Ruth Ladenstein Group

Ruth Ladenstein Group

Ruth Ladenstein
Email: ruth.ladenstein(at)ccri.at

Studies & Statistics for Integrated Research and Projects

We conduct Therapy Optimization Studies (TOS) to guarantee better chances of survival of children and adolescents with cancer.

Team

Background

As the clinical trial unit within the Children’s Cancer Research Institute (CCRI), the Studies and Statistics for Integrated Research and Projects (S2IRP) team is focused on enabling better outcomes for children and adolescents suffering from acute lymphoblastic leukemia, Langerhans cell histiocytosis, and high risk neuroblastoma. In addition, several pediatric hematological diseases are at the center of attention of the S2IRP team, which is understood as an essential link between the CCRI laboratory research activities and the clinical application of trials at the St. Anna Children’s Hospital.

Our research

S2IRP aims at enabling GCP-compliant clinical research by designing, running and analyzing academic clinical trials in the target population. The unit’s portfolio includes investigator-driven clinical trials (IDCTs), cancer subtype registries, close collaborations with the Innovative Therapies for Childhood Cancer Consortium (ITCC) and its early phase trials as well as interactions with pharmaceutical companies to develop further childhood cancer therapeutics.

The importance of data collection

Data collection and evaluation are vital aspects of cancer research. In total, the S2IRP has registered data from more than 9,000 patients for national and international pediatric clinical studies revolving around Langerhans’ cell histiocytosis (study centre of LCH trials I, II, III), neuroblastoma (study centre of the European High Risk Neuroblastoma Study HR-NBL-1/SIOPEN), and stem cell transplantation of acute lymphoblastic leukaemia (study centre of the international ALL-SCT Study). Trial and registry data enable publications on clinical and translational research results, which is a paramount scientific objective.

Standardized operating procedures

S2IRP is supported by CCRI‘s quality management team. Together they have developed standard operating procedures. According to these, monitoring is provided through central monitoring as well as S2IRP monitors. All pharmacovigilance tasks are carried out by dedicated personnel, who tracks and reports severe adverse events (Suspected Unexpected Serious Adverse Reactions, SUSAR) in ongoing clinical trials to the responsible authorities on a national and European level, and drafts the annual clinical trial safety report.

Collaboration is key

S2IRP’s work relies on the support of and close collaboration with international clinical trial groups and research communities. Together they aim at a better understanding of new disease profiles, development of stratifying diagnostic markers to facilitate optimized and risk-adapted treatments with traditional chemotherapy as well as innovative drugs.

Projects

National projects

  • AGPHO: Ruth Ladenstein coordinates the Austrian Working Group for Pediatric Hematology-Oncoloy (AGPHO), in particular the group’s activities in relation to the biannual meetings held to share recent and updated results of past and active trials and registries relevant for Austrian investigators. S²IRP enables sharing of ongoing clinical trials in the field of hemato-oncology in Austria and their relevant up-to-date documents for daily practice.
  • OKIDS: The Medicines for Children Research Organization (OKIDS) coordinates numerous tasks by networking the five Austrian university sites and the St. Anna Children’s Hospital through a national headquarters. The overarching aim is to increase availability of appropriate medicines for young patient groups. OKIDS provides study nurse capacity to its respective sites to foster industry-led and academic drug development for children and works closely with the sites’ leadership. As such, it also supports S2IRP trials in need of study nurse capacity at the St. Anna Children’s Hospital. OKIDS responds to feasibility requests and supports set up and management of clinical trials. Since its initiation, it has run 130 feasibilities and supported 220 trials and registries with over 700 children recruited. In addition, OKIDS aims to raise public awareness through dissemination & educational activities.

