Visual Outcome after Proton Beam Irradiation of Uveal Melanoma

doi:10.1016/S0161-6420(86)33700-X

Ophthalmology

Volume 93, Issue 5, May 1986, Pages 666-674

https://doi.org/10.1016/S0161-6420(86)33700-X Get rights and content

Abstract

Prognostic factors for visual loss following proton irradiation of uveal melanoma were evaluated for 440 eyes treated from 1975 to 1984, with visual acuity 20/200 or better before treatment. Analysis involved Kaplan-Meier survival curves and Cox proportional hazards analysis with visual outcome defined as worse than 20/200. Prognostic factors were tumor height: rate ratio (ratio of rate of visual loss for one category of the variable relative to the rate of visual loss for a reference category of that variable) of 5.26 (95% confidence interval, 2.66–10.39) for tumors greater than 5 mm compared to tumors 3.0 mm or less in height; distance of tumor from the optic disc and fovea: rate ratio 2.59 (1.63–4.11) for tumors 2DD or less from both the optic disc and fovea compared to those greater than 2 DD from these structures. Also predictive of visual loss were tumor location close to disc only, or close to fovea only, macular detachment, worse pretreatment vision, and higher radiation doses delivered to both the disc and fovea, and lens. Regression analysis using a visual acuity scale gave similar results.

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Cited by (100)

