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Combination therapy an aid in macular retinoblastoma

Philadelphia—The outcomes when macular retinoblastomas are treated with both chemoreduction and thermotherapy are a bit better than when they are treated with chemoreduction alone, reported Carol L. Shields, MD.

Philadelphia-The outcomes when macular retinoblastomas are treated with both chemoreduction and thermotherapy are a bit better than when they are treated with chemoreduction alone, reported Carol L. Shields, MD.

The decision about the treatment approach rests on the location of the tumor and the status of the contralateral eye.

As a thought-provoking example, Dr. Shields presented a complicated case report of a 6-month-old child with one eye already enucleated. The remaining eye had a macular retinoblastoma that was scheduled for chemoreduction.

If the scar shrinks well, she asked, should the clinician consolidate the scar? Without consolidation, the child will have blurred distance vision with chemoreduction alone; with chemoreduction and full thermotherapy, the child will have a central scotoma for life; with chemoreduction and extrafoveal thermotherapy, some of the central vision might be spared.

"Our philosophy in the management of retinoblastomas with chemoreduction is to consolidate all extramacular tumors with thermotherapy or cryotherapy," said Dr. Shields, co-director, Oncology Service, Wills Eye Hospital, Philadelphia.

"However, regarding those in the macula, we still debate whether it is necessary to do fovea-sparing thermotherapy or no thermotherapy," she added.

To determine the most appropriate avenue of treatment, Dr. Shields and colleagues conducted a prospective nonrandomized study that included 68 eyes with macular retinoblastoma treated with six cycles of chemoreduction that included vincristine, etopaside, and carboplatinum. The patients were treated with either chemoreduction alone or chemoreduction and thermotherapy. The patients in the chemoreduction group had an average tumor diameter of 12 mm and thickness of 6.8 mm, which was similar to the patients who received combination therapy, according to Dr. Shields. The groups were also similar in the amount of subretinal fluid and seeding.

"After treatment in both groups, the tumors decreased to about 7 mm in diameter and about 3 mm in thickness with resorption of the subretinal fluid in all cases," she said.

Less recurrence However, there was a major difference between the two treatment groups.

In the group that received chemoreduction and thermotherapy, there was tumor recurrence in 15% of cases. However, in the group treated with chemoreduction alone, the tumors recurred in 32% of cases.

According to Dr. Shields, when the investigators analyzed the two treatment arms, they found diffuse recurrence in six patients treated with chemoreduction alone, peripheral in two patients, and central in one patient, which was relatively similar to the distribution in the combination therapy group.

She pointed out that in cases in which there is tumor recurrence, the eye can be salvaged with additional thermotherapy or radiotherapy.

"Using Kaplan-Meier estimates, at 4 years follow-up the group treated with chemoreduction alone had recurrence in 35% of cases and the group treated with chemoreduction plus thermotherapy had recurrence in 17% of cases," she said.

"It appears that chemoreduction plus thermotherapy gave better results in these patients than chemoreduction alone," Dr. Shields said. "Even though these groups were similar, however, this was not a randomized trial."

The risk factors for recurrence for all patients included absent seeds, small tumor, and unilateral disease, she reported.

"Based on these risk factors, the smaller tumor is more likely to recur, which was surprising. Perhaps these tumors are better-differentiated retinoblastoma and are less responsive to chemotherapy," she explained. "Another possibility is that the tumor has smaller feeder vessels that receive an inadequate dose of chemotherapy. This result was also observed in a study conducted at Moorfields Hospital in London; those investigators found that tumors less than 2 mm were at greater risk for recurrence."

Macular retinoblastoma can be controlled with chemoreduction.

"Those [patients] treated with chemoreduction alone had recurrence in 35% of cases at 4 years, while those treated with extrafoveal thermotherapy and chemoreduction showed recurrence in 17% of cases at the same time point," Dr. Shields concluded. "The final therapeutic decision depends on a number of factors including precise tumor location and, most importantly, the status of the opposite eye."

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