[Local, regional and systemic dissemination of choroidal melanoma : Clinical and pathological correlation from 2 cases]. / Dissémination locorégionale et systémique du mélanome choroïdien : corrélation anatomoclinique à partir de 2 cas.

PURPOSE: To describe didactically the local, regional and systemic spread of choroidal melanoma. PATIENTS AND METHODS: Two patients who had undergone primary enucleation for the management of choroidal melanoma in 2018 at the University Hospital of Nice were included. Extrascleral extension and invasion of the vortex veins were evaluated, as well as synchronous and metachronous metastases, based on our database. RESULTS: Patient 1 was diagnosed with large choroidal melanoma with partial scleral invasion and vortex vein involvement. Cytogenetic analysis demonstrated a loss of chromosome 3, and a gain of chromosome 8q. Systemic work-up was unremarkable. Patient 2 was diagnosed with a large choroidal melanoma with extrascleral extension and vortex vein involvement. Cytogenetic analysis demonstrated a loss of chromosome 3 and a gain of chromosome 8q. Systemic work-up revealed several liver metastases. A total of 1762 patients were included in our database. Eighty-five patients (4.8 %) and 46 patients (2.6 %) experienced vortex vein invasion and extrascleral extension respectively. Patients with vortex vein invasion were diagnosed with synchronous and metachronous liver metastases in 1.2 % and 18.8 % respectively. Patients with extrascleral extension had synchronous and metachronous liver metastases in 6.5 % and 30.4 % respectively. The mean follow-up was 49.4 months (1-180). CONCLUSION: Extrascleral extension and vortex vein invasion illustrate the local, regional and systemic spread of choroidal melanoma. The latter are often associated with genetically aggressive tumours associated with high metastatic risk.

Tumour Response in Uveal Melanomas Treated with Proton Beam Therapy.

AIMS: Post-proton therapy surveillance of uveal melanomas relies on decreased thickness on repeat ultrasound B every 6 months for 2 years and yearly thereafter. Earlier pseudoprogression, a phenomenon described in other tumour types within the first months of irradiation, can also be observed in uveal melanomas and may lead to inappropriate enucleation. The Collaborative Ocular Melanoma Study (COMS) has defined ultrasound criteria to identify tumour progression after brachytherapy. We aimed to determine the reliability of ultrasound as a means to measure tumour height after proton therapy and predict local relapse. MATERIALS AND METHODS: All 1992-2012 consecutive patients with at least three ultrasound B measurements during follow-up were included. RESULTS: There were 55 local relapses of 886 patients (6.2%). Ultrasound B reliability was highest at 24 months, with specificity higher than 95% starting at 18 months. CONCLUSION: Before 18 months post-proton therapy, the risk of falsely concluding in favour of a relapse exceeds 5% and should prompt repeat measurements 3 and 6 months later but should not prompt enucleation without further clinical assessment.

[Malignant tumours of the eye: Epidemiology, diagnostic methods and radiotherapy]. / Tumeurs malignes ophtalmologiques : indications de la radiothérapie et techniques.

Malignant tumours of the eye are not common, barely representing 1 % of all cancers. This article aims to summarise, for each of the main eye malignant diseases, aspects of epidemiology, diagnostic methods and treatments, with a focus on radiation therapy techniques. The studied tumours are: eye metastasis, intraocular and ocular adnexal lymphomas, uveal melanomas, malignant tumours of the conjunctive, of the lids, and retinoblastomas. The last chapter outlines ocular complications of radiation therapy and their management.

Management of choroidal metastases.

BACKGROUND: Choroidal metastases (CM) are the most common malignant intraocular lesion observed in up to 4-12% of necropsy series of patients with solid cancer. The spectrum of presentations varies from prevalent CM in disseminated cancer to isolated CM. CM are responsible for visual deterioration. Depending on the primary cancer, estimated life expectancy, overall cancer presentation and ocular symptoms, the management of CM varies widely. We address the multidisciplinary management of CM and technical aspects of radiotherapy. MATERIAL AND METHODS: A systematic review of literature was performed from 1974 to 2014. RESULTS: Choroidal metastases occur preferentially in breast and lung carcinomas but are reported in all cancer types. The standard treatment remains external beam radiotherapy, applying 30Gy in 10 fractions or 40Gy in 20 fractions. The reported complete response and improved visual acuity rates are 80% and 57% to 89%, respectively. Some chemotherapy or new targeted therapy regimens yield promising CM response rates. DISCUSSION: Radiation therapy consistently shows rapid symptom alleviation, yield excellent local control and functional outcomes. However, there are only few reports on late toxicities after 6months given the unfavorable prognostic of CM patients. Selected patients may live more than two years, underlying the need to better assess mean and long term outcomes. Some authors have favored exclusive systemic strategies with omission of irradiation. The current literature suffers from the scarcity of prospective trials. Duration of tumor response following systemic therapy is rarely reported but appears less favorable as compared to radiotherapy. Systemic treatments may be proposed for pauci-symptomatic CM in a polymetastatic context while radiation therapy remains necessary in symptomatic CM either upfront or as an alternating treatment. Focalized radiation like brachytherapy and proton therapy may be proposed for isolated CM with long disease-free interval between primary and CM, as these techniques have the potential to yield better tumor and functional outcomes in patients with long life expectancy.

