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

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.
Competing Interests: Craig ErkerConsulting or Advisory Role: Novartis Canada Pharmaceuticals Inc Martin MynarekEmployment: Novartis, BioNTech SE Maura MassiminoConsulting or Advisory Role: Oncoscience, Novartis Juliette HukinStock and Other Ownership Interests: AbbVieConsulting or Advisory Role: AstraZeneca, Novartis Vijay RamaswamyHonoraria: AstraZenecaConsulting or Advisory Role: AstraZeneca Canada Alvaro LassalettaStock and Other Ownership Interests: Gilead SciencesConsulting or Advisory Role: Jazz Pharmaceuticals, Servier, Alexion Pharmaceuticals Sébastien PerreaultLeadership: BayerStock and Other Ownership Interests: NovocureHonoraria: BayerConsulting or Advisory Role: BayerSpeakers' Bureau: BayerExpert Testimony: Bayer Cassie N. KlineResearch Funding: Regeneron (Inst), Curis (Inst), Midatech Pharma (Inst), Ipsen (Inst), Day One Therapeutics (Inst), Bristol Myers Squibb (Inst), Kazia Therapeutics (Inst), Chimerix (Inst) Eric S. SandlerConsulting or Advisory Role: Protara Therapeutics Lindsey M. HoffmanHonoraria: AstraZeneca Kathleen DorrisStock and Other Ownership Interests: Amgen, Gilead SciencesConsulting or Advisory Role: Day One Biopharmaceuticals Helen ToledanoConsulting or Advisory Role: AstraZeneca, Novartis Derek S. TsangTravel, Accommodations, Expenses: Mevion Medical Systems Jeffrey KnipsteinEmployment: PRA Health Sciences, ServierConsulting or Advisory Role: Atheneum Zhihong J. WangHonoraria: AstraZenecaConsulting or Advisory Role: AstraZenecaSpeakers' Bureau: AstraZeneca Kenneth J. CohenConsulting or Advisory Role: Novartis, Bristol Myers Squibb, DNAtrixResearch Funding: Novartis, Bristol Myers Squibb Jordan R. HansfordStock and Other Ownership Interests: AnteotechConsulting or Advisory Role: Bayer Sabine MuellerResearch Funding: Regeneron (Inst), DayOne Pharmaceuticals (Inst), Curis Pharamceuticals (Inst), Curis Pharamceuticals (Inst), Bristol Myers Squibb (Inst) Amar GajjarConsulting or Advisory Role: Roche/Genentech, QED Therapeutics, Day One Therapeutics, Geanno BioResearch Funding: Genentech (Inst), Kazia Therapeutics (Inst) Stefan RutkowskiConsulting or Advisory Role: Bristol Myers Squibb GmbH & Co. KGaA, Germany, Celgene, Roche Pharma AG, Grenzach-Wyhlen, Bayer Germany Giles RobinsonResearch Funding: Novartis (Inst), Genentech/Roche (Inst), Novartis (Inst), SpringWorks Therapeutics (Inst) Eric BouffetConsulting or Advisory Role: NovartisResearch Funding: Roche (Inst) Lucie Lafay-CousinHonoraria: Servier, Innomar StrategiesNo other potential conflicts of interest were reported.