What`s new in retinoblastoma research and treatment?

Research on retinoblastoma is being done at many medical centers, university hospitals, and other institutions around the world.

Genetics, genetic counseling, and gene therapy

The defective gene responsible for retinoblastoma (the RB1 gene) was identified in 1986. This discovery, together with technical advances in analyzing DNA changes, has made genetic testing a possibility.

A great deal of research has gone into figuring out how certain DNA changes in retinal cells cause them to become cancerous. Scientists understand these changes better for retinoblastoma than for most other cancer types. Although probably still years away, researchers hope that this understanding will one day lead to gene therapies, very specific treatments that can repair or counteract these DNA changes.

For example, researchers have recently identified an oncogene known as SYK that is overactive in retinoblastoma cells. Drugs that target the protein this gene makes are now being developed. Another gene called MDM4 also seems to be involved in the development of retinoblastoma, and drugs aimed at blocking its effects are being studied.

Treatment

Research is continuing the progress made in treating retinoblastoma over the past few decades.

Radiation therapy

External radiation therapy can effectively treat retinoblastoma, but it can cause side effects because the radiation often reaches nearby tissues as well. This limits its usefulness. Newer forms of radiation therapy such as intensity modulated radiation therapy (IMRT) and proton beam therapy are better able to target the tumor yet spare nearby tissues. These techniques, which are described in the section “Radiation therapy for retinoblastoma,” may help doctors limit the side effects from radiation therapy.

Other local treatments

Doctors continue to improve the instruments used for cryotherapy, laser therapy, and other local treatments. The goal is to more precisely kill tumor cells while sparing other parts of the eye.

Chemotherapy

Chemotherapy has played a more prominent role in treating many retinoblastomas in recent years.

Systemic chemotherapy

Chemotherapy given into a vein (IV) is now commonly used to shrink tumors before local treatments such as cryotherapy or laser therapy. Doctors are now studying whether giving chemotherapy after local treatments (known as adjuvant chemotherapy) might help prevent the recurrence of retinoblastoma, especially outside the eye. Doctors are also studying the use of different chemotherapy drugs such as topotecan, as well as new ways of combining current drugs, to try to improve the effectiveness of chemotherapy.

Localized chemotherapy

Chemotherapy can help shrink most retinoblastomas, but when it is given into the bloodstream it can cause side effects in different parts of the body. This limits the doses that can be given. Newer techniques may help keep the chemotherapy concentrated in the areas around the tumors. This may help doctors get higher doses of chemotherapy to the tumors while reducing some of these side effects.

Subtenon (subconjunctival or periocular) chemotherapy: Doctors are studying injecting the chemotherapy into the areas around the diseased eye. This might allow higher doses of chemotherapy to reach the tumor while limiting side effects elsewhere. There has been some success, but many doctors still consider this to be an experimental approach. New methods for periocular delivery are being studied, including placing small reservoirs loaded with chemotherapy outside the eye, which would release the drug into the eye for prolonged periods. If it proves to be useful, it will most likely be combined with other treatments (including systemic chemotherapy).

Intra-arterial chemotherapy: Another new approach is to inject chemotherapy directly into the ophthalmic artery, the main artery feeding the eye, using a long, thin catheter (see “Chemotherapy for retinoblastoma”). When intra-arterial chemotherapy is used, the dose of the chemo drug is much lower than when is given by vein (less than 10% of the systemic dose), and the side effects related to the chemotherapy are minimal.

Early results with this technique in eyes with advanced tumors have been promising, with good tumor control and few side effects in most cases. In most cases it has allowed doctors to save an eye that otherwise would have needed to be removed. Some doctors are already using this new approach, although further study is needed to be sure it is safe and effective.

Intravitreal chemotherapy: Some doctors are studying injecting chemotherapy directly into fluid inside the eyeball (the vitreous) to treat tumors that are widespread within the eye and not helped by other treatments. The main concern with this technique is that placing the needle into the eye to give the chemo might open a small hole that could allow tumor cells to spread outside of the eye, so doctors are being very cautious with this approach. It is still in the very earliest stages of testing and is not commonly used.

High-dose chemotherapy and stem cell transplant

Retinoblastomas that have spread widely are much harder to treat than those still confined to the eye. The doses of chemotherapy that can be given are limited by the side effects they cause, especially in the bone marrow (where new blood cells are made). Researchers are now testing the value of giving very high-dose chemotherapy, followed by a stem cell transplant to replace the body’s bone marrow cells, which were killed by the chemotherapy. Several clinical trials are studying this approach.