Characteristics of children ≤36 months of age with DIPG: A report from the international DIPG registry

Author:

Bartlett Allison L12,Lane Adam2ORCID,Chaney Brooklyn3,Escorza Nancy Yanez3,Black Katie3ORCID,Cochrane Anne14,Minturn Jane5,Bartels Ute6ORCID,Warren Kathy7,Hansford Jordan8,Ziegler David910,Diez Blanca11,Goldman Stewart12,Packer Roger13,Kieran Mark14,DeWire-Schottmiller Mariko1ORCID,Erker Craig15ORCID,Monje-Deisseroth Michelle16,Wagner Lars17,Koschmann Carl18ORCID,Dorris Kathleen19ORCID,Shih Chie-Schin20,Hassall Tim21,Samson Yvan22,Fisher Paul23,Wang Stacie S8,Tsui Karen24,Sevlever Gustavo11,Zhu Xiaoting125,Dexheimer Phillip26,Asher Anthony3,Fuller Christine27ORCID,Drissi Rachid2829ORCID,Jones Blaise30,Leach James30ORCID,Fouladi Maryam2931ORCID

Affiliation:

1. Brain Tumor Center, Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center , Cincinnati, Ohio , USA

2. Division of Bone Marrow Transplantation and Immune Deficiency, Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center , Cincinnati, Ohio , USA

3. Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center , Cincinnati, Ohio , USA

4. University of Cincinnati College of Medicine , Cincinnati, Ohio , USA

5. Division of Oncology, Children’s Hospital of Philadelphia and Perelman School of Medicine , Philadelphia, Pennsylvania, USA

6. Department of Pediatrics, Division of Oncology, University of Toronto and The Hospital for Sick Children , Toronto, Ontario , Canada

7. Department of Pediatric Oncology, Dana Farber Cancer Institute/Boston Children’s Hospital , Boston, Massachusetts , USA

8. Children’s Cancer Centre, Royal Children’s Hospital; Murdoch Children’s Research Institute; University of Melbourne , Melbourne , Australia

9. Children’s Cancer Institute Australia, Lowy Cancer Research Centre, UNSW and Kids Cancer Centre, Sydney’s Children Hospital , Randwick, Sydney NSW , Australia

10. School of Women’s and Children’s Health, University of New South Wales , Sydney , Australia

11. FLENI (Fundacion para Lucha contra las Enfermedes Neurologicas de Infantes ), Buenos Aires , Argentina

12. Division of Pediatric Hematology and Oncology, Center for Cancer and Blood Disorders, Ann & Robert H. Lurie Children’s Hospital of Chicago , Chicago, Illinois, USA

13. Department of Neurology, Center for Neuroscience and Behavioral Medicine, Children’s National Hospital , Washington, DC , USA

14. Department of Pediatrics, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and Harvard Medical School , Boston, Massachusetts , USA

15. Department of Pediatrics, Dalhousie University and IWK Health Center , Halifax, Nova Scotia , Canada

16. Department of Neurology, Neurosurgery, Pediatrics, and Pathology, Stanford University School of Medicine , Stanford, California , USA

17. Division of Pediatric Hematology/Oncology, Kentucky Children’s Hospital, University of Kentucky , Lexington, Kentucky , USA

18. Department of Pediatrics, C.S. Mott Children’s Hospital and University of Michigan School of Medicine , Ann Arbor, Michigan , USA

19. Department of Pediatrics, University of Colorado School of Medicine , Aurora, Colorado , USA

20. Division of Hematology/Oncology, Department of Pediatrics, Indiana University School of Medicine, Riley Hospital for Children at Indiana University Health , Indianapolis, Indiana , USA

21. Queensland Children’s Hospital , Brisbane, Queensland , Australia

22. Department of Hematology-Oncology, Université de Montréal and CHU Sainte-Justine , Montréal, Québec , Canada

23. Department of Neurology, Division of Child Neurology, Stanford University , Palo Alto, California , USA

24. Starship Blood and Cancer Centre, Starship Children’s Health , Auckland , New Zealand

25. Department of Electrical Engineering and Computer Science, University of Cincinnati College of Engineering and Applied Science , Cincinnati, Ohio , USA

26. Department of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center and University of Cincinnati , Cincinnati, Ohio , USA

27. Department of Pathology, Upstate Medical University , Syracuse, New York , USA

28. Center for Childhood Cancer & Blood Disorders, Nationwide Children’s Hospital , Columbus, Ohio , USA

29. The Ohio State University College of Medicine , Columbus, Ohio , USA

30. Division of Radiology, Cincinnati Children’s Hospital Medical Center , Cincinnati, Ohio , USA

31. Pediatric Neuro-Oncology Program, Nationwide Children’s Hospital , Columbus, Ohio , USA

Abstract

Abstract Background Children ≤36 months with diffuse intrinsic pontine glioma (DIPG) have increased long-term survival (LTS, overall survival (OS) ≥24 months). Understanding distinguishing characteristics in this population is critical to improving outcomes. Methods Patients ≤36 months at diagnosis enrolled on the International DIPG Registry (IDIPGR) with central imaging confirmation were included. Presentation, clinical course, imaging, pathology and molecular findings were analyzed. Results Among 1183 patients in IDIPGR, 40 were eligible (median age: 29 months). Median OS was 15 months. Twelve patients (30%) were LTS, 3 (7.5%) very long-term survivors ≥5 years. Among 8 untreated patients, median OS was 2 months. Patients enrolled in the registry but excluded from our study by central radiology review or tissue diagnosis had median OS of 7 months. All but 1 LTS received radiation. Among 32 treated patients, 1-, 2-, 3-, and 5-year OS rates were 68.8%, 31.2%, 15.6% and 12.5%, respectively. LTS had longer duration of presenting symptoms (P = .018). No imaging features were predictive of outcome. Tissue and genomic data were available in 18 (45%) and 10 patients, respectively. Among 9 with known H3K27M status, 6 had a mutation. Conclusions Children ≤36 months demonstrated significantly more LTS, with an improved median OS of 15 months; 92% of LTS received radiation. Median OS in untreated children was 2 months, compared to 17 months for treated children. LTS had longer duration of symptoms. Excluded patients demonstrated a lower OS, contradicting the hypothesis that children ≤36 months with DIPG show improved outcomes due to misdiagnosis.

Funder

Cure Starts Now Foundation

The Cure Starts Now Australia

Brooke Healey Foundation

Wayland Villars Foundation

Aidan’s Avengers

Aubreigh’s Army

Austin Strong

Cure Brain Cancer

Jeffrey Thomas Hayden Foundation

Laurie’s Love Foundation

Love Chloe Foundation

Musella Foundation

Pray Hope Believe

Reflections Of Grace

Storm the Heavens Fund

Whitley’s Wishes

Gabriella’s Smile Foundation

The Gold Hope Project

The Isabella and Marcus Foundation

Lauren’s Fight for Cure

Robert Connor Dawes Foundation

Ryan’s Hope

Benny’s World

Lily Larue Foundation

Marlee’s Mission

RUN DIPG

American Childhood Cancer Organization

The DIPG Collaborative

Snapgrant.com

Kyler Strong Foundation

Keris Kares

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Neurology (clinical),Oncology

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