Ruthenium Plaque Radiotherapy Research Articles

Current Therapies in Superficial Malignant Tumors

This article is a review of diagnostic and therapeutic possibilities in common epibulbar malignant tumors, such as basal cell carcinoma, conjunctival lymphoma, squamous cell carcinoma and conjunctival melanoma. Most importantly, for every tumor patient there is a detailed anamnesis, split lamp examination and photo documentation. Further regular controls after therapy are required due to the risk of recurrences. Basal cell carcinoma is the most common tumor of the periocular skin, divided into three subtypes (nodular, superficial and morphea). The treatment consists of total excision with a sufficient safety margin.The most common tumor of the orbital and ocular adnexa are lymphoma. They can appear primary or secondary, as lymphatic system disease. The gold standard therapy is a percutaneous irradiation.Squamous cell carcinoma and its precancerous stages (CIN I-III) are frequently diagnosed on the conjunctiva. A complete tumor excision is required, but sometimes it is not possible due to large tumor growth. Therefore, an adjuvant therapy with mitomycin C eyedrops, brachytherapy with ruthenium plaque or proton radiotherapy is required.Conjunctival melanoma is a rare, but life-threatening disease. Melanosis with atypia has a high risk for degeneration and requires further treatment with mitomycin C eyedrops. In cases of malignant tumor growth, an excision with a non-touch technique and adjuvant therapy with brachy or proton irradiation should be applied.

Current Therapies in Superficial Malignant Tumors

This article is a review of diagnostic and therapeutic possibilities in common epibulbar malignant tumors, such as basal cell carcinoma, conjunctival lymphoma, squamous cell carcinoma and conjunctival melanoma. Most importantly, for every tumor patient there is a detailed anamnesis, split lamp examination and photo documentation. Further regular controls after therapy are required due to the risk of recurrences.Basal cell carcinoma is the most common tumor of the periocular skin, divided into three subtypes (nodular, superficial and morphea). The treatment consists of total excision with a sufficient safety margin.The most common tumor of the orbital and ocular adnexa are lymphoma. They can appear primary or secondary, as lymphatic system disease. The gold standard therapy is a percutaneous irradiation.Squamous cell carcinoma and its precancerous stages (CIN I - III) are frequently diagnosed on the conjunctiva. A complete tumor excision is required, but sometimes it is not possible due to large tumor growth. Therefore, an adjuvant therapy with mitomycin C eyedrops, brachytherapy with ruthenium plaque or proton radiotherapy is required.Conjunctival melanoma is a rare, but life-threatening disease. Melanosis with atypia has a high risk for degeneration and requires further treatment with mitomycin C eyedrops. In cases of malignant tumor growth, an excision with a non-touch technique and adjuvant therapy with brachy or proton irradiation should be applied.

MALIGNANT TRANSFORMATION OF A CHOROIDAL NEVUS IN AN EYE TREATED FOR CHOROIDAL MELANOMA

To report a case of a choroidal melanoma and a discrete choroidal nevus that has transformed into a malignant melanoma 5 years after initial diagnosis. Retrospective case report. A diffuse macular choroidal melanoma and a discrete choroidal nevus located superonasal to the optic disk were diagnosed in the right eye of a 63-year-old woman in 2009. The patient was treated by ruthenium plaque radiotherapy for the choroidal melanoma, which consequently flattened and scarred. On a routine eye check in 2014, the nevus was found to have been transformed into a choroidal melanoma. It was treated with ruthenium plaque radiotherapy. Although extremely rare, patients with a uveal melanoma can develop an additional discrete uveal melanoma. This case highlights the importance of monitoring benign choroidal nevi in patients with a history of choroidal melanoma.

Conjunctival squamous cell neoplasia: the Liverpool Ocular Oncology Centre experience.

