The majority of TP53- associated adrenocortical carcinomas (ACC) develop by 12 years of age, with most of these occurring by 5 years. 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.
There is evidence for screening with abdominal ultrasound and/or blood tests in children with a TP53 pathogenic variant. 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 nonrandomised study of 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. 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% (47.2-75.2) in the non-surveillance group (p=0.0132). Less than 5% of patients 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 patients was not reported, but 5 cancers were detected in the surveillance group before 18 years of age.r
The French LIFSCREEN study, which randomised patients to clinical examination, MRI brain (and breast if >20 years old) 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%) of participants were children, with the interim report detecting cancer in screened patients as young as 6 years of age.r
In a meta-analysis of 13 studies that included baseline whole-body MRI in LFS patients, 134 of 578 participants were children. Twelve cancers were detected with single screening test, of which all were localized and treated with curative intent. The false positive rate with baseline whole body MRI in LFS patients was 15-87%.rr Initial MRI screening is known from previous studies in other conditions to be associated with higher rate of false positive results.
There is growing international consensus for routine screening of core cancers in children with LFS with whole-body MRI however this has to be weighed against the need for a general anaesthetic in young patients for a screening MRI. Studies are ongoing and further results are awaited, particularly with respect to survival, and tolerability of comprehensive testing, including psychosocial impact on patients and their families. Surveillance ideally should be coordinated through a multidisciplinary service with expertise in LFS, with discussion of enrolment in clinical trials encouraged
TP53 pathogenic variants are believed to cause radiation sensitivity, due to impaired recognition and repair of DNA damage and there are numerous reports of second primary malignancies developing in areas previously treated with radiation therapy. Minimising radiation therapy is recommended where possible, especially if other treatment modalities with comparable cure rates are available. Similarly 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.