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.

Aflac Cancer and Blood Disorder Center Children's Healthcare of Atlanta and Emory University Atlanta Georgia USA

Cancer and Blood Disease Institute Children's Hospital Los Angeles Keck School of Medicine of University of Southern California Los Angeles California USA

Center for Cancer and Blood Disorders Phoenix Children's Hospital Phoenix Arizona USA

Centre Hospitalier Universitaire Sainte Justine Université de Montreal Montreal Quebec Canada

Children's Cancer Centre The Royal Children's Hospital Murdoch Children's Research Institute University of Melbourne Melbourne Victoria Australia

Children's Hospital London Health Sciences Division of Pediatric Hematology Oncology Western University London Ontario Canada

Children's Hospital of Colorado and University of Colorado School of Medicine Denver Colorado USA

Department of Child and Adolescent Oncology Gustave Roussy Paris Saclay University Villejuif France

Department of Neurology Neurosurgery and Pediatrics University of California San Francisco San Francisco California USA

Department of Oncology St Jude Children's Research Hospital Memphis Tennessee USA

Department of Oncology University Children's Hospital Zurich Switzerland

Department of Paediatric Haematology and Oncology 2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic

Department of Pediatric Hematology and Oncology Hospital Infantil Universitario Niño Jesús Madrid Spain

Department of Pediatric Hematology and Oncology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Pediatric Hematology Oncology King Hussein Cancer Center Amman Jordan

Department of Pediatrics and Division of Hematology and Oncology Mount Sinai New York USA

Department of Pediatrics Centre Mère enfant Soleil du CHU de Quèbec Université Laval Quebec City Quebec Canada

Department of Pediatrics University of Calgary and Alberta Children's Hospital Research Institute Calgary Alberta Canada

Department of Pediatrics University of Zurich Switzerland

Departments of Pediatric Hematology and Oncology Dell Children's Medical Center of Central Texas and University of Texas Austin Texas USA

Departments of Pediatrics and Radiation Oncology The Ohio State University College of Medicine Columbus Ohio USA

Division of Haematology Oncology Department of Paediatrics The Hospital for Sick Children and University of Toronto Toronto Ontario Canada

Division of Hematology and Oncology Children's Hospital of Richmond and Virginia Commonwealth University Richmond Virginia USA

Division of Hematology Oncology and Blood and Marrow Transplant Nationwide Children's Hospital and The Ohio State University Columbus Ohio USA

Division of Hematology Oncology Bone Marrow Transplant Department of Pediatrics British Columbia Children's Hospital and University of British Columbia Vancouver British Columbia Canada

Division of Hematology Oncology Department of Paediatrics IWK Health Centre and Dalhousie University Halifax Nova Scotia Canada

Division of Oncology The Children's Hospital of Philadelphia Philadelphia Pennsylvania USA

Division of Pediatric Hematology and Oncology Children's Mercy Hospital Kansas City Missouri USA

Division of Pediatric Hematology Oncology and Bone Marrow Transplant Washington University School of Medicine in St Louis St Louis Missouri USA

Division of Pediatric Hematology Oncology Cook Children's Medical Center Fort Worth Texas USA

Division of Pediatric Oncology BMT Instituto de Oncologia Pediátrica GRAACC UNIFESP São Paulo Brazil

Divisions of Neurology and Hematology Oncology Bone Marrow Transplant Department of Pediatrics British Columbia Children's Hospital and University of British Columbia Vancouver British Columbia Canada

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

Mildred Scheel Cancer Career Center HaTriCS4 University Medical Center Hamburg Eppendorf Hamburg Germany

Pediatric Cancer Center Barcelona Hospital Sant Joan de Déu Barcelona Spain

Pediatric Oncology The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland USA

Pediatrics 3 Pediatric Oncology and Hematology University Hospital Essen Essen Germany

Research Methods Unit Nova Scotia Health Authority Halifax Nova Scotia Canada

Section of Pediatric Hematology and Bone Marrow Transplantation Alberta Children's Hospital Calgary Alberta Canada

Service of Hematology Oncology Hospital JP Garrahan Buenos Aires Argentina

The University of Texas Health Science Center Department of Pediatric Hematology Oncology San Antonio Texas USA

Wolfson Childhood Cancer Research Centre Newcastle University Centre for Cancer Newcastle upon Tyne UK

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