TY - JOUR
T1 - Outcomes of Infants and Young Children With Relapsed Medulloblastoma After Initial Craniospinal Irradiation Sparing Approaches
T2 - An International Cohort Study
AU - Erker, Craig
AU - Mynarek, Martin
AU - Bailey, Simon
AU - Mazewski, Claire M.
AU - Baroni, Lorena
AU - Massimino, Maura
AU - Hukin, Juliette
AU - Aguilera, Dolly
AU - Cappellano, Andrea M.
AU - Ramaswamy, Vijay
AU - Lassaletta, Alvaro
AU - Perreault, Sébastien
AU - Kline, Cassie N.
AU - Rajagopal, Revathi
AU - Michaiel, George
AU - Zapotocky, Michal
AU - Santa-Maria Lopez, Vicente
AU - La Madrid, Andres Morales
AU - Cacciotti, Chantel
AU - Sandler, Eric S.
AU - Hoffman, Lindsey M.
AU - Klawinski, Darren
AU - Khan, Sara
AU - Salloum, Ralph
AU - Hoppmann, Anna L.
AU - Larouche, Valérie
AU - Dorris, Kathleen
AU - Toledano, Helen
AU - Gilheeney, Stephen W.
AU - Abdelbaki, Mohamed S.
AU - Wilson, Beverly
AU - Tsang, Derek S.
AU - Knipstein, Jeffrey
AU - Oren, Michal Yalon
AU - Shah, Shafqat
AU - Murray, Jeffrey C.
AU - Ginn, Kevin F.
AU - Wang, Zhihong J.
AU - Fleischhack, Gudrun
AU - Obrecht, Denise
AU - Tonn, Svenja
AU - Harrod, Virginia L.
AU - Matheson, Kara
AU - Crooks, Bruce
AU - Strother, Douglas R.
AU - Cohen, Kenneth J.
AU - Hansford, Jordan R.
AU - Mueller, Sabine
AU - Margol, Ashley
AU - Gajjar, Amar
AU - Dhall, Girish
AU - Finlay, Jonathan L.
AU - Northcott, Paul A.
AU - Rutkowski, Stefan
AU - Clifford, Steven C.
AU - Robinson, Giles
AU - Bouffet, Eric
AU - Lafay-Cousin, Lucie
N1 - Publisher Copyright:
© 2023 American Society of Clinical Oncology.
PY - 2023/4/1
Y1 - 2023/4/1
N2 - PURPOSEInfant and young childhood medulloblastoma (iMB) is usually treated without craniospinal irradiation (CSI) to avoid neurocognitive late effects. Unfortunately, many children relapse. The purpose of this study was to assess salvage strategies and prognostic features of patients with iMB who relapse after CSI-sparing therapy.METHODSWe assembled a large international cohort of 380 patients with relapsed iMB, age younger than 6 years, and initially treated without CSI. Univariable and multivariable Cox models of postrelapse survival (PRS) were conducted for those treated with curative intent using propensity score analyses to account for confounding factors.RESULTSThe 3-year PRS, for 294 patients treated with curative intent, was 52.4% (95% CI, 46.4 to 58.3) with a median time to relapse from diagnosis of 11 months. Molecular subgrouping was available for 150 patients treated with curative intent, and 3-year PRS for sonic hedgehog (SHH), group 4, and group 3 were 60%, 84%, and 18% (P =.0187), respectively. In multivariable analysis, localized relapse (P =.0073), SHH molecular subgroup (P =.0103), CSI use after relapse (P =.0161), and age â ‰¥ 36 months at initial diagnosis (P =.0494) were associated with improved survival. Most patients (73%) received salvage CSI, and although salvage chemotherapy was not significant in multivariable analysis, its use might be beneficial for a subset of children receiving salvage CSI < 35 Gy (P =.007).CONCLUSIONA substantial proportion of patients with relapsed iMB are salvaged after initial CSI-sparing approaches. Patients with SHH subgroup, localized relapse, older age at initial diagnosis, and those receiving salvage CSI show improved PRS. Future prospective studies should investigate optimal CSI doses and the role of salvage chemotherapy in this population.
AB - PURPOSEInfant and young childhood medulloblastoma (iMB) is usually treated without craniospinal irradiation (CSI) to avoid neurocognitive late effects. Unfortunately, many children relapse. The purpose of this study was to assess salvage strategies and prognostic features of patients with iMB who relapse after CSI-sparing therapy.METHODSWe assembled a large international cohort of 380 patients with relapsed iMB, age younger than 6 years, and initially treated without CSI. Univariable and multivariable Cox models of postrelapse survival (PRS) were conducted for those treated with curative intent using propensity score analyses to account for confounding factors.RESULTSThe 3-year PRS, for 294 patients treated with curative intent, was 52.4% (95% CI, 46.4 to 58.3) with a median time to relapse from diagnosis of 11 months. Molecular subgrouping was available for 150 patients treated with curative intent, and 3-year PRS for sonic hedgehog (SHH), group 4, and group 3 were 60%, 84%, and 18% (P =.0187), respectively. In multivariable analysis, localized relapse (P =.0073), SHH molecular subgroup (P =.0103), CSI use after relapse (P =.0161), and age â ‰¥ 36 months at initial diagnosis (P =.0494) were associated with improved survival. Most patients (73%) received salvage CSI, and although salvage chemotherapy was not significant in multivariable analysis, its use might be beneficial for a subset of children receiving salvage CSI < 35 Gy (P =.007).CONCLUSIONA substantial proportion of patients with relapsed iMB are salvaged after initial CSI-sparing approaches. Patients with SHH subgroup, localized relapse, older age at initial diagnosis, and those receiving salvage CSI show improved PRS. Future prospective studies should investigate optimal CSI doses and the role of salvage chemotherapy in this population.
KW - Brain Neoplasms/therapy
KW - Cerebellar Neoplasms/radiotherapy
KW - Child
KW - Child, Preschool
KW - Chronic Disease
KW - Cohort Studies
KW - Craniospinal Irradiation/adverse effects
KW - Hedgehog Proteins
KW - Humans
KW - Infant
KW - Medulloblastoma/radiotherapy
KW - Neoplasm Recurrence, Local
KW - Prospective Studies
UR - https://www.scopus.com/pages/publications/85151312540
U2 - 10.1200/JCO.21.02968
DO - 10.1200/JCO.21.02968
M3 - Article
C2 - 36548930
AN - SCOPUS:85151312540
SN - 0732-183X
VL - 41
SP - 1921
EP - 1932
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 10
ER -