Clinical Outcomes and Patient-Matched Molecular Composition of Relapsed Medulloblastoma-Reference-Cited by-同舟云学术

Clinical Outcomes and Patient-Matched Molecular Composition of Relapsed Medulloblastoma

Published:2021-03-01 Issue:7 Volume:39 Page:807-821
ISSN:0732-183X
Container-title:Journal of Clinical Oncology
language:en
Short-container-title:JCO

Author:

Kumar Rahul¹²^ORCID,Smith Kyle S.¹,Deng Maximilian³,Terhune Colt⁴,Robinson Giles W.⁴^ORCID,Orr Brent A.⁵^ORCID,Liu Anthony P. Y.¹⁴^ORCID,Lin Tong⁶,Billups Catherine A.⁶^ORCID,Chintagumpala Murali⁷,Bowers Daniel C.⁸^ORCID,Hassall Timothy E.⁹^ORCID,Hansford Jordan R.¹⁰^ORCID,Khuong-Quang Dong Anh¹⁰^ORCID,Crawford John R.¹¹,Bendel Anne E.¹²,Gururangan Sridharan¹³^ORCID,Schroeder Kristin¹³^ORCID,Bouffet Eric¹⁴^ORCID,Bartels Ute¹⁴^ORCID,Fisher Michael J.¹⁵,Cohn Richard¹⁶,Partap Sonia¹⁷^ORCID,Kellie Stewart J.¹⁸,McCowage Geoffrey¹⁸,Paulino Arnold C.¹⁹,Rutkowski Stefan²⁰,Fleischhack Gudrun²¹^ORCID,Dhall Girish²²,Klesse Laura J.⁸^ORCID,Leary Sarah²³^ORCID,Nazarian Javad²⁴,Kool Marcel²⁵,Wesseling Pieter²⁶^ORCID,Ryzhova Marina²⁷^ORCID,Zheludkova Olga²⁸^ORCID,Golanov Andrey V.²⁹^ORCID,McLendon Roger E.³⁰,Packer Roger J.³¹,Dunham Christopher³²^ORCID,Hukin Juliette³³^ORCID,Fouladi Maryam³⁴,Faria Claudia C.³⁵,Pimentel Jose³⁶,Walter Andrew W.³⁷^ORCID,Jabado Nada³⁸,Cho Yoon-Jae³⁹,Perreault Sebastien⁴⁰,Croul Sidney E.⁴¹,Zapotocky Michal⁴²^ORCID,Hawkins Cynthia⁴³^ORCID,Tabori Uri⁴³^ORCID,Taylor Michael D.⁴³,Pfister Stefan M.²⁷^ORCID,Klimo Paul⁴⁴,Boop Frederick A.⁴⁴,Ellison David W.⁵,Merchant Thomas E.⁴⁵^ORCID,Onar-Thomas Arzu⁶,Korshunov Andrey⁴⁶,Jones David T. W.³⁴⁷,Gajjar Amar⁴^ORCID,Ramaswamy Vijay⁴³⁴⁸^ORCID,Northcott Paul A.¹

Affiliation:

1. Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN

2. Graduate School of Biomedical Sciences, St Jude Children's Research Hospital, Memphis, TN

3. Pediatric Glioma Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

4. Department of Oncology, St Jude Children's Research Hospital, Memphis, TN

5. Department of Pathology, St Jude Children's Research Hospital, Memphis, TN

6. Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN

7. Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX

8. Division of Pediatric Hematology and Oncology, University of Texas Southwestern Medical Center, Dallas, TX

9. Department of Pediatric Oncology, Lady Ciliento Children's Hospital, South Brisbane, Queensland, Australia

10. Department of Haematology and Oncology, Royal Children's Hospital, Parkville, Victoria, Australia

11. Department of Neurosciences and Pediatrics, University of California San Diego and Rady Children's Hospital, San Diego, CA

12. Department of Hematology-Oncology, Children's Hospital of Minnesota, Minneapolis, MN

13. Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC

14. Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

15. Division of Oncology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA

16. Kid's Cancer Centre, Sydney Children's Hospital and School of Woman's and Children's Health, Sydney, New South Wales, Australia

