IARC 60th Anniversary - 19-21 May 2026
Session : Childhood Cancer Research in Action: Bridging Population Science and Discovery
Treatment and Genetic Predisposition: Contribution to the Risk of Subsequent Primary Neoplasms in Childhood Cancer Patients in the CRICCS study
MAKOHUSOVA M. 1,2, SUNGUC C. 1,3, COLOMBET M. 1, DOLYA A. 1, HJORTH L. 4, PRITCHARD-JONES K. 5, STILLER C. 6, STELIAROVA-FOUCHER E. 1
1 Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France; 2 Faculty of Medicine, Comenius University & National Institute of Children’s Diseases, Bratislava, Slovakia; 3 Faculty of Medicine, Selcuk University, Konya, Turkey; 4 Lund University, Skane University Hospital, Department of Clinical Sciences Lund, Paediatrics, Lund, Sweden; 5 University College London, London, United Kingdom; 6 National Cancer Registration & Analysis Service, NHS England, United Kingdom
Background
One of the most serious late effects following cancer in childhood is the development of a subsequent primary neoplasm, which may be influenced by treatment-related exposures and underlying genetic predisposition. Study Cancer Risk in Childhood Cancer Survivors (CRICCS), supported by Children with Cancer UK, was set up to evaluate the extent of this risk.
Objectives
To quantify the cumulative incidence of second primary neoplasms (SPN) among childhood cancer patients and to evaluate the contribution of treatment modalities and genetic predisposition to SPN risk.
Methods
We conducted a population-based cohort study of childhood cancer patients from four population-based cancer registries contributing data to the CRICCS study. The outcome measure was the occurrence of SPN, defined as a new malignant neoplasm distinct from the first primary neoplasm (FPN). Follow-up time was calculated as the difference between the date of FPN and the date of SPN diagnosis, death, or last follow-up, whichever occurred first. Death without prior SPN was treated as a competing event. Cumulative incidence functions (CIF) were used to estimate the risk of SPN at different follow-up time points, stratified by treatment modality. Genetic predisposition was proxied using registry-reported congenital anomalies and cancer predisposition syndromes such as Beckwith–Wiedemann, Neurofibromatosis type 1, Tuberous sclerosis, WAGR, and Xeroderma pigmentosum.
Results
From 1985 to 2019, 455 SPNs were identified in 17,981 patients diagnosed with childhood cancer before age 15. Mean follow up time was 11.0 years. The cumulative incidence of SPN increased with time across all treatment groups and differed substantially according to treatment modality and tumour type. The highest cumulative incidence was observed among patients with lymphomas (N = 2,146; SPN = 98; 30-year CIF = 17.1%) and malignant bone tumours (N = 815; SPN = 36; 30-year CIF = 16.0%). High risk was seen in patients receiving intensive or combined treatments, namely combined chemo-radiotherapy (N = 4,268; SPN = 201; 30-year CIF = 10.5%), bone marrow transplantation (N = 1,593; SPN = 63; 30-year CIF = 11.9%), and radiotherapy (N = 5,141; SPN = 235; 30-year= 10.5%). In contrast, patients treated with only either surgery or chemotherapy experienced lower cumulative incidence at 30 years (N = 2,896; SPN = 37; CIF = 5.5% and N = 4,496; SPN = 69; CIF = 6.4%).
A high CIF was observed for patients with cancer predisposition syndromes (N = 669; SPN = 31), and the SPN presented earlier. The 10-year CIF of 4.3% increased to 9.2% at 20 years and to 12.5% at 27 years (based on one registry).
Conclusions
SPN risk among childhood cancer patients increases markedly over time and varies substantially according to treatment and genetic predisposition. Data collected routinely in some population-based registries allow identification of high-risk groups of patients needing specific follow-up with the aim to prevent SPN or reduce their impact on health of survivors by early detection and management.