Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma
Summary: Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this gap in knowledge, an international...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-06-01
|
| Series: | Cell Reports Medicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666379120300501 |
| id |
doaj-fe064d5dfe04450eab73d80ac7fe7dce |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Liana Nobre Michal Zapotocky Sara Khan Kohei Fukuoka Adriana Fonseca Tara McKeown David Sumerauer Ales Vicha Wieslawa A. Grajkowska Joanna Trubicka Kay Ka Wai Li Ho-Keung Ng Luca Massimi Ji Yeoun Lee Seung-Ki Kim Shayna Zelcer Alexandre Vasiljevic Cécile Faure-Conter Peter Hauser Boleslaw Lach Marie-Lise van Veelen-Vincent Pim J. French Erwin G. Van Meir William A. Weiss Nalin Gupta Ian F. Pollack Ronald L. Hamilton Amulya A. Nageswara Rao Caterina Giannini Joshua B. Rubin Andrew S. Moore Lola B. Chambless Rajeev Vibhakar Young Shin Ra Maura Massimino Roger E. McLendon Helen Wheeler Massimo Zollo Veronica Ferruci Toshihiro Kumabe Claudia C. Faria Jaroslav Sterba Shin Jung Enrique López-Aguilar Jaume Mora Carlos G. Carlotti James M. Olson Sarah Leary Jason Cain Lenka Krskova Josef Zamecnik Cynthia E. Hawkins Uri Tabori Annie Huang Ute Bartels Paul A. Northcott Michael D. Taylor Stephen Yip Jordan R. Hansford Eric Bouffet Vijay Ramaswamy |
| spellingShingle |
Liana Nobre Michal Zapotocky Sara Khan Kohei Fukuoka Adriana Fonseca Tara McKeown David Sumerauer Ales Vicha Wieslawa A. Grajkowska Joanna Trubicka Kay Ka Wai Li Ho-Keung Ng Luca Massimi Ji Yeoun Lee Seung-Ki Kim Shayna Zelcer Alexandre Vasiljevic Cécile Faure-Conter Peter Hauser Boleslaw Lach Marie-Lise van Veelen-Vincent Pim J. French Erwin G. Van Meir William A. Weiss Nalin Gupta Ian F. Pollack Ronald L. Hamilton Amulya A. Nageswara Rao Caterina Giannini Joshua B. Rubin Andrew S. Moore Lola B. Chambless Rajeev Vibhakar Young Shin Ra Maura Massimino Roger E. McLendon Helen Wheeler Massimo Zollo Veronica Ferruci Toshihiro Kumabe Claudia C. Faria Jaroslav Sterba Shin Jung Enrique López-Aguilar Jaume Mora Carlos G. Carlotti James M. Olson Sarah Leary Jason Cain Lenka Krskova Josef Zamecnik Cynthia E. Hawkins Uri Tabori Annie Huang Ute Bartels Paul A. Northcott Michael D. Taylor Stephen Yip Jordan R. Hansford Eric Bouffet Vijay Ramaswamy Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma Cell Reports Medicine medulloblastoma WNT subgroup chemotherapy radiation wingless |
| author_facet |
Liana Nobre Michal Zapotocky Sara Khan Kohei Fukuoka Adriana Fonseca Tara McKeown David Sumerauer Ales Vicha Wieslawa A. Grajkowska Joanna Trubicka Kay Ka Wai Li Ho-Keung Ng Luca Massimi Ji Yeoun Lee Seung-Ki Kim Shayna Zelcer Alexandre Vasiljevic Cécile Faure-Conter Peter Hauser Boleslaw Lach Marie-Lise van Veelen-Vincent Pim J. French Erwin G. Van Meir William A. Weiss Nalin Gupta Ian F. Pollack Ronald L. Hamilton Amulya A. Nageswara Rao Caterina Giannini Joshua B. Rubin Andrew S. Moore Lola B. Chambless Rajeev Vibhakar Young Shin Ra Maura Massimino Roger E. McLendon Helen Wheeler Massimo Zollo Veronica Ferruci Toshihiro Kumabe Claudia C. Faria Jaroslav Sterba Shin Jung Enrique López-Aguilar Jaume Mora Carlos G. Carlotti James M. Olson Sarah Leary Jason Cain Lenka Krskova Josef Zamecnik Cynthia E. Hawkins Uri Tabori Annie Huang Ute Bartels Paul A. Northcott Michael D. Taylor Stephen Yip Jordan R. Hansford Eric Bouffet Vijay Ramaswamy |
| author_sort |
Liana Nobre |
| title |
Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma |
| title_short |
Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma |
| title_full |
Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma |
| title_fullStr |
Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma |
| title_full_unstemmed |
Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma |
| title_sort |
pattern of relapse and treatment response in wnt-activated medulloblastoma |
| publisher |
Elsevier |
| series |
Cell Reports Medicine |
| issn |
2666-3791 |
| publishDate |
2020-06-01 |
| description |
