Results of chemoreduction and focal consolidation therapy as a primary treatment modality of the remaining eye in bilateral retinoblastoma

Abstract

Purpose The aim of this study was to quantify the rates of eye preservation, patient survival, local tumor control, recurrence, and development of new tumors in the remaining eye of children with bilateral retinoblastoma after chemoreduction and focal consolidation therapy as a primary treatment modality and also to evaluate the need for secondary treatment procedures to preserve the remaining eye. Patients and methods This prospective noncomparative case study included 46 children newly diagnosed with bilateral intraocular retinoblastoma between February 2003 and May 2012. Advanced disease was present in at least one eye. Enucleation of the more advanced eye was performed, and the remaining eye was treated conservatively using a sixtreatment cycle of chemoreduction therapy. Eyes that responded to chemoreduction therapy received focal treatments after the second chemoreduction treatment, if necessary, to achieve complete tumor regression. Patients with unresponsive disease were treated using external beam radiotherapy (EBRT). An intra-arterial injection (ophthalmic artery) of melphalan was used as a last resort before enucleation. Results The mean follow-up duration was 73.2 months (range: 18.0–113.0 months). Chemoreduction was successful in the treatment of retinal tumors in five eyes (10.8%); additional focal therapies were used in 35 eyes (76.2%). One eye (2.2%) with unresponsive disease was enucleated for tumor control after the second treatment. Five eyes (10.8%) showed some improvement after two chemoreduction treatments but could not be treated with focal methods because of extensive retinal tumors, vitreous seeds, or subretinal seeds and thus were treated successfully with EBRT. Fourteen eyes (31.0%) developed recurrence or new tumor formation after a mean duration of 15.84 months (range: 2.0–60.0 months) from completing their treatment protocol. EBRT was successful in preserving six eyes. Four eyes responded well to additional focal treatment with chemoreduction therapy. Eventually, three eyes that did not respond to EBRT were subjected to repeat infusions of intra-arterial melphalan for each eye. However, this modality of treatment failed to salvage them. Overall, chemoreduction+ / – focal therapy succeeded in globe preservation of 32/46 (69.5%) of the remaining retinoblastoma eyes. Unresponsive, recurrent, and new tumors were treated by EBRT in 13/46 (28.3%) eyes, and enucleation was the end result in four eyes (8.7%). The 10-year survival rate was 95.6%. The globe salvage rate was 91.3%. Two patients (4.3%) died during the follow-up period from intracranial extension. Presence of vitreous seeds at presentation increases the risk of new tumor growth and recurrence. Conclusion Chemoreduction combined with early focal therapy is the safest and most efficient primary method for treatment of eyes with low stages of retinoblastoma. Presence of vitreous seeds at presentation increases the risk of recurrence or development of new tumors necessitating EBRT and/or enucleation. Continued follow-up of at least 5 years after completion of chemoreduction and focal therapy is important for early detection of tumor recurrence and proper management and preservation of both the eye and life. Intra-arterial chemotherapy injection needs further large and long-term studies to define its indications, long-term effectiveness, and safety in treatment of intraocular retinoblastoma.