A review of Leila Rose Foundation support for families affected by rare childhood cancer in Australia over the past decade

Abstract Background The Leila Rose Foundation (“the Foundation”) was established in April 2011, to address financial toxicity as well as the gaps in knowledge and support for families affected by a rare childhood cancer diagnosis in Australia. Aim The aim of this brief report is to analyze the diagnostic trends surrounding the rare cancer diagnoses for patients referred to the Foundation over the past decade and to present case studies evaluating the role of the Foundation's Family Support Coordinator in providing tailored, individualized support for families. Methods Eligibility for family support is restricted to children ≤ 14 years of age at diagnosis with a cancer that has an incidence less than 5% of all childhood cancers in Australia as reflected by national registry data. The analysis of diagnostic trends in this report, was based upon a systematic review of enrolment records. The role of the Family Support Coordinator is presented in four different case studies. Results As at 1 November 2020, the Foundation has supported 197 families affected by rare childhood cancer. Financial support of $825,000 has been provided directly to these families. Enrollment records demonstrate that 35 patients representing 18% of all enrollments have had a unique diagnosis that has not been recorded for any other enrolled patient highlighting that these diagnoses are very rare. The most frequent diagnoses have included Medulloblastoma, Ewing's Sarcoma and Wilm's Tumor (20, 19, 19 patients respectively). The Family Support Coordinator role has provided individualized support for families which has been greatly appreciated based upon ad hoc family feedback. Conclusions Challenges remain in terms of improving outcomes for families affected by rare childhood cancer. The Foundation is committed to leaving no stone unturned and delivering its unique support services to families in order to reduce the burden caused by a rare childhood cancer diagnosis both now and in the future.


| BACKGROUND
The Leila Rose Foundation ("the Foundation") was established in 2011 by Dr Andrew and Tracy Chow following the passing of their daughter Leila Rose, from a rare childhood cancer. Based in Warrnambool, in the state of Victoria, Australia, the Foundation was set up specifically to provide support for families affected by rare childhood cancer. Rare childhood cancer is defined by the Foundation as a cancer with an incidence less than 5% of all childhood cancers in Australia, in children ≤14 years of age at diagnosis. 1,2 Due to the low numbers and great heterogeneity, rare childhood cancers are difficult to study in a systematic way and tend to lag in terms of funding and resource support. The philosophy of the Foundation is to leave no stone unturned in supporting families affected by rare childhood cancer.
This article reviews the impact of the Foundation over 10 years, provides some themes emerging from the data associated with the children for whom the Foundation has provided support and presents cases, which illustrate the diversity of support provided. The article also highlights some challenges and opportunities for the management of rare childhood cancer in the future.

| INTRODUCTION
Leila Rose (pronounced Layla) was 10 months old when she was diagnosed with a rare and aggressive rhabdoid tumor in 2009. After her initial treatment regimen failed, a subsequent experimental regimen showed real promise as her tumor reduced in size and general health improved. Tragically the tumor reduction was temporary and the cancer regrew resulting in Leila losing her battle at the age of only twenty-one months.
After the passing of Leila, her parents wondered how many other families had experienced this turmoil and how many are still suffering through it, and with this they established the Leila Rose Foundation in 2011, in memory of their daughter.
In Australia, approximately 770 children will be diagnosed with cancer each year. 3 It is estimated that up to 208 or 27% of these children will have a rare childhood cancer. 2 Based on published mortality rates, it is estimated that around 25 children diagnosed with a rare cancer will die per year. 3,4 By way of comparison, in the United States approximately 10,500 children under the age of 15 will have been diagnosed with cancer in 2021. 5 Further estimated incidences of rare childhood cancers in the United States suggest that of all childhood cancers approximately 1,600 could be classified as rare under the Foundation's eligibility criteria. 6 Accordingly, the numbers associated with a rare childhood cancer diagnosis are very small, especially in Australia with a total population of only 25.6 million. 7 Of the children diagnosed with a rare cancer in a 12 month period, and based upon the Foundation's definition, only 27% to 36% receive support from the Leila Rose Foundation nationally. There is a range of potential answers as to why this is the case. It could be that the Foundation's penetration of the referral base is incomplete resulting in patchy referral patterns. Another possibility is that the Foundation's definition of what constitutes a rare childhood cancer may overstate the real incidence of truly "rare," childhood cancers. The utility of the eligibility criteria for Foundation support are constantly being evaluated and assessed.
Very early in the history of the Leila Rose Foundation the role of Family Support Coordinator was created. An experienced oncology professional, the Family Support Coordinator is available to provide support to the family for their entire cancer journey and tailor that support to their specific needs. Accordingly, the Family Support Coordinator role is unique in the pediatric cancer field in Australia in that it is confined to only rare childhood cancer, available throughout the cancer journey, with the autonomy to tailor appropriate support based upon need.
The assistance provided by the Family Support Coordinator may also include facilitating access to the Foundation's financial support.
This financial assistance aims to reduce the burden of day-to-day expenses so that the family can focus on their child's health.
In a small number of circumstances, Leila Rose Foundation has provided additional increased funding to support new diagnostic approaches or management based upon the recommendation of the treating oncologist. This has included funding to assist a personalized medicine approach, which is being formally evaluated in Australia via the PRISM study, 8 the results of which are eagerly awaited. The need for the Foundation to provide funding for genomic analysis has been relieved in the past few years by the Australian government's Genomics Health Futures Mission funding. 9 The Foundation does not generally view advocacy as an important part of its role rather preferring to provide navigational support and work in conjunction with the pediatric care team to achieve the best outcomes for the patient and their family.

