SIOPEN High-Risk Neuroblastoma Study 2: Progress Update
As of May 2026, the SIOPEN High-Risk Neuroblastoma 2 (HR-NBL2) Trial continues to make strong progress across Europe, with UK centres playing a leading role in this important international study.
We spoke with our Trustee, Martin Elliott, UK Principal Investigator for the trial, to learn more about the latest developments.
A Truly International Effort
"The trial is sponsored and centrally coordinated by Institut Gustave Roussy in Paris and is currently recruiting in 17 countries," explains Martin. "In the UK, 20 of 21 children's oncology centres are now open and recruiting patients."
Since opening in 2020, recruitment has remained firmly on target, with almost 800 patients enrolled internationally. The UK has become the second-highest recruiting country, highlighting the commitment of families, clinicians and researchers across the country.
The study is expected to continue recruiting until at least the end of 2028, ensuring sufficient data can be collected to answer some of the most important questions in high-risk neuroblastoma treatment.
Expanding Treatment Opportunities for Children
One of the most significant developments came in 2023, when the trial was amended to offer an intensified treatment pathway for children whose disease does not respond adequately to initial chemotherapy.
This pathway provides access to:
Combined chemotherapy and immunotherapy using dinutuximab-beta, an approach that has shown encouraging evidence of increased effectiveness in chemotherapy-resistant disease.
Tandem (double) high-dose chemotherapy, designed to maximise treatment response and reduce the risk of disease progression or relapse.
Importantly, these treatment options are not routinely available in the UK outside of participation in the clinical trial, meaning the study is helping to provide access to promising therapies while generating valuable evidence for the future.
Strong Recruitment Across Key Research Questions
Alongside evaluating new treatment approaches, the trial continues to investigate several important questions about how best to treat high-risk neuroblastoma.
Recruitment is progressing particularly well in studies examining:
Whether a single or tandem high-dose chemotherapy procedure offers better long-term outcomes.
Whether an additional radiotherapy boost benefits patients whose primary tumour cannot be completely removed through surgery.
The radiotherapy study is recruiting even better than originally anticipated, while recruitment to the tandem high-dose chemotherapy comparison continues steadily across participating countries.
As with all major international clinical trials, patients need to be treated and followed up over several years before reliable results can be reported. The safety and toxicity data is continually reviewed by an independent safety monitoring committee.
Learning from Every Part of the Trial
The study also included a comparison of two induction chemotherapy regimens: Rapid COJEC and the German GPOH regimen.
Although this part of the trial closed earlier than planned because a key drug used in the GPOH treatment became unavailable, data from the patients who were recruited will still be analysed and will contribute valuable information to the wider understanding of treatment approaches.
Looking Ahead: Precision Medicine and ALK-Targeted Therapy
Another exciting development is expected later in 2026, with plans to introduce a further amendment investigating the use of ALK inhibitors for children whose tumours carry abnormalities in the ALK gene.
Approximately 10–15% of children diagnosed with neuroblastoma have ALK gene alterations, which are associated with a higher risk of treatment resistance or relapse.
All newly diagnosed neuroblastoma samples in the UK are already tested for ALK abnormalities through the Neuroblastoma Central Reference Laboratory in Newcastle. The proposed amendment will explore whether introducing targeted ALK inhibitors as part of first-line treatment can improve outcomes for this group of patients.
Like the intensified treatment pathway, these targeted therapies are not routinely available outside of a clinical trial setting.
Building the Evidence for Better Treatments
While final trial results remain several years away, the study continues to reach important milestones and expand opportunities for children with high-risk neuroblastoma.
The knowledge gained from this research will help shape future treatment approaches and builds on decades of progress achieved through international clinical trials. Improvements in survival and outcomes over the last 20 years have been driven largely by research studies such as this one.
"We remain extremely grateful to the patients and families participating in this research, to the clinical teams delivering the trial, and to the funding charities that have made this work possible."
Martin Elliott
UK Principal Investigator – SIOPEN High-Risk Neuroblastoma 2 Trial
