Daniel A Morgenstern1,2, Ulrike Pötschger3, Lucas Moreno4, Vassilios Papadakis5, Cormac Owens6, Shifra Ash7, Claudia Pasqualini8, Roberto Luksch9, Alberto Garaventa10, Adela Canete11, Martin Elliot12, Aleksandra Wieczorek13, Geneviève Laureys14, Per Kogner15, Josef Malis16, Ellen Ruud17, Maja Beck-Popovic18, Gudrun Schleiermacher19, Dominique Valteau-Couanet8, Ruth Ladenstein20. 1. Paediatric Haematology/Oncology, Hospital for Sick Children and University of Toronto, Toronto, Canada. 2. Paediatric Haematology/Oncology, Great Ormond Street Hospital and UCL Institute of Child Health, London, UK. 3. Studies and Statistics on Integrated Research and Projects, St Anna Kinderkrebsforschung, Vienna, Austria. 4. Paediatric Haematology/Oncology, Hospital Nino Jesús, Madrid, Spain. 5. Paediatric Haematology/Oncology, Agia Sofia Children's Hospital, Athens, Greece. 6. Paediatric Haematology/Oncology, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland. 7. Paediatric Haematology/Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel. 8. Department of Paediatric and Adolescent Oncology, Institut Gustav Roussy, Viellejuif, France. 9. Dipartimento di Ematologia e Onco-ematologia Pediatrica, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 10. Paediatric Oncology, Istituto Giannia Gaslini, Genova, Italy. 11. Pediatric Oncology Unit, Hospital Universitario y Politecnico La Fe, Valencia, Spain. 12. Paediatric Oncology, Leeds Teaching Hospital NHS Trust, Leeds, UK. 13. Department of Pediatric Oncology and Hematology, Institute of Pediatrics, Jagiellonian University Medical College, Krakow, Poland. 14. Department of Pediatric Hematology/Oncology and Stem Cell Transplantation University Hospital Ghent, Ghent, Belgium. 15. Department of Women's and Children's Health, Karolinska Institutet, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden. 16. Department of Pediatric Hematology and Oncology, University Hospital Motol, Prague, Czech Republic. 17. Department of Paediatric Medicine, Rikshospitalet, Oslo University Hospital, Oslo, Norway. 18. Department of Pediatrics and Pediatric Surgery, Pediatric Haematology Oncology Unit, University Hospital Lausanne, Lausanne, Switzerland. 19. Department of Paediatrics, Institut Curie, Paris, France. 20. Paediatric Haematology/Oncology, St Anna Kinderspital and St Anna Kinderkrebforschung, Vienna, Austria.
Abstract
BACKGROUND: Risk stratification is crucial to treatment decision-making in neuroblastoma. This study aimed to explore factors present at diagnosis affecting outcome in patients aged ≥18 months with metastatic neuroblastoma and to develop a simple risk score for prognostication. PROCEDURE: Data were derived from the European high-risk neuroblastoma 1 (HR-NBL1)/International Society for Paediatric Oncology European Neuroblastoma (SIOPEN) trial with analysis restricted to patients aged ≥18 months with metastatic disease and treated prior to the introduction of immunotherapy. Primary endpoint was 5-year event-free survival (EFS). Prognostic factors assessed were sex, age, tumour MYCN amplification (MNA) status, serum lactate dehydrogenase (LDH)/ferritin, primary tumour and metastatic sites. Factors significant in univariate analysis were incorporated into a multi-variable model and an additive scoring system developed based on estimated log-cumulative hazard ratios. RESULTS: The cohort included 1053 patients with median follow-up 5.5 years and EFS 27 ± 1%. In univariate analyses, age; serum LDH and ferritin; involvement of bone marrow, bone, liver or lung; and >1 metastatic system/compartment were associated with worse EFS. Tumour MNA was not associated with worse EFS. A multi-variable model and risk score incorporating age (>5 years, 2 points), serum LDH (>1250 U/L, 1 point) and number of metastatic systems (>1, 2 points) were developed. EFS was significantly correlated with risk score: EFS 52 ± 9% for score = 0 versus 6 ± 3% for score = 5 (P < 0.0001). CONCLUSIONS: A simple score can identify an "ultra-high risk" (UHR) cohort (score = 5) comprising 8% of patients with 5-year EFS <10%. These patients appear not to benefit from induction therapy and could potentially be directed earlier to alternative experimental therapies in future trials.