Summary: Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this gap in knowledge, an international cohort of 93 molecularly confirmed WNT MB was assembled, where 5-year progression-free survival is 0.84 (95%, 0.763–0.925) with 15 relapsed individuals identified. Maintenance chemotherapy is identified as a strong predictor of relapse, with individuals receiving high doses of cyclophosphamide or ifosphamide having only one very late molecularly confirmed relapse (p = 0.032). The anatomical location of recurrence is metastatic in 12 of 15 relapses, with 8 of 12 metastatic relapses in the lateral ventricles. Maintenance chemotherapy, specifically cumulative cyclophosphamide doses, is a significant predictor of relapse across WNT MB. Future efforts to de-escalate therapy need to carefully consider not only the radiation dose but also the chemotherapy regimen and the propensity for metastatic relapses. |
| topic |
medulloblastoma WNT subgroup chemotherapy radiation wingless |
| url |
http://www.sciencedirect.com/science/article/pii/S2666379120300501 |
| work_keys_str_mv |
AT liananobre patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT michalzapotocky patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT sarakhan patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT koheifukuoka patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT adrianafonseca patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT taramckeown patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT davidsumerauer patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT alesvicha patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT wieslawaagrajkowska patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT joannatrubicka patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT kaykawaili patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT hokeungng patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT lucamassimi patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT jiyeounlee patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT seungkikim patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT shaynazelcer patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT alexandrevasiljevic patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT cecilefaureconter patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT peterhauser patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT boleslawlach patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT marielisevanveelenvincent patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT pimjfrench patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT erwingvanmeir patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT williamaweiss patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT nalingupta patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT ianfpollack patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT ronaldlhamilton patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT amulyaanageswararao patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT caterinagiannini patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT joshuabrubin patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT andrewsmoore patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT lolabchambless patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT rajeevvibhakar patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT youngshinra patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT mauramassimino patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT rogeremclendon patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT helenwheeler patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT massimozollo patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT veronicaferruci patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT toshihirokumabe patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT claudiacfaria patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT jaroslavsterba patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT shinjung patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT enriquelopezaguilar patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT jaumemora patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT carlosgcarlotti patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT jamesmolson patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT sarahleary patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT jasoncain patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT lenkakrskova patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT josefzamecnik patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT cynthiaehawkins patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT uritabori patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT anniehuang patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT utebartels patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT paulanorthcott patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT michaeldtaylor patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT stephenyip patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT jordanrhansford patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT ericbouffet patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma AT vijayramaswamy patternofrelapseandtreatmentresponseinwntactivatedmedulloblastoma |
