In a worldwide cooperation, scientists of the St. Anna Children's Cancer Research Institute (CCRI) and St. Anna Children´s Hospital have gained new insights into how to increase the survival rate in the high-risk form of neuroblastoma, the most common solid tumor in early childhood. Within a multimodal treatment approach, the complete surgical excision of the tumor is an important element in improving the survival of small cancer patients. This remarkable study was published in the Journal of Clinical Oncology.
Neuroblastoma is the most common tumor in infants and toddlers and develops from immature cells of the sympathetic nervous system. The special feature of this form of cancer is its variability. There are very mild forms that are closely monitored but require little or no treatment. However, there are also high-risk variants in which all available forms of therapy must be used to give the child the best possible chance of survival. Thanks to close cooperation between researchers and clinicians, neuroblastomas can now be identified and diagnosed quickly and reliably. However, there is still an urgent need for action, particularly in the high-risk form of neuroblastoma. This applies not only to research into the causes of the disease, but also to the selection of the most promising therapy combinations. Because of its dangerous nature, high-risk neuroblastoma is treated with a multimodal approach using all available means, including chemotherapy, surgery, radiation and immunotherapy. Nevertheless, it is still unclear how individual therapy factors influence survival.
In an international study led by Prof. Dr. Ruth Ladenstein and Dr. Ulrike Pötschger from St. Anna Children´s Cancer Research Institute and St. Anna Children´s Hospital, and recently published in the scientific "Journal of Clinical Oncology", the surgical aspect of a multimodal high-risk neuroblastoma therapy in relation to the other forms of therapy has now been successfully examined.
Experts from 128 medical centers in 18 different countries observed a total of 1,531 high-risk childhood neuroblastoma patients over more than six years. Considering the rarity of childhood cancers, this considerable number of patients is remarkable in that it allows for a highly reliable statistical analysis of the results and thus enables clear new therapy recommendations. The cancer patients in this study received induction chemotherapy, surgical interventions and high-dose chemotherapy with stem cell infusion in a selected order depending on the clinical course, followed by local radiotherapy and, if already available, immunotherapy. The focus of this study was to determine the influence of surgical intervention on the survival of high-risk neuroblastoma patients.
The surgical resection of a neuroblastoma is a very difficult procedure. Due to the nature of the tumor, it is not always completely successful and numerous factors such as the localization of the tumor and the preservation of important organs such as the kidneys for the subsequent high-dose chemotherapy must be taken into account. Therefore, the question arises whether the highly complicated complete macroscopic removal of the tumor has an advantage over incomplete tumor resection.
"Our analysis has clearly shown that the goal must continue to be the complete surgical removal of the tumor within the current complex standard therapy concept in order to improve the survival of these childhood cancer patients," said Univ. Prof. Dr. Ruth Ladenstein.
The results of the study showed that there is a significantly higher overall (OS) survival both with and without immunotherapy. With the immunotherapy, also developed in collaboration with the St. Anna Children's Cancer Research Institute, and macroscopic removal of the primary tumor, more than 50% of children now survive for more than 5 years, whereas about two decades ago, only about 10% of children were observed to have a longer survival. From this, it can be seen that through the concerted application of research innovation and therapy optimization in a clinical research concept, decisive improvements can be achieved in large international studies.
Influence of Surgical Excision on the Survival of Patients With Stage 4 High-Risk Neuroblastoma: A Report From the HR-NBL1/SIOPEN Study
Keith Holmes*, ChM, DCH; Ulrike Potschger*, MSc; Andrew D. J. Pearson, MD; Sabine Sarnacki, MD; Giovanni Cecchetto, MD; Javier Gomez-Chacon, MD; Roly Squire, MBBS; Enrique Freud, MD; Adam Bysiek, PhD; Lucas E. Matthyssens, MD; Martin Metzelder, MD, PhD; Tom Monclair, MD, PhD; Jakob Stenman, MD, PhD; Michal Rygl, PhD; Lars Rasmussen, MD; Jean-Marc Joseph, MD, PhD; Sabine Irtan, MD, PhD Stefano Avanzini, MD; Jan Godzinski, MD, PhD; Kristin Bjornland, PhD; Martin Elliott, MBChB, PhD; Roberto Luksch, MD; Victoria Castel, MD, PhD; Shifra Ash, MD; Walentyna Balwierz, MD, PhD; Genevieve Laureys, PhD, MD; Ellen Ruud, PhD; Vassilios Papadakis, MD, PhD; Josef Malis, MD; Cormac Owens, MBBS; Henrik Schroeder, MD, DrMedSci; Maja Beck-Popovic, MD; Toby Trahair, MBBS, PhD; Ana Forjaz de Lacerda, MD, MSc; Peter F. Ambros, PhD; Mark N. Gaze, MD; Kieran McHugh, MB, BCh; Dominique Valteau-Couanet, MD, PhD; and Ruth Lydia Ladenstein, MD, PhD for the International Society of Paediatric Oncology Europe Neuroblastoma Group (SIOPEN). Journal of Clinical Oncology, 8. Juli 2020. https://doi.org/10.1200/JCO.19.03117
(*, K.H. and U.P. share 1st authorship)
Supported in part by European Commission 5th Framework Grant No. QLRI-CT-2002-01768 (SIOPEN-R NET www.siopen-r-net.org), and Pierre Fabre Medicament provided free drug supply of Busilvex. M.N.G. is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre.
Clinical Trial Information:
NCT01704716 and EudraCT 2006-001489-17
Picture f.l.t.r: Dr. Ulrike Pötschger und Univ.-Prof. Dr. Ruth Ladenstein, CCRI