G Willerding

Ten-year results of transscleral resection of large uveal melanomas: local tumour control and metastatic rate

Aims To describe the long-term tumour control and metastatic rate after transscleral resection (TSR) of large uveal melanomas in a single-centre study. Methods The sample included 210 patients with large uveal melanomas. Univariate analysis of local tumour control and metastatic risk by Kaplan–Meier survival curves and log-rank testing. Cox proportional HR analysis with forward and backward selection was used to identify independent prognostic factors in patients submitted to TSR of a large uveal melanoma. Results A residual tumour was diagnosed in 6% of the patients. The 5- and 10-year local tumour recurrence rates were 24% and 32%, respectively. Older age, a large basal tumour diameter, the lack of adjuvant ruthenium brachytherapy and retinal detachment led to a 2.6, 2.4, 4.4 and 7.8 times higher risk of melanoma recurrence, respectively. The 5- and 10-year metastatic rates were 28% and 44%, respectively, and were statistical significantly affected by extraocular spread, tumour thickness and local tumour recurrence. Conclusions TSR is an alternative to enucleation for the treatment of large uveal melanomas. Results should improve with better patient selection and more effective methods of adjuvant radiotherapy.

Ifosfamide or trofosfamide in patients with intraocular lymphoma

We evaluated response, progression-free survival (PFS), overall survival (OS), relapse patterns and long-term toxicity of intraocular lymphoma (IOL) patients treated with ifosfamide (IFO) or trofosfamide (TRO). In a prospective single center study, IFO or TRO were given to 10 patients with IOL. The median patient age was 73 (range 46–83) years. Six patients were pretreated with up to four treatment regimens for ocular or cerebral lymphoma, and four were therapy-naive. All patients responded, including nine complete remissions and one partial remission, with a median PFS of 18 (7–36) months. Seven patients relapsed: five in the eye and two in the brain. Median OS was 32 (7–37+) months. No long-term toxicity was observed in patients treated with IFO or TRO alone. IFO or TRO were active and well tolerated in this study. Thus, they may represent suitable combination partners for other cytostatics used for PCNSL and IOL treatment.

Proton Beam Therapy of Parapapillary Choroidal Melanoma

PURPOSE To analyze the functional outcome with regard to the development of visual acuity and radiation-induced optic neuropathy of patients with parapapillary choroidal melanoma treated with proton beam therapy. DESIGN Clinical case series, retrospective study. METHODS We evaluated 147 consecutive patients with parapapillary choroidal melanoma who received proton beam therapy as primary tumor treatment at the Helmholtz Center in Berlin from 1998 to 2005. A cumulative dose of 60 Cobalt Gray Equivalents (CGE) was delivered to the tumor and the optic disc received a minimum of 50 CGE. Kaplan-Meier analysis was used to assess ocular outcome and survival rates. For trend analysis of functional development, Wilcoxon-Mann-Whitney U test was used to compare the medians of 2 groups and Kruskal-Wallis test was used in the case of more than 2 groups. RESULTS The mean follow-up time was 6.5 years (range 0.3-11.7 years). The most common side effects were radiation-induced optic neuropathy, retinopathy, and cataract. The median visual acuity before and within the first year after therapy was 0.4 logMAR (20/50), lapsing to 1.3 logMAR (20/400) after 3 years and 1.4 logMAR (20/500) after 5 years. During follow-up, no light perception developed in 17 cases (11.6%), mostly attributed to radiation-induced retinopathy, optic neuropathy, and secondary glaucoma. Enucleation was carried out in 14 patients (9.5%) because of local recurrence or severe side effects. CONCLUSION Radiation-induced optic neuropathy is an expected issue after proton beam therapy of parapapillary choroidal melanoma, and visual impairment is common during long-term follow-up, but some useful vision can be preserved in a considerable number of patients.

Proton beam radiotherapy of diffuse iris melanoma in 54 patients

Background Treatment modalities in iris melanoma include excision, plaque radiotherapy, photon or proton beam therapy and enucleation. In extensive tumours and diffuse seeding, radiotherapy remains as an alternative to enucleation. Methods This study is a retrospective, consecutive, interventional, single-institutional case series. 54 patients with a diffuse and non-resectable iris melanoma diagnosed from September 1998 to June 2012 were included. A 68-megaelectron volt proton beam was used to treat the anterior segment with a total dose of 4×12.5 cobalt grey equivalent. The cases were evaluated for local tumour control, eye retention, functional outcome and local complications after treatment. Results During a mean follow-up of 62.7 months (median 54.8 months, range 5.5–159.6 months), local tumour control was achieved in 96.3% of the patients. Cataract and glaucoma were the main complications developing after irradiation in 42.6% and 55.6%, respectively. In 34 of 44 patients (77.3%) who underwent cataract removal, a visual acuity of 20/40 or better following surgery was preserved. Enucleation was performed in three patients. The reason was suspected tumour recurrence in one and glaucoma in two. Hepatic metastasis occurred in one patient. Conclusions As an alternative to enucleation, whole anterior segment fractionated proton beam radiotherapy offered excellent local tumour control in diffuse iris melanoma. Given the limited alternatives, the rate of complications appears acceptable and visual function could be preserved in the majority of the patients during follow-up.