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.
Corneal Substructure Dosimetry Predicts Corneal Toxicity in Patients With Uveal Melanoma Treated With Proton Beam Therapy
2019, International Journal of Radiation Oncology Biology Physics
This study examines the relationship between dose to corneal substructures and incidence of corneal toxicity within 6 months of proton beam therapy (PBT) for uveal melanoma. We aim to develop clinically meaningful dose constraints that can be used to mitigate corneal toxicity.
Ninety-two patients were treated with PBT between 2015 and 2017 and evaluated for grade 2+ (GR2+) intervention-requiring corneal toxicity in our prospectively maintained database. Most patients were treated with 50 Gy (relative biological effectiveness [RBE]) in 5 fractions, and all had complete six-month follow-up. Analyses included Mann-Whitney, χ², Fisher exact, and receiver operating curve tests to identify risk factors for GR2+ toxicity. Bivariate logistic regression was used to identify independent dose-volume histogram (DVH) predictors of toxicity after adjustment for the most important clinical risk factor.
The 6-month PBT GR2+ corneal toxicity rate was 10.9%, with half of patients experiencing grade 2 toxicity and half experiencing grade 3 toxicity, with no grade 4 events. Patients with anterior chamber tumors had a higher risk (58.3%) for toxicity than those with posterior tumors (0%) or posterior tumors extending past the equator (25%, P < .0001). On univariate analysis, larger size according to Collaborative Ocular Melanoma Studies was associated with increased toxicity rate (P < .004). DVH analysis revealed that cutoffs of 58% for V25, 32% for V45, 51.8 Gy (RBE) for maximum dose, and 32 Gy (RBE) for mean dose to the cornea separated patients into groups experiencing and not experiencing toxicity with 90% sensitivity and ≥96% specificity. Bivariate logistic regression indicated that corneal V25, V45, and mean dose independently predicted for toxicity after adjusting for tumor location.
Patients receiving PBT for anterior uveal melanomas experience a high rate of GR2+ corneal toxicity because of increased corneal dose. Anterior location and corneal DVH parameters independently predict toxicity risk. We propose dosimetric constraints to facilitate treatment planning and toxicity mitigation.
Cataract surgery after proton-beam irradiation for uveal tumors
2017, Journal of Cataract and Refractive Surgery
To study the risks associated with cataract surgery in patients with previous proton-beam irradiation (PBI), focusing on preoperative risk factors, intraoperative findings, and postoperative complications.
Massachusetts Eye & Ear Infirmary, Boston, Massachusetts, USA.
Retrospective case series.
Electronic medical records of patients who had PBI and cataract surgery between January 1, 2006, and October 1, 2016, were reviewed.
The study comprised 29 eyes of 29 patients. Preoperative evaluation found dry eye (72.4%), posterior synechiae (24.1%), peripheral anterior synechiae (13.8%), anterior capsule fibrosis (10.3%), and iris atrophy (10.3%). Intraoperative findings included poor red reflex requiring trypan blue capsule staining (37.9%), synechiae requiring synechialysis (24.1%), evidence of previous inflammation prompting sub-Tenon triamcinolone injection (17.2%), and miosis (10.3%). Postoperative complications included posterior capsule opacification (PCO) by 1 year (48.3%), intraocular pressure spike of 23 mm Hg or greater at 1 day (24.1%), anterior chamber inflammation at 1 month (24.1%), and cystoid macular edema (CME) (17.2%). Proximity of the initial tumor to the posterior pole was associated with poor visual outcomes after cataract surgery. Compared with reference data, this cohort had higher rates of anterior chamber inflammation at 1 month, CME, fibrinous inflammation, PCO by 1 year, intraoperative requirement for trypan blue, and synechialysis.
Complications after cataract surgery performed after PBI were similar to those seen in patients with uveitis (prolonged inflammation, CME, fibrinous inflammation, early PCO). Steroid depot administration might be useful to prevent these complications, although further research is needed to determine an optimum regimen.
Clinical Outcomes of Proton Radiotherapy for Uveal Melanoma
2016, Clinical Oncology
Citation Excerpt :
With a median follow-up of 148 months, all-cause mortality (ACM) at 15, 20 and 25 years was 49, 59.6 and 66.8%; melanoma-specific mortality was 24.6 and 26.4% at 15 and 25 years, respectively. These data did not include visual acuity outcomes, but in a previous analysis of 440 patients [15] with visual acuity data, 91.6% had visual acuity better than 20/160 before PBT and 35% of patients had vision worse than 20/200 after PBT. At the University of California, San Francisco, early data compared outcomes in a non-randomised and retrospective manner between particle therapy (PBT and helium ions) and iodine-125 brachytherapy with a 54 month follow-up [16].
Although clinical experience with proton beam radiotherapy (PBT) for most tumours is limited, there is relatively longstanding experience for uveal melanomas. Because of potential to reduce ocular toxicities, PBT is an attractive option for these tumours. However, summative data remain scarce. We systematically reviewed clinical outcomes of uveal melanoma patients treated with PBT, to comprehensively assess outcomes such as tumour control, survival, enucleation rates, toxicity and visual acuity preservation.
A systematic search of PubMed, EMBASE, abstracts from meetings of the American Societies for Radiation Oncology and Clinical Oncology, and the Particle Therapy Co-Operative Group was conducted from 2000 to 2015. Fourteen original investigations from 10 different institutions were analysed.
