Whole‐body MRI for cancer surveillance in ataxia–telangiectasia: A qualitative study of the perspectives of people affected by A‐T and their families

Abstract Background/Objectives Ataxia–telangiectasia (A‐T) is a complex inherited disease associated with an increased risk of malignancy. Surveillance guidelines have demonstrated significant health benefits in other cancer predisposition syndromes. However, evidence‐based guidelines for cancer screening are not currently used in the United Kingdom for people affected by A‐T. This study aims to understand how people with A‐T and their parents feel about cancer surveillance using whole‐body magnetic resonance imaging (MRI) to inform the future development of cancer surveillance guidelines. Design/Methods We conducted semistructured interviews with people affected by A‐T. Data were analysed inductively using thematic analysis. Results Nine parents of children with A‐T and four adults with A‐T were interviewed. Five main themes emerged from the data, including (1) cancer screening was considered invaluable with the perceived value of early detection highlighted; (2) the cancer fear can increase anxiety; (3) the perceived limitations around current practice, with the responsibility for monitoring falling too strongly on parents and patients; (4) the need for effective preparation for cancer screening, including clear communication and (5) the challenges associated with MRI screening, where specific recommendations were made for improving the child's experience. Conclusion This study suggests that stakeholders are positive about the perceived advantages of a cancer screening programme. Ongoing support and preparation techniques should be adopted to maximise adherence and minimise adverse psychosocial outcomes. Patient or Public Contribution People with A‐T and parents of people with A‐T were actively involved in this study by giving their consent to be interviewed. An independent parent representative contributed to the study, supporting the research team in interpreting and commenting on the appropriateness of the language used in this report.


| INTRODUCTION
Ataxia-telangiectasia (A-T) is a rare inherited disease that results in cerebellar neurodegeneration, elevated cancer risk, radiation sensitivity, immunodeficiency and respiratory disease. [1][2][3] The estimated prevalence of A-T in the United Kingdom is approximately 1 in 400,000, 4 with 170-200 people affected. 4,5 A-T is a progressive condition that manifests in early childhood. 2 The life expectancy of people with A-T is estimated to be 25 years, with cancer being the most frequent reason for mortality. 2,[5][6][7] Cancer in A-T has been reported as early as 2 years old with a median age of diagnosis of 12.5 years. 8,9 Cancer surveillance guidelines for individuals affected by some cancer predisposition syndromes (CPS) with elevated cancer risk, such as Li-Fraumeni syndrome (LFS), have been developed and can help to reduce delays to diagnosis and initiation of treatment. 10,11 Despite the high cancer risk that people with A-T experience (22%-24% cumulative incidence up to age 20 years), current guidelines for the management of children and young adults with A-T do not include cancer surveillance. 2,4,8,9,12 An international consensus statement regarding screening in CPS noted that 'Evidence-based standards for cancer screening do not exist for patients with A-T, particularly in childhood'. 10 Developments in magnetic resonance imaging (MRI) technology allow whole-body (WB)-MRI scans to be performed with relatively short acquisition times. 13 17,19,[26][27][28][29] The excellent soft-tissue contrast resolution and ability to demonstrate malignancy contribute to the increased interest in including this technique in cancer surveillance protocols. [17][18][19][20][21]30 However, it is important to consider the challenges associated with this technique, such as the relatively long imaging times and image artefacts caused by motion, which may require the use of sedation or general anaesthesia in young children. 17,31 The high sensitivity of MRI might detect incidental findings (false positives), which could lead clinicians to request unnecessary examinations. 20 Nevertheless, trials of cancer surveillance in families with LFS that include WB-MRI have demonstrated the feasibility of the approach, with significantly improved survival (thus better outcomes), and WB-MRI is now incorporated into clinical guidelines. [27][28][29][32][33][34][35] The lack of ionising radiation in MRI makes this an attractive approach for imaging-based cancer surveillance in people with A-T, but this approach has not yet been systematically evaluated or incorporated into guidelines for people with A-T. In practice, WB-MRI would be combined with blood tests (e.g., to pick up leukaemia) in a surveillance programme.
People with A-T and their families already have the worry of living with a chronic life-limiting childhood-onset disease with a poor overall prognosis and progressive physical disability. 1-3 A cancer surveillance programme could add to this burden with a detrimental effect on both the child with A-T and their family members. It is recognised that surveillance tests can increase anxiety due to the possibility of finding cancer or other pathologies. 20 Data from screening trials related to other CPS have demonstrated mixed psychosocial effects: although anxiety, depression and cancer worry were reported, overall the levels of satisfaction and acceptability were higher. [36][37][38] These trials have shown that having clinical support to provide psychosocial care, such as a long-term framework of clinical consultation, peer support scheme either by telephone or email and support network with educational support groups, is as important as the cancer screening itself. [27][28][29]32 Quality-of-life is affected by A-T, 39

