A legacy of hope: understanding the value of post-mortem brain donation for people with brain cancer and their loved ones

<p dir="ltr">Brain Cancer is a debilitating and insidious disease, the most commonly diagnosed gliomas are grade four and carry an average survival of less than 18 months. The short survival period for such gliomas is complicated by extensive morbidity in the form of cognitive, physical and emotional decline. In the past 30 years there has been no significant change in patient outcomes and there are limited avenues for optimism based on the emerging therapeutic pipeline. To accelerate the trajectory of brain cancer treatment and care, further research is needed to understand the pathophysiology of disease and the potential for new targets and therapeutic agents. To facilitate this, researchers require access to high quality biospecimens that allow scientific investigation of tumour spatial and temporal heterogeneity as well as the tumour microenvironment. Post-mortem brain tissue samples fulfil this need, and as the number of post-mortem brain tissue biobanks increases, so too does the need to understand the human experience of donating to a post-mortem brain cancer biobank. </p><p dir="ltr">The goal of this thesis is to systematically review the existing body of literature to clarify the perceived benefits and harms of brain donation and understand how the process might be improved for both consumers and clinicians. Following this, it will explore the human experience of consenting to, or supporting a loved one to consent to, a post-mortem brain biobank following a brain cancer diagnosis.</p><p dir="ltr">Individual aims of this thesis include;</p><p dir="ltr">1. To demonstrate the relevance and feasibility of post-mortem brain biobanking in regional and rural areas. (Chapter 3)</p><p dir="ltr">2. To characterise the value of post-mortem brain donation from a biomedical standpoint, justifying the ongoing need for, and value of, post-mortem brain biobanking programs. (Chapter 4)</p><p dir="ltr">3. To review the literature describing the impact of brain biobanking on both donors and their loved ones, identifying perceptions of potential benefits and harms. (Chapter 5)</p><p dir="ltr">4. To determine whether there exists a psychosocial value from participating in brain biobanking for patients and for their relatives and friends with an emphasis on legacy, existential purpose and altruism from the perspective of carers and next of kin prior to donation. (Chapter 6)</p><p dir="ltr">5. To characterise the experience of supporting a loved one to donate their brain, exploring the impact of brain donation on the grieving process for relatives and friends of donors following the death of a loved one. (Chapter 7)</p><p dir="ltr">6. To characterise the lived experience of donors consented for post-mortem brain donation, providing insights for clinical teams that can guide and empower them to discuss consent for brain donation when appropriate. (Chapter 8) </p><p dir="ltr">7. To discuss the key findings, strengths and limitations of these studies while also assessing their implications for the relevance and appropriateness of brain biobanking programs worldwide. (Chapter 9)</p><p dir="ltr">To do so, it was pertinent to explore the relevance and feasibility of brain biobanking in regional and rural areas, justify the biomedical value for translational research, review the existing literature to ascertain perceptions of value and harm beyond a brain cancer scope given the limited brain cancer specific literature and then to characterise the lived experience of consented donors with brain cancer and their loved ones. </p><p dir="ltr">This was achieved by this thesis through i) A published commentary on the current operation of post-mortem brain biobanking programs in Australia (Chapter Three), ii) A published biomedical review outlining the practical and technical applications of post-mortem tissues compared with traditional pre-mortem surgical biopsies (Chapter Four), iii) A published systematic review of the available literature capturing n=40 studies exploring perceptions of value and harm from brain donation programs (Chapter Five), iv) A published qualitative pre-donation interview (n=13) with next of kin (NOK) who are supporting a loved one to donate their brain to brain cancer research (Chapter Six), v) published qualitative interviews (n=29) with NOK following the death and brain donation of their loved one (Chapter Seven), and vi) qualitative interviews (n=21) with individuals who had received a brain cancer diagnosis and consented to donate their brain following their death – submitted and undergoing peer review (Chapter Eight).</p><p dir="ltr">The thesis discussion in Chapter Nine of this thesis outlines four key findings. Firstly, providing patients and next of kin (NOK) with an opportunity to become active participants in research tissue donations was found to be a mutually beneficial exercise with the potential to positively impact an individual's sense of hope and empowerment and expedite biomedical research pipelines. In a terminal disease setting such as brain cancer, this has vast implications for the dire need to provide hope and empowerment. Secondly, legacy was found to be an enduring and powerful ideal that can be facilitated by post-mortem brain donation. Acknowledging the establishment of a legacy can have long term positive impacts on loved ones of those who have donated their brain following death from brain cancer and provide immediate comfort to donors struggling with feelings of helplessness or a loss of purpose. This may have implications for both realised and anticipatory grief, impacting potential donors and their loved ones. </p><p dir="ltr">Thirdly, understanding the views and perceptions of those who have engaged with post-mortem programs may help inform health care providers' practice when discussing post-mortem research with patients. This may have a positive impact on addressing the concerns of HCPs who may hold reservations regarding discussions on end-of-life research or organ donation – including brain donation. Lastly, there is a lack of awareness regarding the availability of and practicalities of delivery for post-mortem brain donation programs. Stakeholders have expressed a need for communication and increased dialogue around brain donation programs to address this and to ensure increased acceptability and availability. This can be fostered collaboratively by interdisciplinary teams united behind a shared appreciation of value and impact. </p><p dir="ltr">In conclusion: Brain donation holds clear and undeniable value from a biomedical standpoint and such programs are essential to fuel translational research efforts. This cannot be facilitated without collaboration between the research, clinical and patient communities. People with brain cancer and their loved ones who engage with a post-mortem brain donation program view the process as a pathway for advocacy and contribution. The act of donating one's brain can address overwhelming feelings of helplessness and loss of control, replacing these with a sense of purpose and empowerment. Donors find comfort in knowing they are contributing to a powerful legacy associated with dignity and hope. Supporting a loved one to donate is viewed as a duty for next of kin and a means by which to honour the wishes and character of their loved one. Doing so can have an impact on the grieving process and restore a degree of meaning in the face of devastating loss. Post-mortem brain donation programs are an essential pathway for translational brain cancer research and are highly valued by patients and loved ones.</p>