Most tumours were choroidal and medium-/large-sized, and received 50–70 Cobalt Gray equivalent dose; more recent data reported lower doses. Five year local control rates exceed 90%, which persisted at 10 and 15 years. Five-year overall survival rates ranged from 70 to 85%, 5 year metastasis-free survival and disease-specific survival rates from 75 to 90%, with more recent series reporting higher values. With the removal of smaller studies, 5 year enucleation rates were consistently between 7 and 10%. Many patients (60–70%) showed a post-PBT visual acuity decrease, but still retained purposeful vision (>20/200); more recent, higher-volume series reported superior numbers. Complication rates were quite variable but showed improvements on historical plaque brachytherapy data. Only one randomised trial directly compared particle therapy (helium) with plaque brachytherapy, showing the former to be superior; this is addressed separately.
PBT is an excellent modality to treat uveal melanomas, with high survival outcomes and visual acuity preservation. Although there are low toxicity and enucleation rates, the recent development of supportive therapies for radiation toxicities can further decrease clinical adverse effects.
Outcomes after Proton Beam Therapy for Large Choroidal Melanomas in 492 Patients
2016, American Journal of Ophthalmology
Citation Excerpt :
Visual outcomes are heterogeneous among studies and correlate with tumor location and the distance to the macula and optic disc. Initial poor visual acuity is another important determinant of ultimate visual acuity that is itself related to tumor size and location,42,43 and in that sense our patients had unfavorable initial characteristics compared to other study patients. Finally, proton beam therapy may be considered as a safe and efficient alternative to enucleation in patients with large choroidal melanomas (defined as AJCC stage T3 and T4) with respect to survival rates, local control, and visual acuity.
To evaluate proton beam therapy (PBT) as a means to preserve the eye and spare some vision while not deteriorating survival in patients with large choroidal melanomas.
This is a retrospective, consecutive cohort study of patients with T3-4 choroidal melanomas according to the 7th edition of the American Joint Cancer Classification treated with PBT over a 24-year period.
A total of 492 patients were included. Mean (range) tumor thickness and diameter were 8.77 (2–15) mm and 14.91 (7–24.1) mm, respectively. Mean macular and optic disc distance were 4.56 (0–19.9) mm and 4.59 (0–22.1) mm, respectively. Mean follow-up was 61.9 months. Rates of neovascular glaucoma (NVG) and enucleation (mainly for local recurrence or NVG) were 27.0% and 19.5%, respectively. Enucleation rates decreased over time. The 5-year local control was 94%. Mean baseline visual acuity was 20/63, and visual acuity ≥20/200 was preserved in 20% of patients. At 5 years, 25% of T3 patients presented with metastasis; overall and specific survival rates were 65% and 75%, respectively.
Local control after PBT remained good with increasingly manageable complications and fewer secondary enucleations over time for these large melanomas. As PBT does not seem to deteriorate survival in these patients having a high risk of metastasis, PBT may be considered as a safe and efficient alternative to enucleation in patients with large choroidal melanoma, and may help to spare some vision.
Intraoperative localization of tantalum markers for proton beam radiation of choroidal melanoma by an opto-electronic navigation system: A novel technique
2012, International Journal of Radiation Oncology Biology Physics
External beam proton radiation therapy has been used since 1975 to treat choroidal melanoma. For tumor location determination during proton radiation treatment, surgical tantalum clips are registered with image data. This report introduces the intraoperative application of an opto-electronic navigation system to determine with high precision the position of the tantalum markers and their spatial relationship to the tumor and anatomical landmarks. The application of the technique in the first 4 patients is described.
A navigated reference base was attached noninvasively to the eye, and a navigated pointer device was used to record the spatial position of the tantalum markers, the tumor, and anatomical landmarks. Measurement accuracy was assessed on ex vivo porcine eye specimen by repetitive recording of the tantalum marker positions. The method was applied intraoperatively on 4 patients undergoing routine tantalum clip surgery. The spatial position information delivered by the navigation system was compared to the geometric data generated by the EYEPLAN software.
In the ex vivo experiments, the maximum repetition error was 0.34 mm. For the intraoperative application, the root mean square error of paired-points matching of the marker positions from the navigation system and from the EYEPLAN software was 0.701–1.25 mm.
Navigation systems are a feasible tool for accurate localization of tantalum markers and anatomic landmarks. They can provide additional geometric information, and therefore have the potential to increase the reliability and accuracy of external beam proton radiation therapy for choroidal melanoma.

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: Presented at an Annual Meeting of the American Academy of Ophthalmology.

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Visual Outcome after Proton Beam Irradiation of Uveal Melanoma

Abstract

Am J Ophthalmol

Ophthalmology

Ophthalmology

Ophthalmology

J Chronic Dis

Am J Ophthalmol

Comparison of survival rates for patients with uveal melanoma after treatment with proton beam irradiation or enucleation

Am J Ophthalmol

Local radiotherapy in the treatment of malignant melanoma of the choroid

Trans Ophthalmol Soc UK