OM Treatment

Once a diagnosis of Ocular Melanoma is made, choice of treatment depends on the location, site of origin within the eye, and size of the tumor, as well as patient age, overall health, visual potential and status of the unaffected eye. Because OM is resistant to conventional systemic therapies, early diagnosis and treatment is essential. In addition, if the melanoma has metastasized, or spread, the melanoma can be more difficult to treat. 

The primary goals of treating the eye tumor include preventing metastasis, sparing the eye and preserving vision. 

Treatment of Primary Ocular Melanoma

Radiation: 

For most small and medium size tumors, radiation is the recommended treatment. The most widely used forms of radiation currently include plaque radiotherapy and proton beam radiotherapy. There are no studies showing that one form of radiation is better than another form.

• Plaque Radiotherapy – This is the most common therapy for posterior ocular melanomas (choroidal and ciliary body). It consists of suturing a small, metallic object, containing radioactive material, to the wall of the eye adjacent to the tumor. Once the tumor has received sufficient radiation to destroy the tumor, the plaque is again removed surgically. Plaque radiotherapy has become the standard of care for most melanoma patients with small or medium size tumors. Depending on the radiation laws of the state in which treatment is given, a patient may be required to stay in the hospital for the entire length of treatment. However, some states allow patients to be at home for the treatment.
• Proton Beam Radiotherapy – Charged particle therapy that delivers a focused dose of radiation to the targeted area while surrounding normal tissue receives minimal radiation. Small tantalum rings are surgically placed around the edges of the tumor to direct the radiation beams.
• Stereotactic Radiotherapy – Provides radioactive dose to tumor in small fractions that convene on the target tumor such that the tumor receives the total dose, while surrounding tissues receive a smaller dose. The two main forms include gamma-knife and linear accelerator (LINAC). To date, there is not widespread use of this treatment for ocular melanoma and more research is needed to understand its specific role.

Surgery:

In some cases, the recommended treatment for ocular melanoma is surgical removal of the tumor. Surgery is often recommended for tumors of large size and for iris melanomas in particular. Also, surgery may be recommended for recurrent disease, if necessary, after initial radiation treatment (see below).

• Enucleation – Removal of the eye is sometimes necessary in cases involving large tumors. Following removal of the eye, an artificial eye can be placed in the socket.
• Iridectomy – Removal of part of the iris where the tumor is present.
• Iridocyclectomy – Removal of part of the iris as well as the adjacent ciliary body where the tumor is present.
• Trans-Sclera Local Resection – The tumor is removed through an opening in the wall of the eye. This is often used when the tumor is large. A radioactive plaque is usually placed over the treated area to reduce tumor recurrence.
• Trans-Retinal Endoresection – The tumor is removed through a hole in the retina. This can be useful when the tumor is located close to the optic nerve. Laser treatment is given to prevent tumor recurrence. 

Additional Treatments that May Be Recommended

• Transpupillary Thermotherapy –  Laser treatment involves heating the tumor for about one minute, using an infrared laser beam. The treatment lasts about half an hour and is delivered under local anesthesia on an outpatient basis. This treatment is suitable for small tumors, when there is uncertainty as to whether the lesion is a benign nevus or a malignant melanoma. It is also useful for melanomas that are leaking excessive amounts of fluid and fat after previous radiotherapy.
• Intraocular Injections –  Intraocular injections, which are quite painless, are given under local anesthetic. These may include steroids for inflammation and or anti-angiogenic factors, which shrink blood vessels.

Adjuvant Treatment:

Based on the ability to determine what patients may be at higher risk for developing metastatic disease, one would like to be able to treat high-risk patients with adjuvant treatment in hopes of preventing metastatic disease after treatment of the primary eye tumor. Unfortunately, new treatment has yet to be identified that can effectively serve this purpose. There are, however, ongoing clinical trials to identify possible effective agents, and such trials can be found using the MRF’s Clinical Trial Finder. 

Surveillance:

Currently, there is no consensus regarding type or frequency of scans following diagnosis and treatment of the primary eye tumor. It is important to speak with your doctors to decide what is right for you. Because, of the 50% of patients who develop metastatic disease, more than 90% of patients will develop liver metastases, the majority of surveillance techniques are focused on the liver . These include: abdominal magnetic resonance imaging (MRI), abdominal ultrasound and liver function tests. The scientific community is currently working to develop guidelines, but until then, each patient must take into consideration their individual clinical situation and discuss appropriate surveillance with their doctors. 

Treatment of Metastatic Ocular Melanoma

Once ocular melanoma (OM) has spread beyond the eye, it is considered to be metastatic. While about 50% of patients will develop metastatic disease, it is rare to have identifiable metastatic disease at the time of diagnosis of the primary eye tumor. The majority of the time (around 90%) the liver is the first site of metastatic disease. In general, prognosis is poor after the tumor has metastasized. Without treatment, the median survival time is between 2-8 months. Note that is is only a median overall survival, but on the other end of the spectrum, can be in the years. Standard chemotherapies, overall, have not proven to be effective in melanoma, either of the skin or of the eye. Although there are currently no approved treatments for metastatic OM, there are several palliative treatments, as well as new clinical trials, offered in the US and Europe. In this section, we will describe some of these. Please discuss further with your doctors and learn more about clinical trials using the MRF Clinical Trial Finder.

