Dino Cordini

Proton Beam Therapy of Parapapillary Choroidal Melanoma

PURPOSEnTo 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.nnnDESIGNnClinical case series, retrospective study.nnnMETHODSnWe 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.nnnRESULTSnThe 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.nnnCONCLUSIONnRadiation-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.

Local Recurrence After Primary Proton Beam Therapy in Uveal Melanoma: Risk Factors, Retreatment Approaches, and Outcome

PURPOSEnTo evaluate the risk factors, recurrence rates, retreatments, and long-term patient outcomes following proton beam therapy for uveal melanoma.nnnDESIGNnRetrospective interventional case series.nnnMETHODSnAll patients treated with primary proton beam therapy for uveal melanoma at the oncology service at Charité-Berlin and Helmholtz-Zentrum-Berlin between May 1998 and December 2008 were reviewed for local recurrence. Of 982 patients, 982 eyes matched the inclusion criteria. The data were obtained from electronic health records, operative reports, discharge letters, and radiation planning. Comparisons of fundus photographs and ultrasound measurements were performed to assess the growth pattern of the tumor and to determine the success of retreatment, in the case that a globe-retaining therapy was undertaken.nnnRESULTSnOf 982 patients, 35 patients (3.6%) developed local recurrence. The median follow-up was 60.7 months (6.0-170.4 months). Local control rate was 96.4% and the overall eye retention rate was 95.0% in this cohort. Local recurrence was correlated with a higher risk for metastasis and reduced survival. Largest tumor diameter was identified as the sole statistically significant risk factor for local recurrence (P = .00001). All globe-retaining retreatment approaches for local recurrence, including proton beam therapy, brachytherapy, and transpupillary thermotherapy used for recurrences at the tumor margins, showed good local tumor control and similar metastasis-free survivals.nnnCONCLUSIONSnThis study showed that each globe-retaining retreatment approach can result in satisfying local tumor control. In case of early detection of local recurrence, preservation of the globe can be warranted. Therefore, regularly performed follow-ups should be ensured.

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 62.7u2005months (median 54.8u2005months, range 5.5–159.6u2005months), 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.

Long-term (4 years) results of choroidal hemangioma treated with proton beam irradiation.

BackgroundThe aim of this retrospective study was to determine the efficacy of proton beam irradiation in choroidal hemangioma in a long-term follow-up.Patients and methodsA total dose of 20 Cobalt Gray equivalent (CGE) was administered to 50 eyes of 50 patients from September 1998 to September 2010. All treated patients presented with a symptomatic tumor. Nine patients were pre-treated by photodynamic therapy (PDT). Visual outcome, tumor regression, and complications resulting from radiation were investigated.ResultsThe mean follow-up was 55.4xa0months (range 13–132). Tumor thickness decreased in all patients. Retinal re-attachment was achieved without evidence of tumor leakage. Visual acuity improved by two lines after onexa0year in 43.4xa0% of patients and after twoxa0years in 36.8xa0% of patients. During the 55.4xa0months of long-term follow-up the visual acuity improved from 6/15 to 6/12 after proton therapy. Twenty-three patients (46.0xa0%) developed radiation retinopathy. According to the Finger classification of 2004, 21 patients (42.0xa0%) showed a stage 1 or 2 (functionally not relevant) retinopathy, and two patients (4.0xa0%) presented a stage 3 or 4 (functionally relevant) retinopathy. Further complications included sicca syndrome in nine cases, cataract formation in 10 cases, and radiation optic neuropathy in four cases.ConclusionProton therapy with 20 CGE is an efficient primary therapy in choroidal hemangioma and is very effective as a secondary treatment after PDT.

Salvage proton beam therapy in local recurrent uveal melanoma.

