Proton Therapy vs Plaque Brachytherapy: Where CyberKnife and Gamma Knife Fit

When an eye melanoma needs radiation, one of the first questions is usually proton therapy vs plaque brachytherapy — and, increasingly, where stereotactic techniques such as CyberKnife and Gamma Knife fit in. All three aim to give the tumor a dose high enough to stop it growing while sparing as much of the eye and its vision as possible. They differ in how the radiation reaches the tumor, how many sessions are needed, which side effects are most likely, and where they are available.

Plaque brachytherapy, in which a radioactive disc is stitched to the eye for several days, has its own page. This page explains the external-beam alternatives and how specialists choose between the options.

Why is radiation the main treatment for eye melanoma?

Radiation lets most patients keep the eye. In the Collaborative Ocular Melanoma Study (COMS), survival after iodine-125 plaque brachytherapy was the same as after removal of the eye for medium-sized melanomas, and practice changed accordingly. In US cancer registry data, radiation alone rose from 1% of treatments in 1975–77 to 58% in 2017–20, while surgery alone fell from 93% to 21% — and 5-year relative survival, about 83%, stayed essentially unchanged over those decades.

Every form of eye radiotherapy is a team effort: the ocular oncologist defines and measures the tumor, a radiation oncologist prescribes the dose, and a medical physicist plans how it is delivered.

What is proton beam therapy for eye melanoma?

Protons are charged particles that deposit most of their energy at a set depth, called the Bragg peak, and then stop. The dose can therefore be shaped closely to the tumor, with a sharp fall-off beyond it.

• How it is done. In a short operation, small tantalum marker clips are stitched to the outer wall of the eye around the tumor so that its position can be checked during treatment. The radiation is then usually given in 4–5 sessions (fractions).
• Who it suits. Large tumors, tumors close to the optic nerve or the macula (the center of sharp vision), and tumors whose shape or position makes a plaque unsuitable.
• Results. The US National Cancer Institute summarizes long-term tumor control at about 95% at 15 years, with about 16% of eyes eventually removed. In one series of large tumors, 5-year local control was 94%; across other series, 10-year control ranged from 87.5% to 92.1% and 10-year eye retention from 70% to 87%. Useful vision is often lost with large tumors: in one such series, only 8.7% of patients kept vision of 20/200 or better at 10 years.
• Side effects. These resemble the effects of a plaque — radiation retinopathy, optic neuropathy and cataract — but neovascular glaucoma (abnormal vessels raising eye pressure) is reported more often: in 23–38% of patients in reviewed series, compared with up to about 17% after plaque. When the beam passes through the front of the eye, lash loss, dry eye, and effects on the eyelids and tear gland can occur.
• Availability. Only a few dozen centers worldwide treat eye tumors with protons, so treatment often involves travel.

What is stereotactic radiosurgery for eye tumors?

Stereotactic techniques aim many narrow beams at the tumor from different directions. Each beam alone carries a small dose; where they meet, the dose is high. No surgery on the eye wall is needed to deliver the radiation.

• Gamma Knife radiosurgery usually treats the tumor in a single session.
• CyberKnife, a compact linear accelerator on a robotic arm, usually divides the dose into a few sessions (fractionated stereotactic radiotherapy).
• LINAC-based stereotactic radiotherapy uses a standard radiotherapy linear accelerator with stereotactic precision, usually over several sessions.

A 2020 meta-analysis of 28 Gamma Knife studies reported local tumor control of 95.6%, tumor regression in 81.8% and later removal of the eye in 5.4%; complications occurred in 31.8%, and vision was stable or improved in only 26.7%. A 2025 meta-analysis of CyberKnife uveal melanoma treatment (10 studies, 2,370 patients) found 3-year local control of 89% and eye preservation of 84% at 3 years and 79% at 5 years, with radiation retinopathy in about 20%, secondary glaucoma in 19% and retinal detachment in 22%.

These figures pool single-center series with different tumor sizes and follow-up. Radiation injury to the retina and optic nerve is common after stereotactic treatment, and vision is often reduced.

Proton therapy vs plaque brachytherapy vs stereotactic radiotherapy: how do they compare?

Comparisons across studies are imperfect, because patients differ in tumor size and location, and follow-up and definitions vary. One direct comparison, a Dublin series of 310 patients treated in 2010–2020, found similar tumor control with ruthenium-106 plaques (96.0%), iodine-125 plaques (95.8%) and protons (95.2%), and similar eye retention (96.0%, 94.4% and 95.2%). Functional vision at the last visit was 50.9%, 27.8% and 39.7%, but the groups had tumors of different sizes, so these vision figures cannot be compared directly.

Which radiotherapy option is right for my tumor?

Specialists weigh several factors together:

• Size. Thickness and base diameter are measured by ultrasound and photographs; plaques are used for tumors up to about 12 mm thick, while very large tumors may need protons or removal of the eye.
• Location. Tumors touching the optic nerve are harder to control with a plaque — in a Dutch series of 719 patients, local failure after ruthenium-106 was 20% for such juxtapapillary tumors versus 6% for others — and protons are often preferred for them.
• Spread. Involvement of the ciliary body or growth through the eye wall changes the stage and may change the plan.
• Your health and preferences. Stereotactic treatment needs no surgery on the eye wall, which matters to some patients.
• Access. Proton centers are few, so travel, cost and time away from home are legitimate considerations.

Long-term survival depends mainly on the tumor's size and genetic profile rather than on the eye treatment: the COMS trial found no survival difference even between a plaque and removal of the eye. The choice between radiation methods is therefore made mainly on the chances of controlling the tumor, keeping the eye and preserving vision. Accurate measurements are the starting point — see how eye tumors are diagnosed — and the outlook is discussed on the uveal melanoma prognosis page.

Can photodynamic therapy be added after radiotherapy?

After radiotherapy, some tumors continue to leak fluid under the retina, which can blur vision. Photodynamic therapy (PDT) — a light-activated drug that closes abnormal blood vessels without radiation — has been studied as an add-on ("adjuvant") treatment in this setting; how it works is explained on the photodynamic therapy page.

The study was small, so it cannot show which patients benefit most. It does illustrate how stereotactic radiotherapy and light-based treatment can be combined for selected tumors at the back of the eye — and why long-term monitoring remains essential even when a tumor shrinks.

What happens after radiotherapy?

Whichever method is used, follow-up is similar: photographs, ultrasound and OCT scans at regular intervals to confirm that the tumor is controlled and to detect radiation effects early, plus body scans according to the tumor's risk group. Radiation maculopathy can often be treated with anti-VEGF or steroid injections; the options are described under side effects of plaque brachytherapy.

Radiotherapy options with Prof. Türkoğlu in Antalya

Prof. Türkoğlu examines the eye, measures the tumor and explains which radiation options are realistic for its size and position, including their likely effect on vision. Proton therapy and stereotactic radiotherapy need specialized facilities, so they are planned and delivered together with radiation oncology and medical physics teams; she plans the treatment with you and those teams and follows the eye afterward. Because few centers treat eye tumors with protons, this may mean treatment in another city or country, with eye examinations before and after. Patients abroad can start with a remote second opinion.