose in a brain tumor located in the center of the brain (7.5 cm depth, the worst scenario), while a spatial fractionation of the dose is retained in the normal tissues in the beam path, potentially leading to a gain in tissue sparing. This is the first complete experimental implementation of this promising technique. Biological experiments are needed in order to confirm the clinical potential of pMBRT.

An experimental approach to the design of a scattering system for a proton therapy beam line dedicated to ophthalmological applications.

PURPOSE: The development of a scattering system for a proton therapy beam line dedicated to ophthalmological applications. METHODS AND MATERIALS: A protontherapy beam line has been developed for the treatment of uveal melanoma at the Orsay synchrocyclotron. The original 200 MeV proton beam is degraded to 76 MeV and the final beam characteristics (range, modulation, flatness, collimation) are obtained with beam modifiers in the treatment room. A passive scattering system is used to obtain a uniform dose distribution in the beam cross-section throughout 30 mm in diameter, with minimal losses in energy and dose rate. We have used an experimental approach for the scattering study. RESULTS: An elliptical ring shaped from 0.1-mm thick lead is the solution we have adopted for the scattering system. For a modulated beam, a flatness of 1% is obtained on transverse profiles. The energy loss introduced by this scatterer is only 0.5 MeV, with no appreciable change in the range over the treatment field. For an unmodulated beam, 21% of intensity is lost when the scatterer is used. The distal and the lateral dose fall-off (90-10%) for a modulated beam are 2.6 mm. These last values are independent of the range and the modulation currently used for the ophthalmic applications. CONCLUSION: A specific passive scattering system can be adapted to a particular beam emittance. A systematic experimental approach can easily be undertaken to obtain the scatterer adapted for small irradiation fields in proton therapy.

Proton dosimetry comparison involving ionometry and calorimetry.

A comparison of the absorbed dose to tissue determined by various ionization chambers, Faraday cups, and an A-150 plastic calorimeter was performed in the 200 MeV proton beam of Orsay, France. Four European proton-therapy centers (Clatterbridge, UK, Louvain la Neuve, Belgium, and Nice and Orsay, France) participated in the comparison. An agreement of better than 1% was observed in the absorbed dose to A-150 measured with the different chambers of the participating groups. The mean ratio of the absorbed dose to A-150 determined with the calorimeter to that determined by the different ionization chambers in the different irradiation conditions was found to be 0.952 +/- 0.007 [1 standard deviation (SD)] according to the code of practice used by all the participating centers, based on Janni's tables of stopping powers and a value of 35.2 J/Coulomb for (W(air)/e)p. A better agreement in the mean ratio calorimeter/chamber, 0.985 +/- 0.007 (1 SD) is observed when using the proton stopping power ratio values recently published by the International Commission on Radiation Units and Measurements in Report no. 49. The mean ratio of these doses determined in accordance with the American Association of Physicists in Medicine protocol and using the new recommended stopping power tables becomes 1.002 +/- 0.007 (1 SD). Two Faraday cups agree in measured charge to within 0.8%; however, the calculation of dose is underestimated by up to 17%; compared with ion chamber measurements and seems to be very sensitive to measurement conditions, particularly to the distance to the collimator.

A preliminary comparative treatment planning study for radiotherapy of age-related maculopathy.

PURPOSE: We present a comparative planning of different approaches for external radiotherapy in age-related maculopathies. MATERIALS AND METHODS: Calculated dose distributions and dose-volume histograms for (a) bilateral irradiation with 6 MV photons, (b) a single lateral-oblique beam using either photons, electrons or protons and (c) an anterior circular proton beam. RESULTS: For lateral photon or electron beams the dose to the lens is usually lower than 10% of the dose to the macula. The entrance doses for bilateral photon beams are about 50% which increase up to 100% at the orbital bone. About 5 mm of optic nerves are irradiated at the maximal dose while the optic chiasma is spared. A single photon beam gives 50% of the dose to the fellow eye. The electron beam spares the fellow eye but gives a rather inhomogeneous dose to the target volume. For a lateral proton beam, 4 mm of optic nerve receives 90% of the dose, the skin dose is at least 70% of the dose to the macula and the lens and the fellow eye are spared. An anterior proton beam gives 90% of the dose to 1 mm of optic nerve and the 50% isodose approaches the periphery of the lens. CONCLUSION: Doses to the critical structures can be dramatically diminished for all the techniques by reducing the beam size, but only if very precise set-up techniques are used. Proton beams are an attractive solution, but the impact of such a choice on the use of proton facilities and on the national health system should be carefully evaluated, as well as the risk of radio-induced secondary neoplasias.