To report the outcome of patients with conjunctival squamous cell neoplasia (CSCN)--including conjunctival squamous cell carcinoma (SCC), conjunctival squamous intraepithelial neoplasia (C-SIN) and carcinoma in situ (CIS)-treated at the Liverpool Ocular Oncology Centre (LOOC). Patients treated between January 1993 and September 2011 were identified and categorised as having 'primary' or 'salvage' treatment, according to whether they had undergone a surgical procedure before referral to our centre. Invasive SCC was treated by excision with adjunctive ruthenium plaque radiotherapy. C-SIN or CIS was treated with topical 5-fluorouracil (5-FU), and in a few cases, cryotherapy. Primary treatment was administered to 20 patients (16 males, four females). Mean age was 62 years (range, 33-85). Histological examination revealed C-SIN/CIS in ten patients and invasive SCC in nine. Median follow-up was 69 months (range, 34-168). Three patients required further topical chemotherapy for persistent/recurrent C-SIN. Salvage therapy was administered to 21 patients (15 males, six females). Mean age was 63 years (range, 26-82). Histology showed C-SIN/CIS in 11 patients and invasive SCC in ten. Median follow-up was 54.5 months (range, 36-120). At the close of this audit, there was no recurrence of invasive or metastatic disease in either the primary or salvage groups. Our established protocol for treatment of CSCN has proven successful in local tumour control, and avoids ocular complications. We advocate adjunctive radiotherapy in patients with invasive SCC and chemotherapy in C-SIN/CIS. For improved patient outcome, prompt referral to a specialist centre is encouraged.

Eccentric ruthenium plaque radiotherapy of posterior choroidal melanoma

The aim of this work is to report on conservation of visual acuity after eccentric ruthenium(106) (Ru-106) brachytherapy of posterior choroidal melanoma. Fifty-four patients with choroidal melanoma extending to within 5mm of the optic disc or fovea were treated at a single institution during the 3years up to July 31, 2007. The plaque was positioned eccentrically with its posterior edge aligned with the posterior tumor margin to reduce the radiation dose to the optic disc and fovea. The main outcome measures were local tumor control and conservation of vision of 6/12 or better, according to baseline variables. The tumors had a mean longest basal diameter of 12.0mm and a mean thickness of 3.1mm. The posterior tumor margin extended to within 3mm of the fovea in 30 patients (56%). In the 24 eyes with the posterior tumor margin located 3.1-5.0mm from the fovea, 74.9% retained visual acuity of 6/12 or better 4years after treatment (95% confidence interval [CI], 55.5-94.3%). In the 30 eyes with tumor extension to within 3.0mm of the fovea, then 3years after treatment only 25.3% retained such vision (95% CI, 5.3-45.3%). Recurrence at the posterior tumor margin occurred in two patients. Eccentric ruthenium(106) plaque radiotherapy of posterior choroidal melanoma achieves good rates of local tumor control and conservation of vision if special measures are taken to ensure that the plaque is positioned correctly.

Choroidal neovascular membrane after endoresection of choroidal melanoma.

The purpose of this study was to report two cases with choroidal melanoma who underwent endoresection and developed choroidal neovascular membrane (CNVM) during follow-up. An interventional case series. A 62-year-old man with choroidal melanoma in his left eye was treated with endoresection with pars plana vitrectomy followed by radioactive ruthenium plaque radiotherapy. Thirteen months after the surgery, the patient developed a CNVM at the superior edge of the surgical excision site and was treated with argon laser photocoagulation. Twenty-eight months after laser photocoagulation, the patient was alive with no sign of CNVM recurrence. A 59-year-old man with choroidal melanoma in his left eye underwent endoresection with pars plana vitrectomy followed by radioactive ruthenium plaque radiotherapy. Twenty-one months later, he developed a CNVM, which was treated by photodynamic therapy. After 45 months of follow-up after photodynamic therapy, the patient had no sign of recurrent CNVM. Choroidal neovascular membrane is a rare complication after endoresection of choroidal melanoma. Being aware of this risk leads to early diagnosis and prompt treatment that can prevent deterioration of vision.

