Collaborative Ocular Melanoma Study Trial Research Articles

Practice Patterns for the Treatment of Uveal Melanoma with Iodine-125 Plaque Brachytherapy: Ocular Oncology Study Consortium Report 5

Background: Treatment planning for I-125 plaque therapy for uveal melanoma has advanced significantly since the Collaborative Ocular Melanoma Study trial, with more widely available image-guided planning and improved dosimetry. Objective: We evaluated real-world practice patterns for I-125 plaque brachytherapy in the United States by studying practice patterns at centers that comprise the Ocular Oncology Study Consortium (OOSC). Methods: The OOSC database and responses to a treatment practice survey were evaluated. The database contains treatment information from 9 institutions. Patients included in the database were treated between 2010 and 2014. The survey was conducted in 2018 and current treatment planning methods and prescriptions were queried. Results: Examination of the OOSC database revealed that average doses to critical structures were highly consistent, with the exception of one institution. Survey responses indicated that most centers followed published guidelines regarding dose and prescription point. Dose rate ranged from 51 to 118 cGy/h. As of 2018, most institutions use pre-loaded plaques and fundus photographs and/or computed tomography or magnetic resonance imaging in planning. Conclusions: While there were differences in dosimetric practices, overall agreement in plaque brachytherapy practices was high among OOSC institutions. Clinical margins and planning systems were similar among institutions, while prescription dose, dose rates, and dosimetry varied.

Mortality after deferral of treatment or no treatment for choroidal melanoma.

Purpose:To report mortality of patients who were eligible for enrollment in the Collaborative Ocular Melanoma Study (COMS) clinical trials of medium-sized choroidal melanoma or large-sized choroidal melanoma but chose to defer treatment or receive no melanoma treatment.Design:Prospective nonrandomized multicenter cohort study as an adjunct to COMS randomized clinical trials.Methods:Patient follow-up procedures included examinations, correspondence, telephone contacts, and National Death Index searches. Primary outcome was patient death measured by all-cause mortality. Secondary outcomes were melanoma treatment and melanoma metastasis.Results:Of 77 patients eligible for COMS clinical trials who chose to defer or receive no melanoma treatment, 61 were appropriate candidates and 45 (74%) enrolled in the natural history study (NHS). In all, 42 patients (42 eyes) had medium melanoma, and the median follow-up was 5.3 years (range, 4–10.7 years). In all, 22 patients (52%) had subsequent melanoma treatment, and 20 (48%) had no melanoma treatment. For the 42 patients, Kaplan–Meier estimate of 5-year mortality was approximately 30% [95% confidence interval (CI), 18%–47%]. For COMS medium melanoma trial, 5-year mortality was 18% (95% CI, 16%–20%), not statistically significantly different from the NHS patients. After adjusting for differences in age and longest basal diameter, the 5-year risk of death for NHS patients versus COMS trial patients was 1.54 (95% CI, 0.93–2.56). Three patients had large melanoma. Melanoma metastasis was confirmed or suspected in 8 (42%) of 19 deaths.Conclusion:Greater mortality and higher risk of death for NHS patients are probative but not conclusive evidence of a beneficial, life-extending effect of medium melanoma treatment.

Collaborative Ocular Melanoma Study randomized trial of I-125 brachytherapy

Although findings from observational studies published in the 1970s and early 1980s suggested that length of remaining life after a diagnosis of uveal melanoma was similar following enucleation (removal of the eye) and local eye-conserving radiotherapy, the majority of ophthalmologists in the United States were not convinced that "saving the eye" would not compromise survival. The Collaborative Ocular Melanoma Study (COMS) was designed to compare enucleation and radiotherapy among similar patients with respect to survival outcomes. A multicenter randomized trial of primary treatment with iodine-125 brachytherapy versus enucleation (i.e., a comparative effectiveness trial) was conducted to provide the evidence required to answer the concerns of ophthalmologists and their patients. Eligibility criteria adopted for the trial were intended to apply to the majority of patients diagnosed with choroidal melanoma who would be suitable candidates for either form of primary treatment. Accrual to this COMS trial began in 1986 and ended in 1998. Participating patients were followed for 5 to 15 years, depending upon date of enrollment, before all clinical follow-up ended in 2003. No difference in survival outcomes and little difference in quality-of-life outcomes were observed between patients in the brachytherapy arm and those in the enucleation arm. Five-year survival was substantially better than anticipated based on a review of the literature when the trial was designed. The choice of brachytherapy for delivery of radiation to the tumor had important advantages but also imposed restrictions regarding eligibility. The multidisciplinary COMS Group not only successfully conducted a randomized trial that answered the primary study questions but also has contributed to clinical and epidemiologic knowledge of choroidal melanoma through numerous publications. As a consequence of the COMS, a standard approach to I-125 brachytherapy for treatment of choroidal melanoma became widely available to affected patients.

