We thank Abramson and associates for their comments regarding our report and welcome the opportunity to clarify our conclusions. In our study, only 1 of 252 patients that had received systemic chemotherapy developed pineoblastoma, while 3 of 156 patients, who did not receive chemotherapy, developed pineoblastoma. Abramson and associates correctly point out that only patients with the genetic form of retinoblastoma are at risk for pineoblastoma and hence only they should be included in the analysis, a fact that we well recognize. However, we wish to point out that their interpretation of our study data is not accurate. In our study, there were 193 bilateral retinoblastoma patients and among the 215 unilateral retinoblastoma patients, 22 were confirmed as having a germline mutation. Therefore, there were 215 patients with the genetic form of retinoblastoma, placing them at risk for the development of pineoblastoma. In this group, 1 of 180 patients that received chemotherapy developed pineoblastoma and 3 of 35 patients that did not receive chemotherapy developed pineoblastoma, and this difference is statistically significant ( P = .014).
In our study, there were total 408 patients and 5 patients were treated primarily with external beam radiation, and none of them developed pineoblastoma. In addition, 35 patients were treated with external beam radiation secondarily, for recurrence following chemoreduction.
Among the 215 patients with germline mutation, there were 36 patients that required external beam radiation and 1 developed pineoblastoma. We found that external beam radiation did not correlate with pineoblastoma ( P = .5).
Abramson and associates suggested that with the elimination of external beam radiation therapy, the incidence of pineoblastoma decreased to 2% in their center and one third of those developed pineoblastoma prior to the diagnosis of retinoblastoma. However, it is possible that the majority, or two thirds, could have been prevented from the development of pineal tumor if they had received systemic chemotherapy.
There has been a decline in the incidence of pineoblastoma worldwide, and this could be attributed to multiple factors including the increased use of systemic chemotherapy, especially in children with bilateral disease, or the decreasing use of external beam radiation. Though the numbers are small and it is difficult to obtain good statistical tests, our study demonstrates a lower incidence of pineoblastoma in patients with the genetic form of retinoblastoma who have received systemic chemotherapy and this effect is independent of the use of external beam radiation.