Forget-me-nots in the care of children with retinoblastoma.

The management of retinoblastoma has gradually evolved over the past years from enucleation to radiotherapy to current techniques of chemotherapy. Eyes with massive retinoblastoma filling the globe are still managed with enucleation, whereas those with small, medium, or even large tumors can be managed with chemoreduction followed by tumor consolidation with thermotherapy or cryotherapy. Despite multiple or large tumors, visual acuity can reach 20/40 or better in many cases, particularly those eyes with extramacular tumors. Previous complications of dry eye, cataract, retinopathy, and facial deformity that were found following external beam radiotherapy are not anticipated following chemoreduction. Recurrence from subretinal and vitreous seeds can be problematic. Long-term follow up for second cancers is advised.

Vitreous relapse following primary chemotherapy for retinoblastoma: is adjuvant diode laser a risk factor?

AIMS: To evaluate rates of vitreous relapse among retinoblastoma patients treated with primary chemotherapy and assess diode laser as a potential risk factor for relapse. METHODS: Retrospective review of all patients treated with primary chemotherapy at a large ocular oncology centre. Eyes that developed vitreous relapse were coded with regard to Reese-Ellsworth Group, laterality, time to relapse, type of relapse (vitreous base or non-vitreous base relapse), treatments used (including adjuvant diode laser), and ocular preservation. Individual tumour foci treated with laser hyperthermia were also coded for laser parameters including power settings, number of treatments, and concomitant administration of systemic chemotherapy (chemothermotherapy). RESULTS: 15 of 106 eyes (14.15%) developed vitreous relapse over a 6 year period. Mean time to relapse was 7.2 months after chemotherapy was completed. Five cases (33%) were of the vitreous base variety. Ocular salvage was attempted in 11 cases using a variety of methods; one patient was lost to follow up. Six of the remaining 10 eyes (60%) were salvaged. Eight of 38 eyes (21%) treated with systemic chemotherapy and laser hyperthermia developed vitreous relapse compared with seven of 68 eyes (10%) treated with primary chemotherapy alone (p<0.005). Laser settings, number of hyperthermia treatments, and the concomitant use of systemic chemotherapy (chemothermotherapy) were not associated with higher rates of vitreous relapse. CONCLUSION: Nearly one in seven eyes with retinoblastoma treated with primary chemotherapy may develop vitreous relapse. The administration of diode laser hyperthermia appears to increase this risk. Despite additional therapy a number of these eyes succumb to enucleation.

Factors predictive of recurrence of retinal tumors, vitreous seeds, and subretinal seeds following chemoreduction for retinoblastoma.

OBJECTIVE: To identify the clinical features of eyes with retinoblastomas that predict the recurrence of retinal tumors, vitreous seeds, and subretinal seeds following treatment with chemoreduction. DESIGN: Prospective nonrandomized single-center clinical trial. SETTING: Ocular oncology service at Wills Eye Hospital of Thomas Jefferson University (Philadelphia, Pa) in conjunction with the division of oncology at Children's Hospital of Philadelphia. PARTICIPANTS: There were 158 eyes with 364 tumors in 103 consecutive patients with retinoblastoma managed with chemoreduction between June 1994 and August 1999. INTERVENTION: All patients received treatment for retinoblastoma with 6 cycles of chemoreduction using vincristine, etoposide, and carboplatin combined with focal treatment (cryotherapy, thermotherapy, or plaque radiotherapy) for each retinal tumor. MAIN OUTCOME MEASURES: The 3 main outcome measures included recurrence of retinal tumors, recurrence of vitreous seeds, and recurrence of subretinal seeds. The clinical features at the initial examination were analyzed for their association with the main outcome measures using a series of Cox proportional hazards regressions. RESULTS: All retinal tumors, vitreous seeds, and subretinal seeds showed an initial favorable response of regression during this treatment regimen. Using Kaplan-Meier estimates, at least 1 retinal tumor recurrence per eye was found in 37% of eyes at 1 year, 51% at 3 years, and no further increase at 5 years. By multivariate analysis, the only factor predictive of retinal tumor recurrence was the presence of tumor-associated subretinal seeds at the initial examination. Of the 54 eyes that had vitreous seeds at the initial examination, vitreous seed recurrence was found in 26% of eyes at 1 year, 46% at 3 years, and 50% at 5 years. By univariate analysis, the only factor predictive of vitreous seed recurrence was the presence of tumor-associated subretinal seeds at the initial examination. Of the 71 eyes that had subretinal seeds at the initial examination, subretinal seed recurrence was detected in 53% of eyes at 1 year, 62% at 3 years, and no further increase at 5 years. By multivariate analysis, factors predictive of subretinal seed recurrence included a tumor base greater than 15 mm and a patient age of 12 months or younger at diagnosis. There were no patients who developed retinoblastoma metastasis, pinealoblastoma, or second malignant neoplasms. CONCLUSIONS: Chemoreduction combined with focal therapy is effective for selected eyes with retinoblastomas. Eyes with subretinal seeds at initial examination are at particular risk for recurrence of retinal tumor and vitreous seeds. Younger patients with large tumors are at risk for recurrence of subretinal seeds. Retinal tumor and subretinal seed recurrence seems to manifest within 3 years of follow-up. Close follow-up of all patients treated with chemoreduction is warranted.

