Long term outcome of adolescent and adult patients with pineal parenchymal tumors treated with fractionated radiotherapy between 1982 and 2003 -- a single institution's experience

Background: To evaluate the effectivity of fractionated radiotherapy in adolescent and adult patients with pineal parenchymal tumors (PPT). Methods: Between 1982 and 2003, 14 patients with PPTs were treated with fractionated radiotherapy. 4 patients had a pineocytoma (PC), one a PPT with intermediate differentiation (PPTID) and 9 patients a pineoblastoma (PB), 2 of which were recurrences. All patients underwent radiotherapy to the primary tumor site with a median total dose of 54 Gy. In 9 patients with primary PB treatment included whole brain irradiation (3 patients) or irradiation of the craniospinal axis (6 patients) with a median total dose of 35 Gy. Results: Median follow-up was 123 months in the PC patients and 109 months in the patients with primary PB. 7 patients were free from relapse at the end of follow-up. One PC patient died from spinal seeding. Among 5 PB patients treated with radiotherapy without chemotherapy, 3 developed local or spinal tumor recurrence. Both patients treated for PB recurrences died. The patient with PPTID is free of disease 7 years after radiotherapy. Conclusion: Local radiotherapy seems to be effective in patients with PC and some PPTIDs. Diagnosis and treatment of patients with more aggressive variants of PPTIDs as well as treatment of PB need to be further improved, since local and spinal failure even despite craniospinal irradiation (CSI) is common. As PPT are very rare tumors, treatment within multi-institutional trials remains necessary

Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes.

Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histologic review, methylation profiling, and custom panel, genome, or exome sequencing. After excluding tumors representing other established entities or subgroups, we identified 130 cases to be part of an "intrinsic" spectrum of disease specific to the infant population. These included those with targetable MAPK alterations, and a large proportion of remaining cases harboring gene fusions targeting ALK (n = 31), NTRK1/2/3 (n = 21), ROS1 (n = 9), and MET (n = 4) as their driving alterations, with evidence of efficacy of targeted agents in the clinic. These data strongly support the concept that infant gliomas require a change in diagnostic practice and management. SIGNIFICANCE: Infant high-grade gliomas in the cerebral hemispheres comprise novel subgroups, with a prevalence of ALK, NTRK1/2/3, ROS1, or MET gene fusions. Kinase fusion-positive tumors have better outcome and respond to targeted therapy clinically. Other subgroups have poor outcome, with fusion-negative cases possibly representing an epigenetically driven pluripotent stem cell phenotype.See related commentary by Szulzewsky and Cimino, p. 904.This article is highlighted in the In This Issue feature, p. 890

A phase I/II study of CY and topotecan in patients with high-risk malignancies undergoing autologous hematopoietic cell transplantation: the St Jude long-term follow-up

Fifty-eight consecutive children with high-risk malignancies were treated with CY, and targeted topotecan followed by autologous hematopoietic cell transplantation (AHCT) in a phase I/II Institutional Review Board-approved study. Twelve participants enrolled in phase I; 5 received dose level 1 of topotecan 3 mg/m(2) per day, with subsequent doses targeted to total systemic exposure of 100±20 ng h/mL and CY 750 mg/m(2) per day. Seven participants received dose level 2. CY dose escalation to 1 g/m(2) per day was considered excessively toxic; one died from irreversible veno-occlusive disease and two experienced reversible hepatotoxicity. These adverse events halted further dose escalation. A total of 46 participants were enrolled in phase II; results are on the 51 participants who received therapy at dose level 1, the maximum tolerated dose. Diagnoses included neuroblastoma (26), sarcoma (9), lymphoma (8), brain tumors (5), Wilms (2) and retinoblastoma (1). Twenty participants (39.3%) were in CR1 at enrollment; median age was 5.1 years. Most common non-hematological grade III-IV toxicity was gastrointestinal (n=37). Neutrophil and platelet engraftment occurred at a median of 15 and 24 days, respectively. Twenty-six (51%) participants remain alive at a median of 6.4 years after AHCT. CY 3.75 g/m(2), and targeted topotecan followed by AHCT are feasible and produce acceptable toxicity in children with high-risk malignancies.Bone Marrow Transplantation advance online publication, 19 March 2012; doi:10.1038/bmt.2012.51