Purpose: To study risk factors and outcome of children with high risk retinoblastoma who receive postenucleation vincristine, doxorubicin, and cyclophosphamide.
Patients and methods: Charts of all patients who received adjuvant chemotherapy for retinoblastoma were reviewed. Thirty-six patients were identified who received chemotherapy for high risk histopathologic features. Histopathology slides of these 36 patients were retrieved and reviewed, and the disease was staged according to the modified St. Jude staging system. The disease was unilateral in 23 patients (64%). There were 9 patients with stage I disease, 18 with stage II, and 9 with stage III. Twenty-four patients (67%) completed 12 of the 12 scheduled chemotherapy cycles, and 11 patients (30%) received 4 to 11 cycles because of relapse, disease progression, or family reasons. A life-threatening complication developed in one patient after the first cycle, and this patient received no further chemotherapy.
Results: Five (3 with unilateral and 2 with bilateral disease) of the 36 patients developed distant metastasis and subsequently died. All had massive tumors; three had choroidal and up to surgical margin optic nerve invasion, and two had tumor extending posterior to lamina cribrosa. Six other patients had local relapse or progressive disease. All of these six patients had bilateral disease and failed in the intact eye during (three patients) or after (three patients) chemotherapy. Only two of the six patients were alive with no disease 50 and 102 months from diagnosis. With a median follow-up of 5.6 years, the 5-year and 10-year actuarial overall survival rates were 86% and 74%, respectively. The 5-year survival rates for patients with modified St. Jude stage I, II, and III disease were 100%, 91% (95% confidence interval, 57% to 100%), and 58% (95% confidence interval, 22% to 94%), respectively (P = 0.008). The survival rate was significantly different among patients with optic nerve involvement anterior to lamina cribrosa, posterior to lamina cribrosa, and surgical margin involvement (100%, 55%, and 41%, respectively; P = 0.003). Multivariate analysis showed that only the degree of optic nerve involvement (and therefore, modified St. Jude stage) was predictive of poor outcome.
Conclusion: Patients with retinoblastoma involving the optic nerve beyond the lamina cribrosa have low survival rate despite local therapy and adjuvant chemotherapy with vincristine, doxorubicin, and cyclophosphamide. Progression of disease in the intact eye of three patients receiving chemotherapy is of concern. Alternative chemotherapeutic agents should be considered for patients with such high risk features.