Clinical science
Proton beam radiotherapy of diffuse iris melanoma in 54 patients Gregor D Willerding,1 Dino Cordini,1,2 Christoph Hackl,1 Bettina Karle,2 Nona Lakotka,1 Michael H Foerster,3 Nikolaos N Bechrakis,4 Jens Heufelder,2 Lutz Moser,2 Antonia M Joussen1 1
Department of Ophthalmology, Charité— Universitätsmedizin Berlin, Berlin, Germany 2 Berlin Protonen at the Helmholtz-Zentrum Berlin, Lise-Meitner-Campus, Berlin, Germany 3 Department of Ophthalmology, DRK Kliniken Westend, Berlin, Germany 4 Department of Ophthalmology, Innsbruck Medical University, Innsbruck, Austria Correspondence to Professor Antonia M Joussen, Department of Ophthalmology, Charité—Universitätsmedizin Berlin, Hindenburgdamm 30, Berlin 12203, Germany; [email protected] GDW and DC contributed equally. Meeting presentation: The material has been presented in part at the meeting of the Deutsche Ophthalmologische Gesellschaft in Berlin, September 2012. Received 25 March 2014 Revised 21 October 2014 Accepted 16 November 2014 Published Online First 10 December 2014
ABSTRACT 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 68megaelectron 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.
INTRODUCTION
To cite: Willerding GD, Cordini D, Hackl C, et al. Br J Ophthalmol 2015;99: 812–816. 812
Uveal melanoma arises in the iris in only 2%–3% of the cases.1 Iris melanomas have been divided into circumscribed and diffuse forms, the term ‘diffuse’ referring to flat, infiltrating growth or to seeding through the anterior chamber.2 Diffuse seeding can involve the posterior and anterior chamber and may lead to hyperchromia and ipsilateral glaucoma. Metastasis of iris melanoma occurs in about 5% of the cases after 10 years1 but in diffuse iris melanoma it has been reported to occur in up to 13% at 6 years.2 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. In 1998, we started to employ proton beam radiotherapy (PBR) in non-resectable iris melanoma and we decided to treat the whole anterior segment to include all potentially malignant seeds when
signs of diffuse seeding were present. Most recently, Konstantinidis et al3 published their experience with whole anterior segment PBR in 12 patients. In the present study, we report our results in 54 patients with a mean follow-up of close to 5 years.
PATIENTS AND METHODS All patients with a clinical or histological diagnosis of iris melanoma who were managed with whole anterior segment PBR between 13 October 1998 and 19 June 2012 were included in this singlecentre, retrospective case series. The indication for this treatment was non-resectable anterior chamber involvement from extensive growth or seeding of an iris melanoma. We excluded patients with tumours extending past the ora serrata and also eyes that had prior tumour treatment (brachytherapy, iridectomy and iridocyclectomy). A complete ophthalmologic examination, assessment of demographic features and informed consent was obtained before radiotherapy. The radiation dose was 4×12.5 cobalt grey equivalent (CGE) in 53 patients and 8×7.5 CGE in the first patient. The dose distribution was planned with EYEPLAN and OCTOPUS software. A full iris aperture was used with a diameter of 18 mm in 41 cases (75.9%), 17 mm in 11 cases (18.5%), 20 mm in two cases (3.7%) and 14 mm in one case. The field had been extended in two patients towards a scleral or a ciliary body extension of the tumour indicated by high-frequency ultrasound and diaphanoscopy and to include a pre-existing filtering bleb in one patient. Localising markers were not placed except in one patient with ciliary body involvement. Irradiation was performed without pupillary dilation. Follow-up examinations were made at 3-month to 12-month intervals during the first 3 years and then at 6-month to 24-month intervals. Screening for metastasis was recommended with 6-monthly liver ultrasound. The results of the latest liver ultrasound were collected at every follow-up visit. In 23 cases, the primary caring ophthalmologist provided the latest follow-up information. In these cases, the latest information on functional and tumour-related data was collected by a standard questionnaire. Additionally in these cases, the local ophthalmologist was asked to report on the known metastatic status of the patient. Statistics included Kaplan–Meier estimate of local tumour control, eye retention, cataract and glaucoma. Glaucoma at presentation was analysed as a risk factor for a visual acuity of
