Because of the poor prognosis of trilateral retinoblastoma, screening neuroimaging is a common practice. While it is not clear whether early diagnosis can impact survival, the frequency of screening with magnetic resonance imaging for those suspected of having hereditary disease or those with unilateral disease and a positive family history has been recommended as often as every 6 months for up to 5 years. Given the short interval between the diagnosis of retinoblastoma and the occurrence of trilateral retinoblastoma, routine screening might detect the majority of cases within 2 years. However, it is not clear that screening by neuroimaging improves survival. Computed tomography scans should be avoided for routine screening in these children because of the perceived risk of exposure to ionizing radiation.
Extracranial metastatic retinoblastoma
Hematogenous metastases may develop in the bones, bone marrow, and less frequently, in the liver. Although long-term survivors have been reported with conventional chemotherapy, these reports should be considered anecdotal; metastatic retinoblastoma is not curable with conventional chemotherapy. In recent years, however, studies of small series of patients have shown that metastatic retinoblastoma can be cured using high-dose marrow-ablative chemotherapy and autologous hematopoietic stem cell rescue.[5,6,7,8,9,10]; [Level of evidence: 3iiA]
There is no clearly proven effective or standard therapy for the treatment of extraocular retinoblastoma, although orbital irradiation and chemotherapy have been used. In the past, palliative therapy with radiation therapy (including craniospinal irradiation when there is meningeal involvement) and/or intrathecal chemotherapy with methotrexate, cytarabine, and hydrocortisone, plus supportive care has been used. A retrospective study showed that extraocular disease, manifested by gadolinium enhancement on MRI of the proximal optic nerve, might respond to treatment with neoadjuvant chemotherapy prior to enucleation.[Level of evidence: 3iiDi]
Treatment Options Under Clinical Evaluation
Two reports suggest that there may be a role for intensive multimodality therapy with autologous stem cell rescue for patients with metastatic retinoblastoma.[2,11][Level of evidence: 3iiA] A few responses were noted in both CNS (including trilateral) and systemic metastases. However, these strategies remain under clinical investigation.
The following is an example of national and/or institutional clinical trials that are currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.
- COG-ARET0321: Patients with metastatic or recurrent retinoblastoma that is beyond the globe are eligible for treatment with combined conventional chemotherapy, high-dose chemotherapy, and stem cell transplant with conventional radiation.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with extraocular retinoblastoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
- Antoneli CB, Ribeiro KB, Rodriguez-Galindo C, et al.: The addition of ifosfamide/etoposide to cisplatin/teniposide improves the survival of children with retinoblastoma and orbital involvement. J Pediatr Hematol Oncol 29 (10): 700-4, 2007.
- Dunkel IJ, Chan HS, Jubran R, et al.: High-dose chemotherapy with autologous hematopoietic stem cell rescue for stage 4B retinoblastoma. Pediatr Blood Cancer 55 (1): 149-52, 2010.
- Dunkel IJ, Jubran RF, Gururangan S, et al.: Trilateral retinoblastoma: potentially curable with intensive chemotherapy. Pediatr Blood Cancer 54 (3): 384-7, 2010.
- Kivel� T: Trilateral retinoblastoma: a meta-analysis of hereditary retinoblastoma associated with primary ectopic intracranial retinoblastoma. J Clin Oncol 17 (6): 1829-37, 1999.
- Namouni F, Doz F, Tanguy ML, et al.: High-dose chemotherapy with carboplatin, etoposide and cyclophosphamide followed by a haematopoietic stem cell rescue in patients with high-risk retinoblastoma: a SFOP and SFGM study. Eur J Cancer 33 (14): 2368-75, 1997.
- Kremens B, Wieland R, Reinhard H, et al.: High-dose chemotherapy with autologous stem cell rescue in children with retinoblastoma. Bone Marrow Transplant 31 (4): 281-4, 2003.
- Rodriguez-Galindo C, Wilson MW, Haik BG, et al.: Treatment of metastatic retinoblastoma. Ophthalmology 110 (6): 1237-40, 2003.
- Dunkel IJ, Aledo A, Kernan NA, et al.: Successful treatment of metastatic retinoblastoma. Cancer 89 (10): 2117-21, 2000.
- Matsubara H, Makimoto A, Higa T, et al.: A multidisciplinary treatment strategy that includes high-dose chemotherapy for metastatic retinoblastoma without CNS involvement. Bone Marrow Transplant 35 (8): 763-6, 2005.
- Jubran RF, Erdreich-Epstein A, Butturini A, et al.: Approaches to treatment for extraocular retinoblastoma: Children's Hospital Los Angeles experience. J Pediatr Hematol Oncol 26 (1): 31-4, 2004.
- Dunkel IJ, Khakoo Y, Kernan NA, et al.: Intensive multimodality therapy for patients with stage 4a metastatic retinoblastoma. Pediatr Blood Cancer 55 (1): 55-9, 2010.
- Rootman J, Hofbauer J, Ellsworth RM, et al.: Invasion of the optic nerve by retinoblastoma: a clinicopathological study. Can J Ophthalmol 11 (2): 106-14, 1976.
- Armenian SH, Panigrahy A, Murphree AL, et al.: Management of retinoblastoma with proximal optic nerve enhancement on MRI at diagnosis. Pediatr Blood Cancer 51 (4): 479-84, 2008.