Management and outcome of children and adolescents with non-medulloblastoma CNS embryonal tumors in Spain: room for improvement in standards of care

Abstract

Non-medulloblastoma CNS embryonal tumors (former PNET/Pineoblastomas) are aggressive malignancies with poor outcome that have been historically treated with medulloblastoma protocols. The purpose of this study is to present a tumor-specific, real-world data cohort of patients with CNS-PNET/PB to analyze quality indicators that can be implemented to improve the outcome of these patients. Patients 0-21 years with CNS-PNET treated in eight large institutions were included. Baseline characteristics, treatment and outcome [progression-free and overall survival (PFS and OS respectively)] were analyzed. From 2005 to 2014, 43 patients fulfilled entry criteria. Median age at diagnosis was 3.6 years (range 0.0-14.7). Histology was pineoblastoma (9%), ependymoblastoma (5%), ETANTR (7%) and PNET (77%). Median duration of the main symptom was 2 weeks (range 0-12). At diagnosis, 28% presented with metastatic disease. Seventeen different protocols were used on frontline treatment; 44% had gross total resection, 42% craniospinal radiotherapy, 86% chemotherapy, and 33% autologous hematopoietic stem cell transplantation (aHSCT). Median follow-up for survivors was 3.5 years (range 1.7-9.3). 3-year PFS was 31.9% (95% CI 17-47%) and OS 35.1% (95% CI 20-50%). Age, extent of resection and radiotherapy were prognostic of PFS and OS in univariate analysis (p < 0.05). Our series shows a dismal outcome for CNS-PNET, especially when compared to patients included in clinical trials. Establishing a common national strategy, implementing referral circuits and collaboration networks, and incorporating new molecular knowledge into routine clinical practice are accessible measures that can improve the outcome of these patients.

Therapeutic implications of improved molecular diagnostics for rare CNS embryonal tumor entities: results of an international, retrospective study

“…[1][2][3]18 Historically, patients with CNS-PNET were treated with age-dependent intensive multimodal treatment strategies resulting in high rates of toxicity and poor survival rates. [13][14][15][16][17][18]24,[43][44][45] Survival rates of the current CNS-PNET re-evaluation cohort are comparable to previously published series. Crucially, our cohort confirms that only a minor proportion of patients included in historical CNS-PNET cohorts can be considered as having CNS embryonal tumors according to current diagnostic methods and criteria.…”

<p>Adverse Factors of Treatment Response and Overall Survival in Pediatric and Adult Patients with Pineoblastoma</p>

“…The use of postoperative radiation has been related to higher OS. [15][16][17][18] Our data indicated a better impact of radiation on favorable prognosis, which did not reach statistical significance, but the tendency that patients with adjuvant radiotherapy had a better survival was notable. Meanwhile, in agreement with previous studies, our cohort demonstrated that adjuvant chemotherapy was a favorable factor for survival.…”

Radiotherapy practice for paediatric brain tumours across Europe and quality assurance initiatives: Current situation, international survey and future perspectives

“…Clinical guidelines are an affordable and straightforward approach towards standardisation of treatments, especially for the management of rare diseases, such as paediatric malignancies. This is particularly important for patients treated outside clinical trials or for whom no clinical trials exist [31]. However, through our survey, we found out that only 48% of the participating countries have national consensus guidelines for the treatment of paediatric CNS tumours.…”