[Benign conjunctival tumors]. / Tumeurs conjonctivales bénignes.

Benign conjunctival tumors include congenital, melanocytic, epithelial and stromal lesions. Clinical observation often fails to make the diagnosis, and complete excisional biopsy must be performed as soon as growth is suspected. Histology remains the best way to exclude malignancy or lesions with a risk of transformation, because malignant lesions carry a poor prognosis and require specific therapy and follow-up. Onco-ophthalmologists must have a perfect knowledge of benign conjunctival tumors, since during adulthood, nevi can be confused with melanomas, and epithelial or stromal lesions with carcinomas. For children and teenagers, surgery is only recommended when growth or functional problems are observed.

Quantification of dose perturbations induced by external and internal accessories in ocular proton therapy and evaluation of their dosimetric impact.

PURPOSE: Proton scattering on beam shaping devices and protons slowing down on media with different densities within the treatment volume may produce dose perturbations and range variations that are not predicted by treatment planning systems. The aim of this work was to assess the dosimetric impact of elements present in ocular proton therapy treatments that may disturb the prescribed treatment plan. Both distal beam shaping devices and intraocular elements were considered. METHODS: A wedge filter, tantalum fiducial marker, hemispherical compensator, two intraocular endotamponades (densities 0.97 and 1.92 g cm(-3)) and an intraocular eye lens (IOL) were considered in the study. For these elements, longitudinal dose distributions were measured and∕or calculated in water in beam alignment for a clinical spread-out Bragg peak. Under the same conditions, the unperturbed dose distributions were similarly measured and∕or calculated in the absence of the element. The dosimetric impact was assessed by comparison of unperturbed and perturbed dose distributions. Measurements and calculations were carried out with two methods. Measurements are based on EBT3 films with dedicated software, which makes use of a calibration curve and correction for the quenching effect. Calculations are based on the Monte Carlo (MC) code MCNPX and reproduce the experimental conditions. Both dose maps are obtained with a resolution of 300 dpi. RESULTS: The degree of disturbance of distal beam shaping devices is low for the wedge filter (2% overdose ripple all along the central axis) and moderate for the hemispherical compensator (two bands of variable overdose of up to 10% downstream the compensator lateral edges and -5% underdose on the plateau at off-axis distance of 5 cm). Tantalum clips produce important dose shadows (-20% behind the clip parallel to the beam and range reduction of 1.1 mm) and bands of overdose (15%). The presence of endotamponades modifies the dose distribution very significantly (-5% underdose on the plateau and 3 mm range prolongation for the tamponade with density 0.97 g cm(-3) and -15% underdose on plateau and 8 mm range reduction for that with density 1.92 g cm(-3)). No dose perturbations were found for the IOL. The high performance of EBT3 film and MC tools used was confirmed and good agreement was found between them (percentage of pixels passing the gamma test >87%). CONCLUSIONS: The degree of disturbance by external beam shaping devices remains low in ocular proton therapy and can be reduced by bringing accessories closer to the eye. Tantalum fiducial markers must be located in such a way that dose perturbation is not projected on the tumor. The treatment of patients with intraocular endotamponades must be carefully managed. It is fundamental that radiation oncologists and medical physicists are informed about the presence of such substances prior to the treatment.

[Surgical management of a recurrent iris stromal cyst]. / Prise en charge chirurgicale d'un kyste du stroma irien récidivant.

INTRODUCTION: Cysts of the iris stroma may be congenital or acquired. They are rare tumors of the anterior segment. We describe the case of a 51-year-old patient presenting with a recurrent iris stromal cyst. OBSERVATION: The patient presented emergently for sudden recurrence of an iris stromal cyst with decreased visual acuity. He had already undergone needle aspiration and argon laser photocoagulation of the cyst 1 year previously. A Ultrasound BioMicroscopy (UBM) examination was performed to rule out any malignant tumor of the iris or ciliary body. Surgical treatment consisted of complete removal of the external layer of the cyst with Implantable Contact Lens (ICL) forceps after marsurpialization with scissors. The postoperative course was uneventful. CONCLUSION: Cysts of the iris stroma are rare benign tumors that pose problems due to their extension into the anterior chamber and recurrence.

[The other pigmented lesions]. / Les autres taches pigmentées.

Not all intraocular pigmented lesions are melanomas or nevi. In this article, we present what we classically consider to be the main pigmented stains other than melanomas and nevi and their possible forms of treatment. Regarding tumor-related stains, we describe melanocytomas, congenital hypertrophy or reactive hyperplasia of the retinal pigment epithelium, combined hamartoma of the retina and retinal pigment epithelium, and acquired vascular pseudotumors. Among the hemorrhage-related stains, we present pseudotumoral age-related macular degeneration, peripheral exudative and hemorrhagic chorioretinopathy, choroidal hematoma, and rupture of macroaneurysms.

