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© 2000 American Society for Clinical Oncology
Chemoreduction for Retinoblastoma May Prevent Trilateral Retinoblastoma
Wills Eye Hospital Thomas Jefferson University To the Editor:We read with interest the comprehensive report by Dr Kivelä on the subject of trilateral retinoblastoma (TRB) or primary intracranial neuroblastic tumor (pineal neuroblastic tumor and ectopic intracranial neuroblastic tumor).1 This systematic review of the published literature on TRB emphasized the almost universally fatal outcome for children who have this disease. Kivelä’s review of the data led him to conclude that early detection might be beneficial, especially if the tumor is smaller than 15 mm at detection. He suggested that children with retinoblastoma have screening for the intracranial neoplasm frequently during the first year after ocular diagnosis and less often thereafter. All of the published series reviewed by Kivelä were compiled before the recently popularized practice of chemoreduction for retinoblastoma.2,3 Chemoreduction involves the administration of chemotherapy for advanced intraocular retinoblastoma with the goal of tumor reduction so that focal ophthalmic therapy can be applied to the partially regressed tumors.4 In most cases, chemoreduction is used for bilateral (germ-line) retinoblastoma and in eyes that in the past would have otherwise been treated with external-beam radiotherapy or enucleation. Since July 1995, approximately 60% of the children that we have managed with retinoblastoma have been treated with six-cycle chemoreduction using vincristine, etoposide, and carboplatin.4 We have recently made an observation regarding children with retinoblastoma treated with chemoreduction that we believe may be important. During the past 4 years, we have used chemoreduction for more than 160 children with intraocular retinoblastoma. Most of these children were bilaterally affected and would, therefore, be at risk for TRB. None of our patients has developed TRB, although based on published data, one would have expected five to 16 patients to do so. During the same period of time, we have seen TRB in children who did not receive chemoreduction. We suspect that chemoreduction may play a protective role, providing early neoadjuvant therapy against the development of the intracranial tumor or delaying the onset of the disease. We welcome comments from other groups who may have a similar experience. REFERENCES
1.
Kivelä T: Trilateral retinoblastoma: A meta-analysis of hereditary retinoblastoma associated with primary ectopic intracranial retinoblastoma. J Clin Oncol 17:1829-1837, 1999
2.
Shields CL, DePotter P, Himmelstein B, et al: Chemoreduction in the initial management of intraocular retinoblastoma. Arch Ophthalmol 114:1330-1338, 1996 3. Ferris FL, Chew EY: A new era for the treatment of retinoblastoma. Arch Ophthalmol 1996;114:1412 4. Shields CL, Shields JA, Needle M, et al: Combined chemoreduction and adjuvant treatment for intraocular retinoblastoma. Ophthalmology 104:2101-2111, 1997[Medline]
ResponseHelsinki University Central Hospital Helsinki, Finland In Reply:Shields et al have raised a highly pertinent point regarding chemoreduction treatment in children with trilateral retinoblastoma, in part inspired by our recent meta-analysis of 106 patients with this intriguing tumor of childhood.1 None of the included children had underwent chemoreduction, an emerging mode of systemic chemotherapy given to shrink intraocular retinoblastoma in order to salvage vision and avoid external-beam radiotherapy.2-5 Our meta-analysis revealed that three children with TRB had survived for more than 5 years after diagnosis, by which time all other affected children were dead.1 These three children, who likely were cured, had had an intracranial tumor 15 mm or smaller in size, and one had received systemic chemotherapy as the only treatment.6 Given the above data, I am inclined to concur with Shields et al in that it is conceivable that, in selected cases and when a sufficient number of chemotherapy cycles are given, chemoreduction might cure a small TRB. In addition to their clinical impression, drugs used in chemoreduction have been considered to be potentially effective in treating TRB.7 The required number of cycles to eradicate an intracranial tumor is unknown, however, as is the frequency of complete responses, if any. Our meta-analysis revealed that 50% of the children with TRB who underwent neuroimaging at the time of diagnosis of the intraocular tumor had their intracranial tumor diagnosed at that time.1 Because baseline neuroimaging is routine in major retinoblastoma centers, it is of note that Shields et al had not observed any TRB among over 160 susceptible children treated with chemoreduction at Wills Eye Hospital; half of the expected five to 16 cases should have been found. This fact might indicate that either series may represent a biased sample as regards the chances of developing TRB. Detailed analysis of the data set might help to resolve this issue and reveal new insights into TRB. Our meta-analysis predicted that approximately one in 100 routine computed tomography and magnetic resonance imaging scans would reveal TRB if children with hereditary retinoblastoma were screened regularly.1 A prospective study was believed to be necessary to show whether this yield would translate into a clinically significant, cost-effective reduction in mortality of children with retinoblastoma. In such a study, chemoreduction would be a necessary stratification variable. Shields et al wisely caution that response to chemoreduction might not be complete. Indeed, it is considered insufficient to cure intraocular tumors, and chemoreduction must be followed by photocoagulation, cryocoagulation, or brachytherapy.2-5 Moreover, new tumors have developed during chemoreduction.8 In view of this, I believe that Shields et al would agree in that it would be ill-advised to abandon neuroimaging solely because of chemoreduction, if such imaging is otherwise believed to be rational in managing retinoblastoma. REFERENCES 1. Kivelä T: Trilateral retinoblastoma: A meta-analysis of hereditary retinoblastoma associated with primary ectopic intracranial retinoblastoma. J Clin Oncol 17:1829-1837, 1999
2.
Gallie BL, Budning A, DeBoer G, et al: Chemotherapy with focal therapy can cure intraocular retinoblastoma without radiotherapy. Arch Ophthalmol 114:1321-1328, 1996 3. Murphree AL, Villablanca JG, Deegan WF III, et al: Chemotherapy plus local treatment in the management of intraocular retinoblastoma. Ophthalmol 114:1348-1356, 1996 4. Shields CL, Shields JA, Needle M, et al: Combined chemoreduction and adjuvant treatment for intraocular retinoblastoma. Ophthalmology 104:2101-2111, 1997
5.
Bechrakis NE, Bornfeld N, Schueler A, et al: Clinicopathologic features of retinoblastoma after primary chemoreduction. Arch Ophthalmol 116:887-893, 1998 6. De Potter P, Shields CL, Shields JA: Clinical variations of trilateral retinoblastoma: A report of 13 cases. J Pediatr Ophthalmol Strab 31:26-31, 1994[Medline] 7. Marcus DM, Brooks SE, Leff G, et al: Trilateral retinoblastoma: Insights into histogenesis and management. Surv Ophthalmol 43:59-70, 1998[Medline] 8. Scott IU, Murray TG, Toledano S, et al: New retinoblastoma tumors in children undergoing systemic chemotherapy. Ophthalmol 116:1685-1686, 1998
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Copyright © 2000 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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