In early November, paediatrician Prof. Dr. Ruth Ladenstein, from the St. Anna Children’s Cancer Research Institute in Vienna, came to Ljubljana as a special guest. This calm, but purposeful and lucid woman has dedicated her entire professional life to neuroblastoma research. What is more, she endeavours to do everything possible at the European level to allow all children in Europe to have the same treatment opportunities for this severe disease. In pursuing this goal, she is persistent.
She came to Ljubljana to receive a special award granted by International Medis Awards for Medical Research. Together with an international group of researchers, she studied and demonstrated the safety and efficacy of dinutuximab beta immunotherapy as a first-line treatment in high-risk neuroblastoma patients. She was granted this award for an oncological study in children and adolescents with a rare cancer called neuroblastoma, conducted in 12 countries, 104 sites and 422 patients. This multicentre, randomised phase III clinical study was published in Lancet Oncology with IF 35.386, with Dr. Ladenstein as the leading author.
She researches therapies and makes them available to all who need them
Silent and modest, she answered our questions with great pleasure. That she was determined to pursue her mission was obvious from afar. Her presence here was much more than just about receiving the award: Dr. Ladenstein strives to ensure that all children in Europe have the same opportunities and access to the best neuroblastoma treatment. “Her work on neuroblastoma treatment would be enough by itself. In addition, she is also very active in the management board of the European Society for Paediatric Oncology, SIOPE, and is among the holders of the European Reference Network on Paediatric Cancer (ERN PaedCan) project, which aims to ensure accessibility to quality treatment for all children in the EU,” said Prof. Dr. Janez Jazbec, paediatric haematooncologist and head of the Haematology and Oncology Department at the Division of Paediatrics in Ljubljana, about the renowned paediatric oncologist.
Persistence and patience
“Dr. Ladenstein’s story is about persistence and patience,” says paediatrician Maja Česen Mazić from the Division of Paediatrics in Ljubljana, who also knows the Professor. Two years ago, the European Medicines Agency (EMA) approved the monoclonal antibody dinutuximab beta for the treatment of neuroblastoma in children. However, the development of this medicine was of a much longer duration, and Dr. Ladenstein was involved throughout, during production of the molecule, and as part of the group that went through all research phases. They finally succeeded after more than a decade, and they established a partnership for manufacturing the medicine.
“The first part of the development of this medicine was conducted with much help and effort provided by the parents of the children and various associations, and we raised the funds ourselves to begin the research. Across Europe, we managed to collect two million euros for the manufacturing and development of this medicine. We had a strong motivation: find a medicine that would provide a long-term cure. We wanted it to be taken over by the industry, which could gradually distribute it throughout Europe and give children more hope for a cure.”
We have to encourage paediatric oncological treatment
To raise as much funds as possible for the treatment of rare malignancies in children was somehow a logical mission. “We had to encourage the development of paediatric oncology. More than eighty per cent of medicines used in paediatric oncology are ‘off-label’. Development is mostly directed towards adult haematological pathologies, and paediatric cancer patients do not benefit much,” she said. Finding a medicine and making it available to all children suffering from this disease is a joint European mission, she added. They would like to broaden the accessibility of medicines, and according to the data on long-term cure and survival rates, the need for improved, effective medicines for paediatric use is extremely high, she highlights.
Fortunately, paediatric cancer is rare, but it encompasses around 60 different entities, so there is still much work left to do. “Only cooperation and collaboration will lead to achievements. One of the reasons I am here is to widen the European reference network of paediatric oncology, which strives to align treatment outcomes across Europe, so that all children have equal access to quality treatment,” said Dr. Ladenstein.
Dismal differences across Europe
Some countries in Europe have significantly worse treatment outcomes, with up to 20 per cent lower likelihood of survival. They lack both funding and professional treatment guidelines. “Currently, we are trying to introduce the protocol from clinical studies, obtain results and implement them into standard guidelines and protocols in countries in order to standardise treatment and management standards as well as offer help in putting them into effect,” she said.
In Europe, there is an ongoing study of high-risk neuroblastoma involving 24 European countries (plus Israel), with more than 3,500 children having been included over the 18 years. “Everything is ready for such a study. For regulatory reasons, full coverage is not available in all countries, which makes the enrolment of children more difficult,” she said.
Big problems with funding for accessibility of medicines
They were ready to face the differences between countries, she says, and were familiar with the circumstances in some countries. They had previously cooperated with many countries through providing training for physicians. There are certain factors in countries, she says, that are purely socio-economic in nature but cannot be controlled because they have to do with funding that is available to the country to make treatments accessible. “We are doing our best to enable them to get the most important, most innovative medicines. Knowledge must be spread, and treatment and care standards should be developed. And of course it is important to get politicians interested in investing in paediatrics and not ignore their needs,” she said.
“Cooperation between professionals and industry is a must, and Europe has all the legislative possibilities that will allow us to participate in the development of medicines. Our patients are waiting for us to find new treatment options. I believe this is worth it. The lesson I learned from this long story, which ended successfully, is that I would do it all over again. Hopefully, in cooperation, we will be able to do it more quickly,” she said.
Written by: Lucija B. Petavs, Editor-in-Chief of ‘Medicina danes’ journal.
Source: Medicina danes, Slovenia, November 2019.