| _version_ |
1724429598144331776 |
| spelling |
doaj-fe064d5dfe04450eab73d80ac7fe7dce2020-11-25T04:07:13ZengElsevierCell Reports Medicine2666-37912020-06-0113100038Pattern of Relapse and Treatment Response in WNT-Activated MedulloblastomaLiana Nobre0Michal Zapotocky1Sara Khan2Kohei Fukuoka3Adriana Fonseca4Tara McKeown5David Sumerauer6Ales Vicha7Wieslawa A. Grajkowska8Joanna Trubicka9Kay Ka Wai Li10Ho-Keung Ng11Luca Massimi12Ji Yeoun Lee13Seung-Ki Kim14Shayna Zelcer15Alexandre Vasiljevic16Cécile Faure-Conter17Peter Hauser18Boleslaw Lach19Marie-Lise van Veelen-Vincent20Pim J. French21Erwin G. Van Meir22William A. Weiss23Nalin Gupta24Ian F. Pollack25Ronald L. Hamilton26Amulya A. Nageswara Rao27Caterina Giannini28Joshua B. Rubin29Andrew S. Moore30Lola B. Chambless31Rajeev Vibhakar32Young Shin Ra33Maura Massimino34Roger E. McLendon35Helen Wheeler36Massimo Zollo37Veronica Ferruci38Toshihiro Kumabe39Claudia C. Faria40Jaroslav Sterba41Shin Jung42Enrique López-Aguilar43Jaume Mora44Carlos G. Carlotti45James M. Olson46Sarah Leary47Jason Cain48Lenka Krskova49Josef Zamecnik50Cynthia E. Hawkins51Uri Tabori52Annie Huang53Ute Bartels54Paul A. Northcott55Michael D. Taylor56Stephen Yip57Jordan R. Hansford58Eric Bouffet59Vijay Ramaswamy60Division of Haematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, CanadaDepartment of Pediatric Hematology and Oncology, Second Faculty of Medicine, University Hospital Motol, Charles University, Prague, Czech RepublicMonash Children's Cancer Centre, Monash University, Melbourne, VIC, Australia; Children’s Cancer Centre, Royal Children’s Hospital, Murdoch Children’s Research Institute, Department of Pediatrics, University of Melbourne, Melbourne, VIC, AustraliaDepartment of Hematology/Oncology, Saitama Children’s Medical Center, Saitama, JapanDivision of Haematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, CanadaDivision of Haematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, CanadaDepartment of Pediatric Hematology and Oncology, Second Faculty of Medicine, University Hospital Motol, Charles University, Prague, Czech RepublicDepartment of Pediatric Hematology and Oncology, Second Faculty of Medicine, University Hospital Motol, Charles University, Prague, Czech RepublicDepartment of Pathology, The Children’s Memorial Health Institute, Warsaw, PolandDepartment of Pathology, The Children’s Memorial Health Institute, Warsaw, PolandDepartment of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, New Territories, Hong KongDepartment of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, New Territories, Hong KongFondazione Policlinico A. Gemelli IRCCS, Catholic University Medical School, Rome, ItalyDepartment of Neurosurgery, Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul, South KoreaDepartment of Neurosurgery, Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul, South KoreaDivision of Pediatric Hematology/Oncology, Western University, London, ON, CanadaDepartment of Pathology and Molecular Medicine, Division of Anatomical Pathology, McMaster University, Hamilton, ON, CanadaDepartment of Pediatrics, Institut d’Hemato-Oncologie Pediatrique, Lyon, FranceSecond Department of Pediatrics, Semmelweis University, Budapest, HungaryDepartment of Pathology and Molecular Medicine, Division of Anatomical Pathology, McMaster University and Department of Pathology and Laboratory Medicine, Hamilton General Hospital, Hamilton, ON, CanadaDepartment of Neurosurgery, Erasmus University Medical Center, Rotterdam, the NetherlandsDepartment of Neurology, Erasmus University Medical Center, Rotterdam, the NetherlandsDepartments of Neurosurgery, Hematology, and Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, GA, USADepartments of Neurological Surgery and Pediatrics, University of California, San Francisco, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USADepartments of Neurological Surgery and Pediatrics, University