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Second cancers following treatment for retinoblastoma

Kleinerman, Ruth (2016). Second cancers following treatment for retinoblastoma. (Unpublished Doctoral thesis, City, University of London)

Abstract

Improvements in treatment over the past century have greatly increased survival for retinoblastoma, a rare childhood tumour of the eye, caused by mutations of the RB1 tumour suppressor gene. However, as survival for retinoblastoma has improved, those with the hereditary form of the disease (RB1 germline mutation) have elevated risks of developing additional cancers, mostly bone and soft tissue sarcomas and melanoma. Despite advances in understanding of second cancer risks following treatment for retinoblastoma, key research questions remained including 1) risks of common adult onset cancers, some of which have somatic mutations in the RB1 pathway and are
associated with ionizing radiation; 2) persistence of increased risks of bone and soft tissue sarcomas into adulthood; 3) clarification of risks of second cancers following chemotherapy to treat retinoblastoma and 4) role of genetic susceptibility to second cancers following retinoblastoma.

In response to these questions, a large cohort of 1852 long-term survivors of retinoblastoma was assembled to evaluate systematically the risk of second cancers. The work described in this thesis, which comprises six major studies, that have used this cohort to identify a higher risk than previously assumed of lung cancer; confirmed the increased risk of second cancers in survivors with a RB1 germline mutation and past radiotherapy; documented for the first time that risk of soft tissue sarcomas varied by subtype; demonstrated that mortality from second cancers exceeded that from retinoblastoma; provided new information on variation in second cancer risk by family history of retinoblastoma; and clarified that chemotherapy in addition to radiotherapy for retinoblastoma confers a higher risk for second cancers compared with radiotherapy alone. These studies collectively have provided risk data that can be used to inform survivors and their health care providers to facilitate screening or surveillance and early identification of second cancers.

Publication Type: Thesis (Doctoral)
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Departments: Doctoral Theses
School of Health & Psychological Sciences
School of Health & Psychological Sciences > School of Health & Psychological Sciences Doctoral Theses
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