| Participants
The target sample size was 15 participants to capture a diverse range of views and ensure data saturation. 40 We invited people with A-T and parents (mothers and fathers) of people with A-T to participate through adverts published on the social media channels of the two A-T UK charities. These charities also contacted their members by email with a brief description of the study. Information sheets, which included a video explaining the study (provided in Supporting Information: Material S1), were sent to everyone who showed interest in the study by emailing the research team. Participants confirming that they had read the participant information sheet were sent a link to complete the electronic consent form and provide demographic information. Participants were recruited between July and November 2021.
Participants with A-T were included if they had a formal diagnosis of A-T and were over the age of 12. The inclusion criterion for parents was to have, or have had, a child with A-T. This study was approved by the University of Nottingham Research Ethics Committee (Ref: 2787), and participants gave electronic consent before the interview.

| Data collection
The semi-structured interviews were conducted by two research

| Data analysis
The interviews were analysed using thematic analysis, as described by Braun and Clarke. 41 Transcripts were read at least three times by two independent researchers (R. N. and B. D. P.) to identify initial patterns (familiarisation). Computer software NVivo 42 was used to analyse the data. The codes identified were combined into possible themes, and the relationship between themes was considered (theme development). The final steps involved reviewing, defining and naming the themes, and forming a clear thematic map driven by the data. The preliminary data analysis was conducted by two research team members (R. N. and B. D. P.) and refined by a discussion with members of the research team (R. D. and C. G.). The clarity and trustworthiness of the data analysis and its reporting were further enhanced by the contribution of a parent and patient representative.

| RESULTS
No children with A-T were recruited. Seventeen adults expressed interest in taking part in the study. One adult with A-T declined to participate in the study after reading the participant information sheet due to the subject of the study and one parent was excluded due to not meeting the inclusion criteria. Two parents did not reply to further emails after expressing their interest in participating in the study. Nine parents of children affected by A-T and four adults with A-T were interviewed in 11 interviews. In two interviews, both parents were present at their request ( Figure 1).
Interviews ranged between 20 and 50 min (mean = 34) for parents and 9-20 min (mean = 15) for adults with A-T. The participants' characteristics are described in Table 1.

Current practice for caring for people with A-T has limitations, (4)
Effective preparation is essential for the cancer screening and (5) MRI screening presents challenges. Five subthemes were identified from four of the five main themes ( Figure 2). The themes with illustrative quotes are shown in Table 2.

| Cancer screening is 'invaluable'
Overall, the participants showed high expectations about cancer screening for people with A-T. All participants expressed positive views about the prospect of a surveillance programme that screened for cancer (quote#1). In addition, some parents considered the regular monitoring that the cancer surveillance offers as proactive care, which is how they would like to see the health system working (quote#2). The families expressed positive views about the safety of MRI, in terms of avoiding the use of ionising radiation (quote#3).

| Early detection is the most important outcome
Early detection was the main anticipated advantage of cancer screening mentioned by most participants, on the assumption that it could lead to earlier treatment and improved outcomes. Participants emphasised that if cancer is detected too late, the person with A-T could experience worse health outcomes (quote#4). Participants reported that cancer surveillance might lead to the detection of other pathologies that might not be related to cancer, which was seen as an advantage of cancer surveillance (quote#5).

| Cancer fears can increase anxiety
This theme captured the strength of fear participants felt about the risk of cancer associated with A-T (quote#6).
F I G U R E 1 Flowchart explaining the recruitment process. A-T, ataxia-telangiectasia.
T A B L E 1 Participant characteristics were included in the data analysis.

One child 5
Two children 2 Type of A-T

| Adults with A-T and parents fear cancer
Participants reported that a diagnosis of A-T is a stressful and lifechanging event on its own. In addition, with this diagnosis comes the awareness of the increased risk of cancer associated with A-T and the lack of treatment options. Therefore, parents are constantly worrying about cancer (quote#7).

| Cancer screening could stir up existing anxieties around A-T
When discussing the implications of having a cancer screening programme in place, the participants explained how they would experience some anxiety before the diagnostic test, not only because of the implications of the results but also because it is a reminder of the A-T condition itself (quote#8 and quote#9). The participants discussed the fact that they could experience anxiety waiting for the results of the cancer screening. However, because they need to attend several medical appointments for other A-T-related issues, some participants mentioned that anxiety is often present in their lives and thus they have learned how to deal with these feelings (quote#10).

