For worldwide coordination

Published : Apr 09, 2004 00:00 IST

Dr. Brenda L. Gallie, Head of the Cancer Informatics Division of the Ontario Cancer Institute and Professor in the Department of Molecular and Medical Genetics, Medical Biophysics and Ophthalmology and the Department of Ophthalmology, University of Toronto, is an expert in clinical research, treatment and care of retinoblastoma, a rare cancer of the eye, which affects children.

Dr. Gallie has authored several research papers on retinoblastoma, and the molecular studies she did more than two decades ago form the basis for understanding how tumour-suppressor genes contribute to cancer in general, and the cancer of the eye in particular. Dr. Gallie's work has set off a trail of research on cancers and today she is one of the authorities on retinoblastoma.

In Chennai on a visit to Sankara Nethralaya, one of the few centres in India that detect and treat retinoblastoma (occurring in infants) and melanoma (affecting adults), Dr. Gallie spoke to Asha Krishnakumar on retinoblastoma, how it occurs, its treatment methods, and the research in the field. Excerpts from the interview:

What is retinoblastoma? How does it present itself?

Blastoma means cancer and retina is a part of the eye. It is a rare cancer in the eye of babies. Parents commonly see the first sign of it only when they actually see the tumour. The pupil, instead of being black, is white. That is a very dramatic appearance. But they do not understand what they see. The biggest problem is that often the doctor does not remember anything about such a problem as he might have read about it 20 years ago in medical school. And, hence, diagnosis is delayed.

When was retinoblastoma first identified?

In an ancient Greek statue, we find a child with retinoblastoma. So, it has always been there. Though it was recognised as a genetic problem in the beginning of this century, the ideas that were significant to understanding this cancer came in 1970. In the 1980s, the gene causing retinoblastoma was identified by a research group in Boston (United States). And since then we have been working hard to find out the exact mistake in the retinoblastoma gene in each family. It is a very difficult job as each family has a unique mistake in its gene. But now, with development in technology, identifying the genetic mistake in each family has become comparatively easy.

Why does each family have a unique mistake in the retinoblastoma gene?

Because it is a big gene, and smoking or cosmic rays or something we do not understand can damage it. Whatever the damage, the gene causes the disease. There is an infinite number of ways to break the gene. You can break it in two halves and put it in two different places. You can chop off a big piece in the middle or make a tiny mistake anywhere in it. It is all random. So, you need to look at the whole gene to find the mistake.

Once the gene causing retinoblastoma is identified, can it be prevented?

No. It cannot be prevented. But it can be predicted. As soon as the baby is conceived we can find out if the child has the risk or not. And if the child carries the mutation his parents or relatives have, we can then test the DNA (deoxyribonucleic acid) and know if the child is going to have retinoblastoma.

What we commonly do is if we know that the foetus is going to have retinoblastoma, we deliver it four weeks prematurely so that the tumour that the baby has even while it is in the womb, which is tiny, can be treated easily with laser. Otherwise it can lead to complications even needing the removal of the eyes.

Why does it happen only in babies?

It only happens in babies because after the child is three-four years the retina does not change. It is only when the retina is developing that a tumour can form.

What are the underlying causes of eye cancer?

We now know that there is one gene, retinoblastoma [gene], in the DNA of everybody. If that gene breaks, then one gets this tumour. It is inherited from the parents. And this shows up only in children.

If it is an inherited disease, can it be prevented?

It is a genetic disease. But it is very difficult to detect because most parents are normal. The child has a new mutation in the retinoblastoma gene. The children of such patients are at 50 per cent risk of getting retinoblastoma.

So, is the main cause of retinoblastoma genetic?

Every single case of the disease is caused by mutations in the gene. But for half of them the mutation does not pass on to the children. In the case of the other half, the mutation passes on to the children.

What is the incidence of retinoblastoma?

It is rare one in 15,000 live births. In Canada, because of the small population, we get only 23 children a year with retinoblastoma. In India, which has the highest number of babies born in the world, 1,500 children are born every year with retinoblastoma. That is a problem in India. But it gives an opportunity for India to study these children and the treatment methods that would make a difference to the whole world. In fact, I think India has a responsibility to study this problem and make a difference.

What are the diagnostic methods to find out retinoblastoma? Can it be identified just by looking at the eye, as the pupil of the baby affected by retinoblastoma is white?