A model for the lateral penumbra in water of a 200-MeV proton beam devoted to clinical applications.

An experimental approach for modeling the lateral penumbra of a proton beam has been investigated. Measurements were made with a silicon diode in a water tank. Several geometrical configurations (phantom position, collimator-to-surface distance, collimator diameter, bolus thickness, air gap, etc.) and beam characteristics (range, modulation, etc.) have been studied. The results show that the lateral penumbra is almost independent of the beam modulation and the diameter of the collimator. The use of scaled variables for depth and penumbra allows us to represent the increase in penumbra with depth for any configuration with a second order polynomial function, provided that the penumbra at the entrance of the medium and at the depth of the range are known.

Experimental determination and verification of the parameters used in a proton pencil beam algorithm.

We present an experimental procedure for the determination and the verification under practical conditions of physical and computational parameters used in our proton pencil beam algorithm. The calculation of the dose delivered by a single pencil beam relies on a measured spread-out Bragg peak, and the description of its radial spread at depth features simple specific parameters accounting individually for the influence of the beam line as a whole, the beam energy modulation, the compensator, and the patient medium. For determining the experimental values of the physical parameters related to proton scattering, we utilized a simple relation between Gaussian radial spreads and the width of lateral penumbras. The contribution from the beam line has been extracted from lateral penumbra measurements in air: a linear variation with the distance collimator-point has been observed. Analytically predicted radial spreads within the patient were in good agreement with experimental values in water under various reference conditions. Results indicated no significant influence of the beam energy modulation. Using measurements in presence of Plexiglas slabs, a simple assumption on the effective source of scattering due to the compensator has been stated, leading to accurate radial spread calculations. Dose measurements in presence of complexly shaped compensators have been used to assess the performances of the algorithm supplied with the adequate physical parameters. One of these compensators has also been used, together with a reference configuration, for investigating a set of computational parameters decreasing the calculation time while maintaining a high level of accuracy. Faster dose computations have been performed for algorithm evaluation in the presence of geometrical and patient compensators, and have shown good agreement with the measured dose distributions.

Intraocular inflammation after proton beam irradiation for uveal melanoma.

AIM: To describe the inflammatory reaction that can occur following proton beam irradiation of uveal melanomas based on a large series of patients and to try to determine the risk factors for this reaction. METHODS: Data from a cohort of patients with uveal melanoma treated by proton beam irradiation between 1991 and 1994 were analysed. The presence of inflammation was recorded and evaluated. Kaplan-Meier estimates and statistical analysis of general and tumour related risk factors were performed. RESULTS: 28% of patients treated during this period presented with ocular inflammation (median follow up 62 months). Risks factors were essentially tumour related and were correlated with larger lesions (height > 5 mm, diameter > 12 mm, volume > 0.4 cm(3)). Multivariate analysis identified initial tumour height and irradiation of a large volume of the eye as the two most important risk factors. Ocular inflammation usually consisted of mild anterior uveitis, resolving rapidly after topical steroids and cycloplegics. The incidence of inflammation after proton beam irradiation of melanomas seems higher than previously reported and is related to larger lesions. Evidence of inflammation associated with uveal melanoma has been described and seems to be associated with tumour necrosis (spontaneous or after irradiation). The appearance of transient inflammation during the follow up of these patients may be related to the release of inflammatory cytokines during tumour necrosis. CONCLUSION: Inflammation following proton beam irradiation is not unusual. It is correlated with larger initial tumours and may be related to tumour necrosis.

[Conformal index and radiotherapy].

Goal of radiotherapy is to treat patient with the best therapeutic ratio, i.e. the highest local control and the lowest toxicity rates. The conformal approach, three-dimensional conformal radiotherapy or intensity-modulated radiotherapy, is based on imageries, up-dated 3-D treatment planning systems, immobilization systems, restricted quality assurance and treatment verification. The aim is to ensure a high dose distribution tailored to the limits of the target volume, while reducing exposure of normal tissues. The evaluation tools used for optimizing treatment are the visual inspection of the dose distribution in various planes, and the dose-volume histograms, but they do not fully quantify the conformity of dose distributions. The conformal index is a tool for scoring a given plan or for evaluating different treatment plans for the same patient. This paper describes the onset and evolution of conformal index and his potential application field.