Severe keratitis following corneal cross-linking for keratoconus

performed and the patient underwent proton beam radiotherapy. Two years after proton beam radiotherapy, the tumour thickness was 3.5 mm but the patient developed a recurrent vitreous haemorrhage and neovascular glaucoma requiring enucleation. Pathological examination showed a partially necrotic choroidal melanoma of epithelioid cell type, with vascular hyalinization from the radiotherapy. The mitotic count was 1 ⁄ 40 high power fields. Numerous macrophages were seen. The sclera adjacent to the tumour showed collagen degeneration and calcification (Fig. 2). Apical tumour recurrence after ruthenium plaque radiotherapy is rare, even with eccentric plaque placement (Damato et al. 2005; Lommatzsch et al. 2000; Summanen et al. 1993). This case therefore raises the possibility that treatment failure occurred because of intrascleral calcification beneath the tumour. We suggest that this finding should prompt a higher dose of brachytherapy or an alternative form of radiotherapy, such as proton beam radiotherapy.

Retinal Hemangioblastoma in von Hippel–Lindau Disease

An 18-year-old woman presented with a 2-month history of visual loss in the right eye. Visual acuity was 20/100 in the affected eye and 20/20 in the left eye. Ophthalmoscopy revealed an orange–yellow tumor (Panel A, arrow) with tortuous feeding vessels and optic-disk edema (Panel A, arrowhead), indicating retinal hemangioblastoma. The patient underwent ruthenium plaque radiotherapy, cryotherapy, and photodynamic therapy, which induced complete tumor regression and sclerosis of the dilated vessels (Panel B). After treatment, the visual acuity improved, to 20/70. A systemic evaluation, including magnetic resonance imaging of the brain, computed tomography of the abdomen, and measurement of urinary . . .

An audit of eccentrically‐positioned ruthenium plaque radiotherapy of choroidal melanoma in Liverpool

Abstract Purpose Brachytherapy is usually administered with the plaque overlapping the entire tumour margin by at least 1‐2mm. With posterior tumours, our practice is to position the plaque with its posterior edge aligned with the posterior tumour margin. We audited ocular outcomes after eccentrically‐placed ruthenium plaque radiotherapy of choroidal melanoma. Methods Patients were included if receiving primary ruthenium brachytherapy for choroidal melanoma during the three years up to the 31st July 2007. A perforated template was used to facilitate plaque positioning. For posterior tumors, the template was positioned so that trans‐illumination produced a glow at the posterior tumour margin (‘sunset sign’). Minimum doses of 300‐350 Gy and 80‐90 Gy were prescribed to the sclera and apex, respectively. Results The cohort comprised 162 patients (93 female and 69 male). The time to the last known visual acuity had a median of 23 months. The initial visual acuity was 20/40 or better in 94.6%, 20/60 to 20/200 in 13.0% and worse than 20/200 in 1.9% of patients. The tumours had a mean basal diameter of 11.7mm. Ten tumours exceeded 5.4 mm in height. Tumour extension to within 5mm of optic disc, fovea or both occurred in 18 (11.1%), 28 (17.3%) and 27 (16.7%) cases respectively. Risk factors for visual loss were proximity to optic disc or fovea, initial visual acuity worse than 20/40 and tumour height exceeding 5.4 mm. In 66 patients with none of these risk factors, 92% retained 20/40 or better and 5 had vision of 20/60 – 20/200. In 72 with one risk factor, 74.3% retained 20/16 – 20/40 and 95.7% had vision of 20/200 or better. In 12 patients with 2 risk factors, these percentages were 25.0% and 91.7%. Only 3 patients had 3 risk factors and one retained vision of 20/200 or better. Tumours distanced < 5 mm to fovea were divided in 3 groups, and visual acuity analysed. Three patients had local tumour recurrence and were treated respectively by proton beam radiotherapy, plaque radiotherapy and enucleation (the only eye lost in this series). Conclusion Eccentric plaque radiotherapy of choroidal melanoma achieves good rates of local tumour control, ocular retention and preservation of vision.