PURPOSEnTo evaluate survival and ocular outcome in recurrent uveal melanoma treated with proton beam therapy as salvage therapy.nnnDESIGNnRetrospective, interventional case series.nnnMETHODSnWe evaluated 48 patients with local recurrence of uveal melanoma after primary treatment with brachytherapy, transpupillary thermotherapy, proton beam therapy, laser photocoagulation, CyberKnife radiation, or photodynamic therapy. All patients received proton beam therapy as a salvage therapy at the Helmholtz Zentrum Berlin between July 2000 and December 2010. Kaplan-Meier analysis was used to obtain survival rates.nnnRESULTSnThe Kaplan-Meier estimator for local tumor control was 92.1% at 10 years after secondary treatment with proton beam therapy. Local recurrence developed in 3 patients; 1 of them underwent enucleation. During follow-up, 20.8% of the patients died (16.7% of metastasis, 4.1% of other causes or not specified). The most frequent surgical interventions were phacoemulsification (20.8%) and pars plana vitrectomy (10.4%). The Kaplan-Meier estimators were 77.4% for survival and 70.1% for the absence of metastasis 10 years after the primary treatment.nnnCONCLUSIONSnProton beam therapy as a salvage treatment resulted in high local tumor control rates in recurrent uveal melanoma, especially if the primary therapy was transpupillary thermotherapy or plaque brachytherapy. Preservation of the globe was possible in most patients. Enucleations were indicated only in case of re-recurrences of uveal melanoma, but not because of secondary complications like intractable pain or secondary glaucoma. Retreatment was associated with vision deterioration, but loss of vision remained exceptional. Further larger prospective studies are needed to confirm the presented results of our retrospective analysis.

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 3.2u2005years. Local recurrence occurred in five cases with an estimated risk of 4.2% and 10.4% at 3 and 5u2005years after treatment, respectively. Enucleation was performed in 10 cases with an estimated risk of 9.2% and 18.4% at 3 and 5u2005years, respectively. Significant risk factors for local recurrence were not evident. Metastasis was estimated to occur in 28.4% at 3u2005years and 40.3% at 5u2005years, 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.

Long-term results after proton beam therapy for retinal papillary capillary hemangioma.

PURPOSEnTo evaluate the potential benefit and risk of proton beam therapy in the treatment of symptomatic retinal papillary capillary hemangioma.nnnDESIGNnRetrospective interventional case series.nnnMETHODSnThis study included patients presenting with symptomatic exudative retinal papillary capillary hemangioma with or without association with von Hippel-Lindau disease. All patients were treated either as a first or a secondary treatment option by proton beam therapy between 2001 and 2009. The minimum follow-up was 30 months.nnnRESULTSnEight eyes of 8 patients (3 male and 5 female, with a mean age of 36 years [range 22-80 years]) were treated for symptomatic papillary retinal hemangioma. The median interval between onset of macular edema and proton beam therapy was 1.7 months (range 0.5-3.3 months). The median follow-up period was 84 months (range 32-106 months) between proton beam treatment and last follow-up. Exudation completely resolved in all but 1 patient after 4.2 months on average (range 2.8-7.2 months). Mean visual acuity prior to proton beam irradiation was 0.7 logMAR (0.2 DIN (DIN 58220 norm)) (range 2-0.3 logMAR) and declined to 0.8 logMAR (0.16 DIN; range 2-0.1 logMAR) at last follow-up examination (no statistical significance, P=.071).nnnCONCLUSIONnThe anatomic outcome after proton beam therapy for retinal papillary hemangioma is convincing, whereas functional outcome may be compromised because of tumor location, long-persisting macular edema, extensive exudation, and poor initial visual acuity. In patients with extended retinal detachment surgical intervention was still necessary. Although proton beam therapy is proven to be a therapeutic option, treatment will remain challenging.

Predictive risk factors for radiation retinopathy and optic neuropathy after proton beam therapy for uveal melanoma