17. Departments of Neurology and Pediatrics, Stanford University, Palo Alto, CA

18. Department of Pediatric Oncology, Children's Hospital at Westmead, Westmead, New South Wales, Australia

19. Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX

20. Department of Hematology and Oncology, University Hospital Hamburg-Eppendorf, Hamburg, Germany

21. Department of Pediatrics, University Hospital Essen, Essen, Germany

22. Division of Pediatric Hematology/Oncology, Children's Hospital of Los Angeles, Los Angeles, CA

23. Department of Hematology-Oncology, Seattle Children's Hospital, Seattle, WA

24. Research Center for Genetic Medicine, Children's National Health System, Washington, DC

25. Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

26. Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands

27. Department of Neuropathology, NN Burdenko Neurosurgical Institute, Moscow, Russia

28. Department of Neuro-Oncology, Russian Scientific Center of Radiology, Moscow, Russia

29. Department of Neuroradiology, NN Burdenko Neurosurgical Institute, Moscow, Russia

30. Department of Pathology, Duke University Medical Center, Durham, NC

31. Children's National Hospital, Washington, DC

32. Department of Pathology and Laboratory Medicine, Division of Anatomical Pathology, BC Children's Hospital, Vancouver, British Columbia, Canada

33. Department of Pediatrics, Division of Neurology, BC Children's Hospital, Vancouver, British Columbia, Canada

34. Department of Pediatrics, Division of Oncology, Cincinnati Children's Hospital, Cincinnati, OH

35. Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal

36. Department of Neurology, Hospital de Santa Maria, Lisbon, Portugal

37. Department of Hematology/Oncology, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE

38. Department of Pediatrics, Research Institute of the McGill University Health Center, Montreal, Québec, Canada

39. Department of Pediatrics, Pediatric Neurology, Oregon Health & Science University, Portland, OR

40. Division of Neurology, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Québec, Canada

41. Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada

42. Prague Brain Tumor Research Group, Charles University and University Hospital Motol, Prague, Czech Republic

43. Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Ontario, Canada

44. Division of Pediatric Neurosurgery, Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN

45. Department of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, TN

46. Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

47. Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany

48. Division of Haematology/Oncology, Hospital for Sick Children, Toronto, Ontario, Canada

Abstract

PURPOSE We sought to investigate clinical outcomes of relapsed medulloblastoma and to compare molecular features between patient-matched diagnostic and relapsed tumors. METHODS Children and infants enrolled on either SJMB03 (NCT00085202) or SJYC07 (NCT00602667) trials who experienced medulloblastoma relapse were analyzed for clinical outcomes, including anatomic and temporal patterns of relapse and postrelapse survival. A largely independent, paired molecular cohort was analyzed by DNA methylation array and next-generation sequencing. RESULTS A total of 72 of 329 (22%) SJMB03 and 52 of 79 (66%) SJYC07 patients experienced relapse with significant representation of Group 3 and wingless tumors. Although most patients exhibited some distal disease (79%), 38% of patients with sonic hedgehog tumors experienced isolated local relapse. Time to relapse and postrelapse survival varied by molecular subgroup with longer latencies for patients with Group 4 tumors. Postrelapse radiation therapy among previously nonirradiated SJYC07 patients was associated with long-term survival. Reirradiation was only temporizing for SJMB03 patients. Among 127 patients with patient-matched tumor pairs, 9 (7%) experienced subsequent nonmedulloblastoma CNS malignancies. Subgroup (96%) and subtype (80%) stabilities were largely maintained among the remainder. Rare subgroup divergence was observed from Group 4 to Group 3 tumors, which is coincident with genetic alterations involving MYC, MYCN, and FBXW7. Subgroup-specific patterns of alteration were identified for driver genes and chromosome arms. CONCLUSION Clinical behavior of relapsed medulloblastoma must be contextualized in terms of up-front therapies and molecular classifications. Group 4 tumors exhibit slower biological progression. Utility of radiation at relapse is dependent on patient age and prior treatments. Degree and patterns of molecular conservation at relapse vary by subgroup. Relapse tissue enables verification of molecular targets and identification of occult secondary malignancies.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

Link

https://ascopubs.org/doi/pdfdirect/10.1200/JCO.20.01359

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