While some childhood cancers like leukaemia have seen improved outcomes, brain cancer remains a formidable challenge. Global collaboration is key to bridging survival gaps and advancing treatments.
Global collaboration is key to bridging survival gaps and advancing treatments of childhood brain cancer. Photo: Anna Shvets
Every day, more than 1,000 children across the world are diagnosed with cancer. Whether they live or die will depend on what type of cancer they have, how advanced it is, and—crucially—which country they live in. In high-income countries as many as 80% or more will survive, but in some low- and middle-income countries (LMICs) survival rates can be as low as 30%.
For children with better-understood cancers like leukaemia, pathways to treatment can be more straightforward. Others, like brain cancer, can be more difficult to cure. Even in a high-income country like the US, survival rates among children for more common brain cancers range from as high as 95% to as low as 20%.
The World Health Organization’s Global Initiative for Childhood Cancer (GICC), which launched in 2018, aims to improve the survival rate of children, increasing it to at least 60% by 2030. More than eight in 10 children are cured when they receive the best available treatment and care.
For children with brain cancer, global collaboration and the development of new treatments can provide hope and offer the potential for improved survival rates and a better quality of life.
Charting success curing childhood leukaemia
A standout success story in childhood cancer treatment has been the transformation of survival rates for children with some types of childhood acute lymphoblastic leukaemia (ALL), which accounts for one third of all childhood cancers.
Five-year survival rates (the percentage of a patient group that is alive five years after diagnosis) for ALL are now more than 90%, and approaching 100% in some high-income countries. So impressive are advancements in treatment and care that the disease has been described as “one of the most curable human cancers”.
Dr Simon Ridley, director of research and advocacy at Leukaemia UK, says some of the most significant advances in ALL treatment include the use of bone marrow transplants, which were first introduced in the 1970s, and tyrosine kinase inhibitors, a type of targeted chemotherapy that keeps cancer cells from growing. One of the newest, most promising treatments is chimeric antigen receptor (CAR) T-cell therapy, which uses immune cells called T cells that are genetically altered to destroy cancer cells more effectively.
“There’s been a lot of research into leukaemia and we now have a greater understanding of it. We have seen the benefits of investment in academic science and clinical trials,” Ridley says.
Part of the success is attributed to the tractability of leukaemia. “Some cancers are far less tractable,” Ridley says. Cost and ease of diagnosis also play a part; Ridley explains that leukaemia can be diagnosed with a cheap, full blood count test.
But these success rates are far from universal across the globe. CONCORD, a programme run by the London School of Hygiene & Tropical Medicine to surveil cancer survival trends, published the study CONCORD-3 in 2022. The study looked at survival rates for all leukaemias in 160,000 children, adolescents, and young people between 2000 and 2014 from 258 population-based cancer registries in 61 countries, and found huge variations between different countries and age groups. Five-year survival rates for ALL in children, adolescents, and young adults ranged from 43% in Ecuador to more than 80% in parts of Europe, Oceania, Asia, and North America. Survival rates were found to be higher in children than in adolescents and young adults.
Dr Georgia Papacleovoulou, head of policy and advocacy at Leukaemia UK, says challenges remain in LMICs. “Some of [these discrepancies] can be explained by lack of healthcare infrastructure; for example, in high-income countries we have specialist paediatric oncology hospitals, whereas this won’t be the case in some LMICs,” he says. “There may also be differences in access to treatments and speed of diagnosis.”
Brain cancer treatment challenges
The same cannot be said, however, for another of the most common childhood cancers: brain cancer, which remains the biggest cancer killer of children and people under 40.
Dr Dominik Sturm, clinician scientist in paediatric glioma research at Hopp Children’s Cancer Centre Heidelberg (KiTZ) in Germany, says slower progress in improving cure rates for paediatric brain tumours compared to other childhood cancers like leukaemia can be attributed to several key challenges.
"Unlike leukaemia, where certain types have shown significant responsiveness to specific treatments, brain tumours often require highly individualised approaches."
“These include the fact that brain tumours are biologically extremely diverse, and we have only recently successfully started to unravel their biological complexity and heterogeneity,” he says. “This diversity makes it challenging to develop a one-size-fits-all treatment. Unlike leukaemia, where certain types have shown significant responsiveness to specific treatments, brain tumours often require highly individualised approaches.”