Local tumor control after 106Ru brachytherapy of choroidal melanoma

To report on local tumor control after (106)Ru brachytherapy for choroidal melanoma. A total of 458 patients with choroidal melanoma were treated at a single institution between January 1993 and December 2001. The tumors had a median longest basal dimension of 10.6 mm and a median height of 3.2 mm. The brachytherapy was administered using a 15- or 20-mm plaque. For posterior tumors, the plaque was positioned eccentrically with its posterior edge aligned with the posterior tumor margin to reduce the radiation dose to the optic disk and fovea. A minimal scleral dose sufficient to cause visible choroidal atrophy provided a permanent ophthalmoscopic record of the distribution of choroidal irradiation. If radiotherapy to the posterior tumor was uncertain, adjunctive transpupillary thermotherapy was administered 6 months postoperatively. The actuarial rates of tumor recurrence were 1%, 2%, and 3% at 2, 5, and 7 years, respectively. Local tumor recurrence correlated with the longest basal tumor dimension (Cox univariate analysis, p = 0.02, risk ratio 1.41, 95% confidence interval 1.06-1.88). Seven of the nine eyes with recurrent tumor were salvaged with additional conservative therapy. The low rate of local tumor recurrence suggests that ruthenium plaque radiotherapy is effective with good case selection and if special measures are taken to ensure that the plaque is positioned correctly.

Rhegmatogenous retinal detachment after transscleral local resection of choroidal melanoma

Objective To report on the incidence and outcome of rhegmatogenous retinal detachment after transscleral local resection of choroidal melanoma. Design Prospective, noncomparative, interventional case series. Participants One hundred fifty-six patients with choroidal melanoma treated by transscleral local resection between January 1993 and June 2000. Intervention Transscleral choroidectomy or cyclochoroidectomy for uveal melanoma, with ocular decompression by single-port pars plana vitrectomy and, in most patients, adjunctive ruthenium plaque radiotherapy. Main outcome measures Incidence of rhegmatogenous retinal detachment according to predictive factors and outcomes reported in terms of anatomic success, visual acuity, and ocular conservation. Results Rhegmatogenous retinal detachment occurred in 28 (18%) eyes and was significantly more common in patients with thick tumors (Cox univariate analysis, P = 0.001) and in males (Cox univariate analysis, P = 0.013), with posterior tumor extension being of borderline significance (Cox univariate analysis, P = 0.069). Surgical treatment of the retinal detachment was performed in 25 patients; it was undertaken at our center in 22 patients and at the referring hospital in 3 patients. Anatomic success was achieved in 21 (84%) of these 25 patients, with 7 eyes retaining counting fingers vision, and 3 eyes seeing 6/60 or better. Ten eyes treated for retinal detachment were enucleated because of recurrent tumor (four eyes), retinal detachment (three eyes), wound dehiscence (one eye), phthisis (one eye), and poor visual acuity (one eye). Eleven eyes known to have a retinal tear underwent prophylactic vitreoretinal surgery at the end of the local resection, with only one (9%) of these subsequently developing retinal detachment. Conclusions Rhegmatogenous retinal detachment after transscleral choroidectomy or cyclochoroidectomy for uveal melanoma is a serious complication requiring early vitreoretinal surgery.

Transpupillary thermotherapy as an adjunct to ruthenium plaque radiotherapy for choroidal melanoma.