[Surgery and additional protontherapy for treatment of invasive and recurrent squamous cell carcinomas: technique and preliminary results]. / Association chirurgie-protonthérapie dans le traitement des carcinomes invasifs et récidivants de la conjonctive: technique et résultats préliminaires.

INTRODUCTION: Invasive squamous cell carcinomas are uncommon neoplasias with high recurrence and mortality rates. The improvement of tumoral control requires additional treatments such as cryotherapy, topical chemotherapy, and radiotherapy. We present the technique and preliminary results of associating treatment with surgery and proton beam therapy for recurrent and invasive squamous cell carcinomas. MATERIALS AND METHODS: From June 2001 to September 2008, 15 patients were treated in our ocular oncologic center for squamous cell carcinomas either with recurrences or with invaded resection margins. The treatment combined new surgical resection with protontherapy. Specific improvements in proton beam therapy have been made at the Nice Cyclotron to adapt the treatment to conjunctival tumors. Proton beam carving consists in using a specific device to treat the thickness of the whole lesion site and the adjacent conjunctiva and to spare the surrounding healthy structures. RESULTS: Patients were staged according to the TNM classification of malignant tumors in T2: 3; T3: 5; T4: 7. Mean follow-up was 39.1 months (range, 6-90 months). Our 15 patients included 12 males and three females. Left eyes were involved in eight cases. The mean age at first consultation was 63.7 years (range, 46-80 years). In 13 cases (86.8%), the bulbar and limbic conjunctiva was involved, in five of these cases the cornea was invaded, and the anterior chamber was involved in one case. In one case, the tumor was located on bulbar conjunctiva near the caruncle (6.6%) and in one case in the fornix (6.6%). One patient died of another cancer after 48 months of follow-up. We obtained local tumor control for 13 patients (86.8%) and recurrences for two patients (13.2%). One of them has presented with cervical node metastases. These two patients who presented recurring and extensive tumors had had previous repeated surgeries in other centers. Moreover, proton beam therapy was performed more than 6 months after the initial treatment. Exenteration and enucleation had to be performed to treat these recurrences 6 and 24 months after proton beam therapy. The exentered patient has been lost to follow-up. No patients developed recurrences with additional proton beam therapy performed within 6 months after initial surgical resection. As for side effects, seven patients suffered from sicca syndrome, six needed cataract surgeries, three unesthetic dilatations of episclera vessels, two conjunctival postradiation dysplasias, two experienced eyelash loss, one stenosis of the lacrimal duct, and one glaucoma controlled by monotherapy. Conjunctiva and amniotic grafts had to be performed on one of the patients presenting with dysplasia. Due to the rarity and diversity of these cases, it is nearly impossible to carry out prospective and comparative studies. CONCLUSION: Traditional adjuvant treatments often failed to control recurring and invasive squamous cell carcinomas. We often ended up performing exenteration to control local recurrences. The preliminary results of the present study suggest that proton beam therapy may be considered as a good alternative to traditional treatments with acceptable side effects.

[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.

["Melanoma 92". epidemiological study of uveal melanoma in France]. / "Mélanome 92". Etude épidémiologique des mélanomes uvéaux en France.

PURPOSE: The purposes of this study were to evaluate the incidence of uveal melanoma in France in 1992, to describe the characteristics of the tumors and their treatments. METHODS: This was a retrospective and multicentric study. First a questionnaire was sent to 4575 French ophthalmologists asking whether they had established a diagnosis of uveal melanoma during 1992, and if so, to describe the tumor and its management. Then the patients files were reviewed in the specialized treatment centers (Paris, Lyon, Nice, Strasbourg, Bordeaux, Clermont-Ferrand). All the data were statistically analysed. RESULTS: 412 new cases of uveal melanomas were registered (incidence 0.7/100000) affecting 234 females and 178 males. The cases ranged in age from 7 to 93 years (mean 61.5 years). There were 5 (1%) isolated tumors of the iris, 75 (18%) of the ciliary body, either isolated (10%) either associated to iris and/or to choroïdal tumors and 332 (81%) choroïdal melanomas. 201 (53%) tumors were posterior to the equator and 153 (40%) had a margin at less than 3 mm of the optic disc; 87 (21%) melanomas were detected in asymptomatic patients. In 29 (7%) other cases, the diagnosis was established after enlargement of the tumor. In all other eyes, symptoms were present. 17% of the melanomas were T1, 34% were T2, et 48% were T3. 353 (86%) melanomas were pigmented, 30 (7%) were achromic and 29 (7%) of the mixed color type. 156 (38%) tumors were associated with a retinal detachment. In 12 cases (3%), at presentation there was an extrascleral extension. 9 patients (2%) had metastases (7 to the liver, 1 to the lungs and 1 to the lungs and bones). The study of the patients residence and work did not show any environmental risk factor. The initial treatment was protontherapy in 251 patients (63%), plaque therapy in 91 (23%), enucleation in 40 (10%), and other methods in 18. CONCLUSION: This was the first epidemiologic study conducted in France on this subject. It describes the clinical features of the disease, its geographical display and its management in this country.