Psychosocial effects of whole-body MRI screening in adult high-risk pathogenic TP53 mutation carriers: a case-controlled study (SIGNIFY)

Abstract

BackgroundGermline TP53 gene pathogenic variants (pv) cause a very high lifetime risk of developing cancer, almost 100% for women and 75% for men. In the UK, annual MRI breast screening is recommended for female TP53 pv carriers. The SIGNIFY study (Magnetic Resonance Imaging screening in Li Fraumeni syndrome: An exploratory whole body MRI) study reported outcomes of whole-body MRI (WB-MRI) in a cohort of 44 TP53 pv carriers and 44 matched population controls. The results supported the use of a baseline WB-MRI screen in all adult TP53 pv carriers. Here we report the acceptability of WB-MRI screening and effects on psychosocial functioning and health-related quality of life in the short and medium terms.MethodsPsychosocial and other assessments were carried out at study enrolment, immediately before MRI, before and after MRI results, and at 12, 26 and 52 weeks’ follow-up.ResultsWB-MRI was found to be acceptable with high levels of satisfaction and low levels of psychological morbidity throughout. Although their mean levels of cancer worry were not high, carriers had significantly more cancer worry at most time-points than controls. They also reported significantly more clinically significant intrusive and avoidant thoughts about cancer than controls at all time-points. There were no clinically significant adverse psychosocial outcomes in either carriers with a history of cancer or in those requiring further investigations.ConclusionWB-MRI screening can be implemented in TP53 pv carriers without adverse psychosocial outcomes in the short and medium terms. A previous cancer diagnosis may predict a better psychosocial outcome. Some carriers seriously underestimate their risk of cancer. Carriers of pv should have access to a clinician to help them develop adaptive strategies to cope with cancer-related concerns and respond to clinically significant depression and/or anxiety.

The psychological impact and experience of breast cancer screening in young women with an increased risk of breast cancer due to neurofibromatosis type 1

“…Although several women enrolled in this study were subjected to recall and biopsy, these investigations were not associated with further impact on psychological measures. This finding is reflected in other small studies, where recall after MRI was not associated with increased anxiety in a small cohort of women with a family history of breast cancer [ 40 ], nor were there adverse psychosocial outcomes in those requiring further investigations in a LFS whole body MRI screening study [ 67 ]. In contrast, previous studies of recall after MRI- or mammogram-based surveillance for other cohorts with cancer susceptibility syndromes demonstrated adverse psychological effects, which were transient [ 39 , 68 , 69 ].…”

Whole‐body magnetic resonance imaging as surveillance for subsequent malignancies in preadolescent, adolescent, and young adult survivors of germline retinoblastoma: An update

“…13 It is also possible, however, that participation in a screening program provided some psychological benefit, as has been reported for other individuals with cancer predisposition syndromes. [13][14][15] There has recently been much enthusiasm for the use of WB-MRI as a screening technique in individuals with cancer predisposition syndromes, 16,17 especially in the setting of Li-Fraumeni syndrome (LFS). 7,8,18,19 Among individuals with LFS, WB-MRI has been shown to enable early diagnosis and treatment of a diverse array of tumor with curative intent.…”

“…While not directly assessed, it is possible that these call‐backs for further testing resulted in unnecessary and added anxiety for patients and their families, and increased health‐care costs 13 . It is also possible, however, that participation in a screening program provided some psychological benefit, as has been reported for other individuals with cancer predisposition syndromes 13‐15 …”

Blood functional assay for rapid clinical interpretation of germline TP53 variants

“…Furthermore, TP53 variant carriers should have specific surveillance protocols, including annual whole-body MRI, 5 6 whose efficiency for early tumour detection has recently been shown by numerous studies. [5][6][7][8][9][10][11][12][13][14] Interpretation of germline TP53 variants, which are mainly missense variants, remains particularly complex. Whereas germline variants of TP53 were initially detected in Li-Fraumeni syndrome (LFS, MIM#151623), [15][16][17] our perception of cancers related to germline alterations of TP53 has drastically evolved over time.…”