Understanding Risk of Second Primary Malignancies in Patients with Retinoblastoma

A major retinoblastoma research project in the Center for Childhood Cancer Research at Children's Hospital of Philadelphia is directed at gaining greater understanding of the risk of second primary malignancies (SPMs) in patients with retinoblastoma.

Treatment for retinoblastoma depends on extent of disease and can include systemic chemotherapy, intra-arterial chemotherapy, intravitreal chemotherapy, external beam radiotherapy, plaque radiotherapy, laser photocoagulation, cryotherapy, and enucleation. Most retinoblastoma patients who have access to these therapies and expert physicians survive and live into adulthood. However, their genetic predisposition and/or exposure to therapies put them at increased risk of SPMs, and in fact are believed to be the leading cause of death in patients with heritable Rb.

Heritable Rb patients are known to be at risk of pineoblastoma, osteosarcoma, melanoma and epithelial cancers, but the breadth of diagnoses, rates of occurrence and likelihood of cure of these second malignancies are not fully understood. Moreover, it is believed various types of RB1 mutations appear to be more often involved in SPM than others. Finally, exposure to therapies such as external beam radiation significantly increases the risk of second malignancies, but again the full breath of cancers is not recognized. A large population is required to study such aspects and, for retinoblastoma, it will require an international effort.

Our objectives in this project are to understand the following:

  1. What is the influence of chemotherapy on the risk of site-specific second primary malignancies?
  2. What is the long-term effect of radiation therapy on the risk of second primary malignancies?
  3. What is the influence of RB1 mutations on the risk of second primary malignancies?

Our team at CHOP is collaborating on this project with a large number of international hospitals caring for retinoblastoma patients to better understand this risk of second primary malignancies (SPMs) in patients with retinoblastoma. This international consortium, named the International Retinoblastoma and Second Cancers (IRiSC) consortium, consists of approximately 15 institutions, but the number is growing. Dr. Ann-Marie Leahey sits on the inaugural IRiSC Review Board as the only pediatric oncologist. We estimate data on nearly 10,000 patients will be collected and analyzed for this and future projects — the largest ever collected for retinoblastoma. Importantly, the cohort of patients cared for jointly at Children's Hospital of Philadelphia and Wills Eye Hospital in Philadelphia will be approximately 2,000 patients.

The initial funding for this very important and far-reaching project at CHOP is supported by the Gottstein Family Research Fund. We would appreciate any contributions to further the efforts of this or other research projects related to retinoblastoma. If you would like to make a charitable, tax-exempt contribution to retinoblastoma research at CHOP, please see all the ways you can make your donation, and address your generous gift to "Retinoblastoma research."

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