ID #959 Group 3/4 Medulloblastoma of early childhood – risks and benefits of a CSI-sparing therapy approach in young children
Christian Fiedler, Lisa Bussenius, Marthe Sönksen, Till Milde, Dominik Sturm, Felix Sahm, Kristian Pajtler, Tobias Goschzik, Torsten Pietsch, Denise Obrecht-Sturm, Mina Langhein, Anne Rossius, Michael Bockmayr, Rudolf Schwarz, Nina Struve, Annika Hardt, Brigitte Bison, Stefan Pfister, Ulrich Schüller, Rolf-Dieter Kortmann, Stefan Rutkowski, Martin MynarekAbstract
Purpose
Contemporary therapy protocols suggest to delay or avoid craniospinal irradiation (CSI) by applying intensive chemotherapy in children with medulloblastoma up to the age of three to five years due to the high long-term toxicity of CSI in very young children. The optimal age for switching to a CSI-containing strategy needs to be evaluated.
Methods
This is a retrospective analysis of a German patient cohort. Patients were eligible if diagnosed with non-WNT/non-SHH medulloblastoma under 7 years of age and DNA- methylation-based classification profiling was available. Treatment was classified as “infant-type”, if CSI was not planned upfront, planned in the case of incomplete response or progression, or was delivered as an individual decision after “infant-type” chemotherapy [max dose 24 Gy] and as “childhood/adult-type” if CSI in standard doses (max dose 24 Gy in standard risk or 35.2/36 Gy for high-risk disease] was delivered first-line treatment.
Results
372 patients (263 M/109 F) were eligible. The median age at diagnosis was 4.2±1.5 years. With a median follow-up of 5.7 years in surviving patients, 156 patients relapsed, and 129 died. Overall, 194 patients (52.2%, median age: 3.5, range 0.9-7.0) received “infant-type” treatment and 130 patients (34.9%, median age: 5.1, range 2.6-7.0) were treated according to “childhood/adult-type” strategy.
The “infant type” approach was associated with significant inferior progression-free survival (PFS) (5-yearPFS: “infant-type” 38.6%±4.1% vs. “childhood/adult-type” 56.3%±5.0%; pPFS=0.001), and overall-survival (OS) (5-yearOS: “infant-type” 55.0%±4.1% vs. “childhood/adult-type” 68.3%±4.8% pOS = 0.01). This was retained when restricting the analysis to patients between three and five years (n = 163): 5-yearPFS: “infant-type” 42.6%±6.0% vs. “childhood/adult type” 56.0%±7.7%; pPFS=0.03; 5-yearOS: “infant-type” 57.4±6.0% vs. “childhood/adult-type” 69.9%±7.5% pOS = 0.05. Outcome according to molecular classification and neurocognitive testing will be presented at the meeting.
Conclusion
“Infant-type” CSI-sparing approaches were associated with less favourable PFS and OS compared with “childhood/adult-type” strategies including upfront craniospinal irradiation.