Adjuvant chemotherapy with vincristine, doxorubicin, and cyclophosphamide in the treatment of postenucleation high risk retinoblastoma

Purpose: To study risk factors and outcome of children with high risk retin oblastoma who receive postenucleation vincristine, doxorubicin, and cycloph osphamide. Patients and Methods: Charts of all patients who received adjuvant chemothe rapy for retinoblastoma were reviewed. Thirty-six patients were identified who received chemotherapy for high risk histopathologic features. Histopath ology slides of these 36 patients were retrieved and reviewed, and the dise ase was staged according to the modified St. Jude staging system. The disea se 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 II cycles because of relapse, disease progression, or famil y reasons. A life-threatening complication developed in one patient after t he first cycle, and this patient received no further chemotherapy. Results: Five (3 with unilateral and 2 with bilateral disease) of the 36 pa tients 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 patien ts had local relapse or progressive disease. All of these six patients had bilateral disease and failed in the intact eye during (three patients) or a fter (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 5.5 years, the 5-year and 10-year actuarial overall survival rates were 86% and 74%, respectively. The 5-year survival rates for patients with modi fied St. Jude stage I, II, and ITT disease were 100%, 91% (95% confidence i nterval, 57% to 100%), and 58% (95% confidence interval, 22% to 94%), respe ctively (P = 0.008). The survival rate was significantly different among pa tients with optic nerve involvement anterior to lamina cribrosa, posterior to lamina cribrosa, and surgical margin involvement (100%, 55%, and 41%, re spectively; P = 0.003). Multivariate analysis showed that only the degree o f optic nerve involvement (and therefore, modified St. Jude stage) was pred ictive of poor-outcome. Conclusion: Patients with retinoblastoma involving the optic nerve beyond t he lamina cribrosa have low survival rate despite local therapy and adjuvan t chemotherapy with vincristine, doxorubicin, and cyclophosphamide. Progres sion 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.