Psychosocial morbidity in TP53 mutation carriers: is whole-body cancer screening beneficial?

Abstract

Germline TP53 mutation carriers are at high risk of developing a range of cancers. Effective cancer risk management is an important issue for these individuals. We assessed the psychosocial impact in TP53 mutation carriers of WB-MRI screening as part of the Surveillance in Multi-Organ Cancer (SMOC+) protocol, measuring their unmet needs, anxiety and depression levels as well as cancer worry using psychological questionnaires and in-depth interviews about their experiences of screening. We present preliminary psychosocial findings from 17 participants during their first 12 months on the trial. We found a significant reduction in participants' mean anxiety from baseline to two weeks post WB-MRI (1.2, 95% CI 0.17 to 2.23 p = 0.025), indicative of some benefit. Emerging qualitative themes show most participants are emotionally supported and contained by the screening program and are motivated by their immediate concern about staying alive, despite being informed about the current lack of evidence around efficacy of screening for people with TP53 mutations in terms of cancer morbidity or mortality. For those that do gain emotional reassurance from participating in the screening study, feelings of abandonment by the research team are a risk when the study ends. For others, screening was seen as a burden, consistent with the relentless nature of cancer risk associated with Li-Fraumeni syndrome, though these patients still declared they wished to participate due to their concern with staying alive. Families with TP53 mutations need ongoing support due to the impact on the whole family system. These findings suggest a comprehensive multi-organ screening program for people with TP53 mutations provides psychological benefit independent of an impact on cancer morbidity and mortality associated with the syndrome. The benefits of a multi-organ screening program will be greater still if the screening tests additionally reduce the cancer morbidity and mortality associated with the syndrome. These findings may also inform the care of individuals and families with other multi-organ cancer predisposition syndromes.

Families’ and health care professionals’ attitudes towards Li‐Fraumeni syndrome testing in children: A systematic review

“…Almost one in three participants was found to have a false positive requiring future investigation leading to potential distress, medical morbidity and cost . Despite this, a recent study on the acceptability of WBMRI in the LFS population observed that screening reduced anxiety and may provide psychological benefit for participants …”

“…15 Despite this, a recent study on the acceptability of WBMRI in the LFS population observed that screening reduced anxiety and may provide psychological benefit for participants. 16 One of the main perceived deterrents cited by parents was insurance implications and fear of decreased employment opportunities. 38,42 Due to the rarity of LFS no studies have captured the effect of this syndrome on insurance and employment; however, Huntington's disease and Li-Fraumeni have been compared in the literature because of the potential to develop the diseases in adolescents.…”

“…Recent studies have suggested improved medical and psychological outcomes for TP53 mutation carrier undergoing rigorous screening . The Toronto protocol, which incorporates WBMRI among other modalities, including brain MRI and quarterly abdominal ultrasound, was associated with improved survival .…”

Translating genomic risk into an early detection strategy for sarcoma

“…Psychological distress resulting from undergoing inappropriate surveillance has also been postulated as a justification for caution . However, TP53 mutation carriers participating in surveillance derive psychological benefit . The recent whole‐body MRI data are changing this situation, with the American Association of Cancer Researchers and the US National Comprehensive Cancer Network Guidelines for management of LFS issuing surveillance recommendations that include whole‐body MRI.…”

Whole body MRI of the non-human primate using a clinical 3T scanner: initial experiences

“…Whole body MRI techniques have been explored generally to examine the anatomical structures of multiple organs (such as neck, chest, abdomen, spine, pelvis, and extremities) and disease conditions including bleeding, edema, lymphoma, skeletal metastases in patients (6)(7)(8)(9)(10)(11), whole body inflammation (12), diabetes (13), or virtual autopsy (14). Also, it has been applied for evaluating the distribution of extensive local lesions and that of multi-organ systemic disease and lipodystrophy and fat distribution in HIV patients (15,16), and to identify inflammation and structural damages in patients with rheumatoid arthritis in order to assess the staging and treatment response during medical treatment (17).…”