Recommendations for dosimetry and dose prescription of eye plaques based on analysis of long-term treatment outcomes
Creators: name: Hackett, Seval
Publisher: name: RMIT University
Year: 2024

description: Ocular melanoma is a rare but potentially fatal disease. Radiation therapy, which enables both disease control and preservation of the eye, can be delivered by temporarily suturing radioactive sources held in a plaque to the eye. This method is widely used but the treatment protocol varies between institutions. Further, the dose distribution around the sources depends on the construction of the sources and eye plaque. The use of different sources, eye plaques and dosimetric assumptions precludes straightforward comparison of treatments between institutions. The work presented in this thesis compares the dosimetry and outcome for patients treated with eye plaques at Royal Perth Hospital (RPH) with those of the largest clinical trial of eye plaque therapy, the Collaborative Ocular Melanoma Study (COMS), and identifies treatment parameters that affect outcome. <br>All doses delivered at RPH were re-calculated using specific dosimetric assumptions. Doses re-calculated for the COMS were obtained from the literature. The re-calculated doses indicated that the average dose delivered under the RPH study was 17% lower than that delivered in the COMS.<br>Cumulative incidence models, incorporating the competing risk of death from unrelated causes, were used to determine 5-year rates of mortality, local recurrence and poor visual outcome. The relative effects of patient and treatment parameters on the probabilities of these outcomes were examined using Cox proportional hazard models. The 5-year mortality rate for the RPH patients of 12% was consistent with the mortality rate achieved in the COMS. The 5-year rate of recurrence for the RPH patients was 19%, close to double that observed in the COMS. However, the 5-year rate of poor visual outcome for the RPH cohort was 28%, significantly lower than the 5-year rate of 49% in the COMS. These differences are consistent with the expectation that a lower dose to the tumour, and therefore the surrounding tissue, would reduce the probability of tumour control and of normal tissue complications. <br>The treatment parameters strongly associated with greater risk of mortality were the dose rate and biologically effective dose (BED) to the tumour apex. The dose to the sclera, at the base of the tumour, strongly predicted the risk of tumour recurrence. No treatment parameter was found to influence the visual outcome of the treatment. <br>It was concluded that the prescription dose, and therefore the dose to the sclera, should be increased to a value consistent with the COMS, with recognition that the rate of poor visual outcome will likely increase. The probabilities of successful prevention of metastasis and good visual outcome could be increased by optimising the BEDs to the tumour and nearby ocular structures at risk. A treatment time of around four days would deliver a higher dose rate, and therefore a higher BED, to the tumour apex. Such a treatment would be appropriate for patients considered at low risk of poor visual outcome, as indicated by the distance between the tumour and ocular structures at risk. <br>