Outcomes of Infants and Young Children With Relapsed Medulloblastoma After Initial Craniospinal Irradiation-Sparing Approaches: An International Cohort Study

TY - JOUR

T1 - Outcomes of Infants and Young Children With Relapsed Medulloblastoma After Initial Craniospinal Irradiation-Sparing Approaches: 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

PY - 2023/4/1

Y1 - 2023/4/1

N2 - PURPOSE: Infant 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.METHODS: We 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.RESULTS: The 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 ≥ 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).CONCLUSION: A 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 - PURPOSE: Infant 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.METHODS: We 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.RESULTS: The 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 ≥ 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).CONCLUSION: A 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.

U2 - 10.1200/JCO.21.02968

DO - 10.1200/JCO.21.02968

M3 - SCORING: Journal article

C2 - 36548930

VL - 41

SP - 1921

EP - 1932

JO - J CLIN ONCOL

JF - J CLIN ONCOL

SN - 0732-183X

IS - 10

ER -