Proton Radiotherapy for the Treatment of Pediatric Retinoblastoma

Reporter: Jacob E. Shabason MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 4, 2013

Presenter: Kent Mouw, MD, PhD
Presenter's Affiliation: Harvard Radiation Oncology Program, Boston, MA


  • Retinoblastoma is the most frequent intraocular tumor of childhood with 300 new cases diagnosed in the United States annually.
  • 40% of cases are hereditary, harboring a germline mutation in the RB1 tumor suppressor gene, and 60% are sporadic.
  • Previously, external beam radiation therapy was used as a common primary definitive treatment modality for retinoblastoma, but now is typically reserved for recurrent or refractory disease.
  • Proton radiotherapy has the ability to spare more normal tissue and therefore may decrease the risk of secondary malignancies. The risk of second malignancies is particularly important in patients with a germline RB1 mutation, as these patients are already at increased risk for second cancers.
  • Proton radiotherapy may also decrease associated toxicity, particularly by sparing radiation to the contralateral eye and other sensitive surrounding structures.
  • The purpose of this study was to investigate the long-term outcomes of pediatric retinoblastoma patients treated with proton radiotherapy.


  • The authors reviewed all of the pediatric retinoblastoma patients treated with definitive proton therapy at Massachusetts General Hospital from 1985-2010.
  • Patients were required to have at least one year of follow up.


  • 49 total patients with a median age at diagnosis of 6 months were included in the analysis and 60 eyes were treated with proton radiotherapy.
  • All patients were treated under general anesthesia with a singe lateral proton beam to a median dose of 44 Gy.
  • With a median follow up of 8 years none of the 49 patients developed metastatic disease or died as a result of retinoblastoma.
  • Only one patient developed a second malignancy, which was an osteosarcoma of the femur, far from the radiation field.
  • 11 of the 60 irradiated eyes eventually required an enucleation, mainly for progressive disease or ocular complications. 3 out of the 27 of patients with stage A or B tumors needed enucleation compared to 7 out of 31 patients with stage C or D tumors. All enucleations occurred within first several years of radiation.
  • 12 out of the 60 irradiated eyes eventually developed non-visual ocular complications requiring a procedure, including 2 enucleations.
  • Patients with earlier stage tumors without optic nerve or macular involvement had better visual preservation outcomes.
  • Cosmetic outcomes were generally good with the most common complications including orbital hypoplasia and soft tissue fibrosis.

Author's Conclusions

  • Overall, proton radiotherapy appears to be a safe and effective treatment for pediatric retinoblastoma.
  • Functional eye preservation rates were high in both early and advanced stage disease, although patients with earlier stage disease did better.
  • The long-term toxicity and secondary malignancy risk of proton therapy appears to be minimal.

Clinical Implications

  • Overall, this retrospective study of patients treated with proton therapy has important clinical implications and shows the safety and efficacy of proton radiotherapy.
  • With a median follow up of 8 years long term toxicity appeared to be minimal and second malignancies were not yet observed, however continued follow up is certainly necessary.
  • One major limitation in interpreting the results of this study is the fact that it reviews patients treated over the span of the past 3 decades. During his time period the role of external beam radiotherapy in the management of retinoblastoma has changed dramatically, from commonly being used for upfront definitive management, to now only being reserved for patients with refractory or recurrent disease. As such, patients who are referred for radiotherapy in the current era tend to have very advanced disease compared to those treated decades ago.
  • Nonetheless, regardless of stage, proton therapy appears to be safe and effective, however as expected early stage patients required less salvage therapy and had superior visual outcomes.

Given this apparent safety and efficacy, future investigation should consider the incorporation of proton radiation therapy for the up front management of retinoblastoma.


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