Neoadjuvant proton beam irradiation followed by transscleral resection of uveal melanoma in 106 cases

Aims To describe results after neoadjuvant proton beam irradiation followed by transscleral resection of large uveal melanoma. Methods Retrospective interventional case series, including 106 consecutive patients. Local tumour control, enucleation and metastasis development were assessed with survival curves. Predictors of local recurrence and metastasis were investigated with log-rank testing. Results Mean follow-up was 3.2 years. Local recurrence occurred in five cases with an estimated risk of 4.2% and 10.4% at 3 and 5 years after treatment, respectively. Enucleation was performed in 10 cases with an estimated risk of 9.2% and 18.4% at 3 and 5 years, respectively. Significant risk factors for local recurrence were not evident. Metastasis was estimated to occur in 28.4% at 3 years and 40.3% at 5 years, correlating with patients age only (p=0.01). Seventy four patients (69.8%) underwent vitreoretinal surgery for complications after tumour resection. Median visual acuity (VA) was 20/50 at diagnosis and 20/400 in the third year after treatment. VA preservation of 20/200 or better was achieved in 33 patients (31.1%). Conclusion Neoadjuvant proton beam irradiation may help to prevent local recurrence after transscleral resection. Additional vitreoretinal surgery was frequently needed in the presented series. The majority of patients avoided enucleation and functional blindness.

Diagnostik und Therapie choroidaler Melanome

BACKGROUND Prognosis evaluation of patients with choroidal and ciliary melanoma has experienced recent progress through tumour sampling and cytogenetic analysis of metastatic risk. By allocating tumor extension, height and linear basal diameter to defined TNM stages, an estimation of prognosis can also be made without invasive tissue sampling. METHODS Therapeutic strategies of organ preserving irradiation using different sources have clearly come to the forefront. RESULTS Due to microscopic haematogenous spreading of tumour cells prior to treatment, the metastatic risk following radiation of any form is not influenced in comparison to primary enucleation. CONCLUSION However, metastatic disease still remains a fatal condition which currently may only be influenced by early detection and treatment of uveal melanomas.

Results and complications after implantation of a black iris-lens diaphragm in patients with traumatically induced aphakia and aniridia.

Purpose. The black iris-lens diaphragm (ILD) can be used in the treatment of traumatic aniridia and aphakia. The aim of our study was to show postoperative functional and anatomic results and complications in a small case series. Methods. We retrospectively analyzed the files of 16 patients managed with a black ILD or a sole iris diaphragm in the period 1994–2007. Four of them were female and 12 were male. The mean age of the group was 50±17 years. At the time of the implantation, all of the eyes had already undergone primary surgical repair. Results. The preoperative best-corrected visual acuity in half of the patients was ≥0.1 and remained stable after the first postoperative year. During the follow-up years, one eye developed a subluxation of the implant and one eye an anterior chamber hemorrhage. At the same time, out of 8 eyes carrying a silicone tamponade in the vitreous cavity, silicone oil entered the anterior chamber in 3 cases. In one case, enucleation was undertaken due to phthisis. Conclusions. In the case of severely traumatized eyes with aniridia and aphakia, the implantation of a black ILD can have a positive effect on functional and anatomic stabilization.

Surgical treatment modalities in uveal melanomas

The treatment of large uveal melanomas poses a therapeutic challenge, due to the expected treatment-related side-effects. After sole radiotherapy the majority of patients are faced with radiogenic complications secondary to the large amount of tumour necrosis. Alternative treatment modalities addressing this issue are transscleral resection in arterial hypotension in anteriorly located tumours and endoresection via pars plana vitrectomy in posteriorly located tumours. A surgical resection treatment was applied in 292 patients with large uveal melanomas. In 150 patients the tumour was treated by transscleral resection and postoperative adjuvant (106)ruthenium brachytherapy and 142 patients were treated by primary proton beam irradiation and secondary endoresection. The mean follow-up time was 3.8 and 2.5 years, respectively. Local tumour control was achieved in 76 % and 98 %, respectively. The 5-year metastatic rates were 28 % and 21 % and eye retention was achieved in 82 % and 97 %, respectively. Surgical resection of uveal melanomas with adjuvant radiotherapy is the treatment of choice in cases of large tumours, avoiding enucleation in the vast majority of cases in the long term, without increasing the incidence of tumour-related risks.

