Abstract
BACKGROUND
Pineoblastoma (PB) is an aggressive embryonal tumor that has been uniformly treated with high-dose craniospinal irradiation (CSI). Herein, we describe patients diagnosed with PB treated on 2 multi-center, prospective trials with risk-adapted radiation regimens.
METHODS
Patients <3yr received chemotherapy with/without focal irradiation (SJYC07). Patients ≥3yr received risk-adapted CSI (23.4Gy for localized disease, 36–39.6Gy for metastatic) and chemotherapy (SJMB03). DNA methylation was performed using Infinium MethylationEPIC BeadChip and profiled on DKFZ molecularneuropathology2.0 classifier.
RESULTS
40 patients were enrolled (SJMB03=28; SJYC07=12) with 6.07yr median age (range: 0.37–20.4) and 3.8yr median follow-up (range: 0.37–13.1). Twenty-two were stratified as high-risk (HR). All 28 SJMB03 patients received CSI; 6 SJYC07 patients received focal RT and 6 were not irradiated. All but one patient received chemotherapy (parental refusal). On SJMB03, 10/11 non-HR patients receiving 23.4Gy CSI survived without progression (5yr-PFS 100%) as compared to 8/17 HR patients (5yr-PFS 56.3 ± 12.4%). On SJYC07, 11/12 progressed (5yr-PFS 8.3 ± 8.0%). 23/40 tumors (58%) were methylation profiled into the following categories: PBgroupB (N=11), PBgroupA(N=2), pineal parenchymal tumor (N=1), choroid plexus tumor (CPT) (subclass pediatric B) (N=1), with 6 samples having calibrated score <0.9 (associated with medulloblastomagroup3=4, CPT=1, PBgroupB=1, no-match=2). All patients with PB-B were aged ≥3yr with 67% (8/12) surviving progression-free. Patients <3yr had PBgroupA/medulloblastoma/CPT and only 14% (1/7) survived progression-free.
CONCLUSION
Non-metastatic PB in children ≥3yr has excellent survival with average-risk medulloblastoma therapy. The poor survival of young children and HR-PB might be explained by underlying molecular heterogeneity, and clustering of pineal tumors with MBgroup3 or CPT warrants further investigation.