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Abstract
Background: Despite intensified frontline therapy for medulloblastoma, 20-30% of patients still experience disease failure. Outcomes for recurrent disease remain poor, largely due to the lack of standardized salvage strategies. This study evaluated treatment patterns and outcomes of salvage therapy in recurrent or progressive medulloblastoma.

Methods: Patients aged ≤ 21 years with histologically confirmed medulloblastoma diagnosed between 2000 and 2020 were analyzed. Inclusion criteria required prior surgery or biopsy followed by postoperative radiotherapy and completion of initial therapy. Disease recurrence or progression was confirmed by MRI and clinical assessment. Local control treatment (LCT) was defined as salvage radiotherapy or surgery. Primary endpoints were progression-free survival (PFS) and overall survival (OS) from initial recurrence.

Results: Seventy-six patients from five centers were included. The median time to first failure was 23.9 months (IQR, 14.9-36.2). Salvage treatments included chemotherapy alone (n = 26), LCT alone (n = 11), and combined LCT and chemotherapy (n = 30); 9 patients received best supportive care. The 1- and 3-year PFS rates were 47.4% and 7.2%, while OS rates were 81.1% and 42.8%, respectively. In univariate analysis, MYCN non-amplification, chemotherapy, and LCT were associated with improved PFS. In multivariate analysis, both chemotherapy (HR, 0.39; p = 0.003) and LCT (HR, 0.51; p = 0.013) remained significant prognostic factors for PFS. For OS, focal relapse and chemotherapy were associated with improved survival.

Conclusions: Outcomes for recurrent medulloblastoma remain unfavorable. However, LCT was associated with improved PFS, while chemotherapy was associated with both improved PFS and OS.

Affiliations

Seok-Joo Chun 1, Nalee Kim 2, Do Hoon Lim 2, Joo-Young Kim 3, Chan Woo Wee 4 5, Hong In Yoon 4 5, Seung Hyuck Jeon 6, In Ah Kim 6, Joo Ho Lee 7 8 9
1Department of Radiation Oncology, Ilsan Dongguk University Hospital, Goyang, the Republic of Korea.
2Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, the Republic of Korea.
3Proton Therapy Center, Research Institute and Hospital, National Cancer Center, Goyang, the Republic of Korea.
4Department of Radiation Oncology, Yonsei Cancer Center, Heavy Ion Therapy Research Institute, Yonsei University College of Medicine, Seoul, the Republic of Korea.
5Brain Research Institute, Yonsei University College of Medicine, Seoul, the Republic of Korea.
6Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam, the Republic of Korea.
7Department of Radiation Oncology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, the Republic of Korea.
8Cancer Research Institute, Seoul National University College of Medicine, Seoul, the Republic of Korea.
9Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, the Republic of Korea.