Tumor diagnosis, therapies improve over past 20 years

Iowa City, IA-Over the past 20 years, advances in diagnosis of posterior segment tumors have been achieved as well as improved understanding of the cellular biology, immunology, and genetics of lesions.

However, there is still room for improvement in the therapies available for patients with micrometastatic melanoma and advanced retinoblastoma, reported H. Culver Boldt, MD, associate professor of ophthalmology, University of Iowa, Iowa City.

"Some of the advances we've seen over the last 20 years have been the result of improvements in our ability to image, visualize, and characterize tumors. These have come through improvements in wide-field imaging, digital photography, high-resolution ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography," Dr. Boldt commented.

When considering melanomas specifically, eye-sparing therapies are now the treatment of choice for small and medium melanomas. Radiation, particularly brachytherapy with iodine-125 and charged particles, provides excellent control of local tumors.

Transpupillary thermotherapy has been used for about 10 years to treat small tumors. More recently, transpupillary thermotherapy or surgical resection have been utilized with radiation to try to control tumors with less local morbidity, explained Dr. Boldt.

The Collaborative Ocular Melanoma Study, which was started almost 20 years ago, yielded important findings for the treatment of posterior segment tumors. The pathology data that have come out of the Collaborative Ocular Melanoma Study centers around the country continue to be useful in evaluating new treatment modalities.

"Surgeons can comfortably recommend brachytherapy to patients with medium tumors, as a vision-sparing treatment. Enucleation was shown to have no survival advantage for up to 12 years of follow-up. For large tumors, there is no survival benefit to using pre-enucleation radiation, so that has fallen out of favor," he said.

Improved prognosis

Dr. Boldt also pointed out that indicators of prognosis have improved in the last 20 years when initially cell type and tumor size were used to predict mortality.

"We can improve diagnostic and prognostic information with extracellular matrix patterns and different immunologic assays. Noninvasive means to assess tumors include ultrasound parameter imaging and confocal indocyanine green angiography. In the future, genetic alterations will be important. We hope to be able to unlock some of the changes that lead to the malignant transformation of tumors," he said.

Management

A controversial issue is the management of indeterminant melanocytic choroidal lesions. The recommendation has been that the tumors be observed until growth becomes evident, but early treatment has been advocated over the last 10 years. The results of studies of cutaneous melanoma lend support to the early-treatment strategy, in that early detection and treatment of the tumors has reduced mortality.

The question remains about whether the results would be similar for choroidal melanoma. However, early treatment of those tumors has not provided a survival advantage compared with close observation of the tumors. Early treatment does increase the morbidity and costs associated with the tumors.

An area of limited options is the treatment of metastatic melanoma, according to Dr. Boldt. Effective systemic therapies seem to be the key to achieving gains in this area.

Retinoblastomas

The classification of retinoblastomas has been evolving from the use of the Reese-Ellsworth classification to those that reflect management therapies used today, Dr. Boldt explained.

"There has been a trend to minimize the use of external-beam radiation to treat retinoblastoma, especially when treating children who are less than 1 year of age. However, external-beam radiation probably is safer now than when it was administered 20 years ago. There also has been a trend toward the use of chemoreduction with focal consolidation for treatment of small tumors, for lesions that touch the disc, and for lesions that involve the fovea," he explained.

A case illustrative of this approach is that of a patient with posterior pole lesions who underwent five cycles of chemotherapy and focal consolidation with transpupillary thermotherapy. The anatomic and visual outcomes were good. But, as Dr. Boldt noted, vitreous and subretinal seeds can be refractory to treatment, and external-beam radiation may still be required to attempt to salvage the eye.