Palladium-103 plaque radiotherapy for choroidal melanoma: an 11-year study

doi:10.1016/S0360-3016(02)03751-3

International Journal of Radiation OncologyBiologyPhysics

Volume 54, Issue 5, 1 December 2002, Pages 1438-1445

https://doi.org/10.1016/S0360-3016(02)03751-3 Get rights and content

Abstract

$Purpose$ : To describe 11 years of experience with ¹⁰³Pd ophthalmic plaque brachytherapy for intraocular melanoma.

$Methods and Materials$ : Since 1990, 152 patients have been diagnosed with uveal melanoma, found to be negative for metastatic disease, and treated with ¹⁰³Pd radioactive plaque radiotherapy. This study presents the first 100 patients treated with ¹⁰³Pd and followed for ≥2 years. Plaques were sewn to the episclera to cover the base of the intraocular tumor. Treatment involved delivery of a mean apical radiation dose of 80.5 Gy during 5–7 days’ continuous treatment. Patients were evaluated for local tumor control, visual acuity, radiation damage (retinopathy, optic neuropathy, cataract), and metastatic disease.

$Results$ : Patients in this series were followed for a mean of 4.6 years (55.4 months). ¹⁰³Pd seeds were found to be equivalent to ¹²⁵I with respect to plaque manufacture and ease of dosimetric calculations. We noted a local control rate of 96% and six secondary enucleations. Including the enucleated patients, the visual acuity evaluations revealed that 35% lost six or more lines of vision and 73% had vision of 20/200 or better.

$Conclusion$ : Long-term results now exist describing the use of ¹⁰³Pd plaque radiotherapy for uveal (iris, ciliary body, and choroidal) melanoma. Compared with the results from centers using ¹²⁵I, patients in this series experienced equivalent local control rates and better visual function.

Introduction

Choroidal melanomas are most commonly treated by enucleation and radiotherapy (RT) 1, 2. In North America, more centers are using radioactive plaque therapy than any other eye- and vision-sparing alternative to enucleation (3). In the 1970s, Sealy et al.(4), Packer et al.(5), and Robertson et al.6, 7 introduced ¹²⁵I plaque RT (8), and Lommatzsch (9) investigated ¹⁰⁶Ru in Europe. Both were introduced as safer alternatives to ⁶⁰Co (10). For example, low-energy radiation from ¹²⁵I seeds is blocked by the gold seed carrier, eliminating >99% of the radiation to the sides and posterior of the plaque (11). Similarly, plaques containing ¹⁰⁶Ru primarily emit β-particles that typically travel 4–5 mm, thereby limiting unnecessary radiation 1, 12. Compared with ⁶⁰Co, both ¹²⁵I and ¹⁰⁶Ru were found to deliver significantly less radiation to normal ocular structures on the opposite side of the eye (from the tumor and plaque) and to operating surgeons.

When ¹⁰³Pd seeds became available for the treatment of cancer, several studies demonstrated that the lower energy photons generated from ¹⁰³Pd seeds (21 KeV) were more rapidly absorbed in tissue than those derived from ¹²⁵I (28 KeV) 13, 14. When a ¹⁰³Pd plaque was sewn to the episclera, ¹⁰³Pd photons were more rapidly absorbed by the tumor and less likely to reach most normal ocular structures (15). One study showed that when equivalent tumor apex doses were prescribed, the use of ¹⁰³Pd resulted in an increased dose within the targeted zone (tumor) and a decrease in irradiation to most normal ocular tissues compared with ¹²⁵I (16).

Like those who switched from ⁶⁰Co to ¹²⁵I or ¹⁰⁶Ru, we sought to improve our patient’s radiation dose distribution and safety further by using ¹⁰³Pd (17). We report on >11 years of experience with ¹⁰³Pd for ophthalmic plaque brachytherapy.

Section snippets

Patients and methods

Our methods of patient selection, diagnosis, and follow-up have been previously reported 16, 18, 19. It is important to note that each patient participated in a detailed discussion of the risks and benefits of observation, enucleation, radiation (various forms), and alternative investigational therapies as they related to their tumor’s size, location, and risk of metastasis (1). Small melanomas were typically followed for evidence of growth before treatment (20).