International projects

  • SIOPEN: The Society of Pediatric Oncology Europe Neuroblastoma Group (SIOPEN) fosters neuroblastoma research and enables long-term sustainability of the group. Currently, the SIOPEN association has 432 active members in 34 countries. A total of 29 countries are involved in SIOPEN studies.
  • Other international projects: European Expert Paediatric Oncology Reference Network for Diagnostics and Treatment (ExPO-r-Net, https://www.expornet.eu/), European Reference Network on Paediatric Cancer (ERN PaedCan, https://paedcan.ern-net.eu/), European Reference Network on Paediatric Cancer Connecting Facility (ERN-PaedCan-CEF, CEF-TC-2018-4 - eHealth), Paediatric Rare Tumours Network - European Registry (PARTNER, https://www.raretumors-children.eu/partner-project/), Predictive In-silico Multiscale Analytics (PRIMAGE, H2020-SC1-DTH-2018-2020), European Joint Programme on Rare Diseases (EJP RD, https://www.ejprarediseases.org/), Integrated and Standardized NGS Workflows for Personalised Therapy (INSTAND-NGS4P, https://www.instandngs4p.eu/), Optimized Diagnostics for Improved Treatment Stratification in Invasive Fungal Diseases (FUNGITECT, FP7-HEALTH.2013-INNOVATION-1), Collaborative Network for European Clinical Trials For Children (conect4children) (OKIDS project, http://okids-net.at/), Twinning in Research and Education to improve survival in Childhood Solid Tumours in Lithuania (TREL, H2020-EU.4.b.).

 

 

Selected Articles

  • Bellini A*, Pötschger U*, Bernard V, Lapouble E, Baulande S, Ambros PF, Auger N, Beiske K, Bernkopf M, Betts BR, Bhalshankar J, Bown N, de Preter K, Clément N, Combaret V, Font de Mora F, George SL, Jiménez I, Jeison M, Marques B, Martinsson B, Mazzocco K, Morini M, Mühlethaler-Mottet A, Noguera R, Pierron G, Rossing CM, Taschner-Mandl S, Van Roy N, Vicha A, Chesler L, Balwierz W, Castel V, Elliott M, Kogner P, Laureys G, Luksch R, Malis J, Popovic-Beck M, Ash S, Delattre O, Valteau-Couanet D, Tweddle DA**, Ladenstein RL**, Schleiermacher G**. Frequency and prognostic impact of ALK amplifications and mutations in the European Neuroblastoma Study Group (SIOPEN) high-risk neuroblastoma trial (HR-NBL1) J Clin Oncol 2021, June 11. DOI: 10.1200/JCO.21.00086. https://ascopubs.org/doi/abs/10.1200/JCO.21.00086
    * Both authors contributed equally to this work and are to be considered as joint first authors
    ** All 3 authors contributed equally to this work and are to be considered joint senior authors
  • Garaventa A, Poetschger U, Valteau-Couanet D, Luksch R, Castel V, Elliott M, Ash S, Chan GCF, Laureys G, Beck-Popovic M, Vettenranta K, Balwierz W, Schroeder H, Owens C, Cesen M, Papadakis V, Trahair T, Schleiermacher G, Ambros P, Sorrentino S, Pearson ADJ, Ladenstein RL. Randomised trial of two induction therapy regimens for high-risk neuroblastoma HR-NBL1.5 International Society of Paediatric Oncology European Neuroblastoma Group Study Journal of Clinical Oncology 2021, June 21. Doi: 10.1200/JCO.20.03144, https://ascopubs.org/doi/abs/10.1200/JCO.20.03144
  • Holmes K, Pötschger U, Andrew D. J. Pearson ADJ; Sarnacki S, Cecchetto G,Gomez-Chacon C, Squire R, Freud E, Bysiek A, Matthyssens LE, Metzelder M, Monclair T, Stenman J, Rygl M, Rasmussen L, Joseph JM, Irtan S, Avanzini S, Godzinski J, Bjornland K, Elliott M, Luksch R, Castel V, Ash S, Balwierz W, Laureys G, Ruud L, Papadakis V, Malis J, Owens C, Schroeder H, Beck-Popovic M, Trahair T, Forjaz de Lacerda A, Ambros PF, Gaze MN, McHugh K, Valteau-Couanet D, Ladenstein RL, for the International Society of Paediatric Oncology Europe Neuroblastoma Group (SIOPEN). Influence of Surgical Excision on the Survival of Patients With Stage 4 High-Risk Neuroblastoma: A Report From the HR-NBL1/SIOPEN Study Journal of Clinical Oncology, 8. Juli 2020. https://doi.org/10.1200/JCO.19.03117
  • Ladenstein R, Pötschger U, Pearson ADJ, Brock P, Luksch R, Castel V, Yaniv I, Papadakis V, Laureys G, Malis J, Balwierz W, Ruud E, Kogner P, Schroeder H, de Lacerda AF, Beck-Popovic M, Bician P, Garami M, Trahair T, Canete A, Ambros PF, Holmes K, Gaze M, Schreier G, Garaventa A, Vassal G, Michon J, Valteau-Couanet D; SIOP Europe Neuroblastoma Group (SIOPEN). 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 2017.18(4):500-514. [https://pubmed.ncbi.nlm.nih.gov/28259608/]
  • Viprey V, Gregory WM, Corrias MV, Tchirkov A, Swerts K, Vicha A, Dallorso S, Brock P, Luksch R, Valteau-Couanet D, Papadakis V, Laureys G, Schreier G, Pearson AD, Ladenstein R, Burchill S. Neuroblastoma mRNAs predict outcome in children with stage 4 neuroblastoma: a European HR-NBL1/SIOPEN study. J Clin Oncol. 2014 Apr 1;32(10):1074-83. [https://pubmed.ncbi.nlm.nih.gov/24590653/]

