Does Proton Beam Radiotherapy Diminish the Reliability of Prognostic Genetic Analysis of Choroidal Melanoma?

Abstract

Purpose : Controversy exists regarding the prognostic value of genetic analysis of choroidal melanoma after radiotherapy. There are concerns that such treatment may influence chromosome 3. We performed retrospective observational clinical studies to (1) correlate metastatic mortality with genetic analysis of choroidal melanoma after proton beam radiotherapy (PBR), (2) compare metastatic mortality after PBR with that after excision (using this group as a surrogate for pre-radiotherapy biopsy), and (3) determine whether PBR influences the known relationship between chromosome 3 loss and basal tumor diameter.

Methods : Patients were included if they underwent genetic tumor analysis after PBR, local resection or enucleation for choroidal melanoma and if resident in mainland Britain. Tumors were analyzed by multiplex ligation probe amplification (MLPA) or, if the sample was insufficient, by microsatellite analysis (MSA). Patients were flagged with the UK National Health Service Cancer Registry, which automatically notified us of the date and cause of death. Logrank analysis was used to correlate metastatic mortality with chromosome 3 status after PBR and to compare irradiated with non-irradiated monosomy 3 melanomas. We investigated the influence of radiotherapy on survival and on the relationship between chromosome 3 loss and basal tumor diameter by comparing proton-beam irradiated tumors with non-irradiated tumors, using Cox and logistic regression respectively.

Results : After PBR chromosome 3 loss was detected in 63 (45.0%) of 140 tumors and was associated with a 48% 8-year actuarial metastatic mortality as compared to 0% in patients with a disomy 3 melanoma (Logrank, p<0.0005). The non-irradiated patients were treated by exoresection (43), endoresection (49) or enucleation (389). In 156 patients with a TNM T3 melanoma there was no significant difference in metastatic mortality in patients by excision or by PBR (Logrank, p = 0.875). Multivariate Cox analysis excluded treatment type (and hence radiotherapy) from the model (p=0.514). The relationship between basal tumor diameter and chromosome 3 loss was not influenced by radiotherapy (Logistic regression, OR 1.01, p =0.858).

Conclusions : Our results suggest that MLPA/MSA of choroidal melanoma reliably determines tumor lethality even after PBR. Such treatment does not influence chromosome 3 loss detected with these methods.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.