Outcomes of Infants and Young Children With Relapsed Medulloblastoma After Initial Craniospinal Irradiation–Sparing Approaches: An International Cohort Study
Craig Erker, Martin Mynarek, Simon Bailey, Claire Mazewski, Lorena Baroni, Maura Massimino, Juliette Hukin, Dolly Aguilera, Andréa Maria Cappellano, Vijay Ramaswamy, Álvaro Lassaletta, Sébastien Perreault, Cassie Kline, Revathi Rajagopal, George Michaiel, Michal Zápotocký, Vicente Santa‐María López, Andrés Morales La Madrid, Chantel Cacciotti, Eric Sandler, Lindsey M. Hoffman, Darren Klawinski, Sara Khan, Ralph Salloum, Anna L. Hoppmann, Valérie Larouche, Kathleen Dorris, Helen Toledano, Stephen W. Gilheeney, Mohamed S Abdelbaki, Beverly Wilson, Derek S. Tsang, Jeffrey Knipstein, Michal Oren, Shafqat Shah, Jeffrey C. Murray, Kevin Ginn, Zhihong J. Wang, Gudrun Fleischhack, Denise Obrecht, Svenja Tonn, Virginia L. Harrod, Kara Matheson, Bruce Crooks, Douglas Strother, Kenneth J. Cohen, Jordan R. Hansford, Sabine Mueller, Ashley Margol, Amar Gajjar, Girish Dhall, Jonathan L. Finlay, Paul A. Northcott, Stefan Rutkowski, Steven C. Clifford, Giles Robinson, Éric Bouffet, Lucie Lafay‐Cousin
Abstract
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.