S²IRP

Univ.-Prof. Dr. Ruth Ladenstein (MD) MBA, cPM, Head of S2IRP Email: ruth.ladenstein(at)ccri.at

Mag. Anke Emberger, Senior Operations Manager Email: anke.emberger(at)ccri.at

Ulrike Pötschger,  PhD, Teamleader Statistics Email: ulrike.poetschger(at)ccri.at

Scientific Assistant, Scientific Assistant*: Claudia Zeiner, MSc Statisticians: Ulrike Pötschger, PhD, teamleader statistic l Evgenia Glogova, MSc, statistician (maternal leave) l Helga Björk Arnadottir, MSc, statistician l Paulina Kurzmann, MSc, statistician  Leukaemia and Lymphoma Studies Dipl.-Ing. Adnan Becirovic, CRA, l Ekaterina Werderits, CRA l Corinne Grafl, CRA l Nora Mühlegger, MSc, CRA l Marek Nykiel, CRA l Assoc. Prof. Georg Mann, MD, CC** (ALL and Lymphoma Studies) l Assoc. Prof. Andishe Attarbashi, MD, CC (ALL and Lymphoma Studies) l Assoc. Prof. Michael Dworzak, MD, CC (AML, MDS, CML Studies) Studies in Solid Tumours Jenny Mader, PhD, CRA l Ljubica Mandic, MSc, CRA l Markus Mair, PhD, CRA l Eva Sorz, CRA l Univ. Prof. Ruth Ladenstein, MD, MBA, cPM, CC (Neuroblastoma, Soft Tissue Tumours, Ewing Sarcoma) l Assoc. Prof. Leo Kager, MD, CC (Osteosarcoma, Nephroblastoma)

LCH-Studies Elfriede Thiem, MSc, CRA l Prof. Milen Minkov, MD, CC Stem Cell Transplantation Studies Tijana Frank, MD, MScEng, CRA l Susanne Karlhuber, PhD, CRA l Barbara Kristufek, CRA l Dr. Herbert Pichler, MD (Allogeneic Stem Cell Transplantation) l Prof. Christina Peters, MD, CC (Allogeneic Stem Cell Transplantation) l Univ. Prof. Ruth Ladenstein, MD, MBA, cPM, CC (Autologous Stem Cell Transplantation) Phase I/II/III Studies Sponsored by the Pharmaceutical Industry Assoc. Prof. Michael Dworzak, MD, CC l Univ. Prof. Ruth Ladenstein, MD, MBA, cPM l Prof. Christina Peters, MD, CC *CRA: Research and Study Assistant **CC: Clinical Studies Leader and Collaborator

About the Clinical Trials Unit S²IRP

Collecting and evaluating patient data is of utmost importance for clinical trials. In total, the S2IRP has registered data from more than 9,000 patients. International studies focus on the fields of Langerhans’ cell histiocytosis (study centre of LCH trials I, II, III), neuroblastoma (study centre of the European High Risk Neuroblastoma Study HR-NBL-1/SIOPEN) and the stem cell transplantation of acute lymphoblastic leukaemia (study centre of the international ALL-SCT Study). Activities of the S2IRP/Coordinating Centre for paediatric-oncological trials. The Clinical Trial Unit has been developed and trained towards the necessary  expertise and manages the full scope of tasks as required according to GCP and European Directives as well as national legal requirements (AMG [Arzneimittelgesetz] - Austrian Pharmaceuticals Act). For more details, please visit the S2IRP section.

Affiliated Clinicians

Assoc. Prof. Dr. Andishe Attarbaschi, MD Assoc. Prof. Dr. Leo Kager, MD Assoc. Prof. Dr. Georg Mann, MD Univ. Prof. Dr. Milen Minkov, MD Univ. Prof. Dr. Christina Peters