There are some other eye conditions that look very similar. So you need to look very carefully, knowing what you are looking for. But most of the time, if the doctors know about retinoblastoma they can identify it easily. They do not need any other test. But sometimes it can be confusing and doctors do such tests as ultrasound and CT scan, to confirm retinoblastoma. These tests can also show if the tumour has spread outside the eye, which is a possibility.

Apart from genetics, has any other cause been found for retinoblastoma?

Not much work has been done in this field. But there are studies to show that if the father of the child was in the military or working in some metal works, it can lead to retinoblastoma in children. Most important is smoking. Had the parents of the child been smokers, then, among many other ill effects, it could be exposing their children to retinoblastoma.

What are the treatment options for retinoblastoma? Can it be cured?

It is one of the most curable cancers. Nearly 90-95 per cent of the cases are cured. But the cost of cure sometimes is blindness. If both eyes are affected, which happens often, then the children go blind, as the only treatment might be to take out both eyes.

But we have very good treatment now using lasers if the tumours are very small. This is perfect. It is only shining a light in the eye, burning the tumour and watching very carefully so that if it recurs it is treated quickly. Laser therapy and cryo-therapy (burning the tumour, and freezing it) are the best treatment procedures.

But if the tumour is a little bigger, then this will not work. We treat it with radiation. In the 1990s, chemotherapy a combination of four drugs became the standard treatment for the bigger tumours. Learning from the first kind of chemotherapy and advancing the drugs, we have changed protocols and the response is very good. So, now, it is unusual to lose both eyes. Most commonly, the children keep at least one eye, and often keep both eyes because of chemotherapy.

Is the treatment a long-drawn process? Are there standard treatment protocols?

Chemo is given every three weeks over a long period. The children, of course, get sick as they do from chemotherapy given for any type of cancer.

We have developed a special protocol in Toronto that we think gives the best results. We add to the protocol a commonly used drug that is not part of the therapy to prevent the tumour from being resistant to the chemotherapy. That protocol is now the basis for a new international clinical trial. We shall now do the exact protocol in Toronto (Canada), Dublin (Ireland) and Chennai and share our results so that we can learn from one another and make it better for the future.

One of the treatments is to use a radioactive `plaque' to radiate the tumour directly instead of radiating the whole eye, which causes many problems. In India, the Bhabha Atomic Research Centre has made it possible for that to be done in the country. This has happened within the last six months. Earlier, the little iodine bits that have to be put in the `plaque' to make the radiation were made only in the U.S. and they were very expensive. But now they are made in India. So the treatment in India is excellent as good as anywhere else. Sankara Nethralaya does this. It puts the `plaque' in the eye, radiates the tumour and then takes the `plaque' off.

What kind of research is going on internationally in retinoblastoma?

It is an interesting cancer because it is very rare and special as it affects only the retina. But by studying the genetics of the tumour cells in this rare cancer we have learnt a lot about cancers (breast, lung and so on) in general. It has contributed to understanding cancer far beyond the number of patients affected by retinoblastoma.

How many centres treat retinoblastoma in the world?

There are five in the U.S., two in the U.K. and one in Canada doing a lot of work in this field. There are countries with one or two centres. In India, there are several centres treating retinoblastoma. But doctors seeing one patient a year or one in 10 years may not give the best treatment. So, it is best to coordinate.

What efforts are you taking to coordinate data on retinoblastoma?

We are trying to create an international database. My hospital in Toronto and Sankara Nethralaya in Chennai are planning to coordinate genetic studies and clinical trials. We are also developing special databases and doing studies worldwide through the Internet. In the clinical trial, the countries involved include England, Ireland, the U.S., India and Canada. We are also developing a new classification worldwide. When a child comes for treatment, we first have to assess the severity of the disease in each eye to determine the right treatment. Working with 20 centres in 20 countries, we have designed this new classification and we are now testing that on an Internet study.

What is the nature of this new classification?

The classification depends on the severity of the tumour. If the tumour is very severe and the eye has to be removed, it is classification E. And if the mother brings the child early and the tumour is very small and can be easily treated with laser, it is A. From A to E, the severity increases.

We are asking ophthalmologists worldwide who treat retinoblastoma to enter in a database on the Internet the details of each child they have treated since 1997. We have already collected the treatment of 550 eyes in the database of how the tumour looked, how it was treated and if the treatment did not work what was the next line of treatment, and so on. There will be one group that coordinates all the work in the world to help every family with retinoblastoma.

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