| DATA AND OBSERVATIONS FROM ENROLLMENT RECORDS
As at 1 November 2020, 197 eligible families supporting a child diagnosed with a rare childhood cancer have been provided with assistance by the Leila Rose Foundation.
As highlighted above, support is provided for families with children less than or equal to 14 years of age at diagnosis who: • are a citizen or permanent resident of Australia, and • have been diagnosed with a rare childhood cancer with an incidence equal to, or less than 5% of all childhood cancers in Australia per year, ass documented in the "Childhood Cancer Incidence in Australia, 1983 to 2015" report published by the Cancer Council of Queensland. 1,4 Qualification for Foundation support is determined by a formal application to the Eligibility Sub-Committee, which consists of the Founding Director who is a family general practitioner, a second family physician, a registered nurse and a consumer representative.
Since establishment in 2011, the Leila Rose Foundation has distributed funds of over AUD$825,000 to eligible families, largely to assist with day-to-day expenses so that the family can focus on their child and the management of their rare cancer. The financial support provided by the Foundation consists of two main tiers as follows: 1. Tier 1: $2,500 financial assistance with day-to-day bills and incidental expenses per year for 2 years from the date of acceptance.
2. Tier 2: Up to $10,000 for a limited number of recipients to support whole genome analysis or other tailored management approaches as deemed appropriate by the treating oncologist.
Over the past decade, a total of 6 families or 3% of all supported families have received Tier 2 funding for a total of AUD$51,000 representing 6% of total funds distributed.
As highlighted above, the Medical Research Futures Fund as part of the Australian government's Genomics Health Futures Mission initiative has relieved the need for support of genomic analysis more recently. 9 Many scientific reviews and analyses point to the impact of financial toxicity, on cancer outcomes in the United States of America and Australia. [10][11][12][13] While these analyses have focused mainly on adult cancer, Santacroce and Kneipp focused on the impact of financial toxicity in pediatrics and highlight the indirect impact on the affected child. 14 The Foundation has been mindful of the financial impact of a rare childhood cancer diagnosis on the family based upon the personal experience of the founding directors. Invariably, parents are required to take time away from work to care for their sick child and this adds to pressure and stress for the family as a whole. This appears to be particularly pronounced for many families located in rural and remote communities due to the need to attend large specialized metropolitan children's hospitals.
The Foundation's enrollment records for children diagnosed with a rare cancer are shown in Table 1. Due to the small numbers, and the fact that these data subsets do not represent true population-based frequencies, care must be taken when interpreting the data; however, there appear to be some interesting themes never-the-less.
In almost 10 years of enrollment, a total of 197 patients diagnosed with a rare childhood cancer have been accepted for support with an average age of 6 years at acceptance. idea that for these tumors at least, the period between diagnosis and enrolment with the Foundation is very short.
The remaining tumor types are generally associated with broader age ranges or the numbers are too small to draw out any themes.
The Foundation provides support for families in metropolitan as well as regional and rural areas. For the purpose of our analysis postcodes (Zip codes) outside of the major metropolitan boundaries across Australia are defined as "rural." As highlighted in Figure 1, the metropolitan: rural split for the Foundation-supported patients is 56% and 44% respectively. Rural and regional families have particular challenges as they are often located a long distance from the major citybased treatment centers and family members may be required to relocate or travel over long distances for treatment, assessment or ongoing management adding to the stress on the family unit as a whole.
It is estimated that 29% of the Australian population live in rural and remote areas. 18 Accordingly, the proportion of families provided with support by the Foundation is significantly above the population potential underlining the greater apparent level of need among rural and remote families. This observation requires further investigation to fully understand the needs and motivations at play.
Notwithstanding the above observations, there is no restriction on enrolment with the Foundation from an ethnic, socioeconomic or location-perspective. Enrollment is largely determined by the referring cancer center as long as the diagnostic and age-range criteria are met.