PurposeThis study was performed in order to evaluate the incidence of radiation retinopathy and optic neuropathy occurring after proton beam therapy for uveal melanoma.MethodsIncluded in this study were all patients who had been treated with primary proton beam therapy for uveal melanoma at the oncology service between May 1998 and June 2014 with a minimum follow-up of 12xa0months. Excluded were all patients who underwent re-irradiation, or vitrectomy due to exudative retinal detachment or for tumor-resection.ResultsDuring this period, 1127 patients matched the inclusion criteria, of whom 768 (68.1xa0%) and 463 (41.0xa0%) developed radiation retinopathy and optic neuropathy after a median time of 18.9xa0months (2.0–99.84xa0months) and 19.8xa0months (0.2–170.4xa0months), respectively. Mean follow-up was 53.4xa0months (12–170.4xa0months). Included were 558 men (49.5xa0%) and 569 women (50.5xa0%). Mean age was 61xa0years (16–89 years). Visual acuity slightly decreased from initial levels of 0.3 logMAR–0.4 logMAR in patients without developing any radiation-induced complication but severely decreased to 1.0 logMAR or 1.5 logMAR in the case of developing radiation retinopathy only or optic neuropathy, respectively. Independent risk factors for radiation retinopathy were a centrally (<2.5xa0mm from sensitive structures) located tumor or a thick tumor located more than 2.5xa0mm from sensitive structures, while those for radiation optic neuropathy comprised a short distance and applied dose to the optic disk.ConclusionThe risk for radiation retinopathy is higher in central uveal melanoma.Mid-/peripheral tumors are at high risk for radiation retinopathy and maculopathy if presenting with increased thickness.

Cataract development in patients treated with proton beam therapy for uveal melanoma

PurposeTo evaluate the incidence, risk factors, and dosages of proton beam therapy associated with cataract development, and long-term visual outcomes after treatment of uveal melanoma.MethodsAll patients receiving primary proton beam therapy for uveal melanoma between 1998 and 2008 with no signs of cataract before irradiation were included. A minimum follow-up of 12xa0months was determined. Exclusion criteria included all applied adjuvant therapies such as intravitreal injections, laser photocoagulation, tumor resections, or re-irradiation. For subgroup analysis, we included all patients who underwent brachytherapy between 1998 and 2008 for uveal melanoma, considering the above mentioned inclusion and exclusion criteria.ResultsTwo hundred and fifty-eight patients matched our inclusion criteria. Median follow-up was 72.6xa0months (12.0-167.4xa0months). Of these 258 patients, 71 patients (66.3xa0%) presented with cataract after 31.3xa0months (0.7–142.4xa0months), of whom 35 (20.4xa0%) required surgery after 24.2 (0.7–111.1xa0months) to ensure funduscopic tumor control. Kaplan–Meier estimates calculated a risk for cataract of 74.3xa0% after 5xa0years. There was no increase in metastasis or local recurrence in these patients. Patient’s age was the sole independent statistically significant risk factor for cataract development. The probability of cataract occurrence significantly increased with doses to lens exceeding 15–20 CGE. Neither the appearance of cataract nor cataract surgery influenced long-term visual outcome.ConclusionCataract formation is the most frequent complication after irradiation. There is no benefit vis-a-vis brachytherapy with regard to cataract development. Data indicate a dose–effect threshold of 0.5 CGE for cataractogenesis, with significantly increasing risk above a dose of 15 CGE. Furthermore, cataract surgery can be performed without an increased risk for metastasis.

Trabeculectomy in patients with uveal melanoma after proton beam therapy.

BackgroundRetrospective evaluation of intraocular pressure, use of topical and systemic anti-glaucoma medication, secondary complications, local tumor control and survival in patients treated with trabeculectomy for the regulation of the intraocular pressure (IOP) after proton beam therapy for uveal melanoma.MethodsIn this retrospective clinical case series we evaluated the follow-up of 15 patients receiving a trabeculectomy as surgical treatment if the IOP could not be lowered adequately by medications or laser surgery. All patients had received proton beam therapy for uveal melanoma at the Helmholtz-Zentrum Berlin between 1998 and 2010.ResultsThe median IOP decreased significantly from 35xa0mmHg ± 8.8 before TE to 16xa0mmHg ± 8.2 (=52.3xa0%) six months after TE (Wilcoxon-Mann–Whitney-U Test, p<0.01). None of the patients needed any glaucoma medication six months after trabeculectomy. Two patients developed local recurrence during follow-up, which were independent of the trabeculectomy. One patient had to be enucleated due to intractable pain and suspected remaining tumor activity. One patient died due to metastasis.ConclusionsTrabeculectomy is an option in intractable glaucoma in patients with uveal melanoma after proton beam therapy in single cases. Secondary interventions are common. Inoculation metastases are possible. Secure local tumor control must be a prerequisite for filtrating operations.