Chemotherapy in retinoblastoma: current status and future directions.

In the past, chemotherapy has had only a minor role in the treatment of retinoblastoma. There are three clinical settings in which chemotherapy may be useful, namely, in intraocular retinoblastoma, in cases of micrometastatic spread, and where there are overt extraocular metastases. Clinical trials in all three settings have been impeded by biological, statistical, and ethical limitations. Extensive review of the literature, including case reports, small retrospective series, and occasional prospective studies, does not lead to any clear conclusions. However, responsiveness of retinoblastoma to chemotherapy in each of the above categories has been documented, and cyclophosphamide is consistently the most effective single agent. For small intraocular tumors, there may be a role for a combination of nonoperative treatment modalities. Whether decreased occurrence of extraocular relapse is produced by the use of adjuvant chemotherapy for presumed micrometastatic disease remains controversial A prospective randomized study of stratified high-risk categories of patients needs to be done on an international level. The most widely accepted regimen in this setting is the combination of cyclophosphamide and vincristine. Improving the survival of patients with overt metastases is a major challenge, which is especially relevant to the less developed parts of the world. Several multiagent regimens, particularly in combination with bone marrow transplantation, offer some promise. Experimental models are being used to overcome some of the limitations of clinical studies. Evaluations of responsiveness to chemotherapy, both in cell culture and animal models, are being conducted. Other areas being investigated include pharmacologic enhancement of radiotherapy and hematoporphyrin photodynamic therapy, use of tumor cell targeting techniques, differentiating agents, vitamin D, and immunotherapy. The nude mouse intraocular xenograft model appears to confirm clinical observations for responsiveness to conventional therapeutic agents.

Analysis of treatment results in 36 children with retinoblastoma treated by scleral plaque irradiation.

This is a retrospective analysis of treatment results in 36 patients with retinoblastoma treated by the Radiation Oncology Department of Hahnemann University Hospital and the Division of Oncology of Wills Eye Hospital between January 1975 and December 1986. There were 14 females and 22 males; ages ranged from 2 months to 4 1/2 years of age at presentation. Leukocoria was the most common clinical sign of presentation. These patients were treated with external beam radiation therapy in combination with scleral plaque irradiation in 20 patients and with scleral plaque alone in 16 patients. Cobalt-60, Iodine-125, Iridium-192, and Ruthenium-106, scleral plaques were used. The dose delivered to the mid plane of the globe was 40 Gy and the scleral dose adjacent to the plaque was in the range of 180-200 Gy. The treatment was successful in 30 of 36 patients. Complications of radiation therapy were minimal in patients treated by scleral plaque alone. The advantages of this treatment modality are discussed.