| Case study-a personalized medicine approach
In P1's specialists explained that this type of cancer was not responsive to chemotherapy and that the dose of radiation required to successfully treat his disease would significantly damage his heart.
Contrasting management alternatives of watch and wait against VAC chemotherapy were considered but subsequently dismissed by P1's parents in consultation with his medical team. 4.2 | Case study-assistance provided posttreatment when care needs were greatest Patient 2 (P2) is a three-year-old boy, who lives with his parents, and younger brother in metropolitan Melbourne. P2's mother began to notice that something was wrong with P2's vision, when they would play hide and seek. He would ask where his mother was when she was standing directly in front of him. He would also continuously run into walls and objects that were in plain sight, and when reading he was not able to discern pictures of his favorite characters in picture books. In a dimly lit room, his mother also noticed a white glow from his pupil. Concerned, P2's mother, took him to the local doctor where they suggested that he may be color blind or that he required glasses, so P2 was referred to an ophthalmologist. Following the doctor's appointment, that night P2 complained of a severe headache and so P2's mother took him to the Royal Children's Hospital, emergency room, where he saw a specialist pediatric ophthalmologist. The ophthalmologist requested a number of assessments and with those, P2 was confirmed as having severe bilateral retinoblastoma.
With the confirmation of his rare cancer diagnosis, P2's mother self-referred him to the Leila Rose Foundation via the Family Support Coordinator. His application was accepted. The Family Support Coordinator also put P2's mother in contact with some occupational therapy outlets that provided "hands-on," games and activities while the financial support offered by the Foundation helped the family to cover the cost of an indoor playset for P2, as well as the games and activities. These items not only helped to assist P2 in developing his fine motor skills but also taught him about colors while he still had vision. They were also delivered to P2's family in the midst of the 2020 Covid-19 pandemic, which meant that P2 and his younger brother had safe, indoor activities away from potential exposure to Covid-19. This was particularly important as P2 was immunocompromized as a result of his chemotherapy. His parents were extremely grateful for this support. His mother commented: "I'm so thankful to the Leila Rose Foundation for sending Gemma (the Family Support Coordinator) into our lives. Her advice, support, and just remembering the little details I once mentioned makes me feel like I matter. Knowing that I can always come to her has been a much-needed breath of fresh air!"

| Case study-support in the face of financial toxicity
Since the establishment of Leila Rose Foundation in 2011, it has become apparent that "financial toxicity" can have a profound negative impact on families affected by rare childhood cancer. This is why financial support with day-to-day expenses has been a focus of the Foundation's support from establishment.
In 2013, Patient 3 (P3) was a very petite, healthy young 6-year-old girl, however when she became unwell, she was rushed to the local regional hospital where she was found to have a mass on her brain.

| Case study-a second opinion
In a small number of cases the support provided by Leila Rose Foundation may include referring families to the "Best Doctors" network.
This process is undertaken with the acknowledgement and in collaboration with the child's treating specialist. The Best Doctors network is drawn upon when very little is known about the child's cancer or when treatment options are very limited. This approach is in line with the Foundation's philosophy of "leaving no stone unturned." The "Best Doctors" organization draws on a panel of medical opinion leaders from around the world that specialize in very specific health issues, in this case rare childhood cancer.
In early 2015, Patient 4 (P4) had just turned 14 and was thriving.
Her mother became concerned when she started to complain of back pain and took her to a local health center where routine x-rays discovered she suffered from scoliosis. P4 was then referred to an orthope- and her mother had peace of mind knowing that "no stone was left unturned" in P4's cancer battle.

| AN ONGOING FOCUS TO LEAVE NO STONE UNTURNED
The above cases, exemplify the diverse needs of a small number of families affected by rare childhood cancers. In Australia, Leila Rose Foundation and other cancer charities and associated services, support one another and collaborate where possible to achieve optimal patient outcomes from diagnosis to bereavement or survivorship. Although the Foundation's scope of practice is broad, there may at times be a readymade solution for a particular family's situation. It is the Family Support coordinator's role to source and recommend appropriate support services to ensure the best possible health and wellbeing outcomes.
Additional tier 2 funding has also been utilized in a small number of cases, whereby Leila Rose Foundation via the Family Support Coordinator, works in collaboration with the family's oncologist providing financial support for chosen management approaches, which may not be reimbursed under the Australian health system.
Unfortunately, despite the treating team and the Foundation's best efforts, approximately 25 Australian families with a child diagnosed with a rare cancer will be told that nothing can be done for their child in a given year. 4 One of the key roles of the Family Support Coordinator is to provide informal emotional and bereavement support, by providing an empathetic, listening ear or where appropriate referring onto psychological services and peer support groups.

| CONCLUSION
The diagnosis of a rare childhood cancer is a shattering experience for a family. The Leila Rose Foundation, through the Family Support Coordinator seeks to ensure that no stone is left unturned while reducing the financial pressures of day-to-day expenses that distract from the battle against the cancer that threatens their child's precious life. Rare childhood cancer by its very nature remains a difficult area for research, where the extremely small number of patients globally limits the scope for controlled studies. The outcome for many children diagnosed with childhood cancer has improved substantially over the past decade, however due to the small numbers and the lack of specific epidemiological data no conclusions can be drawn in terms of survival of children affected by rare cancers. 19 Notwithstanding this, overall survival rates are still low relative to more common cancers and the Foundation is committed to delivering its unique support services to families now and in the future with a view to reducing the burden on families and particularly with respect to the financial toxicity which often accompanies a rare childhood cancer diagnosis.