Liver Directed Treatments:

• Resection - Surgical removal of metastatic tumor. Only about 9% of patients are eligible for resection because of the presence of multiple tumors in the liver at the time of diagnosis
• Ablation - Can be done percutaneously (through the skin) or surgically. Ablation involves inserting small probes into tumors and heating (i.e. radio frequency ablation, microwave ablation) or freezing (cryoablation) the tumors to kill them.
• Radiation - Targeted radiation can be used to treat liver disease. Targeted radiation such as stereotactic radiosurgery (i.e., Gamma Knife and Cyber Knife) can be used to target specific tumors while sparing normal tissue.

Transarterial Catheter-Directed Liver Therapies

A particular substance is infused into the liver through a catheter that is inserted into an artery. Unlike ablation, these therapies treat an entire side of the liver or can treat both sides at once.

• Hepatic Arterial Chemoinfusion (HAI): Infusion of chemotherapy into the liver through a specialized infusion system in which a catheter is placed into the hepatic artery to directly and continuously deliver the chemotherapy to the liver. This direct infusion minimizes the side-effects of the chemotherapy and allows high doses to be administered.
• Transarterial Chemoembolization (TACE): Infusion of chemotherapy into the liver through the hepatic artery. Unlike HAI, this procedure results in episodic doses of chemotherapy. Also, unlike HAI, TACE exerts its actions in two ways: 1) delivering chemotherapy to the tumors, and 2) the procedure results in intermittent decrease of blood to tumor tissue. The goal is tumor death.
• Immunoembolization: Similar to TACE, but infusion of immunotherapy agent into the liver (e.g. GMCSF) rather than a chemotherapeutic agent.
• Radioembolization: Similar to TACE, but infusion of radioactive beads into the liver. The radioactive beads lodge in the small blood vessels around the tumor and radiate the tumor. The goal is tumor death. Two examples of this treatment include Sirspheres and Theraspheres.
• Isolated Hepatic Perfusion (IHP): A different type of procedure to deliver high doses of chemotherapy to the liver. In IHP, a catheter is placed into the artery that provides blood to the liver; another catheter is placed into the vein that takes blood away from the liver. This temporarily separates the liver’s blood supply from blood circulating through the rest of the body and allows high doses of chemotherapy to be directed to the liver only. When it is done percutaneously, or in a less invasive method, it is referred to as Percutaneous Hepatic Perfusion (PHP).  

Other Local Interventions that May be Recommended:

• Radiation - Described above, radiation can be used to treat other areas of the body including lung, bone, and brain. Depending on the location of the tumors, regular external beam radiation therapy may be better suited than stereotactic radiosurgery. Radiation therapy can be used to treat isolated metastases or to relieve symptoms caused by a specific lesion.
• Ablation - Described above, ablation can be used in other areas of the body beyond the liver, such as lung, kidney, and soft tissue. 

Systemic Treatments

Although, currently, there are no approved systemic treatments for metastatic ocular melanoma, some providers recommend treatment with systemic agents, such as Yervoy, that have been approved for melanoma of the skin.  Alternatively, there are ongoing clinical trials in which patients have access to systemic agents before they are approved.  To see what clinical trials you are eligible for, please visit the MRF's Clinical Trial Finder, our searchable clinical trials database.

• Chemotherapy - Overall, chemotherapy has not been shown to be effective for melanoma. The types of systemic therapy that have proven to be effective in cutaneous melanoma have not yet shown applicability to ocular melanoma. However, they may still be recommended in some cases and could include the following:

1. Dacarbazine (DTIC): the only FDA approved chemotherapy agent for the treatment of Stage IV melanoma. It is administered as an intravenous infusion.
2. Temozolomide: an oral chemotherapy that is considered an oral form of DTIC.
3. Other chemotherapy agents that may be used include the taxanes (i.e. docetaxel, paclitaxel) and platinum agents (i.e. cisplatin, carboplatin).

• Immunotherapy - a type of systemic therapy given in an attempt to activate a person’s own immune system so that it will destroy any ocular melanoma cells within the body. Like chemotherapy, however, the response rate for ocular melanoma patients has been less than what is seen in cutaneous melanoma. The latest drug in this category is Yervoy (Ipilimumab or “Ipi”) which was approved for the treatment of melanoma in March 2011. Yervoy is a monoclonal antibody that binds to CTLA-4, an inhibitory molecule on T lymphocytes. T lymphocytes are blood cells that may be highly effective in inhibiting cancer growth. When Yervoy binds to CTLA-4, it releases the "brake" from the immune system and T cells can become activated to destroy tumor cells. Unfortunately, response rates in OM are not well documented. 
• Targeted therapy - is a form of treatment in which drugs are developed with the goal of destroying cancer cells while leaving normal cells intact. These drugs are designed to interfere with the specific molecules that are driving the growth and spread of the tumor. Because they are “targeted” to the tumor, these therapies may be more effective and associated with fewer side effects compared to chemotherapy. A targeted approach allows the classification of melanoma into different “subtypes” based on the genetic profile of the tumor.  This facilitates personalized treatment as patients receive drugs based on the unique genetic profile, or subtype, of their tumor. For example, 50% of cutaneous melanomas have a BRAF mutation and will respond to a BRAF inhibitor. Unlike melanoma on the skin, ocular melanoma does not express a BRAF mutation and so will not respond to a BRAF inhibitor. About 80% of ocular melanomas express either the GNAQ or GNA11 mutations and studies are ongoing to identify what targeted therapies will work in these mutations. Learn more about clinical trials by using MRF’s Clinical Trial Finder.  

Treatment Complications

Because many complications can result from both primary and metastatic treatments outlined above, it is important to have regular follow-up with an ophthalmologist and medical oncologist.