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According to the World Health Organization, around 400 000 children and adolescents develop cancer every year. Survival rates in high-income countries can be as high as 80 %.
Yet “in Lithuania, survival rates are 10-20 % below the European average,” notes Jelena Rascon, project coordinator of the EU-funded TREL project. “With only around 80 new child cancer cases annually, it is difficult to develop the clinical expertise these children deserve.”
A lack of investment in Lithuanian oncology infrastructure has also resulted in few researchers and reduced transnational knowledge sharing opportunities.
To turn things around, TREL has twinned 10 multidisciplinary teams (comprising 32 specialists) from Vilnius University Hospital Santaros Klinikos (VULSK, the project coordinator) with nine specialist international research partners.
“This has increased our capacity to initiate our own research, run clinical trials and, ultimately, treat cancer more effectively,” says Rascon. “Partners have also said their own knowledge has benefited from reviewing our cases and learning of our challenges.”
Delivering better diagnoses
TREL focused on solid cancerous tumours – which occur in many parts of the body – selecting those most common in children.
VULSK researchers joined European paediatric oncology groups working on paediatric brain tumours (SIOP-BTG), neuroblastoma (SIOPEN) and renal tumours (SIOP- RTSG), with nine professionals participating in various knowledge transfer activities.
After training on renal tumour sampling, biobanking and biomarker interpretation at the Princess Máxima Center in the Netherlands, VULSK doctors are now contributing to the international SIOP UMBRELLA paediatric study.
Additionally, a VULSK molecular biologist was seconded to the Austrian Children’s Cancer Research Institute (CCRI) in Vienna to learn about liquid biopsy techniques, molecular diagnostics and sample handling. This has enabled VULSK researchers to start sampling neuroblastoma (cancer that develops in immature nerve cells) material from blood and bone marrow, to detect tumour biomarkers.
“We previously had to send serum samples from our neuroblastoma patients away for analysis, now we are developing the capacity to do this ourselves,” remarks Renata Blackutė, VULSK project manager.
Revolutionising risk profiling
A key TREL goal is to develop the bioinformatics expertise needed for whole genome sequencing (WGS), which can identify individuals and families susceptible to cancer and so inform clinical decisions.
As a result of twinning activities and a secondment with Rigshospitalet in Copenhagen, Denmark, the team are currently developing bioinformatics standard operating procedures at VULSK, while continuing to advance their sequencing capability.
“While we are currently only performing WGS in research studies, we are running whole exome sequencing, which sequences the protein-coding regions of genes, for diagnostics. This has already picked up rare genetic variants in our patients, and TREL’s transnational expertise has helped us evaluate their risk,” says Blackutė,
“Additionally, asymptomatic at-risk relatives have been tested. For those with variants, surveillance recommendations were provided,” she adds.
The team are planning to use WGS in diagnostics in the near future.
Meanwhile, a pathologist from Lithuania was seconded to the University Medical Center Hamburg-Eppendorf in Germany to be trained on modern neuropathological techniques, such as methylation arrays which genetically classify tumours. This helps predict likely response to treatment.
“Now, central nervous system cancer patients treated at VULSK routinely have their biopsied tumours assessed using these techniques, and we plan to roll it out to other tumour types,” says Blackutė.
Towards more effective treatments
VULSK pharmacists and oncologists were also seconded to Rigshospitalet to receive training on cytostatic drugs for children, including: how to administer them, the facilities needed and the associated regulations.
The team have subsequently implemented standard operating procedures for the administration of the drug, busulfan, already in use in clinical practice and to be used in upcoming clinical trials. To date, five agreements have been signed to initiate three international multicentre clinical trials and two observational studies.
Additionally, prompted by the results of a national survey and after training with the Princess Máxima Center, VULSK is developing fertility care plans which include using in vitro technologies to retransplant cancer-free ovarian tissue into survivors of cancer.
Already bearing benefits
TREL’s objectives align well with Europe’s Beating Cancer Plan, especially its ‘Helping Children with Cancer’ initiative, as well as the European Cancer Mission’s science-based approach toward reducing cancer burden and inequities across the EU.
Indeed, two cancer Survivorship Passports have already been issued to children and outline their post-cancer care plan. Available in several languages, these ensure continuity of care across borders.
“Best of all, 32 children have benefited from the expertise of international multidisciplinary teams, resulting in individual treatment recommendations. This has really inspired confidence in the quality of care provided by Lithuanian professionals,” concludes Rascon.