To review the Swedish experience using transpupillary thermotherapy (TTT) as an adjunct to ruthenium plaque radiotherapy for choroidal melanoma. A retrospective chart review of 27 patients receiving TTT for juxtapapillary or juxtafoveal growth present at the time of diagnosis, or recurrent growth at the tumour margin, or significant exudation following ruthenium brachytherapy for choroidal melanoma. Follow-up ranged from 6 to 29 months (median=20 months). Tumour growth regressed completely (n=8), regressed partially (n=11), remain unchanged (n=6) or progressed (n=2). Complications included focal lens opacity with or without associated posterior synechiae (n=3), retinal haemorrhage (n=2) and retinal vein occlusion (n=1). Seventeen patients (63%) maintained or improved visual acuity and 2 eyes were enucleated following combined treatment. Many of the treated eyes would have been enucleated in the past, suggesting that TTT used in combination with ruthenium brachytherapy improves the short term globe salvage rate. Ocular side effects do occur but are usually not significant.

Endoresection of choroidal melanoma

AIMSThe results of 52 endoresections for choroidal melanoma are reported.METHODSThe current technique involves vitrectomy, retinal incision over or peripheral to the tumour, haemostasis by raising intraocular pressure and by moderate...

Results following episcleral ruthenium plaque radiotherapy for posterior uveal melanoma. The Swedish experience.

The Swedish experience of ruthenium 106 plaque radiotherapy for posterior uveal melanoma includes 266 patients treated between 1979 and 1995. The median dose delivered at the tumour apex was 100 Gy and the median follow-up after radiotherapy was 3.6 years (range = 0.5 to 12.5 years) with no patient being lost to follow-up. Visual acuity deteriorated moderately following treatment but appeared to stabilize after 5 to 6 years. Treatment failure defined as enucleation following plaque treatment occurred in 46 of the 266 (17%) studied patients. The cumulative 5-year probability of retaining the eye after radiotherapy was 82% and by univariate analysis tumour height, tumour diameter and tumour stage each predicted subsequent treatment failure, whereas in multivariate analysis no single covariate retained a predictive value. Forty-five of the 266 patients died of any cause during follow-up; 27 of these deaths were melanoma-related. The cumulative 5-year survival proportion (based on melanoma-related deaths only) was 86%. Death in metastatic disease appeared to be more common among patients that failed ruthenium plaque radiotherapy, however these patients also tended to have large tumours.

Radiation related complications after ruthenium plaque radiotherapy of uveal melanoma.

To analyse radiation related complications and secondary enucleation after irradiation of malignant uveal melanoma with ruthenium-106 plaques. A series of 100 consecutive eyes irradiated in 1981-91 was analysed using the life table method and the Cox proportional hazards model. The median apical and scleral tumour dose was 100 Gy (range 15-200 Gy) and 1000 Gy (range 200-1200 Gy), respectively. The median follow up time was 2.8 and 2.0 years (range 1 month to 10 years) for anterior and posterior segment complications, respectively. The 3 and 5 year probabilities of being without radiation cataract were 73% and 63%, without neovascular glaucoma 91% and 81%, without vitreous haemorrhage 83% and 74%, without radiation maculopathy 85% and 70%, and without radiation optic neuropathy 90% and 88%, respectively. The risk of radiation cataract was highest with large tumour size (T1 + T2 v T3, p = 0.0027; height < or = 5 v > 5 mm, p = 0.029; largest basal diameter (LBD) < or = 15 v > 15 mm, p < 0.0001) and location of anterior tumour margin anterior v posterior to the equator (p = 0.0003); the risk of neovascular glaucoma with large size (T1 + T2 v T3, p = 0.039; LBD < or = 15 mm v 15 mm, p = 0.021); and the risk of maculopathy and optic neuropathy with proximity of the posterior tumour margin to the fovea and the optic disc (< or = 1.5 v > 1.5 mm; p = 0.030 and p = 0.0004, respectively). In Cox's multivariate analysis the strongest risk indicator for radiation cataract (RR 1.5, 95% CI 1.4-1.6) and vitreous haemorrhage (RR 1.6, 95% CI 1.4-1.8) was the height of the tumour; for neovascular glaucoma the TNM class (RR 6.2, 95% CI 2.7-13.8); for radiation maculopathy location of posterior tumour margin within 2 mm from the fovea (RR 3.4, 95% CI 2.0-6.0); and for radiation optic neuropathy location of tumour margin within 1 DD of the optic disc (RR 6.1, 95% CI 3.0-12.4). The 3 and 5 year probabilities of avoiding enucleation were 92% and 85%, respectively. Ten eyes were enucleated--six because of recurrent tumour growth, three because of treatment complications, and one because of mistakenly suspected extraocular growth. The results suggest that the frequency of radiation related complications after ruthenium brachytherapy of uveal melanoma is acceptable, in particular as regard irradiation of small and medium sized tumours for which ruthenium therapy generally is recommended.