BACKGROUND: Risk stratification is crucial to treatment decision-making in neuroblastoma. This study aimed to explore factors present at diagnosis affecting outcome in patients aged ≥18 months with metastatic neuroblastoma and to develop a simple risk score for prognostication. PROCEDURE: Data were derived from the European high-risk neuroblastoma 1 (HR-NBL1)/International Society for Paediatric Oncology European Neuroblastoma (SIOPEN) trial with analysis restricted to patients aged ≥18 months with metastatic disease and treated prior to the introduction of immunotherapy. Primary endpoint was 5-year event-free survival (EFS). Prognostic factors assessed were sex, age, tumour MYCN amplification (MNA) status, serum lactate dehydrogenase (LDH)/ferritin, primary tumour and metastatic sites. Factors significant in univariate analysis were incorporated into a multi-variable model and an additive scoring system developed based on estimated log-cumulative hazard ratios. RESULTS: The cohort included 1053 patients with median follow-up 5.5 years and EFS 27 ± 1%. In univariate analyses, age; serum LDH and ferritin; involvement of bone marrow, bone, liver or lung; and >1 metastatic system/compartment were associated with worse EFS. Tumour MNA was not associated with worse EFS. A multi-variable model and risk score incorporating age (>5 years, 2 points), serum LDH (>1250 U/L, 1 point) and number of metastatic systems (>1, 2 points) were developed. EFS was significantly correlated with risk score: EFS 52 ± 9% for score = 0 versus 6 ± 3% for score = 5 (P < 0.0001). CONCLUSIONS: A simple score can identify an "ultra-high risk" (UHR) cohort (score = 5) comprising 8% of patients with 5-year EFS <10%. These patients appear not to benefit from induction therapy and could potentially be directed earlier to alternative experimental therapies in future trials.
Authors: Kevin Campbell; Derek Shyr; Rochelle Bagatell; Matthias Fischer; Akira Nakagawara; Adela Canete Nieto; Garrett M Brodeur; Katherine K Matthay; Wendy B London; Steven G DuBois Journal: Pediatr Blood Cancer Date: 2019-05-21 Impact factor: 3.167
Authors: Luis Martí-Bonmatí; Ángel Alberich-Bayarri; Ruth Ladenstein; Ignacio Blanquer; J Damian Segrelles; Leonor Cerdá-Alberich; Polyxeni Gkontra; Barbara Hero; J M García-Aznar; Daniel Keim; Wolfgang Jentner; Karine Seymour; Ana Jiménez-Pastor; Ismael González-Valverde; Blanca Martínez de Las Heras; Samira Essiaf; Dawn Walker; Michel Rochette; Marian Bubak; Jordi Mestres; Marco Viceconti; Gracia Martí-Besa; Adela Cañete; Paul Richmond; Kenneth Y Wertheim; Tomasz Gubala; Marek Kasztelnik; Jan Meizner; Piotr Nowakowski; Salvador Gilpérez; Amelia Suárez; Mario Aznar; Giuliana Restante; Emanuele Neri Journal: Eur Radiol Exp Date: 2020-04-03
Authors: Wayne H Liang; Sara M Federico; Wendy B London; Arlene Naranjo; Meredith S Irwin; Samuel L Volchenboum; Susan L Cohn Journal: JCO Clin Cancer Inform Date: 2020-10
Authors: Angela Bellini; Ulrike Pötschger; Virginie Bernard; Eve Lapouble; Sylvain Baulande; Peter F Ambros; Nathalie Auger; Klaus Beiske; Marie Bernkopf; David R Betts; Jaydutt Bhalshankar; Nick Bown; Katleen de Preter; Nathalie Clément; Valérie Combaret; Jaime Font de Mora; Sally L George; Irene Jiménez; Marta Jeison; Barbara Marques; Tommy Martinsson; Katia Mazzocco; Martina Morini; Annick Mühlethaler-Mottet; Rosa Noguera; Gaelle Pierron; Maria Rossing; Sabine Taschner-Mandl; Nadine Van Roy; Ales Vicha; Louis Chesler; Walentyna Balwierz; Victoria Castel; Martin Elliott; Per Kogner; Geneviève Laureys; Roberto Luksch; Josef Malis; Maja Popovic-Beck; Shifra Ash; Olivier Delattre; Dominique Valteau-Couanet; Deborah A Tweddle; Ruth Ladenstein; Gudrun Schleiermacher Journal: J Clin Oncol Date: 2021-06-11 Impact factor: 50.717
Authors: Meredith S Irwin; Arlene Naranjo; Fan F Zhang; Susan L Cohn; Wendy B London; Julie M Gastier-Foster; Nilsa C Ramirez; Ruthann Pfau; Shalini Reshmi; Elizabeth Wagner; Jed Nuchtern; Shahab Asgharzadeh; Hiroyuki Shimada; John M Maris; Rochelle Bagatell; Julie R Park; Michael D Hogarty Journal: J Clin Oncol Date: 2021-07-28 Impact factor: 50.717