Quality of Life After Iodine 125 Brachytherapy vs Enucleation for Choroidal Melanoma

To describe health- and vision-targeted quality of life following treatment with iodine 125 brachytherapy vs enucleation for choroidal melanoma in a subgroup of patients who were treated and observed prospectively as part of a large randomized clinical trial. Difficulty with driving, near vision activities, and activities using stereopsis or binocularity; anxiety; and depression. Two hundred nine patients who enrolled in the Collaborative Ocular Melanoma Study trial for medium-sized tumors between March 1995 and July 1998 and gave informed consent prior to randomization to participation in an ancillary study of quality of life. Patients were interviewed by telephone by a trained interviewer from the Collaborative Ocular Melanoma Study Coordinating Center at baseline (prior to randomization), at 6 months, and on annual anniversaries of enrollment. The questionnaire battery included the Medical Outcomes Study Short Form 36, the Activities of Daily Vision Scale, the National Eye Institute Visual Function Questionnaire, and the Hospital Anxiety and Depression Scale. Additional questions concerning satisfaction with posttreatment appearance and concerns about cancer recurrence also were included in posttreatment interviews. There was a significant increase in both treatment groups in levels of reported difficulty for most vision-oriented activities, and in bodily and ocular pain, 6 months following treatment. Differences in visual function between treatment groups reported during follow-up were relatively small, but significant differences favoring brachytherapy-treated patients were observed for driving during the first year of follow-up and for peripheral vision during the first 2 years of follow-up. Anxiety levels in both groups decreased significantly following treatment, but patients treated with brachytherapy with symptoms of anxiety were less likely to report later resolution of symptoms than patients with symptoms of anxiety who were treated with enucleation. This study was unable to assess impact of treatment on satisfaction with appearance and concern about cancer recurrence during the first year after treatment, but no treatment-related differences were found on these measures at 2 years and later follow-up times. Patients treated with brachytherapy reported significantly better visual function than patients treated with enucleation with respect to driving and peripheral vision for up to 2 years following treatment. Differences between treatments in visual function diminished by 3 to 5 years posttreatment, paralleling decline in visual acuity in brachytherapy-treated eyes. Patients treated with brachytherapy were more likely to have symptoms of anxiety during follow-up than patients treated with enucleation. Given that no significant differences in survival between enucleation and brachytherapy have been found, the differences demonstrated here for driving and anxiety will allow the individual patient and physician to make informed choices regarding treatment based on personal preferences.

Ten-year follow-up of fellow eyes of patients enrolled in Collaborative Ocular Melanoma Study randomized trials: Coms report no. 22

Purpose To report findings observed in fellow eyes during prospective follow-up of patients with unilateral choroidal melanoma after treatment with standard enucleation or 1 of 2 radiotherapy methods, either iodine 125 (I 125) brachytherapy or pre-enucleation external radiation, in order to document long-term outcomes and to identify any adverse effect of radiotherapy on the contralateral eye. Design Two multicenter randomized trials conducted by the Collaborative Ocular Melanoma Study (COMS) Group. Participants Eligible patients assigned randomly to standard enucleation or to the radiotherapy protocol adopted for tumors of the specified size and location and treated as assigned: 994 patients of 1003 enrolled in the COMS trial of pre-enucleation radiation and 1296 patients of 1317 enrolled in the COMS trial of I 125 brachytherapy. Outcomes Changes in best-corrected visual acuity (VA), intraocular pressure, and other findings in fellow eyes from baseline to examinations conducted at 6 and 12 months after enrollment and annually thereafter. Results Five years after enrollment, 1307 of 2290 fellow eyes were examined; 358 fellow eyes were examined 10 years after enrollment. Mean change in VA of fellow eyes from baseline to each examination was one letter (0.2 lines) or less. Cumulative 5-year incidence rates of cataract surgery and visually significant cataract in initially phakic eyes with good VA and no lenticular opacity were 8% in both trials; 10-year rates were 18% in the trial of pre-enucleation and 15% in the trial of I 125 brachytherapy. Intraocular pressures changed by less than 1 mmHg from baseline to each examination. Apart from lower rates of incident cataracts among fellow eyes of patients treated with pre-enucleation radiation, findings within each trial were similar in the 2 treatment arms. Conclusions Almost all surviving patients retained good VA in fellow eyes throughout 5 years of follow-up after treatment for choroidal melanoma. These findings persisted through 10 years of follow-up among patients eligible for examinations beyond 5 years. There was no evidence that fellow eyes of patients whose affected eye was treated with pre-enucleation radiation or with I 125 brachytherapy were at greater risk of loss of VA or new ophthalmic diagnoses than eyes of patients treated with enucleation alone.