of California, San Francisco, San Francisco, CA, USADepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USADepartment of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USADivision of Pediatric Hematology/Oncology, Mayo Clinic, Rochester, MN, USADepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USADepartments of Pediatrics, Anatomy, and Neurobiology, Washington University School of Medicine, St. Louis, MO, USAQueensland Children’s Medical Research Institute, Children’s Health Queensland, Brisbane, QLD, Australia; Division of Oncology, Children’s Health Queensland, Brisbane, QLD, AustraliaDepartment of Neurological Surgery, Vanderbilt Medical Center, Nashville, TN, USADepartment of Pediatrics, University of Colorado Denver, Aurora, CO, USADepartment of Neurosurgery, University of Ulsan, Asan Medical Center, Seoul, South KoreaFondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyDepartment of Pathology, Duke University, Durham, NC, USAKolling Institute of Medical Research, The University of Sydney, Sydney, NSW, AustraliaDipartimento di Medicina Molecolare e Biotecnologie Mediche DMMBM, Università di Napoli Federico II, Naples, ItalyDipartimento di Medicina Molecolare e Biotecnologie Mediche DMMBM, Università di Napoli Federico II, Naples, ItalyDepartment of Neurosurgery, Kitasato University School of Medicine, Sagamihara, Kanagawa, JapanDivision of Neurosurgery, Centro Hospitalar Lisboa Norte, Hospital de Santa Maria, Lisbon, PortugalDepartment of Pediatric Oncology, School of Medicine, Masaryk University, Brno, Czech RepublicDepartment of Neurosurgery, Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hospital and Medical School, Hwasun-gun, Chonnam, South KoreaDivision of Pediatric Hematology/Oncology, Hospital Pediatría Centro Médico Nacional Century XXI, Mexico City, MexicoDevelopmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, SpainDepartment of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto, University of Sao Paulo, São Paulo, BrazilClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USACancer and Blood Disorders Center, Seattle Children’s Hospital, Seattle, WA, USAMonash Children's Cancer Centre, Monash University, Melbourne, VIC, AustraliaDepartment of Pathology and Molecular Medicine, University Hospital Motol, Second Faculty of Medicine, Charles University, Prague, Czech RepublicDepartment of Pathology and Molecular Medicine, University Hospital Motol, Second Faculty of Medicine, Charles University, Prague, Czech RepublicDivision of Pathology, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, CanadaDivision of Haematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, CanadaDivision of Haematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, CanadaDivision of Haematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, CanadaDepartment of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN, USAThe Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, CanadaDepartment of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, CanadaMonash Children's Cancer Centre, Monash University, Melbourne, VIC, Australia; Children’s Cancer Centre, Royal Children’s Hospital, Murdoch Children’s Research Institute, Department of Pediatrics, University of Melbourne, Melbourne, VIC, AustraliaDivision of Haematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, CanadaDivision of Haematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; Corresponding authorSummary: Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this gap in knowledge, an international cohort of 93 molecularly confirmed WNT MB was assembled, where 5-year progression-free survival is 0.84 (95%, 0.763–0.925) with 15 relapsed individuals identified. Maintenance chemotherapy is identified as a strong predictor of relapse, with individuals receiving high doses of cyclophosphamide or ifosphamide having only one very late molecularly confirmed relapse (p = 0.032). The anatomical location of recurrence is metastatic in 12 of 15 relapses, with 8 of 12 metastatic relapses in the lateral ventricles. Maintenance chemotherapy, specifically cumulative cyclophosphamide doses, is a significant predictor of relapse across WNT MB. Future efforts to de-escalate therapy need to carefully consider not only the radiation dose but also the chemotherapy regimen and the propensity for metastatic relapses.http://www.sciencedirect.com/science/article/pii/S2666379120300501medulloblastomaWNTsubgroupchemotherapyradiationwingless |