Abstract
High-risk medulloblastomas (HR-MB) may not respond to induction chemotherapy, with either post-induction stable (SD) or progressive disease (PD). There is no consensus regarding their optimal management. A retrospective, multicentre study investigated patients with non-responder HR-MB treated according to the PNET HR + 5 protocol (NCT00936156) between 01/01/2009 and 31/12/2018. After two courses of etoposide and carboplatin (induction), patients with SD or PD were analyzed. Upon clinician's decision, the PNET HR + 5 protocol was either pursued with tandem high-dose chemotherapy (HDCT) and craniospinal irradiation (CSI) (continuation group) or it was modified (switched group). Forty-nine patients were identified. After induction, 37 patients had SD and 12 had PD. The outcomes were better for the SD group: the 5-y PFS and OS were 52% (95% CI 35-67) and 70% (95% CI 51-83), respectively, in the SD group while the 2-y PFS and OS were 17% (95% CI 3-41) and 25% (95% CI 6-50), respectively, in the PD group (p < 0.0001). The PNET HR + 5 strategy was pursued for 3 patients in the PD group, of whom only one survived. In the SD group, it was pursued for 24/37 patients whereas 13 patients received miscellaneous treatments including a 36Gy CSI in 12 cases. Despite that continuation and switched group were well-balanced for factors impacting the outcomes, the latter were better in the continuation group than in the switched group: the 5-y PFS were 78% (95% CI 54-90) versus 0% (p < 0.001), and the 5-y OS were 78% (95% CI 54-90) versus 56% (95% CI 23-79) (p = 0.0618) respectively. In the SD group, multivariate analysis revealed that MYC amplification, molecular group 3, and a switched strategy were independent prognostic factors for progression. Patients with post-induction SD may benefit from HDCT and CSI, whereas patients with early PD will require new therapeutic approaches.
Highlights
Medulloblastoma (MB) is the most common type of malignant brain tumor in childhood, accounting for 20% of all brain tumors [1]
Patients with post-induction Stable disease (SD) may benefit from high-dose chemotherapy (HDCT) and craniospinal irradiation (CSI), whereas improvement of the way patients with early progressive disease (PD) are treated will require new therapeutic approaches
These treatments encompass the use of induction chemotherapy followed by CSI [3]; CSI followed by four courses of tandem high-dose chemotherapy (HDCT)[4]; and induction chemotherapy followed by hyperfractionated accelerated CSI followed by either HDCT or maintenance therapy according to the pre-irradiation status [5]
Summary
Medulloblastoma (MB) is the most common type of malignant brain tumor in childhood, accounting for 20% of all brain tumors [1]. Various chemotherapy regimens have been developed in a number of different countries and combined with historically used craniospinal irradiation (CSI) with the objective of improving outcomes These treatments encompass the use of induction chemotherapy followed by CSI [3]; CSI followed by four courses of tandem high-dose chemotherapy (HDCT)[4]; and induction chemotherapy followed by hyperfractionated accelerated CSI followed by either HDCT or maintenance therapy according to the pre-irradiation status [5]. After removal of the primary tumor, the therapy consisted of two courses of induction chemotherapy followed by tumor reassessment and tandem thiotepa-based HDCT, CSI, and maintenance therapy. Details of this strategy are provided in the Methods section. The modified “Saint Jude” strategy consisting of CSI followed by four cycles of cisplatin, vincristine, and cyclophosphamide HDCT [4] is occasionally used in a salvage setting
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