Sturm says successful treatment is also often complicated by the location of tumours, with tumours in certain parts of the brain difficult or impossible to remove surgically without causing severe neurological damage.
“In contrast, leukaemia, being a blood cancer, doesn't face these anatomical challenges,” he says, explaining that the blood-brain barrier prevents many drugs from entering the brain tissue, making it difficult to deliver effective therapy to brain tumours. “Whereas leukaemia cells are directly accessible to treatments circulating in the bloodstream,” Sturm says.
Brain cancer remains the biggest cancer killer of children and people under 40. Photo: Tima Miroshnichenko
The brain is a highly sensitive and complex organ, and this also limits the intensity and types of treatments that can be safely administered. “In leukaemia, treatment regimens have long been refined to balance effectiveness with manageable side effects—advances that are harder to achieve in brain tumours,” Sturm adds.
How AI-assisted classification can help
One of the key steps to better treatment of childhood brain tumours is diagnosing the type of tumour as precisely as possible.
In 2018, researchers at KiTZ launched a new type of AI-assisted classifier, which analyses methylation patterns in brain tumours. It is hoped that the AI-based approach can significantly improve precision diagnostics for children and adolescents with brain tumours.
The team at KiTZ have made their AI algorithm available so researchers all over the world can compare their tissue samples with 100,000 others stored on the system.
Dr Felipe D’Almeida Costa, a cancer pathologist at the AC Carmago Cancer Center in Sao Paulo, Brazil, uses the KiTZ database. He says it helps children in Brazil receive more accurate diagnoses and have a better chance of survival.
“We have only around 300 pathologists in Brazil, with only 50 specialising in cancer diagnostics. This often means patients face a two- to four-month delay between presenting to their doctor and getting a diagnosis,” D’Almeida Costa says.
“In this chaotic scenario we need initiatives that can give more patients better access to improved diagnostic tools, and this is why we signed up to use the KiTZ system.”
Sturm says it is an approach he hopes to see replicated across the world. “Finding ways to globally disseminate and sustain DNA methylation profiling, as part of routine neuropathological assessment for all newly diagnosed brain tumours in children and adolescents, needs to be one of our immediate goals,” he says.
Brain tumour research breakthroughs
Compared to leukaemia, scientific breakthroughs in brain cancer treatment “take proportionally more funding” because they “require more specialities working together”, says Professor Darren Hargrave, a consultant at Great Ormond Street Hospital, London, researcher at University College London, chair of the UK’s Children’s Cancer Group, and medical adviser to The Brain Tumour Charity.
He says the UK’s National Institute for Health and Care Research (NIHR) and the Tessa Jowell Brain Cancer Mission announced £40 million (US$51.8 million) funding for brain tumour research earlier this year. The NHS has also invested in proton beam therapy centres in London and Manchester to deliver more targeted radiotherapy, which causes less collateral damage to healthy tissue in the brain.
The discovery of the BRAF gene’s role in skin cancer in 2002 and later the specific role it plays in some brain tumours has also led to the development of targeted oral chemotherapy drugs which are able to cross the blood-brain barrier. These are now used to treat children with BRAF-mutated gliomas. Gliomas are the most common type of brain cancer in children and young people.
Hargrave’s research, which was published in the New England Journal of Medicine in 2023 using a combination of two targeted therapies called dabrafenib and trametinib, found the treatment was four times more effective than conventional chemotherapy with half the side effects.
"A lot of patients are cured of brain cancer now even though there is a huge number of different types of brain tumours."
CAR T-cell therapies used for leukaemia are also being used in trials to treat some brain tumours. For children with diffuse intrinsic pontine glioma (DIPG), a rare, fast-growing and malignant brain tumour where survival has not improved in 30–40 years, international collaboration is crucial.
“Some of the methods being discussed include implanting micro-catheters directly into the tumours to deliver drugs and using ultrasound waves to create micro-bubbles that temporarily open up the blood-brain barrier,” Hargrave says, “so chemotherapy drugs can pass across more easily and we don’t have to use such large doses.”
For many children with brain cancer, these developments are transformative. “A lot of patients are cured of brain cancer now even though there is a huge number of different types of brain tumours,” Hargrave says.
Indeed, they highlight a significant issue that will continue to be a focus of future research: post-treatment quality of life.
“One of the big problems is the neurological deficits that children are left with from conventional treatments such as surgery, including learning and speech difficulties and inability to walk, which in some cases can leave them unable to live independently,” Hargrave says.
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