Adjuvant Ab Interno Tumor Treatment After Proton Beam Irradiation

doi:10.1016/j.ajo.2017.03.027

American Journal of Ophthalmology

Volume 178, June 2017, Pages 94-100

https://doi.org/10.1016/j.ajo.2017.03.027 Get rights and content

Purpose

This study was performed to show long-term outcomes concerning globe preservation in uveal melanoma patients after proton beam therapy with the main focus on outcomes according to different adjuvant ab interno surgical procedures.

Design

Retrospective cohort study.

Methods

All patients treated with primary proton beam therapy for choroidal or ciliary body melanoma between June 1998 and June 2015 were included.

Results

A total of 2499 patients underwent primary proton beam therapy, with local tumor control and globe preservation rates of 95.9% and 94.8% after 5 years, respectively. A total of 110 (4.4%) patients required secondary enucleation. Unresponsive neovascular glaucoma was the leading cause of secondary enucleation in 78 of the 2499 patients (3.1%). The 5-year enucleation-free survival rate was 94.8% in the endoresection group, 94.3% in the endodrainage group, and 93.5% in the comparator group. The log-rank test showed P = .014 (comparator group vs endoresection group) and P = .06 (comparator group vs endodrainage-vitrectomy group). Patients treated with endoresection or endodrainage-vitrectomy developed less radiation retinopathy (30.5% and 37.4% after 5 years, P = .001 and P = .048 [Kaplan-Meier], respectively) and less neovascular glaucoma (11.6% and 21.3% after 5 years, P = .001 and P = .01 [Kaplan-Meier], respectively) compared with the comparator group (52.3% radiation retinopathy and 57.8% neovascular glaucoma after 5 years).

Conclusion

This study suggests that in larger tumors the enucleation and neovascular glaucoma rates might be reduced by adjuvant surgical procedures. Although endoresection is the most promising adjuvant treatment option, the endodrainage-vitrectomy is recommended in patients who are ineligible for endoresection.

Section snippets

Methods

This study was approved by the institutional review board of the Charité-Universitätsmedizin Berlin, Berlin, Germany, and was in accordance with the tenets of the Declaration of Helsinki. All patients with diagnosed choroidal or ciliary body melanoma that were treated with primary proton beam therapy between June 1998 and June 2015 were included. In our oncology service, proton beam therapy is applied to centrally located tumors close to sensitive structures or to peripheral tumors beyond the

Results

Between June 1998 and June 2015, a total of 2499 patients were treated with primary proton beam therapy for choroidal or ciliary body melanoma. There were 1324 (53%) men and 1175 (47%) women with an average age of 61 years (range, 15–92 years for choroidal and 25–94 years for choroidal ciliary body melanoma) at the time of diagnosis. Median follow-up time was 51.2 months (range, 12–170 months).

According to the American Joint Committee on Cancer (AJCC) tumor staging system,10, 11 697 (27.9%)

Discussion

Our results concerning local tumor control and globe preservation with an overall local tumor control rate of 95.9% and an eye-retaining rate of 94.8% after 5 years are in accordance with previously published literature.3, 12, 13, 14, 15, 16

Our results concerning the 3 different adjuvant strategies showed that patients who underwent endoresection or endodrainage-vitrectomy required half of the enucleations compared with patients of the comparator group, who presented with large and exudative

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Cited by (15)

