A Danish investigation into the relationship between chromosome status and the local recurrence of uveal melanoma found that patients with somatic alterations in chromosomes 3 and 8q tended to experience earlier recurrence than patients without these genetic abnormalities, despite having equivalent overall incident rates.
Study design
A retrospective chart review of patients with ciliary body or choroidal melanoma who underwent Ru-106 brachytherapy at the Copenhagen University Hospital was performed. Chromosome 3 and 8q status, the incidence of local recurrence, and disease-specific mortality were all documented, and the effects of chromosome mutation on the outcomes were analyzed using Cox-regression modeling and Kaplan-Meier.
Outcomes
Local recurrence was noted in 16% of patients. Although the incidence of local recurrence was not affected by chromosome 3 or 8q status, patients with aberrations in chromosome 3 or 8q developed recurrence earlier than those with normal copy numbers of chromosome 3 and 8q. While Cox regression demonstrated that local recurrence was an independent risk factor for disease-specific mortality, disease-specific mortality remained low in patents with normal copy numbers of chromosome 3 and 8q who developed local recurrence.
Limitations
The authors of this study discuss the different types of recurrence patterns (including marginal, diffuse, extraocular, and a new location) and the possibility that diffuse recurrence may represent resistance to radiation as opposed to inaccurate plaque placement. However, they also acknowledge that the study was not powered appropriately to do meaningful subset analysis of the risk of metastasis depending on the type of recurrence. Another important consideration, which they also mention, is that local recurrence occurred much sooner in patients with abnormal chromosome 3 and/or 8q. It is therefore possible that patients with normal copy numbers of chromosome 3 and 8q and local recurrence from lesions could also develop metastasis at increased rates, but recurrences may develop later than this study's timeframe would allow.
Clinical significance
This study demonstrates that local recurrence of uveal melanoma seems to happen regardless of the DNA profile of the disease, but patients with more aggressive genetic profiles have an even higher risk of metastasis if recurrence happens. For patients with melanomas who have abnormalities in chromosome 3 and/or 8q, it is even more important to have excellent tumor coverage; surgeons may consider ultrasound at placement and removal of plaque brachytherapy to confirm appropriate tumor coverage. A mattress suture in the setting of plaque tilt at placement and either adjuvant transpupillary thermotherapy or extended radiation time can be considered if plaque tilt is noted at the planned time of removal, suggesting the apex of the tumor did not receive the planned dose of radiation. However, biopsy for prognostication often occurs at the time of treatment, so prior knowledge of the tumors most likely to cause metastasis in the setting of recurrence may not be available.
Financial Disclosures: Dr. Basil Williams discloses financial relationships with Allergan, Castle Biosciences, EyePoint Pharmaceuticals, Genentech, Regeneron Pharmaceuticals (Consultant/Advisor).