Collaborative Ocular Melanoma Study Group Research Articles

Air pollution exposure monitoring among pregnant women with and without asthma

Plaque brachytherapy (BT) and Gamma Knife radiosurgery (GKRS) are highly conformal treatment options for choroidal melanoma. This study objectively compares physical dose and biologically effective dose (BED) distributions for these two modalities.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.Published institutional prescriptive practices generally lead to larger tumor and OAR physical doses from COMS BT vs. GKRS. Radiobiologic dose conversions, however, revealed variable BEDs. Medium and large tumors receive >1.3 times higher BEDs with COMS BT vs. GKRS. OAR BEDs have even greater dependence on tumor size, location, and treatment modality. For example, COMS BT maximum BEDs to the optic nerve are lower than from GKRS for large anterior and all posterior tumors but are higher for anterior small and medium tumors.BT and GKRS for choroidal melanoma have different physical dose and BED distributions with potentially unique clinical consequences. Using published institutional prescriptive practices, neither modality is uniformly favored, although COMS BT delivers higher physical doses and BEDs to tumors. These results suggest that lowering the physical prescription dose for COMS BT to more closely match the BED of GKRS might maintain equivalent tumor control with less potential morbidity.

Dosimetric and radiobiologic comparison of 103Pd COMS plaque brachytherapy and Gamma Knife radiosurgery for choroidal melanoma

PurposePlaque brachytherapy (BT) and Gamma Knife radiosurgery (GKRS) are highly conformal treatment options for choroidal melanoma. This study objectively compares physical dose and biologically effective dose (BED) distributions for these two modalities. Methods and MaterialsTumor 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. ResultsPublished institutional prescriptive practices generally lead to larger tumor and OAR physical doses from COMS BT vs. GKRS. Radiobiologic dose conversions, however, revealed variable BEDs. Medium and large tumors receive >1.3 times higher BEDs with COMS BT vs. GKRS. OAR BEDs have even greater dependence on tumor size, location, and treatment modality. For example, COMS BT maximum BEDs to the optic nerve are lower than from GKRS for large anterior and all posterior tumors but are higher for anterior small and medium tumors. ConclusionsBT and GKRS for choroidal melanoma have different physical dose and BED distributions with potentially unique clinical consequences. Using published institutional prescriptive practices, neither modality is uniformly favored, although COMS BT delivers higher physical doses and BEDs to tumors. These results suggest that lowering the physical prescription dose for COMS BT to more closely match the BED of GKRS might maintain equivalent tumor control with less potential morbidity.

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.

Infiltrating macrophages in extratumoural tissues after brachytherapy of uveal melanoma

To compare distribution of macrophages in extratumoural ocular tissues in enucleated eyes with irradiated and nonirradiated uveal melanomas to find out how irradiation affects distribution of macrophages so as to gain insight into their potential routes of migration and changes in local inflammatory responses. Thirty-four matched pairs of primarily enucleated nonirradiated and secondarily enucleated irradiated eyes with choroidal and ciliary body melanoma were stained with mAb PG-M1, and the extratumoural immunopositive elements were counted under the microscope. Main outcome variables were the number of macrophages in the sclera underlying the tumour, in the choroid adjacent to the tumour, and in the ciliary body. The number of macrophage aggregates in the anterior ipsi- and contralateral episclera adjacent to the limbus was also counted. Macrophages were more numerous within the sclera under the tumour in irradiated eyes when compared to primarily enucleated eyes (median 1514 versus 619/mm², p = 0.0001), and more aggregates of episcleral macrophages adjacent to the limbus were found after irradiation (ipsilateral side, median 132 versus 0, p = 0.0034; contralateral side, median 79 versus 0, p = 0.014). In primarily enucleated eyes, increasing numbers of tumour-infiltrating macrophages were associated with presence of higher numbers of macrophages in the ciliary body (p = 0.003) and the adjacent choroid (p = 0.044), whereas in the irradiated eyes, increasing numbers of tumour-infiltrating macrophages (p = 0.010) and increasing extent of necrosis (p < 0.001) were associated with higher numbers of intrascleral macrophages underlying the tumour. Resident macrophages are present in extratumoural tissues in eyes with uveal melanoma. Brachytherapy may alter their route of migration and increase the number of macrophages in the sclera and episclera. Histopathologically detectable episcleral aggregates of macrophages adjacent to the limbus are detected predominantly after irradiation, a population of which is clinically visible as episcleral deposits after irradiation.

Choroidal melanoma treated with iodine-125 episcleral plaque: Analysis of dose on disease control and visual outcome

The Collaborative Ocular Melanoma Study (COMS) group randomized trial has established the use of episcleral I125 plaques as an alternative treatment to enucleation for medium sized choroidal malignant melanoma (CMM). The COMS protocol utilizes a dose of 85 Gy to the tumor apex or a minimum 5 mm height, which ever is greater. The optimal prescribed dose to ensure acceptable disease free survival, yet minimize radiation related ocular complications, is uncertain. We have often used doses that are lower than the COMS group trial and have prescribed dose to the tumor apex even when tumors were < 5 mm in height.

Choroidal melanoma treated with iodine-125 episcleral plaque: Analysis of dose on disease control and visual outcome

The Collaborative Ocular Melanoma Study (COMS) group randomized trial has established the use of episcleral I125 plaques as an alternative treatment to enucleation for medium sized choroidal malignant melanoma (CMM). The COMS protocol utilizes a dose of 85 Gy to the tumor apex or a minimum 5 mm height, which ever is greater. The optimal prescribed dose to ensure acceptable disease free survival, yet minimize radiation related ocular complications, is uncertain. We have often used doses that are lower than the COMS group trial and have prescribed dose to the tumor apex even when tumors were < 5 mm in height.