| Current practice for caring for people with A-T puts pressure on families
Participants discussed a range of medical specialists involved in the care of people with A-T but reported a lack of oncological support (quote#11). The parents (particularly) reported constantly looking after their children's health, suggesting that they felt as if they were acting as doctors (quote#12).

| Effective preparation is essential for the cancer screening
This theme captured the need for tailored communication with ageappropriate education and information before cancer screening.

| MRI screening presents challenges
This theme captured the challenges and some concerns regarding the practical and emotional aspects of the MRI scan.
The participants expressed some concerns related to the practical aspects of having an MRI scan, such as claustrophobia, laying still, the noise, the length of the scan and the need for anaesthesia for some people (quote#18). Particularly, a participant with A-T felt that from personal experience, people with A-T should have the option to be anesthetised as it was quite difficult for her to lay still in the MRI scan, as the results could be inconclusive due to excessive movement (quote#19). However, the parents expressed worries related to the implications of being anaesthetised, which for them is one of the most concerning aspects of the cancer surveillance programme (quote#20).

| MRI should be available locally
Participants expressed that having the MRI available locally would provide a better experience by minimising the challenges of travelling to a distant centre. Nevertheless, they reported that they would be willing to travel far if that ensured they could have the cancer screening (quote#21). bring additional psychosocial burdens to people with LFS. 36,37 In fact, the regular monitoring implied in a cancer screening provides a sense of control to people with LFS. 36,37 Participants felt that screening could temporarily increase their levels of anxiety before the screening test, during the scan and while waiting for the MRI results. This was balanced by the recognition that living with A-T is already emotionally demanding and as a result, they had built up the resilience needed to cope with any additional shortterm anxiety. These results are in accordance with previous studies

| DISCUSSION
showing that the highest anxiety levels are at baseline but then are reduced a few weeks after the scan, especially after getting the results. 36,37 The concept of 'scanxiety' is recognised in the oncology field as the feeling related to the anticipation of having the scan and its results. 20,43 'People with A-T need to have the option to be anesthetised because it was very difficult for me to be awake and keeping still for all that time… This means that. I can't sit here and, uh, to move'. (Adult AT_08) quote#19 'We know obviously it's upsetting. I mean, because MRI means he's going to get knocked out basically for it to be done. I don't know how it is when they get older, but yeah, as children as far as I'm aware, they need to be under general anaesthetic, I think it was, and that is, that's upsetting'. (Parent_03) quote#20 Subtheme MRI should be available locally 'Clearly, it will be more efficient if it could be local, rather than always having to go to, I don't know, Nottingham, Papworth, whatever it might be, or London hospital. It will be useful if that could be localised and I don't know if that's potentially possible, but that'd make it easier for parents to attend from a logistics point of view and also a cost, you know'. (Parent_07) quote#21 Note: The Bold font corresponds to the main themes.
Some potential strategies to manage the anxiety and concerns associated with cancer surveillance protocols were identified.

| Study limitations
This study has limitations that should be considered. First, the adults with A-T interviewed were all female, so our study does not have the perspectives of male adults with A-T. Second, we did not have the chance to assess the feelings of children with A-T between twelve and eighteen years old about cancer surveillance. Our difficulty recruiting people with A-T in this age group may have been due to parental reluctance to bring their children into discussions on this sensitive and potentially upsetting topic. Thirdly, overall recruitment was lower than expected, possibly due in part to the COVID-19 pandemic, as we had hoped to recruit through parent workshops and A-T family events. Although online interviews offered convenience, and participants were provided with details of additional support in our patient information sheet, it may have been more acceptable and appropriate to recruit to face-to-face interviews in supportive settings. However, a sample size of 13 exceeds the suggested minimum of 12 interviews necessary to ensure data saturation (39). 40 A larger and more diverse sample may have revealed other views, but we believe the risk of this is low given the small target population and the evident data saturation achieved in our analysis. Finally, we gathered the perspectives of parents and people with A-T about the hypothetical use of WB-MRI for cancer screening before participating in such a programme. Thus, their views may differ after undergoing surveillance. However, it is important to note that we aimed to understand their views before conducting a feasibility trial to have their perspectives implemented in the trial design.

| CONCLUSION
In summary, our results suggest that WB-MRI for cancer screening will be accepted and welcomed by people with A-T and their families.
The responsibility and pressure of managing a life-limiting condition such as A-T was acknowledged by participants in this study, and our results suggest that parents and people with A-T perceive that the benefits of early cancer detection would outweigh the additional psychological burdens of screening. In addition, parents and adults with A-T were able to suggest strategies to reduce the psychological impact of a cancer surveillance programme, including ongoing clinical support and continuous communication to provide psychosocial care. NEVES ET AL.