Subsequent primary and secondary neoplasms in childhood cancer survivors

To count and review cases of subsequent malignant neoplasms (SMNs) in childhood cancer survivors, which are estimated to occur at a tenfold higher frequency than in the general population.

Data of 60 patients with SMNs from a tertiary referral center for pediatric solid tumors were analyzed: gender, age at diagnosis, treatment, time between diagnoses, subsequent cancer's association with radiotherapy, observation time, status: alive/dead, genetic background.

Median age at time of diagnosis of the index tumor (IT) was 6.8 years (0.1-22.1), of subsequent neoplasm 14.9 years (2.1-36.6). Median time between diagnosis of first and subsequent neoplasm was 6.3 years (0.8-26.2). In 16 patients, secondary tumors developed in irradiated sites. Eleven patients (18.3%) had cancer predisposition syndromes (CPS): 3 RB1 mutation, 5 Li-Fraumeni syndrome, 4 neurofibromatosis type 1; one had both Li-Fraumeni syndrome and RB1 mutation. Four patients (3 with CPS) had a third malignant neoplasm, and three had a fourth. Thirty-seven patients (61.6%) are alive, 23 (38.4%) died. Median observation time is 15.0 years (1.3-43.1). The overall 5-year survival rate in the whole group is 85% from diagnosis of IT. The overall 5-year survival rate from diagnosis of the second tumor is 63%.

Due to risk of SMNs, life-long cancer screening is required for childhood cancer survivors. In CPS, this risk is multiplied, as it results from both genetic factors and previous treatment; in these patients, multiple primary cancers must be taken into account. When assessing imaging studies of patients with a history of malignancy, clinicians should consider not only recurrence and metastases but also the possibility of a new malignancy of a different histopathological nature.