Mortality after deferral of treatment or no treatment for choroidal melanoma

PurposeTo report mortality of patients who were eligible for enrollment in the Collaborative Ocular Melanoma Study (COMS) clinical trials of medium-sized choroidal melanoma or large-sized choroidal melanoma but chose to defer treatment or receive no melanoma treatment. DesignProspective nonrandomized multicenter cohort study as an adjunct to the COMS randomized clinical trials. MethodsPatient follow-up procedures included examinations, correspondence, telephone contacts, and National Death Index searches. Primary outcome was patient death measured by all-cause mortality. Secondary outcomes were melanoma treatment and melanoma metastasis. ResultsOf 77 patients eligible for the COMS clinical trials who chose to defer or receive no melanoma treatment, 61 were appropriate candidates and 45 (74%) enrolled in the natural history study. Forty-two patients (42 eyes) had medium melanoma, and median follow-up was 5.3 years (range, 4–10.7 years). Twenty-two patients (52%) had subsequent melanoma treatment, and 20 (48%) had no melanoma treatment. For the 42 patients, the Kaplan-Meier estimate of 5-year mortality was approximately 30% (95% confidence interval [CI], 18%–47%). For the COMS medium melanoma trial, 5-year mortality was 18% (95% CI, 16% –20%), not statistically significantly different from the natural history study patients. After adjusting for differences in age and longest basal diameter, the 5-year risk of death for natural history study patients vs COMS trial patients was 1.54 (95% CI, 0.93–2.56). Three patients had large melanoma. Melanoma metastasis was confirmed or suspected in eight (42%) of 19 deaths. ConclusionsGreater mortality and higher risk of death for natural history study patients are probative but not conclusive evidence of a beneficial, life-extending effect of medium melanoma treatment.

Changing concepts in the management of choroidal melanoma

PurposeTo review emerging information related to changing concepts in the management of choroidal melanoma. Design and methodsThis perspective reviews and discusses selected studies from the past two decades that have influenced management strategies for large, medium, and small-size choroidal melanomas. ResultsLarge choroidal tumors continue to be managed primarily by enucleation. The large tumor trial of the Collaborative Ocular Melanoma Study (COMS) demonstrated neither a positive nor negative effect on 5- and 8-year mortality rates among more than 1,000 patients whose eyes containing large choroidal melanomas were randomized to treatment between enucleation alone or enucleation preceded by external radiation. The medium-size tumor trial of the COMS randomized more than 1,300 patients between iodine-125 brachytherapy and enucleation. Mortality rates following brachytherapy did not differ from mortality rates following enucleation for up to 12 years after treatment. Iodine-125 has become the most commonly used isotope for brachytherapy in North America. Ten-year follow-up of eyes treated with helium ion and 20 years of experience with proton beam confirm the relative safety and efficacy of these modalities for treatment of choroidal melanoma. Although there is a trend toward earlier treatment of small melanomas, controversy exists regarding the indications for treatment as well as the choice of specific therapy. Recurrences of melanoma after eye-sparing treatment appear to be associated with an increased rate of metastatic disease. Effective adjunctive therapy to prevent or treat melanoma metastasis is lacking. ConclusionsChoroidal melanoma is a lethal tumor. Although evidence suggests that patients with untreated choroidal melanomas have a poorer prognosis than patients who receive treatment, our current treatments are unable to prevent tumor-related deaths for many patients. The use of preoperative external radiation as an adjunct to enucleation for large choroidal melanomas is unsupported by data from the COMS trial. The use of radiation with either brachytherapy or charged particles for the management of medium-size choroidal melanomas is well supported on the basis of long-term follow-up studies. There is a trend toward treatment of smaller choroidal melanomas. Treatment of melanomas should be directed toward minimizing the potential for recurrences as recurrent melanomas are associated with an increased rate of metastatic disease. Gains in our ability to manage choroidal melanoma will likely be modest at best until effective systemic therapies can be identified.

Quality of Life assessment in the Collaborative Ocular Melanoma Study: Design and Methods COMS-QOLS Report No. 1

The Collaborative Ocular Melanoma Study (COMS) is a set of randomized clinical trials sponsored by the National Eye Institute of the National Institutes of Health. The COMS is being conducted to evaluate the role of radiotherapy in the treatment of patients with choroidal melanoma. Primary choroidal melanoma can enlarge or metastasize and eventually cause death in a significant percentage of cases. The primary COMS trial is designed to determine whether enucleation (removal of the eye) or radiotherapy without removal of the eye provides the patient with the longest remaining lifespan. More than 40 clinical centers in the United States and Canada are participating in the COMS. The objective of the COMS is to assess the effect of treatment upon 5-year and 10-year survival and the reduction or elimination of the disease process in patients randomly assigned to receive either radiation or enucleation. An ancillary component of the COMS, referred to as the COMS-QOLS, was designed to measure the impact of disease and its treatment on quality of life. The two treatment approaches being investigated, enucleation and radiation therapy, are likely to have different psychological and physiological effects on the patients receiving them. The COMS-QOLS assessments include the SF-36 Health Survey, the Activities of Daily Vision Scale (ADVS), the Visual Functioning Questionnaire (VFQ), and the Hospital Anxiety and Depression Scale (HADS). Patients are interviewed at selected intervals during follow-up; in addition, 200 patients will be interviewed before randomization and have repeat interviews at six months and annually after randomization. The patient's quality of life after treatment will become an important consideration in determining the best form of therapy, particularly in the event that no survival difference between treatment groups is found.