Salvage therapies for first relapse of SHH medulloblastoma in early childhood.
Por:
Erker C, Mynarek M, Simbozel M, Craig BT, Harrod VL, Cappellano AM, Cohen KJ, Santa-María López V, Morales-La Madrid A, Cacciotti C, Baroni L, Salloum R, Margol AS, Michaiel G, Aguilera D, Mazewski CM, Kline CN, Finlay JL, Abdelbaki MS, Murray JC, Dorris K, Crooks B, Ginn KF, Amayiri N, Tippelt S, Fleischhack G, Tonn S, Gerber NU, Lassaletta A, Hansford JR, Khan S, Gilheeney SW, Hoffman LM, Zapotocky M, Larouche V, Shah S, Ramaswamy V, Gajjar A, Perreault S, Mueller S, Hukin J, Cheng S, Wang ZJ, Matheson K, Bailey S, Bouffet E, Clifford SC, Robinson G, Dufour C, Rutkowski S and Lafay-Cousin L
Publicada:
17 sep 2025
Ahead of Print:
1 may 2025
Resumen:
BACKGROUND: Sonic hedgehog (SHH) medulloblastoma is the most common molecular group of infant and early childhood medulloblastoma (iMB) and has no standard of care at relapse. This work aimed to evaluate the post-relapse survival (PRS) and explore prognostic factors of patients with nodular desmoplastic (ND) and/or SHH iMB. METHODS: This international retrospective study included 147 subjects diagnosed with relapsed ND/SHH iMB between 1995 and 2017, <6 years old at original diagnosis, and treated without initial craniospinal irradiation (CSI). Univariable and multivariable Cox models with propensity score analyses were used to assess PRS for those in the curative intent cohort. RESULTS: The 3-year PRS was 61.6% (95% confidence interval [CI], 52.2-69.6). The median age at relapse was 3.4 years (interquartile range [IQR], 2.6-4.1). Those with local relapse (40.8%) more often received salvage treatment with surgery (P < .001), low-dose CSI (=24 Gy; P < .001), or focal radiotherapy (P = .008). Patients not receiving CSI (40.5%) more often received salvage marrow-ablative chemotherapy (HDC + AuHCR [P < .001]). On multivariable analysis, CSI was associated with improved survival (hazard ratio [HR] 0.33 [95% CI, 0.13-0.86], P = .04). Salvage HDC + AuHCR, while clinically important, did not reach statistical significance (HR 0.24 [95% CI, 0.0054-1.025], P = .065). CONCLUSIONS: Survival of patients with relapsed SHH iMB is not satisfactory and relies on treatments associated with toxicities including CSI and/or HDC + AuHCR. Cure at initial diagnosis to avoid relapse is crucial. For patients with localized relapse undergoing resection, alternative salvage regimens that avoid high-dose CSI (>24 Gy) can be considered.
Filiaciones:
Erker C:
Division of Hematology/Oncology, Department of Paediatrics, IWK Health Centre and Dalhousie University, Halifax, NS, Canada
Mynarek M:
Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Simbozel M:
Department of Child and Adolescent Oncology, Gustave Roussy, Paris-Saclay University, Villejuif, France
Craig BT:
Department of Pediatrics, University of Calgary and Alberta Children's Hospital Research Institute (ACHRI), Calgary, AB, Canada
Harrod VL:
Department of Pediatric Hematology and Oncology, Dell Children's Medical Center of Central Texas and University of Texas, Austin, TX, USA
Cappellano AM:
Division of Pediatric Oncology/BMT, Instituto de Oncologia Pedi´ atrica-GRAACC-UNIFESP, São Paulo, Brazil
Cohen KJ:
Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
Santa-María López V:
Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, Barcelona, Spain
Morales-La Madrid A:
Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, Barcelona, Spain
Cacciotti C:
Children's Hospital London Health Sciences, Division of Pediatric Hematology/Oncology, Western University, London, ON, Canada
Baroni L:
Hospital of Pediatrics SAMIC Prof. Dr Juan P. Garrahan, Buenos Aires, Argentina
Salloum R:
Division of Hematology, Oncology and Blood and Marrow Transplant, Nationwide Children's Hospital and The Ohio State University, Columbus, OH, USA
Margol AS:
Department of Pediatrics and Radiation Oncology, The Ohio State University College of Medicine, Columbus, OH, USA
Michaiel G:
Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA
Aguilera D:
Division of Hematology, Oncology/ Bone Marrow Transplant, Department of Pediatrics, British Columbia Children's Hospital and University of British Columbia, Vancouver, BC, Canada