Proton beam radiotherapy of diffuse iris melanoma in 54 patients Gregor D Willerding,1 Dino Cordini,1,2 Christoph Hackl,1 Bettina Karle,2 Nona Lakotka,1 Michael H Foerster,3 Nikolaos N Bechrakis,4 Jens Heufelder,2 Lutz Moser,2 Antonia M Joussen1 1
Department of Ophthalmology, Charité— Universitätsmedizin Berlin, Berlin, Germany 2 Berlin Protonen at the Helmholtz-Zentrum Berlin, Lise-Meitner-Campus, Berlin, Germany 3 Department of Ophthalmology, DRK Kliniken Westend, Berlin, Germany 4 Department of Ophthalmology, Innsbruck Medical University, Innsbruck, Austria Correspondence to Professor Antonia M Joussen, Department of Ophthalmology, Charité—Universitätsmedizin Berlin, Hindenburgdamm 30, Berlin 12203, Germany; [email protected] GDW and DC contributed equally. Meeting presentation: The material has been presented in part at the meeting of the Deutsche Ophthalmologische Gesellschaft in Berlin, September 2012. Received 25 March 2014 Revised 21 October 2014 Accepted 16 November 2014 Published Online First 10 December 2014
ABSTRACT 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 68megaelectron 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.
INTRODUCTION
To cite: Willerding GD, Cordini D, Hackl C, et al. Br J Ophthalmol 2015;99: 812–816. 812
Uveal melanoma arises in the iris in only 2%–3% of the cases.1 Iris melanomas have been divided into circumscribed and diffuse forms, the term ‘diffuse’ referring to flat, infiltrating growth or to seeding through the anterior chamber.2 Diffuse seeding can involve the posterior and anterior chamber and may lead to hyperchromia and ipsilateral glaucoma. Metastasis of iris melanoma occurs in about 5% of the cases after 10 years1 but in diffuse iris melanoma it has been reported to occur in up to 13% at 6 years.2 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. In 1998, we started to employ proton beam radiotherapy (PBR) in non-resectable iris melanoma and we decided to treat the whole anterior segment to include all potentially malignant seeds when
signs of diffuse seeding were present. Most recently, Konstantinidis et al3 published their experience with whole anterior segment PBR in 12 patients. In the present study, we report our results in 54 patients with a mean follow-up of close to 5 years.
PATIENTS AND METHODS All patients with a clinical or histological diagnosis of iris melanoma who were managed with whole anterior segment PBR between 13 October 1998 and 19 June 2012 were included in this singlecentre, retrospective case series. The indication for this treatment was non-resectable anterior chamber involvement from extensive growth or seeding of an iris melanoma. We excluded patients with tumours extending past the ora serrata and also eyes that had prior tumour treatment (brachytherapy, iridectomy and iridocyclectomy). A complete ophthalmologic examination, assessment of demographic features and informed consent was obtained before radiotherapy. The radiation dose was 4×12.5 cobalt grey equivalent (CGE) in 53 patients and 8×7.5 CGE in the first patient. The dose distribution was planned with EYEPLAN and OCTOPUS software. A full iris aperture was used with a diameter of 18 mm in 41 cases (75.9%), 17 mm in 11 cases (18.5%), 20 mm in two cases (3.7%) and 14 mm in one case. The field had been extended in two patients towards a scleral or a ciliary body extension of the tumour indicated by high-frequency ultrasound and diaphanoscopy and to include a pre-existing filtering bleb in one patient. Localising markers were not placed except in one patient with ciliary body involvement. Irradiation was performed without pupillary dilation. Follow-up examinations were made at 3-month to 12-month intervals during the first 3 years and then at 6-month to 24-month intervals. Screening for metastasis was recommended with 6-monthly liver ultrasound. The results of the latest liver ultrasound were collected at every follow-up visit. In 23 cases, the primary caring ophthalmologist provided the latest follow-up information. In these cases, the latest information on functional and tumour-related data was collected by a standard questionnaire. Additionally in these cases, the local ophthalmologist was asked to report on the known metastatic status of the patient. Statistics included Kaplan–Meier estimate of local tumour control, eye retention, cataract and glaucoma. Glaucoma at presentation was analysed as a risk factor for a visual acuity of
