Robert M. Ellsworth

Ultrasonic hyperthermia and radiation in the management of intraocular malignant melanoma

Hyperthermia and radiation were used in combination to treat four patients with choroidal malignant melanoma. This technique uses ultrasonically induced hyperthermia synergistically with radiation to destroy tumor cells. The lower levels of radiation used should avoid the late vascular and inflammatory complications seen in conventional radiation therapy. Tumors were scanned by a computerized diagnostic ultrasound system before treatment and assigned an acoustic tissue type on the basis of a statistical comparison of their ultrasound backscatter spectrum with spectra of tumors of known pathologic status. During the follow-up period, the longest of which was 15 months, all tumors demonstrated regression patterns consistent with choroidal tumors of the same acoustic tissue types treated with conventional radiation therapy.

Significance of Retinoma and Phthisis Bulbi for Retinoblastoma

Genetic counseling of retinoblastoma (RB) patients and their families is difficult and inaccurate. The data in this paper show that two ocular lesions, retinoma and phthisis bulbi, are associated with RB and can be useful in diagnosis and counseling. Phthisis bulbi is the end result of many conditions and can only be linked to RB if other evidence is present. Retinomas, on the other hand, have three distinctive clinical characteristics (irregular translucent retinal mass, calcification, and pigment epithelial disturbance) and quite accurately predict the presence of the RB gene. Recognition of the significance of retinoma and phthisis bulbi with respect to the RB gene is critical in genetic counseling. Of 34 individuals studied, 32 with retinoma and five with phthisis bulbi, two thirds had a family history of RB or RB in the other eye, and 23/37 of their offspring developed RB. The clinical course of RB in the six children known to be at risk on the basis of detection of the gene in the parent was significantly better than in 17 children that were symptomatic at the time of diagnosis.

Ultrasonic tissue characterization of uveal melanoma and prediction of patient survival after enucleation and brachytherapy

We performed survival studies on 136 patients with uveal malignant melanoma who were examined with ultrasonic tissue characterization before treatment with cobalt-60 brachytherapy (74 patients) or enucleation (62 patients). Mean follow-up time was 58.7 months for the brachytherapy group and 59.0 months for the enucleated group. The maximal follow-up time was nearly ten years. Univariate survival analysis showed that patients with small tumors (less than 250 mm3, 49 patients) had a higher five-year survival when treated with brachytherapy than when treated with enucleation. No patients in this study with tumor volumes greater than 1,500 mm3 (13 patients) were treated with brachytherapy. For tumors of intermediate size (74 patients), survival analysis did not indicate appreciable differences between the treatment options. However, multivariate models including two ultrasonic tissue characterization variables, scatterer size and concentration, showed appreciable intergroup differences in the dependence of survival on these factors. Results suggest that tissue properties detectable with ultrasonic techniques are related to differences in patient survival and may be used for treatment planning for tumors of intermediate size.

Manetic Resonance, Imaging in the Evaluation of Optic Nerve Gliomas

Five patients with optic nerve gliomas were evaluated by magnetic resonance imaging (MRI). Images obtained with MRI were equal to computed tomography (CT) in evaluation of the orbital components of these tumors and superior to CT in evaluating the intracanalicular, chiasmal, and post-chiasmal extension of tumor. MRI is unimpeded by artifacts produced by surrounding bone, as encountered in CT, and also proves to be more sensitive in delineating subtle differences in fat content and hydration of neural tissues. Thus, MRI is extremely valuable in furthering our understanding of the natural and therapeutic response of optic nerve gliomas.

Retinoblastoma with Anterior Chamber Extension

Anterior chamber retinoblastoma is a rare clinical entity. The authors have reviewed the records of 1500 patients with retinoblastoma to determine the incidence and prognostic ramifications. Of 30 patients with anterior chamber involvement, 15 were noted on initial examination and 15 during observation after therapy. Despite aggressive multimodality treatment, total response was never achieved and all eyes were eventually lost. Results of pathologic examination showed ciliary body invasion, which was held accountable for the poor response to therapy. Anterior chamber retinoblastoma is a poor prognostic sign which cannot be controlled effectively with current techniques and should be considered an indication for enucleation without delay.

Radiation and Chemotherapy of Parameningeal Rhabdomyosarcoma Involving the Orbit

Eighteen patients with parameningeal rhabdomyosarcoma (RMS) involving the orbit were treated at Memorial Sloan-Kettering Cancer Center (MSKCC) between July 1971 and October 1983. Fifteen patients were children with a mean age of 6 years and three patients were adults with a mean age of 21 years. In four patients, the primary tumor originated in the orbit, while the remaining 14 had other parameningeal primary sites. The tumors were in a very progressive local stage, with destruction of facial bones in most patients. Six patients were treated with the T2 chemotherapy protocol and 12 received the T6 protocol. The radiation treatment plan for all patients was designed to deliver between 4500 and 7200 rad delivered to the primary tumor over 4 to 16 weeks. Eleven of the 18 patients (61%) are alive and well with a median follow-up time of six years. Two patients died of therapeutic complications and five died of tumor spread with central nervous system involvement. Ocular complications included acute and chronic conjunctival, corneal, lens, and retinal changes, which were less severe than those reported in previous series.