Informed consent typically

Results

We report on the first 100 consecutive patients who were treated with ¹⁰³Pd alone and followed for a minimum of 2 years up to 11 years (mean 55.4 months; Table 1). Two patients were lost to follow-up.

Six melanomas had a tumor height >8 mm or a basal dimension ≥16 mm. Thirteen had apical heights ≤2.4 mm. Most (81%) had basal dimensions ≥10 mm or apical heights between 2.5 and 8 mm (Table 1). Thirty-eight tumors were located anterior to the equator, 3 were centered at the equator, and 59 were

Discussion

In 1991, we reported our measurements of the relative dose of ¹⁰³Pd vs. ¹²⁵I for ophthalmic plaque RT 15, 16. Because ¹⁰³Pd seeds were shown to emit lower energy photons than ¹²⁵I seeds, it seemed reasonable to assume that its use would result in more irradiation of the tumor and less to most normal ocular structures (outside the targeted zone) (14). Compared with ¹⁰⁶Ru, the more far-reaching ¹⁰³Pd-generated photons are less rapidly absorbed in the tumor and able to reach the apex of taller

Conclusion

¹⁰³Pd ophthalmic plaque RT has been used to treat 152 patients with uveal melanoma. We have presented an analysis of 100 patients treated by ¹⁰³Pd alone and followed for a minimum of 2 years (range 2–11). Local tumor control was achieved in 96% of cases. At an average of 55.4 months of follow-up, 73% of patients were found to have 20/200 or better visual acuity (Table 5). Although our results are more favorable than those presented from centers using ¹²⁵I, any comparison of Phase I studies

