External beam radiation therapy continues to maintain pediatric Retinoblastoma

Reporter: J. Taylor Whaley, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 12, 2011

Presenter: Andrew L. Chang, David Andolino, Hiral Fontanilla, Anita Mahajan
Presenter's Institution: Indiana University Proton Therapy Cancer Center and M.D. Anderson Proton Therapy Center


  • Retinoblastoma is a malignant tumor, which arises from the retina. The disease is particularly common in the pediatric population with up to 25% of cases presenting with bilateral disease.
  • Bilateral retinoblastoma is associated with a germline mutation in the RB gene and poses an exceptionally difficult dilemma for the treating physician with regard to visual preservation. The population of children carrying this mutation, and developing bilateral retinoblastoma, has also been shown to at very high risk for second malignancies with up to 50% of the population presenting with a new cancer by the age of 50 years old.
  • High risk patients have been shown to have poor disease-related outcomes, with 20-30% of tumors controlled in historic publications.
  • External beam radiation therapy remains an integral component of the treatment of refractory retinoblastoma, but is generally not employed outside of the salvage setting. Up front treatment most often consists of chemotherapy, localized radiotherapy using plaques, laser ablation, and/or enucleation.
  • Although dosimetric studies have suggested a potential advantage of proton beam therapy, no clinical testing has evaluated external beam radiation therapy with respect to proton therapy
  • The goal of the majority of new pediatric cancer protocols are aimed at diminishing both acute side effects as well as long term sequelae. With respect to the treatment retinoblastoma specifically, external beam radiation therapy can result in bony growth abnormalities, visual impairment, endocrinopathies, and secondary malignancies.


  • From 2008-2010, 14 patients with pediatric retinoblastoma were treated at either Midwest Proton Radiotherapy Institute or M.D. Anderson Proton Therapy Center.
  • Retrospective review of these 14 patients were reviewed and clinical outcomes with rates of disease control are presented


  • 12 of 14 patients had bilateral disease; all of the patients were considered high risk
  • All patients were treated in the salvage setting as all patients received treatment in the form of laser coagulation, cryotherapy, or systemic chemotherapy prior to proton therapy.
  • Of those with bilateral disease, 8 received unilateral radiation and 4 received bilateral radiation
  • Two underwent enucleation prior to radiation, for a total of 16 intact eyes treated.
  • Median dose was 1.8 CGE per fraction and 45 CGE total dose (Range 36-45).
  • 100% of the CTV received >95% of the prescribed dose.
  • Field arrangements were heterogeneous as patients were treated at 2 institutions. Possible beam arrangements included single lateral field, single AP field, AP and lateral fields, and oblique and AP fields.
  • Median follow up was 17.8 months; 100% overall survival
  • Local control was 47% overall; in the 16 intact eyes, 6 of 16 (38%) had local control.
  • Of the 10 eyes with progressive local disease after proton therapy, 5 underwent salvage enucleation
  • Toxicity included 3 patients with cataracts and 2 patient with retinal vasculopathies
  • Of the 16 intact eyes treated with proton therapy, useful vision was maintained in 8 patients.

Authors' conclusions

  • In pediatric patients with retinoblastoma who require salvage radiation, proton therapy offers a viable option for organ preservation to potentially avoid bilateral enucleation.
  • In the authors' sample size, local control was comparable to high risk disease found in previous historic publications.
  • Further follow up is required to evaluate the delayed side effects of proton therapy.

Clinical/Scientific Implications

  • Bilateral pediatric retinoblastoma represents a tumor that may be devastating to quality of life in children.
  • This scenario presents a very difficult challenge for the treating physician with organ preservation paramount if possible.
  • In the small cohort of patients presented here, delivery of proton beam radiotherapy for treatment of pediatric retinoblastoma appears to be feasible with crude local control near 50%. Information on late effects associated with this treatment remains unavailable and will certainly contribute to the literature when longer follow-up permits analysis of quality of life following proton beam radiotherapy as opposed to photon-based treatment delivery.
  • Proton therapy may offer a practical solution in the prevention of bilateral enucleation. Further understanding of the risk-benefit ratio of proton therapy in this specific clinical setting may elucidate a role for proton therapy during initial treatment of advanced retinoblastoma rather than the salvage setting alone; however, further long-term data will be essential for appropriate assessment of this ratio.
  • Certainly, prospective randomized trials are needed to further evaluate the role of proton therapy in pediatric retinoblastoma