Introduction

Ocular Melanoma is the most common type of eye cancer and it starts in melanocytes (skin cells in the eye). Ocular melanoma usually develops in the uvea, which is part of the eye consisting of the iris (the coloured part).

The different types of ocular melanomas include:¹ 

• choroidal melanoma, which occurs in the choroid (the layer of blood vessels at the back of the eye) 
• ciliary body melanoma ocular melanoma, which develops in the ciliary body (the muscle fibres around the focal point where light rays converge) 
• iris melanoma, which develops in the iris
• conjunctival melanoma, which occurs in the conjunctiva (the thin part of the eye covering the sclera or white bits, and inside of the eyelids)
• orbital melanoma, which develops in the orbit or the cavity of the eye
• eyelid melanoma, which develops in the insides of eyelids

Proton therapy is a type of radiotherapy that has been used to treat tumours around critical parts of the body, such as the spinal cord and to treat neck, head and brain cancers. Proton therapy does have side effects, however, the side effects are fewer than traditional radiotherapy due to lower damage to the healthy tissues surrounding the tumour. Thus, proton therapy can be used as a treatment for tumours that have developed around sensitive parts of the body, including near the eye, optic nerve, and retina.²

What is proton therapy?

Proton therapy is a different method to treat different types of cancers and consists of using a beam of high energy protons. These protons are targeted specifically at a tumour with extreme precision, which leads to a lower chance of damage to the healthy tissues and organs.²

Proton therapy is still considered to be effective and safe compared to traditional radiotherapy. Traditional radiation therapy consists of using X-rays or beams of photons to aim at the tumour, which is effective as a treatment, however, it can lead to side effects and damage healthy tissues. Alternatively, as proton therapy uses protons to target precisely at the tumours, there is no damage to the healthy tissues.³

Indications for proton therapy in ocular melanoma

In the UK, small tumours in the posterior pole (back of the eye), tumours in the posterior pole affecting fovea (small pits in the eyes), and large anterior (front of the eye) tumours that are too large for brachytherapy (a type of radiotherapy), are all candidates for proton therapy as a treatment method for uveal melanoma.⁴

For proton therapy, selection of patients for the proton therapy is one of the important indications. Priority level 3 radiation patients include those with category 2 (less aggressive) tumours, and radiation therapy is the first defined therapy. Uveal melanoma meets the high priority criteria (overall 50% rate of metastasis or spread) as outcomes could worsen if ocular treatment is delayed. Ocular radiation therapy achieves high levels of local tumour growth. For example, proton therapy achieved a greater than 95% rate of local tumour control after 4-5 fractions (doses).⁵

Furthermore, the Uveal Melanoma Registry (established in the early 1980s) collected the demographic and clinical data of patients who were treated by proton irradiation. The analyses conducted have shown proton radiation is very effective in helping control local eye melanoma without causing any detrimental effects on survival.⁶ 

Mechanisms of proton therapy in ocular melanoma

Proton beam therapy works by disrupting tumour DNA and destroying tumour cells. The protons are separated from hydrogen atoms and are sped up in a particle accelerator. The stream of protons is focused into a thin beam (5 mm wide) using a gantry, which is a special device that can rotate 360 degrees and focus the stream of protons into a thin beam using a magnet. The beam is guided by the magnet and directed at the tumour from different angles while the gantry rotates around the patient. Furthermore, the energy within the proton beam can be adjusted based on the depth of the tumour.⁷

Efficacy of proton therapy in ocular melanoma 

Proton therapy uses proton particle radiation, which is different to the traditional radiotherapy that uses X-rays and gamma rays. Both the proton and photon radiation therapy can cause damage to the tumour cells. However, photon therapy can cause damage that could be irreversible. Furthermore, protons travel a specified distance and deliver the highest level of targeted radiation to the tumour.⁷ 

There are various advantages offered with proton therapy compared to brachytherapy for large tumours, tumours that are close to the optic nerve or insertion of extra-insertion muscles, and for patients who do not tolerate anaesthesia. However, there are challenges in the treatment of uveal melanoma despite the high control rate that has been achieved with definitive management (long-term relief or cure).⁸

Benefits and side effects

Proton therapy improves patient quality of life, reduces overall toxicity, and increases the long-term survival rate for certain types of tumours. Furthermore, proton therapy can treat patients who could have previously received radiation therapies due to experiencing multiple, recurrent tumours. Furthermore, there are no radiation risks to the wider population from patients receiving proton therapy.⁹

The side effects of proton therapy include: 

• Sore, reddened skin in the area where the proton beam entered the body 
• Hair loss in the area of treatment
• Tiredness and fatigue 

Furthermore, other side effects could include headaches and digestive issues, depending on the area of treatment.⁷

Proton therapy treatment process

The process of proton therapy to treat ocular melanoma comprises many stages, including pre-treatment planning and treatment sessions. The pre-treatment planning involves undergoing a simulation before the proton therapy to make an immobilisation device for the patient to use during treatment.

Furthermore, during the treatment, the radiation therapist will explain the daily routine and will position the immobilisation device and use the markings from the simulation procedure to accurately deliver the prescribed proton therapy. The progress is monitored by the radiation oncology nurse who helps the patients manage the side effects from the therapy.⁹

Summary

Proton therapy is an increasingly popular form of treatment for patients with ocular melanoma because it reduces the risks to healthy tissues when treating tumours near sensitive areas of the body, such as the eyes, optic nerves, and retinas. Proton therapy is effective in treating cases of uveal melanoma. However, there are some challenges in the treatment of uveal melanoma, and hence, further research is required to investigate the most effective therapies for patients with ocular melanoma. 

Future research is required to assess whether combined therapies could be an effective way to eradicate distant micro-metastasis and the primary tumour in a synthetic or complementary approach. The combination of therapies could lead to more favourable long-term survival and determine whether radiomic analysis could help to select the appropriate treatment.