Mazewski CM:
Division of Hematology, Oncology/ Bone Marrow Transplant, Department of Pediatrics, British Columbia Children's Hospital and University of British Columbia, Vancouver, BC, Canada
Kline CN:
Aflac Cancer and Blood Disorder Center, Children's Healthcare of Atlanta & Emory University, Atlanta, GA, USA
Finlay JL:
Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA
Abdelbaki MS:
Division of Pediatric Hematology, Oncology, and Bone Marrow Transplant, Washington University School of Medicine in St Louis, St Louis, MO, USA
Murray JC:
Division of Pediatric Hematology/Oncology, Cook Children's Medical Center, Fort Worth, TX, USA
Dorris K:
Children's Hospital of Colorado & University of Colorado School of Medicine, Denver, CO, USA
Crooks B:
Division of Hematology/Oncology, Department of Paediatrics, IWK Health Centre and Dalhousie University, Halifax, NS, Canada
Ginn KF:
Division of Pediatric Hematology and Oncology, Children's Mercy Hospital, Kansas City, MO, USA
Amayiri N:
Department of Pediatric Hematology/Oncology, King Hussein Cancer Center, Amman, Jordan
Tippelt S:
Pediatrics III, Pediatric Oncology and Hematology, University Hospital Essen, Essen, Germany
Fleischhack G:
Pediatrics III, Pediatric Oncology and Hematology, University Hospital Essen, Essen, Germany
Tonn S:
Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Gerber NU:
Department of Oncology, University Children's Hospital, Zurich, Switzerland
Lassaletta A:
Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
Hansford JR:
Children's Cancer Centre, The Royal Children's Hospital
Murdoch Children's Research Institute
University of Melbourne, Melbourne, VIC, Australia
Michael Rice Centre for Hematology and Oncology, The Women's and Children's Hospital
South Australia Health and Medical Research Institute, South Australian immunoGENomics Cancer Institute
University of Adelaide, Adelaide, Australia
Khan S:
Division of Hematology, Oncology and Blood and Marrow Transplant, Nationwide Children's Hospital and The Ohio State University, Columbus, OH, USA
Gilheeney SW:
Department of Pediatrics and Division of Hematology and Oncology, Mount Sinai, New York, NY, USA
Hoffman LM:
Center for Cancer and Blood Disorders, Phoenix Children's Hospital, Phoenix, AZ, USA
Zapotocky M:
Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
Larouche V:
Department of Pediatrics, Centre Mère-enfant Soleil du CHU de Quèbec-Université Laval, Quebec City, QC, Canada
Shah S:
The University of Texas Health Science Center, Department of Pediatric Hematology-Oncology, San Antonio, TX, USA
Ramaswamy V:
Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada
Gajjar A:
Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA
Perreault S:
Centre Hospitalier Universitaire Sainte Justine, Université de Montreal, Montreal, QC, Canada
Mueller S:
Department of Neurology, Neurosurgery and Pediatrics, University of California San Francisco, San Francisco, CA, USA
Department of Pediatrics, University of Zurich, Switzerland
Hukin J:
Division of Neurology and Hematology, Oncology/ Bone Marrow Transplant, Department of Pediatrics, British Columbia Children's Hospital and University of British Columbia, Vancouver, BC, Canada
Cheng S:
Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA
Wang ZJ:
Division of Hematology and Oncology, Children's Hospital of Richmond and Virginia Commonwealth University, Richmond, VA, USA
Matheson K:
Research Methods Unit, Nova Scotia Health Authority, Halifax, NS, Canada
Bailey S:
Wolfson Childhood Cancer Research Centre, Newcastle University Centre for Cancer, Newcastle-upon-Tyne, United Kingdom
Bouffet E:
Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada
Clifford SC:
Wolfson Childhood Cancer Research Centre, Newcastle University Centre for Cancer, Newcastle-upon-Tyne, United Kingdom
Robinson G:
Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA
Rutkowski S:
Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Lafay-Cousin L:
Section of Pediatric Hematology and Bone Marrow Transplantation, Alberta Children's Hospital, Calgary, AB, Canada
Green Submitted, hybrid
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