Clinical and molecular characterization of isolated M1 disease in pediatric medulloblastoma: experience from the German HIT-MED studies

Obrecht D, Mynarek M, Hagel C, Kwiecien R, Spohn M, Bockmayr M, Bison B, Pfister SM, Jones DTW, Sturm D, von Deimling A, Sahm F, von Hoff K, Juhnke BO, Benesch M, Gerber NU, Friedrich C, von Bueren AO, Kortmann RD, Schwarz R, Pietsch T, Fleischhack G, Schüller U, Rutkowski S

Zusammenfassung

Purpose To evaluate the clinical impact of isolated spread of medulloblastoma cells into cerebrospinal fuid without additional macroscopic metastases (M1-only). Methods The HIT-MED database was searched for pediatric patients with M1-only medulloblastoma diagnosed from 2000 to 2019. Corresponding clinical and molecular data was evaluated. Treatment was stratifed by age and changed over time for older patients. Results 70 patients with centrally reviewed M1-only disease were identifed. Clinical data was available for all and molecular data for 45/70 cases. 91% were non-WNT/non-SHH medulloblastoma (Grp3/4). 5-year PFS for 52 patients≥4 years was 59.4 (±7.1) %, receiving either upfront craniospinal irradiation (CSI) or SKKsandwich chemotherapy (CT). Outcomes did not difer between these strategies (5-year PFS: CSI 61.7±9.9%, SKK-CT 56.7±6.1%). For patients<4 years (n=18), 5-year PFS was 50.0 (±13.2) %. M1-persistence occurred exclusively using postoperative CT and was a strong negative predictive factor (pPFS/OS<0.01). Patients with additional clinical or molecular high-risk (HR) characteristics had worse outcomes (5-year PFS 42.7±10.6% vs. 64.0±7.0%, p=0.03). In n=22 patients≥4 years with full molecular information and without additional HR characteristics, risk classifcation by molecular subtyping had an efect on 5-year PFS (HR 16.7±15.2%, SR 77.8±13.9%; p=0.01). Conclusions Our results confrm that M1-only is a high-risk condition, and further underline the importance of CSF staging. Specifc risk stratifcation of afected patients needs attention in future discussions for trials and treatment recommendations. Future patients without contraindications may beneft from upfront CSI by sparing risks related to higher cumulative CT applied in sandwich regimen.