Antiviral Therapy with Ganciclovir for Cytomegalovirus Retinitis and Bilateral Exudative Retinal Detachments in an Immunocompromised Child

A child with bilateral cytomegalovirus (CMV) retinitis, vitritis, and exudative retinal detachments, who was in remission from stage IV neuroblastoma and status post-chemotherapy and autologous bone marrow transplantation, was treated with ganciclovir. The drug is a new acyclic nucleoside antiviral drug with potent antiCMV activity. There was bilateral retinal reattachment, clearing of vitritis and regression of retinal exudates and hemorrhages, with concomitant resolution of viral shedding in urine and blood, on ganciclovir 7.5 mg/kg per day. There was recurrence of exudative detachments, vitritis and retinitis when the dose was reduced to 2.5 mg/kg per day, and regression of these findings when the dose was again increased to 7.5 mg/kg per day. Despite continued therapy at this dose, a relapse occurred. When the dose of drug was doubled to 15 mg/kg per day, there initially was a partial therapeutic response, followed by a subsequent relapse. No further response was seen when the dose was increased to 19.5 mg/kg per day. This patient was treated with ganciclovir for a total of 192 days. No adverse reactions to ganciclovir were seen. On the last day of drug administration, there were persistent bilateral exudative retinal detachments and progressive optic nerve head involvement with optic disc pallor, despite quiescence of the retinitis.

Orbital rhabdomyosarcoma: treatment or overtreatment

In 1972, the Intergroup Rhabdomyosarcoma Study standardized the classification and treatment of orbital rhabdomyosarcoma. It established chemotherapy with external beam radiotherapy as the standard of treatment, yet there was no comparison to treatment with external beam radiotherapy alone. We retrospectively examined the charts of patients with orbital rhabdomyosarcoma treated solely with external beam radiotherapy for the following data: age at diagnosis, gender, tumor recurrence, and tumor-related mortality. We followed 24 patients (mean follow-up 7.9 years) treated with external beam radiotherapy alone. The average age at diagnosis was 5.5 years; there were 15 males and 9 females. Three patients (12.5%) suffered tumor recurrence and there was one (4.2%) tumor-related death. When compared to the Intergroup Rhabdomyosarcoma Study, results suggest that chemotherapy with external beam radiotherapy may offer no advantage to external beam radiotherapy alone for the treatment of orbital rhabdomyosarcoma.

Neuron-specific enolase and retinoblastoma. Clinicopathologic correlations.

Neuron-specific enolase (a glycolytic, ubiquitous, intracellular enzyme) has recently been reported to be detectable in the aqueous humor of eyes containing retinoblastoma. Aqueous humor from 17 patients with histologically proven retinoblastoma was assayed for the presence of neuron-specific enolase (NSE). NSE was detectable in 17 out of 17 patients with levels between 619 and 60,000 ng/ml. A multitude of clinocopathological parameters were examined for statistically significant correlations with levels of aqueous humor NSE. This investigation demonstrated that only two parameters, the presence of tumor invasion into the anterior chamber, and inflammation significantly correlated with aqueous NSE levels. Histological parameters which did not correlate with aqueous NSE levels included tumor necrosis, calcification, Flexner-Wintersteiner rosettes, exophytic/endophytic tumor type, tumor extent relative to the equator, and optic nerve/choroidal invasion. Clinical parameters which showed no correlation included patient sex (M/F), enucleation age, presentation age, family history, laterality, prior treatment, and presence of metastatic disease. Neuron-specific enolase is present in the anterior chamber of eyes enucleated for retinoblastoma, but additional testing is necessary to determine the normal levels of neuron-specific enolase in childrens eyes and the levels in eyes with lesions simulating retinoblastoma.

Cobalt60 plaques in recurrent retinoblastoma

Cobalt60 plaque irradiation is one treatment option for patients with recurrent retinoblastoma following conventional external beam irradiation (ERT). Tumorocidal doses can be delivered without excessive risk of normal tissue injury. In patients not considered candidates for xenon arc or cryotherapy, 60Co is an alternative to enucleation. Between 1968 and 1987, 85 patients were treated with 60Co plaques, 72 of whom had failed prior ERT. Age at diagnosis ranged from 1 week to 4 years. There are 37 males and 35 females. Seventy-one patients had bilateral disease and one had unilateral. Three patients had both eyes plaqued. Prior ERT ranged from 30 to 70 Gy (mean 4200 Gy). Time from initial therapy to failure ranged from 13 to 60 months. Cobalt plaques of 10 mm, 15 mm, or 10 x 15 mm were used depending on tumor size and location. Dose prescribed to the apex of the tumor ranged from 30 to 50 Gy (median 40 Gy) given over 3 to 8 days. Twelve patients had two plaque applications; three patients had three plaque applications. All patients were followed with routine ophthalmoscopic examinations. Follow-up ranged from 2 to 22 years (mean 8.7). Seven patients died of metastatic disease; 10 patients developed non-ocular second tumors. Thirty patients required enucleation. Twenty-two patients had clear tumor progression, two patients had radiation complications, and six patients had a combination of tumor growth and complications. Cobalt60 can salvage eyes in retinoblastoma patients failing ERT. Currently, we are using I125 in an attempt to spare normal ocular tissue and reduce subsequent complications.