Second nonocular tumors among survivors of retinoblastoma treated with contemporary photon and proton radiotherapy

Abstract

Background: The leading cause of death among patients with hereditary retinoblastoma is second malignancy. Despite its high rate of efficacy, radiotherapy (RT) is often avoided due to fear of inducing a secondary tumor. Proton RT allows for significant sparing of nontarget tissue. The current study compared the risk of second malignancy in patients with retinoblastoma who were treated with photon and proton RT.

Methods: A retrospective review was performed of patients with retinoblastoma who were treated with proton RT at the Massachusetts General Hospital or photon RT at Boston Children's Hospital between 1986 and 2011.

Results: A total of 86 patients were identified, 55 of whom received proton RT and 31 of whom received photon RT. Patients were followed for a median of 6.9 years (range, 1.0 years-24.4 years) in the proton cohort and 13.1 years (range, 1.4 years-23.9 years) in the photon cohort. The 10-year cumulative incidence of RT-induced or in-field second malignancies was significantly different between radiation modalities (proton vs photon: 0% vs 14%; P = .015). The 10-year cumulative incidence of all second malignancies was also different, although with borderline significance (5% vs 14%; P = .120).

Conclusions: Retinoblastoma is highly responsive to radiation. The central objection to the use of RT, the risk of second malignancy, is based on studies of patients treated with antiquated, relatively nonconformal techniques. The current study is, to the authors' knowledge, the first to present a series of patients treated with the most conformal of the currently available external-beam RT modalities. Although longer follow-up is necessary, the preliminary data from the current study suggest that proton RT significantly lowers the risk of RT-induced malignancy.

Keywords: proton; retinoblastoma; second cancer; second malignancy.

Figure 1

Cumulative incidence of second malignancy in proton (blue line) and photon (red line) cohorts. A) In-field or radiation-induced malignancies B) All second malignancies.

Figure 2

A) Photon plan (anterior and lateral wedged pair with lens block) used to treat a patient with bilateral disease at CHB in 1985 B) Proton plan (lateral opposed fields) for the same patient in 2012. Both plans treat a clinical target volume confined to the tumor in the posterior retina. Radiation dose as low as 5 Gy significantly increases the risk of second malignancy.