Multidisciplinary Management of Retinoblastoma: Diagnosis

PracticeUpdate: Could you give us a brief overview of the various modalities by which retinoblastoma is diagnosed and the role of each professional in this process?

Dr. Ramasubramanian: Retinoblastoma is a pediatric cancer. It usually is diagnosed in kids less than five years of age. A majority of the kids are diagnosed by the presence of the leukocoria, or the light reflex, which can be detected a majority of times by parents, but pediatricians play a huge role in picking up the leukocoria and referring it to an ophthalmologist. The diagnosis itself is a very clinical diagnosis. It's by indirect ophthalmoscopy, but we also utilize ultrasound MRI mainly to look for brain involvement. We also have other tools to pick up subtle tumors like optical coherence tomography and fluorescein angiography.

PracticeUpdate: What is the typical composition of the care team at your institution?

Dr. Ramasubramanian: The care of retinoblastoma itself is multi-disciplinary. At Phoenix Children's Hospital we have a huge team of specialists that help, and that's the way in almost all centers. We have a pediatric oncologist who is involved with the chemotherapy. The local treatment, and the diagnosis and monitoring for a tumor progression, is done by the ocular oncologist. We have radiation oncologists. We have interventional radiologists who deliver the localized chemo. It's a big group of people that care for these children.

PracticeUpdate: I understand that prenatal diagnosis of retinoblastoma is now feasible. At Phoenix Children's Hospital, how do you approach this? Can you give us a couple of patient scenarios in which this modality has been used?

Dr. Ramasubramanian: Prenatal diagnosis is very important. As you're all aware, retinoblastoma is inherited in an autosomal dominant way. If you have the germline retinoblastoma, you have close to 50% chance of transmitting it to your kids, so we usually focus on prenatal diagnosis in parents who have history of bilateral retinoblastoma or who have history of unilateral retinoblastoma, but have had a gene mutation positive test. That means they are a germline retinoblastoma. Usually the process of discussion with these families at Phoenix Children's starts way before they start planning to have kids, because there are three main routes we can take when it comes to early detection and prevention of disease. The first route is pre-implantation diagnosis. We now can offer where we can make a probe for the gene mutation specifically for that family. We test the sperm and the ova, and we choose the sperm and the ova that does not have the mutation. We do in vitro fertilization, and then the kid will not develop retinoblastoma. That is if the family wants to take that route.

We have early pregnancy testing with the aid of amniocentesis and chorionic villus biopsy, and all those we do in conjunction with our fetal care network. If the family doesn't want to choose the first or second route, then the pregnancy progresses as normal, and around 30 to 32 weeks we start doing special ultrasounds, mainly looking for tumors in the eye, and around 35, 36 weeks, we also get a fetal MRI. Based on if we see the tumor or the tumor progresses, then we either deliver the child earlier, around 36 or 37 weeks, after lung maturity, after discussion with the obstetrician, or we monitor very closely to term if there are no tumors and then deliver the baby and start treatment immediately. This very early treatment and early detection has immensely improved the outcome of retinoblastoma by preserving a maximum visual acuity and minimizing the number of treatments these kids have to have.

PracticeUpdate: Are there any other approaches that can be taken in these early diagnosed neonates that can improve their outcomes?

Dr. Ramasubramanian: At Phoenix Children's, now we are able to detect tumors as small as one millimeter, so if the tumor is very small at that point, we don't even need to administer chemo. We can control that tumor with just local laser or cryotherapy. We are actually completely able to save this kid from chemotherapy. That's a huge change where a kid gets chemo versus no chemo. From that standpoint, it improves the outcome. A lot of these early tumors are usually tumors closer to the central vision, so the smaller they are, the more vision we can salvage. If we have not seen the tumor prenatally, then we start screening at birth, and of course we will send the child for genetic testing also, but if the genetic testing is positive, then we see each of these kids at every two weekly to four weekly interval after birth to look for those small new tumors.