[Initial results of proton therapy in choroidal melanoma at the d'Orsey Center for Proton Therapy; the first 464 cases]. / Résultats préliminaires de la protonthérapie du mélanome de la choroïde au centre de protonthérapie d'Orsay (CPO): les 464 premiers cas.

PURPOSE: Retrospective analysis of the treatment of choroidal melanoma with protontherapy at the Centre de protonthérapie d'Orsay, France. PATIENTS AND METHODS: Between September 1991 and September 1995, 612 patients presenting with choroidal melanoma were treated by protontherapy in Orsay. Following initial management of the first 464 patients, results were analyzed, as were results after a 1-year follow-up for 305 patients, a 2-year follow-up for 169 patients, and a 3-year follow-up for 59 patients. RESULTS: Univariate analysis showed that the actuarial local recurrence rate was 5%, the 3-year survival rate 88%, and the overall metastasic rate 5%. The initial tumor volume was the most significant predictive factor for visual results and metastases. Multivariate analysis revealed that visual results were significantly related to the initial tumor volume, initial retinal detachment, and total dose delivered to the optic nerve and macula. CONCLUSION: Protontherapy of choroidal melanoma allows in most cases conservation of the eye without modification of survival. Visual results mainly depend on the site and size of the tumor.

[Results of proton beam irradiation for treatment of choroidal melanoma]. / Résultats du traitement du mélanome de la choroïde par faisceau de protons.

PURPOSE: To evaluate the results of proton beam irradiation of choroidal melanomas on a large series of patients. PATIENTS AND METHODS: Retrospective analysis of a series of patients treated with proton beam irradiation between 1991 and December 1998. The data were analyzed to evaluate the local tumor control as well as the general progression and metastatic rate of the patients. Statistical analysis served to isolate risk factors for relapse or metastasis. RESULTS: We treated 1062 patients during the study period, with a median follow-up of 38 months. Local control was obtained for 97.1% of the patients. Tumors anterior to the equator were at risk for relapse. The survival rate was 92% at 2 years and 78% at 5 years. 73.1% of the 1062 patients died from metastasis, 6.1% of living patients presented with metastatic disease. The risk factors for death were the initial diameter, the age of the patient, and large tumor volume at diagnosis. Metastasis were essentially hepatic (94.6%). Risk factors for metastasis were: a large tumor volume, a lesion anterior or straddling the equator and the age of the patient. Ocular complications may induce a visual loss of 0.1 and less in 47% of the patients, due to optic nerve head and macular ischemia. 6% of the patients required secondary enucleation due to local complications (neovascular glaucoma). CONCLUSION: Proton beam irradiation of choroidal melanoma allows good tumor control and eye retention. The survival prognosis is associated with the initial volume of the tumor. The functional results may be improved and new therapeutics are needed to treat metastatic disease.

[Optic neuropathy after proton-beam therapy for malignant choroidal melanoma]. / Neuropathie optique après protonthérapie pour mélanome malin de la choroïde.

Proton-beam irradiation is a conservative therapy commonly used for the treatment of uveal malignant melanomas. Some adverse effects such as optic neuropathy can compromise the visual outcome. We were interested in determining the risk factors for radiation papillopathy. Since there is currently no effective therapy, this is an interesting way to improve prevention of optic neuropathy. Six hundred sixty-two eyes had more than 24 month follow-up after proton-beam irradiation for uveal melanoma. In five hundred twenty-two cases, the clinical examination of the optic nerve head by ophthalmoscopy was possible. One-hundred eleven optic discs were pathologic, whereas 411 remained disease-free. Retrospective study of these two groups allowed to quantify the risk factors for optic neuropathy. The irradiation of more than 2mm of optic nerve at 30 Grays-equivalents appeared to be the major risk factor for optic neuropathy. For a given irradiation dose, the observed pattern of clinical responses was heterogeneous. These results are discussed and compared to the previous published reports. Visual results and life prognosis are also discussed, considering the optic nerve head status. Proton-beam therapy can preserve the optic nerve when the tumor location allows to keep it away from the irradiation-field. Patients must be informed about the risk of optic neuropathy after proton-beam irradiation.