Whole Body MRI for Cancer Surveillance in A-T
Condition: Ataxia Telangiectasia
MeSH terms: Ataxia; Cerebellar Ataxia; Ataxia Telangiectasia; Telangiectasis
Study type: Observational [Patient Registry]

Summary: 
      Ataxia Telangiectasia (A-T) is an inherited disorder characterised by cerebellar
      neurodegeneration, immunodeficiency and respiratory disease. People with A-T have abnormal
      DNA repair and consequently have an increased risk of cancer. Despite this, current
      guidelines for management of children and young people with A-T do not include cancer
      surveillance.

      Improvements in MRI technology have allowed whole-body MRI (WB-MRI) scanning with relatively
      short acquisition times. Currently, WB-MRI protocols are used for diagnosing and monitoring
      some primary and secondary cancers, including cancer surveillance in people with the
      Li-Fraumeni syndrome, which is another genetic cancer predisposition syndrome. Therefore, the
      research team believe that whole-body MRI provides a safe method for cancer surveillance in
      children and young people with A-T. However, the investigators do not know whether cancer
      surveillance in children and young people with A-T using whole-body MRI is feasible and
      desirable.

      The research team proposes a feasibility study of MRI-based cancer surveillance with
      qualitative evaluation of participant experience with the primary aim to establish:

        -  feasibility of whole-body MRI for cancer surveillance in children and young people with
           A-T

        -  views of, and psychological impact on, participants and families / carers participating
           in whole-body MRI for cancer surveillance.

        -  feasibility of conducting a formal screening trial in terms of statistical design,
           sample size, screening interval, comparator arms and international collaboration
           Completion of this study will provide us with evidence of technical feasibility, very
           strong evidence of child / family views, a viable formal screening trial design and an
           engaged international research community, allowing us to proceed to a formal trial
           establishing the efficacy of a cancer surveillance programme for children and young
           people with A-T.
    

Detailed description: 
      Ataxia Telangiectasia (A-T) is an autosomal recessive disorder characterised with cerebellar
      neurodegeneration, immunodeficiency, respiratory disease and cancer susceptibility (22% by
      age 20). A-T is a complex disorder caused by mutations in the Ataxia Telangiectasia Mutated
      (ATM) gene which creates highly unstable ATM protein fragments. In the classical clinical
      presentation of A-T there is no kinase activity due to the absence of ATM protein. One
      consequence of this is that cellular DNA-repair pathways are compromised which allows breaks
      in DNA strands leading to genomic instability and/or cell death. As a result, there is an
      increase sensitivity to ionizing radiation and elevated cancer risk. Children less than 16
      years with classical A-T demonstrate a predisposition to the development of different types
      of lymphoid cancers (lymphoma and leukaemia). However non-lymphoid tumours can also occur.

      The current practice at the United Kingdom Paediatric A-T clinic for cancer surveillance is
      to perform blood testing, including full blood account, liver function tests and measurement
      of circulating tumour marker Alpha-fetoprotein. Full blood account can detect an increase
      white cell count and abnormal white cell populations and therefore, is effective in detecting
      most types of leukaemia. Elevation of Alpha-Fetoprotein can be a marker of different types of
      tumours, for example hepatocellular carcinoma and liver metastases, however is also often
      elevated in people with A-T. Therefore, its use for detecting cancer in A-T is uncertain and
      not currently evidence-based. The lack of evidence-based guidelines regarding the optimal
      cancer surveillance strategy in children with A-T could delay the diagnosis and consequently
      the treatment plan.

      Magnetic Resonance Imaging (MRI) technology has progress rapidly since its discovery, making
      it possible currently to perform whole-body MRI scans with relatively short acquisition
      times. Presently, whole-body MRI protocols that include diffusion-weighted imaging and
      structural (T1/Dixon) acquisitions are used for diagnosing and monitoring cancers (sarcomas,
      metastases and haematological tumours like myeloma). A further advantage of this technique
      compared to computed tomography is that does not involve radiation, which is important given
      the elevated radiosensitivity of people with A-T.

      The value of whole-body MRI in people with cancer predisposition has been shown in
      Li-Fraumeni syndrome, syndrome that, like A-T, is associated with increased risk of
      haematological and solid tumours. Despite the successful results of using a multimodality
      protocol for cancer surveillance in Li-Fraumeni syndrome, it cannot be assumed that the
      results will be the same in people with A-T as the also have respiratory and neurological
      dysfunction that could influence the tolerability and image quality of the MRI scans. Also,
      the profile of the tumours differs between these two syndromes. To date, the value of
      whole-body MRI for cancer surveillance in children and young people with A-T has not been
      demonstrated. It is unknown whether is possible to obtain diagnostic images, and the spectrum
      of findings (both cancer and non-cancer) that can be detected has not been reported.

      In addition to technical considerations, it is vital to understand the perspectives of people
      affected by A-T regarding cancer surveillance. Participation in a cancer surveillance
      programme could increase anxiety for both the participant and family, and it is possible that
      negative psychological aspects could outweigh the perceived benefits or earlier cancer
      detection. Compared to other screening programmes, it should be noted that these families are
      already having to deal with a family member with complex progressive chronic disease, and so
      emotional and psychological capacity to deal with added anxiety may be limited. Hence, it is
      important to know, before conducting a full scale trial that will inform the current lack of
      evidence-based guidelines, whether cancer surveillance in children and young people with A-T
      using whole-body MRI is feasible and desirable.
    

Intervention name(s): Magnetic Resonance Imaging and an optional blood test
Intervention type(s): Diagnostic Test
Intervention description(s): One whole-Body MRI that takes approximately 35minutes One blood test, which it is an optional component at this stage
Observational model: Other
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Children and young people with Ataxia Telangiectesia and their parents / carers from United
        Kingdom registred in Paediatric A-T clinic in Nottingham.
      
Keywords: Ataxia Telangiectasia; Whole-body MRI; Cancer Surveillance