A rare childhood cancer

Neuroblastoma, a rare children’s cancer, has a particularly low survival rate. Because its incidence is low, it is difficult to get the number of patients needed to run clinical trials and develop new treatments. Collaboration is key to overcoming this obstacle, between researchers, clinicians and patients from many different countries.

A recently completed clinical trial collaboration called SIOPEN High-Risk Neuroblastoma 1 launched in 2002 and involved 23 partner countries, of which the UK was an integral contributor.

The SIOPEN High-Risk Neuroblastoma 1 trial collaboration has been transformative. So far, the trials have found treatments that offer better survival rates for neuroblastoma, with treatment regimens that offer less toxicity than other drug treatments.

SIOPEN trial changing clinical practice around the world

This trial found that a European high-dose chemotherapy regime increased three-year event-free survival from 38% to 50% compared with an American dose schedule – and treatment toxicity was substantially reduced1. These findings are so impactful that they have already changed clinical practice around the world – including in countries such as the USA, that weren’t involved with the trial.

This trial, with essential contributions from UK researchers, has had a direct and dramatic impact on the survival rates for children with this type of cancer.

The design of the trials within SIOPEN have been innovative, being the first to use remote data entry and utilising a multi-arm, multi-stage design, before this trial type became common. This allowed the researchers to investigate many more questions and options than a simpler trial design. There is support for translational work to run alongside the trials; enabling the project to have a greater benefit for children with neuroblastoma and will bring new treatments and methods into practice sooner.

Collaboration is key

UK researchers involved in the SIOPEN collaboration are members of the NCRI’s Children’s Group. While the Children’s Group members are not the only researchers involved in the collaboration, the structure underpinning the NCRI Groups – bringing researchers together, giving them the space to discuss trials and problem-solve, and giving them the support in influencing trials – has been at the core of the high-quality contribution of the UK-based researchers to this work.

At the NCRI Groups, researchers participate in discussions about studies and the Group is a core structure with regards to the development, support and ultimate funding of clinical trials. Its involvement is essential for successful studies that benefit patients.

UK researchers involved in the SIOPEN collaboration are members of the NCRI’s Children’s Group.

Dr Mark Gaze is the past Chair of the Neuroblastoma Subgroup within the Children’s Group and is a SIOPEN researcher. He believes that collaboration has been at the heart of the project’s success, with the NCRI’s Children’s Group playing an integral role:

It is only fair to say that all these benefits have not come about simply because of the trial, but because of major international collaboration, including the USA and other parts of the world, as well as Europe. There are hundreds of scientists, clinicians from a wide range of specialties, and parents and charities working together to advance research into neuroblastoma. There is a lot more to the progress we have made so far than the NCRI’s Children’s Group, but it does play a very major part.

Following the successful completion of the first SIOPEN trial, a new trial: SIOPEN High-risk Neuroblastoma 2 has been developed, and is now open in France, the Sponsor nation. It is hoped that the trial will also open in the UK soon.


  1. Ladenstein, R et al (2017). Busulfan and melphalan versus carboplatin, etoposide, and melphalan as high-dose chemotherapy for high-risk neuroblastoma (HR-NBL1/SIOPEN): an international, randomised, multi-arm, open-label, phase 3 trial. Lancet Oncol. 2017 Apr;18(4):500-514.

doi: 10.1016/S1470-2045(17)30070-0