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Palladium is one of the six platinum group metals and possesses strong catalytic activity. Demand for palladium is high for its uses in electrical equipment, dental materials, and automobile catalysts. Environmental levels of palladium in water, soil, and ambient air are not high, and environmental exposure and intake from food are not significant, but palladium concentrations are increasing in the general environment because of its increased use in automobile catalysts. Workers in the automotive catalyst manufacturing industry, palladium mines, and refineries are possibly exposed to palladium, as are dental personnel during the processing of dental alloys containing palladium. The general population may be exposed to palladium through inhalation of ambient respirable particles from automobile catalytic converters that incorporate palladium, but relevant data are rare. The oral toxicity of palladium is believed to be low, although it does depend on the water solubility of the palladium compounds. Therefore, similar intravenous LD₅₀ values have been reported for several palladium compounds: from 3 to 6.4 mg/kg body weight. From a 28-day toxicity study of tetraammine palladium hydrogen carbonate in rats performed through gavage, the no-observed-adverse-effect level was 1.5 mg/kg body weight/day. Among the general population, skin exposure may occur through contact with jewelry containing palladium. Many case reports exist describing palladium sensitivity and recovery after removal of dental restorations. The symptoms that have been observed include swelling of the lips and cheeks, stomatitis, oral lichen planus, itching, dizziness, asthma, and chronic urticaria. Recently, ¹⁰³Pd has been used for radioactive sources implanted directly into a malignant tumor; no palladium-related complications have been reported. Although respiratory sensitization effects, such as bronchial asthma, can occur among workers exposed to palladium and its compounds, its incidence is extremely low. On the other hand, its contact sensitivity rate has recently increased. No data are available on carcinogenicity, reproductive toxicity, or other effects in humans.
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The use of external beam not only requires accelerator but also affects multiple tissues through which it travels to get to the tumor, whereas plaque radiation travels through the wall of the eye in order to reach an intraocular tumor; hence, is preferred by ophthalmologists. The most commonly used radioisotopes for eye plaques are 125I, 103Pb and 106Ru [97–101]. Out of these, 106Ru has the longest half life (t1/2: 360 days) and is a β emitter while the other two emit low energy gamma rays.
Ruthenium, mainly ¹⁰⁶Ru, is one of the notorious fission products present in the radioactive wastes. In view of its complex chemistry, it gets partitioned into various processing streams during the radioactive waste management steps. Also, due to the volatile nature of its tetraoxide, RuO₄, it gets deposited in the process pipelines and stacks. Attempts have been made by various researchers, over the years, to separate radio-ruthenium from radioactive feeds including the acidic high level liquid waste (HLLW) as well as the alkaline low level liquid waste (LLLW) or intermediate level liquid wastes (ILLW). Solvent extraction, precipitation, ion-exchange, etc are some of the commonly employed techniques used for the separation of radio-ruthenium from radioactive feeds.
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From 1993 to 2012, our institution treated 160 patients with ¹⁰³Pd (56.1%) and 125 patients with ¹²⁵I (43.9%) plaque brachytherapy. Tumor outcomes, visual acuity (VA), and toxicity were compared. Multivariate analyses (MVAs) and propensity score analysis were used to help address differences in baseline characteristics.
Median followup was longer for ¹²⁵I patients, 52.7 vs. 43.5 months (p < 0.01). At baseline, ¹⁰³Pd patients had lower rates of VA worse than 20/200 (4.4% vs. 16%, p = 0.002), T3–T4 tumors (17.5% vs. 32.8%, p = 0.03), and transpupillary thermotherapy use (3.1% vs. 9.6%, p = 0.001). Both ¹⁰³Pd and ¹²⁵I provided >90% 3-year overall survival and >93% 5-year secondary enucleation-free survival. On MVA, radionuclide was not predictive for tumor outcomes. A higher percentage maintained vision better than 20/40 with ¹⁰³Pd (63% vs. 35%, p = 0.007) at 3 years. MVA demonstrated ¹⁰³Pd radionuclide (odds ratio [OR]: 2.12, p = 0.028) and tumor height ≤5 mm (OR: 2.78, p = 0.017) were associated with VA better than 20/40. Propensity score analysis matched 23 ¹²⁵I with 107 ¹⁰³Pd patients. ¹⁰³Pd continued to predict better VA at 3 years (OR: 8.10, p = 0.014). On MVA for the development of VA worse than 20/200 or degree of vision loss, radionuclide was not significant. Lower rates of radiation retinopathy were seen with ¹⁰³Pd than ¹²⁵I (3 years: 47.3% vs. 63.9%, p = 0.016), with radionuclide significant in MVA.
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Tumor and organ-at-risk (OAR) dose distributions from a CT-defined reference right eye were compared between ¹⁰³Pd COMS (Collaborative Ocular Melanoma Study Group) plaques delivering 70 Gy (plaque heterogeneity corrected) over 120 h to the tumor apex and GKRS plans delivering 22 Gy to the 40% isodose line for a representative sample of clinically relevant choroidal melanoma locations and sizes. Tumor and OAR biologically effective dose-volume histograms were generated using consensus radiobiologic parameters and modality-specific BED equations.
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^☆: Supported by The EyeCare Foundation, Inc., New York City, USA.

¹: Dr. Finger is a scientific consultant for Theragenics Corporation.

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Clinical investigation: eyePalladium-103 plaque radiotherapy for choroidal melanoma: an 11-year study1☆,

Abstract

Introduction

Section snippets

Patients and methods

Results

Discussion

Conclusion

Surv Ophthalmol

Surv Ophthalmol

Ophthalmology

Ophthalmology

Int J Radiat Oncol Biol Phys

Ophthalmology

Ophthalmology

Am J Ophthalmol

Ophthalmology

Int J Radiat Oncol Biol Phys

The treatment of ophthalmic tumours with low-energy sources

Br J Radiol

Irradiation of choroidal melanoma with iodine 125 ophthalmic plaque

Arch Ophthalmol

Radioactive iodine-125 as a therapeutic radiation source for management of intraocular tumors

Trans Am Ophthalmol Soc

Preliminary observations regarding the use of iodine-125 in the management of choroidal melanoma

Trans Ophthalmol Soc UK

Improved iodine-125 plaque design in the treatment of choroidal malignant melanoma

Br J Ophthalmol

Clinical investigation: eye
Palladium-103 plaque radiotherapy for choroidal melanoma: an 11-year study1☆,