Radiotherapy results in decreased time to second cancer in children with Li Fraumeni syndrome.

Abstract

Li Fraumeni Syndrome (LFS) arising from germline TP53 mutation results in defective DNA repair and increased risk of multiple primary cancers beginning in childhood. Curative intent radiotherapy is often used to treat childhood cancer but its impact in children in LFS has not been reviewed. We undertook a retrospective case-series review of 4 children with a solid cancer diagnosed ≤16years to assess time and survival following second cancer diagnosis. Following radiotherapy for the first cancer diagnosis, median time to second primary cancer diagnosis was 13.3 years and median survival 9.7 years. Where no radiotherapy was received median time to second primary cancer diagnosis was 25.1 years [Chi2=14.8, P < .0001; HR = 7.9 (95% CI:2.8-22.6)], and median survival of 29.2 years [Chi2=12.5, P = .004, HR = 3.2 (95% CI : 1.5-6.6)]. Radiotherapy for first cancer in children with LFS is associated with adverse outcomes and ought be considered only in the absence of other potentially curative options. Where unavoidable, second cancer risks must be minimised.