Shields CL, Mashayekhi A, Demirci H, Meadows AT, Shields JA: Practical Approach to Management of Retinoblastoma. Arch Ophthalmol. 2004;122:729-735.

From the Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University (Drs C. L. Shields, Mashayekhi, Demirci, and J. A. Shields), and Division of Oncology, The Children’s Hospital of Philadelphia (Dr Meadows), Philadelphia, Pa. The authors have no relevant financial interest in this article.

ABSTRACT

Objective To present a simplified approach to management of retinoblastoma using basic clinical features.

Design In a prospective, nonrandomized, single-center clinical trial, 158 eyes of 103 patients with retinoblastoma were managed with 6 cycles of chemoreduction (vincristine sulfate, etoposide, and carboplatin). The eyes were classified according to the Reese-Ellsworth classification and were also grouped on the basis of clinical features as follows: group 1, tumor only; group 2, tumor plus subretinal fluid; group 3, tumor plus focal seeds (3a, focal subretinal seeds; 3b, focal vitreous seeds); group 4, tumor plus diffuse seeds (4a, diffuse subretinal seeds; 4b, diffuse vitreous seeds); and group 5, neovascular glaucoma or invasive retinoblastoma.

Main Outcome Measure Treatment success (avoidance of enucleation and external beam radiotherapy).

Results According to the Reese-Ellsworth classification, chemoreduction was successful in 100% of group Ia, 100% of group Ib, 86% of group IIa, 100% of group IIb, 91% of group IIIa, 100% of group IIIb, 50% of group IVa, 77% of group IVb, 50% of group Va, and 27% of group Vb. There was erratic correlation of the Reese-Ellsworth classification with treatment success. In contrast, the simplified grouping system displayed a smooth, nonerratic correlation for treatment success, with 100% success for group 1, 91% for group 2, 59% for group 3, and 12% for group 4 (group 5 always managed by primary enucleation). When all 6 subcategory groups were analyzed, there was consistent correlation for treatment success of 100% for group 1, 91% for group 2, 68% for group 3a, 54% for group 3b, 17% for group 4a, and 11% for group 4b.

Conclusion This practical approach to retinoblastoma using basic clinical features is predictive of treatment success for eyes in which modern conservative therapy for retinoblastoma is used.

INTRODUCTION

The management of retinoblastoma is complex and includes enucleation and nonenucleation (conservative) techniques. Currently, the most popular conservative technique is chemoreduction.1-12 Chemoreduction involves intravenous chemotherapy to reduce the tumor size, followed by focal consolidation with cryotherapy or thermotherapy to permanently devitalize each retinoblastoma.6, 13 Chemoreduction is most successful for tumors without associated subretinal fluid or tumor-related seeding.8 Success, defined as globe salvage, is found in 85% of treated patients by 5 years when the tumor is less advanced (Reese-Ellsworth groups I to IV) and 47% when the retinoblastoma is more advanced (Reese-Ellsworth group V).7

Despite these informative results regarding therapy, most clinicians have difficulty applying Reese-Ellsworth classification to their practice, as it is complex and few ophthalmologists are able to recall its 10 categories.14 Reese and Ellsworth formulated this classification approximately 40 years ago as a method of predicting globe salvage after external beam radiotherapy. In a subsequent publication, Ellsworth stated that the Reese-Ellsworth classification was a “purely arbitrary scheme” with the intention to quantify tumor during an era when eyes with advanced retinoblastoma were being saved.15 This classification may no longer be so useful in predicting globe salvage.

New and improved methods of therapy for retinoblastoma, such as cryotherapy, laser photocoagulation, thermotherapy, chemothermotherapy, chemoreduction, and custom-designed plaque radiotherapy, have subsequently been developed. External beam radiotherapy currently is used far less often because of long-term radiation complications and the success of the newer methods. Current therapies have allowed eyes, previously judged by the Reese-Ellsworth classification as probable failures, to be uncomplicated successes. For example, an eye previously classified as group IIIa (any lesion anterior to the equator) would be “doubtful” for globe salvage by the Reese-Ellsworth classification, but current therapies such as cryotherapy, chemoreduction, or plaque radiotherapy would likely salvage the eye, resulting in a more favorable outcome. The doubtful prognosis for Reese-Ellsworth group IIIa eyes stemmed from failure of external beam radiotherapy to effectively treat tumors anterior to the equator and was not an inherent quality of retinoblastoma located anterior to the equator. The doubtful prognosis was related to the specific method of treatment, external beam radiotherapy, but since this therapy is used much less often today, there is a need to use other criteria for judging success of treatment.

On the basis of extensive clinical experience with retinoblastoma and its complexities and current management, we have developed a practical approach for grouping eyes with retinoblastoma, and this approach may be applicable to future classifications of retinoblastoma. Chemoreduction is currently the leading conservative treatment modality for retinoblastoma; in this study, we applied our grouping to a large cohort of patients with retinoblastoma treated with chemoreduction and evaluated its predictive value for treatment success.

Corresponding author and reprints: Carol L. Shields, MD, Ocular Oncology Service, Wills Eye Hospital, 840 Walnut St, Philadelphia, PA 19107 (e-mail: [email protected])

Submitted for publication March 18, 2003; final revision received August 27, 2003; accepted September 15, 2003.

This study was supported by the Eye Tumor Research Foundation, Philadelphia (Dr C. L. Shields); the Macula Foundation, New York, NY (Dr C. L. Shields); the Rosenthal Award of the Macula Society, Barcelona, Spain (Dr C. L. Shields); and the Paul Kayser International Award of Merit in Retina Research, Houston, Tex (Dr J. A. Shields).

This study was presented at the 11th International Society for Retinoblastoma and Genetic Eye Diseases meeting; May 22, 2003; Paris, France; presented as part of the William Smiddy Memorial Lecture; October 11, 2002; Baltimore, Md (Dr C. L. Shields); and presented as part of the Donders Lecture; April 10, 2003; Rotterdam, the Netherlands (Dr C. L. Shields).