Irene Jiménez1, Marick Laé2,3, Marie-Laure Tanguy4, Alexia Savignoni4, Marion Gauthier-Villars5, Laurence Desjardins6, Nathalie Cassoux6,7, Rémi Dendale8, Joseph Rodriguez9, François Doz7,10, Hervé J Brisse11, Isabelle Aerts1. 1. Institut Curie, SIREDO Oncology Center (Care, Innovation and Research for children and AYA with Cancer), PSL Research University, Paris, France. 2. Institut Curie, Department of Pathology, PSL Research University, Paris, France. 3. Centre Henri Becquerel, Department of Pathology, INSERM U1245, UNIROUEN, University of Normandie, Rouen, France. 4. Institut Curie, Biostatistics Department, PSL Research University, Paris, France. 5. Institut Curie, Genetics Department, PSL Research University, Paris, France. 6. Institut Curie, Ocular Oncology Service, PSL Research University, Paris, France. 7. Université de Paris, Paris, France. 8. Institut Curie, Radiation Oncology Service, PSL Research University, Paris, France. 9. Hôpital Jean Bernard, Department of Surgery, Head and Neck Surgery, Valenciennes, France. 10. Institut Curie, SIREDO Oncology Center (Care, Innovation and Research for Children and AYA with Cancer), Paris, France. 11. Institut Curie, Imaging Department, PSL Research University, Paris, France.
Abstract
BACKGROUND: The long-term survival of germline retinoblastoma patients is decreased due to the risk of second primary tumors (SPTs) that occur years after the diagnosis of retinoblastoma. This risk is related to genetic predisposition and other factors, such as the treatment of retinoblastoma by external beam radiotherapy (EBRT). PROCEDURE: We studied the incidence, risk factors, and prognosis of specific craniofacial SPTs developed within the margins of radiation field in a cohort of 209 patients with germline retinoblastoma treated with EBRT at our institution between 1977 and 2010. Clinical characteristics, survival, incidence, and histology of craniofacial SPTs were recorded. RESULTS: Fifty-three of the 209 patients developed 60 distinct craniofacial SPTs in irradiated field with a median time from EBRT of 16.9 years (4-35) and a median follow-up of 24.8 years (5.3-40). Osteosarcoma (33.3%) and undifferentiated sarcoma (23.3%) were the more prevalent histological entities. Benign tumors (16.7%) also occurred. The cumulative incidence of craniofacial SPTs reached 32.6% at 35 years after EBRT, and the median survival after diagnosis was five years. In our series, irradiation under 12 months of age, bilateral EBRT, or previous treatment of retinoblastoma with chemotherapy did not significantly increase the risk of craniofacial SPTs. CONCLUSIONS: This work presents a strong argument to avoid EBRT in the management of retinoblastoma and emphasizes the high risk and poor prognosis of specific craniofacial SPTs. This study also points to the question of the need and benefits of special programs for early detection of craniofacial SPTs in survivors of irradiated germline retinoblastoma.
BACKGROUND: The long-term survival of germline retinoblastomapatients is decreased due to the risk of second primary tumors (SPTs) that occur years after the diagnosis of retinoblastoma. This risk is related to genetic predisposition and other factors, such as the treatment of retinoblastoma by external beam radiotherapy (EBRT). PROCEDURE: We studied the incidence, risk factors, and prognosis of specific craniofacial SPTs developed within the margins of radiation field in a cohort of 209 patients with germline retinoblastoma treated with EBRT at our institution between 1977 and 2010. Clinical characteristics, survival, incidence, and histology of craniofacial SPTs were recorded. RESULTS: Fifty-three of the 209 patients developed 60 distinct craniofacial SPTs in irradiated field with a median time from EBRT of 16.9 years (4-35) and a median follow-up of 24.8 years (5.3-40). Osteosarcoma (33.3%) and undifferentiated sarcoma (23.3%) were the more prevalent histological entities. Benign tumors (16.7%) also occurred. The cumulative incidence of craniofacial SPTs reached 32.6% at 35 years after EBRT, and the median survival after diagnosis was five years. In our series, irradiation under 12 months of age, bilateral EBRT, or previous treatment of retinoblastoma with chemotherapy did not significantly increase the risk of craniofacial SPTs. CONCLUSIONS: This work presents a strong argument to avoid EBRT in the management of retinoblastoma and emphasizes the high risk and poor prognosis of specific craniofacial SPTs. This study also points to the question of the need and benefits of special programs for early detection of craniofacial SPTs in survivors of irradiated germline retinoblastoma.