Die Behandlung von großen Aderhautmelanomen durch chirurgische Exzisionsverfahren

SummaryThe functional results after treatment of uveal melanomas are dependent on their size and location within the eye. Large tumours have an increased ocular morbidity due to the expected radiogenic side-effects, in addition to the ocular burden that results from increased tumour regression and necrosis related deposition of cellular and cytokine by products. To address these issues combined radiotherapeutical-surgical techniques have been developed, that result in both increased local tumour control and decreased ocular side-effects. In this overview 292 patients treated by either transscleral resection in general hypotension with adjuvant ruthenium-106 brachytherapy or by proton beam irradiation and subsequent endoresection where analysed. The 5-year mortality varied between 21 and 28%. The enucleation rate was 3 and 18% and the local recurrence rate was 2 and 24% in patients treated by ab interno endoresection or ab externo transscleral resection respectively. In patients treated by transscleral resection there was a correlation between recurrence rate and tumour metastasis. The recurrence rate could be reduced to a minimum (2%) when combined with preoperative proton beam irradiation. A combined irradiation- surgical procedure seems to be required in order to reduce treatment related side-effects.ZusammenfassungDie funktionellen Ergebnisse der Behandlung von Aderhautmelanomen ist abhängig von deren Größe und Lage innerhalb des Auges. Große Tumoren haben eine erhöhte okuläre Morbidität wegen der zu erwartenden radiogenen Nebenwirkungen. Hinzu kommt die okuläre Belastung durch die vermehrte Anhäufung von Tumorzerfallprodukten durch den Tumorabbau und die Tumornekrose. Um diese Problematik zu adressieren sind kombinierte strahlentherapeutisch-chirurgische Verfahren entwickelt worden, die sowohl eine sehr gute Tumorkontrolle als auch eine reduzierte okuläre Morbidität zur Folge haben. In dieser Übersichtsarbeit werden 292 Patienten zusammengefasst, bei denen entweder eine transsklerale Resektion in arterielle Hypotonie mit anschließender Ruthenium-106 Brachytherapie oder eine Protonentherapie mit anschließender Endoresektion durchgeführt wurde. Die 5-Jahres Überlebenswahrscheinlichkeit der Patienten schwankte zwischen 21 und 28%. Die Enukleationsraten betrugen 3 und 18% und die lokale Rezidivraten 2 und 24% bei ab interno Endoresektion und ab externo Resektion entsprechend. Bei Patienten deren Tumor ab externo transskleral reseziert wurde fand sich eine Korrelation zwischen erhöhter Rezidivrate und Mortalität. Die Rezidivrate konnte mit einer präoperativen Protonenbestrahlung auf ein Minimum (2%) reduziert werden. Ein kombiniertes strahlentherapeutisch-chirurgisches Vorgehen scheint unter dem Lichte dieser Daten unabdingbar zu sein.

Proton Beam Therapy Leads to Excellent Local Control Rates in Choroidal Melanoma in the Intermediate Fundus Zone

PURPOSE To evaluate long-term outcomes of proton beam radiotherapy in the treatment of choroidal melanoma of the intermediate zone of the fundus. DESIGN Retrospective interventional single-center study. METHODS The study was a retrospective analysis with long-term follow-up of 62 patients with a minimum tumor-to-disc and tumor-to-fovea distance of 2 mm of choroidal melanoma in the intermediate zone of the fundus. Mean values of tumor prominence, largest basal diameter, and tumor distances to the optic disc and fovea were 7.6, 12.8, 5.2, and 4.6 mm, respectively. All patients were irradiated with a total proton dose of 60 cobalt gray equivalents. RESULTS After proton beam radiotherapy, 71.0% of the patients received subsequent endoresection of the tumor. Only 18 patients (29.0%) did not require additional tumor resection and were analyzed as a separate group. For the total of patients, the median follow-up time was 70.3 months. The 5-year Kaplan-Meier rates of local tumor relapse, enucleation, and distant metastasis were 3.9%, 3.7%, and 13.4%, respectively. Cataract surgery was the most frequent secondary treatment in our cohort. CONCLUSIONS In this study we demonstrate the effectiveness of proton beam irradiation in tumor control and preservation of the globe in the analyzed patients. The rate of metastasis was not higher than previously described. Nevertheless, consecutive tumor surgery is frequently required to maintain the eye in patients with large-sized choroidal melanomas. In conclusion, proton beam radiotherapy allows preservation of the eye in mid-zone choroidal melanomas.