The majority of TP53- associated adrenocortical carcinomas (ACC) develop by 12 years of age, with most of these occurring by 5 years of age. As greater than 90% of TP53 pathogenic variant carriers with ACC secrete androgens, or androgens plus cortisol, clinical examination for signs of virilisation and Cushingoid features is important.r
Regular abdominal ultrasound screening is recommended in screening protocols for children with a TP53 pathogenic variantrrr and in international consensus guidelines.r Blood collection is invasive and does not appear to increase cancer detection rate compared with imaging and clinical examination alone, and therefore is not recommended as part of initial screening studies.r
Children have been included in a number of recently reported studies of screening including MRI scanning. A prospective non-randomised study of a comprehensive screening program including regular biochemical and imaging surveillance (MRI of the whole body, brain and breast, and abdominal ultrasound) in germline TP53 pathogenic variant carriers reported 11 year follow-up results and a paediatric and adult cohort. Early tumour detection through surveillance was associated with improved survival; 5-year overall survival was 88.8% (95% CI 78.7-100) in the surveillance group vs 59.6% (95% CI 47.2-75.2) in the non-surveillance group (p=0.0132). Less than 5% of participants had a non-neoplastic (false positive) lesion detected when biopsy/resection was performed due to imaging findings. The total number of children included in this study of 89 participants was not reported, but 5 of the cancers in the surveillance group were detected before 18 years of age.r
The French LIFSCREEN study, which randomised participants to clinical examination, MRI brain (and breast if over 20 years of age) and abdominal ultrasound, with or without annual whole-body MRI, for 5 years recruited children as young as 5 years of age. Nineteen of 107 (18%) participants were children, with the interim analysis reporting detected cancers in participants as young as 6 years of age.r
In a meta-analysis of 13 studies that included baseline whole-body MRI in Li-Fraumeni syndrome (LFS) patients, 134 of 578 participants were children. Twelve cancers were detected with single screening test, of which all were localised and treated with curative intent. The false positive rate with baseline whole-body MRI in LFS patients was 15-87%.rr Studies in other conditions showed the initial screening MRI has a higher false positive rate than subsequent rounds of screening.
There is growing international consensus for routine screening for core cancers in children with LFS using whole-body MRI, however this has to be weighed against the need for a general anaesthetic in young patients. Early paediatric data suggests whole-body MRI surveillance is safe and feasible. However, studies are ongoing and medium and long-term outcomes are awaited, particularly with respect to survival, and psychosocial impact on patients and their families.r Ideally surveillance should be coordinated through a multidisciplinary service with expertise in LFS, with discussion of enrolment in clinical trials encouraged.
Other cancers including Wilms tumour, neuroblastoma, lung, colorectal, stomach and pancreatic cancers have an increased risk compared with the general population, however, this risk is not quantified.
TP53 pathogenic variants may cause radiation sensitivity due to impaired recognition and repair of DNA damage, and there are numerous reports of second primary malignancies developing in a radiation field. Minimising radiation therapy is recommended where possible, especially if other treatment modalities with comparable cure rates are available. Tests using ionising radiation should be avoided if other effective modalities are available.
There is evidence that smoking increases the risk of lung cancers in TP53 pathogenic variant carriers by 3-fold.