Clinical application of proton beams in the treatment of uveal melanoma: the first therapies carried out in Italy and preliminary results (CATANA Project).

BACKGROUND

The first Italian proton therapy facility was realized in Catania, at the INFN-LNS. With its energy (62 MeV proton beam), it is ideal for the treatment of shallow tumors like those of the ocular region: uveal melanoma, first of all (the most common primary intraocular malignancy of adults) and other less frequent lesions like choroidal hemangioma, conjunctiva melanoma, and eyelid tumors.

MATERIAL AND METHODS

The first patient was enrolled in February 2002, and to date 30 patients have been treated. All patients had a localized uveal melanoma, with no systemic metastases, and had specific indications for proton beam radiation therapy: lesions between 5-25 mm basal diameter, not exceeding 15 mm thickness, absence of total retinal detachment or glaucoma. According to the tumor dimensions, 2 patients had a small lesion or T1 (6%), 3 had a medium-sized lesion or T2 (10%), 14 had a large lesion or T3 (47%), and 11 had an extra-large lesion or T3 (37%); no patient had extrascleral invasion or T4 of the TNM-AJCC Staging System. In most cases, the tumor infiltrated only the choroid (14 patients, 47%) or the choroid plus the ciliary body (14 patients, 47%). We also treated a primitive iris melanoma, without diffusion to the ciliary body. The target volume was defined as the tumor plus a safety margin of 2.5 mm, laterally and antero-posteriorly; this margin was increased to 3 mm if ciliary body involvement was present. The treatment was carried out in 4 fractions on 4 consecutive days to a total dose of 54.5 Gy (single fraction 13.6 Gy), which corresponds to 60 CGE (Cobalt Gray Equivalent; single fraction 15 CGE), because the relative biological effectiveness is 1.1.

RESULTS

The first follow-up is planned at 6-8 months after the end of the treatment, and our clinical end points are local control (defined as cessation of growth or tumor shrinkage), eye retention, and maintenance of a good visual function. At the time of this writing, we had preliminary results from 13 patients. Nine patients showed tumor shrinkage (69%), 3 a substantially stable dimension (23%), but almost all patients presented an increased ultrasound reflectivity (a surrogate for tumor control).

DISCUSSION AND CONCLUSIONS

The literature data show that charged particle therapy has allowed an optimal local control in the treatment of uveal melanomas (about 96% in the different series, superior to that obtained with plaquetherapy [between 83% and 92%]), a metastatic rate slightly better than enucleation reports, and a survival rate of almost 90% at 5 years. Our preliminary results show a tumor response in almost all cases, with no major acute or subacute side effects. We thus plan to continue with our treatment procedures and our dose prescription.