Strict definition of high-risk features of pediatric retinoblastoma may
be linked to a 70% reduction in chemotherapy use in those patients, according
to study results.
Murali M. Chintagumpala, MD, a professor of pediatrics at the
Baylor College of Medicine, said there is controversy regarding the definition
of histopathologic high-risk features in enucleated eyes of children with
The contribution of those features to metastases also is controversial.
The number of patients is small, so it has been hard to
define, Chintagumpala said.
The current prospective international trial was the first to have a
panel of histopathologists, Chintagumpala said. The trial was conducted to
determine the prevalence of strictly defined histopathologic high-risk features
that are predictors of recurrence and the role of chemotherapy to prevent
Eligible participants underwent enucleation for unilateral
retinoblastoma. Pathology slides were submitted for central review within 21
days of enucleation.
Three pathologists came up with the criteria that formed the basis
of the study, Chintagumpala said. Tumors that were less than 3 mm
in maximum diameter and didnt reach the sclera were classified as focal.
Massive tumors were greater than 3 mm.
High-risk features included posterior uveal invasion grades IIC and D,
concurrent optic nerve and choroid involvement and post-lamina optic nerve
involvement. If the central review team found evidence of one or more of these
features, the patient was treated with six cycles of chemotherapy consisting of
carboplatin, vincristine and etoposide. All other patients were observed.
Clinicians followed all patients for extraocular recurrences.
Enrollment occurred between February 2005 and May 2010.
The median follow-up duration was 2.2 years.
There were 312 patients evaluated by central histopathology review.
Forty-nine of those patients had their risk classification changed. Thirteen
percent of patients initially determined to have no high-risk features were
re-classified as having high-risk features, while 24% of patients initially
classified as having high-risk features were re-classified as not having them.
There were two incidences of extraocular disease. One fatality of
unknown cause occurred. The death and one of the extraocular relapses occurred
among the 93 patients assigned by the review panel to receive chemotherapy
(2/93=2.2%; upper 95% CI, 3.4%). There were 209 patients assigned to the
observation group. The other extraocular relapse occurred in this group
(1/209=0.5%; upper 95% CI, 0.6%).
No differences in event-free survival or OS were observed between the
These results indicate that we can reliably avoid chemotherapy in
approximately 70% of these children, Chintagumpala said. Isolated
anterior chamber, scleral invasion, iris and ciliary body invasion may not
require adjuvant chemotherapy. More intensive therapy is needed for selected
patients with certain high-risk histopathologic features.
- Chintagumpala MM. Abstract #9515.
- The researchers report no relevant financial disclosures.