Visual Outcome of Eyes With Malignant Melanoma of the Uvea After Ruthenium Plaque Radiotherapy

To analyze the overall visual outcome in 100 consecutive eyes with malignant uveal melanoma irradiated with ruthenium-106 plaques between 1981 and 1991. The follow-up ranged from 4 months to 10.1 years (median 3.0 years). Scattergrams of equal follow-up periods, life-table survival analysis, and Cox's proportional hazards analysis were used to analyze visual outcome. VA increased for some time in 14 eyes. By 3 years, VA of at least 20/70, 20/200, counting fingers, and light perception were retained in 27%, 41%, 67% and 82% of eyes, respectively. Macular pathology cause loss of reading vision; neovascular glaucoma or enucleation caused loss of light perception. In univariate analysis, large tumor size (height > 5 mm or TNM class T3) predicted visual loss of all VA levels. For the loss of light perception, the tumor's largest basal diameter > 15 mm reached significance. In Cox's multivariate analysis tumor height > 5 mm was the only significant independent risk indicator for loss of VA levels 20/70 and 20/200. For the level CF, largest basal tumor diameter also reached significance, but location of the tumor within 1 disc diameter of the optic disc, either alone or in addition to the fovea, had the greatest risk ratio (6.3, 95% CI 4.1-9.8). For losing light perception, large TNM size (T3) was the strongest risk indicator (risk ratio 10.0; 95% CI 4.5-22.5), followed by proximity of the tumor to the optic disc (risk ratio 4.3, 95% CI 2.4-7.8). Ruthenium brachytherapy may retain vision in an eye with a malignant melanoma of the uvea for a considerable period of time. The data presented are useful in patient counseling and allow comparison to subsequent series.

Survival of Patients and Metastatic and Local Recurrent Tumor Growth in Malignant Melanoma of the Uvea After Ruthenium Plaque Radiotherapy

ABSTRACT A series of 100 consecutive patients treated by ruthenium plaque radiotherapy for uveal malignant melanoma from 1981 to 1991 was studied to evaluate local recurrences, métastases, and melanomaspecific mortality. Follow up ranged from 1.0 to 10.1 years (mean, 3.3; median, 3.0 years). Local relapse was observed in 19 patients from 0.1 to 2.7 years (median, 0.7 years) after therapy. Six of these eyes were enucleated. The 5-year probability of local tumor control was 59%. Seven patients with local relapse developed metastasis O to 4.3 years (median. 1.4 years) later. Altogether, 18 patients developed métastases 0.9 to 4.6 years (median, 2.0 years) after the irradiation, and 15 of them died of melanoma 5 days to 3.3 years (median, 0.5 years) after detection of metastases. The 5-year probability of metastasis not developing was 61%. The overall 5-year survival was 78%, excluding causes other than malignant melanoma. Large tumor size and anterior tumor location, with or without ciliary body involvement, predicted poor prognosis both in terms of local growth, métastases, and melanoma-specific mortality. Local recurrent tumor growth was associated with a significant increase in metastasis but a nonsignificant increase in melanoma-specific mortality.