Single-Masked Randomized Phase 2 Study Assessing 2 Forms of Hypofractionated Proton Therapy in Patients With Large Choroidal Melanomas
2023, International Journal of Radiation Oncology Biology Physics
Patients with large uveal melanomas are at major risk of liver metastases. Some patients are reluctant to undergo the standard treatment (ie, immediate enucleation). Proton therapy yields 5-year local control rates and eyeball retention of >85% and ≈20% in large uveal melanomas. Patients with T3/T4 uveal melanomas refusing enucleation were randomized between standard 4 to 13 Gy-fraction or moderately hypofractionated 8 to 6.5 Gy-fraction proton therapy. The main endpoint was the 2-year local recurrence-free survival without enucleation.
A single-masked 1:2 randomized phase 2 trial was conducted between 2015 and 2017 with planned endoresection and distance to the posterior pole as strata. Local events were defined as local relapse, or enucleation due to complications or relapse.
The 32 patients, with a mean age of 64 years, had T3/4 (N = 17/15), M1 (N = 2) uveal melanomas, of mean tumor diameter and thickness of 16.5 mm and 9.1 mm, and of posterior location in 56.5%. Median follow-up was 56.7 months. The 2-year local recurrence-free survival rate without enucleation was 79% (95% confidence interval, 65%-96%), similar in both arms. There were 9 enucleations, 3 at relapse and 6 for toxicities. Twelve patients had distant metastases. The 2-year-overall survival was 72% (95% confidence interval, 58%-89%). At baseline, visual acuity by average logarithm value of the minimum angle of resolution was 0.68 and 0.70 in the standard and experimental arms, and at last follow-up 2 and 1.7, with mean differences of 1.44 and 1.01, respectively (P = .39).
An 8-times 6.5 Gy scheme is feasible without deteriorating local control and with similar toxicity rates in patients with large uveal melanomas. Larger studies incorporating adjuvant treatments are warranted.
Radiation-Induced Optic Neuropathy: Observation versus Intravitreal Treatment: Can Visual Acuity Be Maintained by Intravitreal Treatment?
2019, American Journal of Ophthalmology
Citation Excerpt :
To further examine influences on the development of optic atrophy and visual acuity, systemic risk factors such as age at the time of radiation-induced optic neuropathy, diabetes, arterial hypertension, and smoking history were included in the analysis. The treatment planning protocol of the oncology center for proton beam therapy of uveal melanomas has already been described in detail.5 The dose of proton beam therapy used in all patients was 60 cobalt gray equivalent (CGE) in total (1 CGE = 1.1 Gy), taking a radiobiological effectiveness of 1.1 into account, fractionated in 15 CGE for 4 consecutive days.6
To compare intravitreal therapy with the natural course of radiation optic neuropathy after primary proton beam therapy for choroidal melanoma with respect to long-term visual acuity and development of optic atrophy.
Retrospective comparative case series.
Inclusion criteria: patients treated with primary proton beam therapy for choroidal melanoma with a minimum follow-up of 24 months after the occurrence of radiation optic neuropathy and optic disc imaging during follow-up. Exclusion criteria: pathologic condition of the optic disc before irradiation and intravitreal therapy to treat cystoid macular edema not originating from the optic disc.
Of 93 patients, 48 were observed only after radiation optic neuropathy, and 45 were treated with intravitreal therapy (triamcinolone, bevacizumab, and/or dexamethasone). Median follow-up was 55 months (29-187 months); median interval between onset of radiation optic neuropathy and the last patient visit was 34 months (24-125 months). Of 48 observed patients, 41 (85.4%) developed an optic atrophy after a median of 14 months (3-86 months) after radiation optic neuropathy; and of 45 intravitreally treated patients, 34 (75.5%) presented with an optic atrophy after a median of 12.5 months (1-55 months) following optic neuropathy, indicating no statistically significant differences between the groups. Comparing the change in visual acuity from occurrence of optic neuropathy to final visual acuity, no statistically significant differences were found between either group (P = 0.579).
Patients treated with intravitreal therapy for radiation optic neuropathy showed no statistically significant differences related to visual acuity or optic atrophy development from patients who underwent only observation.
Comparing efficacy of charged-particle therapy with brachytherapy in treatment of uveal melanoma
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2023, Current Oncology
Ocular Complications of Radiotherapy in Uveal Melanoma
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Original articleAdjuvant Ab Interno Tumor Treatment After Proton Beam Irradiation

Purpose

Design

Methods

Results

Conclusion

Section snippets

Methods

Results

Discussion

Saudi J Ophthalmol

Nucl Instrum Methods Phys Res A

Int J Radiat Oncol Biol Phys

Clin Oncol (R Coll Radiol)

Am J Ophthalmol

Inflammatory cytokines in eyes with uveal melanoma and relation with macrophage infiltration

Invest Ophthalmol Vis Sci

Vascular endothelial growth factor a in eyes with uveal melanoma

Arch Ophthalmol

Endoresection of choroidal melanoma

Br J Ophthalmol

Management of exudative retinal detachment in choroidal melanoma

Clin Exp Ophthalmol

Endodrainage, tumor photocoagulation, and silicone oil tamponade for primary exudative retinal detachment due to choroidal melanoma persisting after proton beam therapy

Ocul Oncol Pathol

Original article
Adjuvant Ab Interno Tumor Treatment After Proton Beam Irradiation