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Oncologist
Pediatric Oncology
Retinoblastoma: Review of Current Management
Key Words. Retinoblastoma Chemotherapy Genetics of retinoblastoma Second malignancies Animal models
Disclosure: No potential conflicts of interest were reported by the authors, planners, reviewers, or staff managers of this article.
LEARNING OBJECTIVES
After completing this course, the reader will be able to:
1. Discuss the need for a multidisciplinary approach to the management of children with retinoblastoma.
2. Identify the patient factors that need to be considered when choosing the most appropriate initial and subsequent
treatment for a child with retinoblastoma.
3. Describe the role of genetics in the follow-up of retinoblastoma patients.
CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit at CME.TheOncologist.com
ABSTRACT
The most common ocular cancer in children is retino- therapy along with local ophthalmic therapies can be
blastoma. It affects approximately 300 children in the used in the treatment of retinoblastoma. Cure rates are
U.S. every year. It can affect one or both eyes and the high in children when the tumor is confined to the eye
disease can be inherited. Altered discoloration of the pu- and has not spread systemically or into the orbit or
pil and strabismus are the usual symptoms that lead to brain. Children with the heritable form of retinoblas-
medical attention. Subsequent appropriate diagnostic toma are at high risk for developing subsequent malig-
studies and care provided by a multidisciplinary team, nancies, most commonly sarcomas. This risk is greater
including an ophthalmologist, a pediatric oncologist, a for those children with the heritable form of the disease
radiation oncologist, and a geneticist, among others, of- who were exposed to ionizing radiation at age <1 year.
ten result in optimal short-term and long-term care. Exciting discoveries using animal models are provid-
The best initial and subsequent treatments are based on ing new insights into the development of this disease
whether the child has unilateral or bilateral disease, the and opening new avenues for targeted therapies that
stage of the disease, and the age of the child. Enucle- may lead to high cure rates with minimal toxicities.
ation, chemotherapy, and various forms of radiation The Oncologist 2007;12:12371246
Correspondence: Murali Chintagumpala, M.D., 6701 Fannin Street, Clinical Care Center, 14th Floor, MC CC1410, Houston, Texas
77030, USA. Telephone: 832-822-1482; Fax: 832-825-1503; e-mail: mxchinta@txccc.org Received February 28, 2006; accepted for
publication July 17, 2007. AlphaMed Press 1083-7159/2007/$30.00/0 doi: 10.1634/theoncologist.12-10-1237
tion in blood is presumptive evidence of a germline or con- seeds. A secondary serous retinal detachment is often as-
stitutional mutation. Once the germline mutation is sociated with large retinal tumors and subretinal seeds. To
identified then all siblings or offspring of the patient should confirm the presence of the tumor, a detailed examination
be tested for that specific mutation in order to determine the under anesthesia through dilated pupils is performed.
need for surveillance for retinoblastoma [17]. Identification Ultrasonography of the eyes is often performed to iden-
of the same mutation in another young family member tify and analyze the intraocular mass. Heterogeneity and
should prompt frequent evaluations by an ophthalmologist calcifications provide strong evidence for the diagnosis of
using appropriate examination techniques. The frequency retinoblastoma. Ultrasonography is not as sensitive as com-
of such evaluations may be every 12 months for the first puted tomography (CT), which is the ideal imaging format
year of life, followed by every 23 months for the next year, to detect intraocular calcifications. CT, however, raises the
and then every 3 months until 3 years of age, and finally concern of exposure to radiation in children 1 year of age
every 4 6 months until the age of 6. This schedule can be with germline mutations [22]. However, it is still frequently
modified by the examiner based on his own clinical expe- used to confirm the diagnosis. Magnetic resonance imaging
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1240 Current Management of Retinoblastoma
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1242 Current Management of Retinoblastoma
combination of therapies has been promoted to avoid EBR boplatin, vincristine, and etoposide along with subtenon
therapy and/or enucleation and thereby decrease the poten- carboplatin for group C and D eyes [76, 77]. Eyes with
tial for long-term side effects while salvaging some useful diffuse vitreous seeding present a particularly difficult
vision. The common indications for chemotherapy for in- management problem and, as mentioned above, rarely
traocular retinoblastoma include tumors that are large and respond to chemotherapy alone. Although EBR therapy
that cannot be treated with local therapies alone in children is modestly successful in patients with vitreous seeds,
with bilateral tumors. Chemotherapy can also be used in pa- new approaches are needed. A recent phase I study using
tients with unilateral disease when the tumors are small but adenoviral vectors to deliver the herpes simplex thymi-
cannot be controlled with local therapies alone. Such pa- dine kinase gene followed by ganciclovir demonstrated
tients constitute only 10%15% of all patients with unilat- durable clinical and histopathologic responses in heavily
eral disease. Most patients with unilateral disease are pretreated patients with vitreous seeds [78].
diagnosed with advanced intraocular disease and undergo
enucleation. Numerous studies have been published that
Management of Extraocular Disease
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1244 Current Management of Retinoblastoma
unaffected children. They have also enabled the possibility importance. Animal models to better understand the patho-
of preimplantation genetic diagnosis, an option that is likely genesis and treatment of retinoblastoma are being pursued
to be considered by many affected individuals. Epidemio- vigorously. Initiation of cooperative group trials will fur-
logic and biologic studies to understand the factors that pro- ther define the effectiveness of therapeutic options for this
mote dissemination of the disease are increasingly gaining rare disease.
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