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BACKGROUND Only few data are available on treatment-associated behavior of distinct rare CNS-embryonal tumor entities previously treated as “CNS-primitive neuroectodermal tumors” (CNS-PNET). Respective data on specific entities, including CNS neuroblastoma, FOXR2 activated (CNS NB-FOXR2), and embryonal tumor with multi-layered rosettes (ETMR) are needed for development of differentiated treatment strategies. METHODS Within this retrospective, international study, tumor samples of clinically well-annotated patients with the original diagnosis of CNS-PNET were analyzed using DNA methylation arrays (n=307). Additional cases (n=66) with DNA methylation pattern of CNS NB-FOXR2 were included irrespective of initial histological diagnosis. Pooled clinical data (n=292) were descriptively analyzed. RESULTS DNA methylation profiling of “CNS-PNET” classified 58(19%) cases as ETMR, 57(19%) as HGG, 36(12%) as CNS NB-FOXR2, and 89(29%) cases were classified into 18 other entities. Sixty-seven (22%) cases did not show DNA methylation patterns similar to established CNS tumor reference classes. Best treatment results were achieved for CNS NB-FOXR2 patients (5-year PFS: 63%±7%, OS: 85%±5%, n=63), with 35/42 progression-free survivors after upfront craniospinal irradiation (CSI) and chemotherapy. The worst outcome was seen for ETMR and HGG patients with 5-year PFS of 18%±6% and 22%±7%, and 5-year OS of 24%±6% and 25%±7%, respectively. CONCLUSION The historically reported poor outcome of CNS-PNET patients becomes highly variable when tumors are molecularly classified based on DNA methylation profiling. Patients with CNS NB-FOXR2 responded well to current treatments and a standard-risk-CSI based regimen may be prospectively evaluated. The poor outcome of ETMR across applied treatment strategies substantiates the necessity for evaluation of novel treatments.

PURPOSE Adequate clinical services have yet to be established in the majority of African countries, where childhood cancer survival rates vary from 8.1% to 30.3%. The aim of this review is to describe the landscape of pediatric oncology trials in Africa, identify challenges, and offer future opportunities for research collaborations. METHODS The study includes data from the International Pediatric Oncology Society (SIOP) global mapping survey, meta-research identifying trials in Africa in ClinicalTrials.gov, and a literature overview of publications on the subject of pediatric oncology clinical research supported by expert opinions on the current situation and challenges. RESULTS The SIOP global mapping survey received responses from 47 of 54 African countries, of which 23 have active clinical research programs. A preliminary search of ClinicalTrials.gov showed that only 105 (12.1%) of 868 African oncology studies included children and adolescents. Of these, 53 (50.5%) were interventional trials according to the registry’s classification. The small number of African trials for children and adolescents included palliative care and leukemia trials. In African oncology journals and international pediatric oncology journals, < 1% of the pediatric oncology publications come from Africa. Services and research were strengthened by international collaboration. National studies focused on clinical needs, local challenges, or interventional priorities. Both the literature review and the expert opinions highlight the need to expand clinical research in Africa, despite ongoing regional instability and lack of resources. CONCLUSION While a low number of pediatric clinical treatment trials are open to African children and adolescents, clinical research of high quality is being done in Africa. Several initiatives are stimulating the development of the research capacity across the continent, which should increase the publication output.

Crude ligninolytic enzyme extracts from Phanerochaete chrysosporium fungi were applied to sugarcane bagasse, prior to thermomechanical (TMP) and chemithermomechanical pulping (CTMP), and their properties were compared with the normal TMP and CTMP and also with TMP and CTMP pretreated with Ceriporiopsis subvermispora and P. chrysosporium fungi. The sugarcane bagasse was impregnated with the crude enzyme extract containing lignin peroxidase (LiP), manganese peroxidase (MnP), and laccase (Lac). The results show that pretreatment with enzyme crude extract is an advantageous way to produce TMP and CTMP from sugarcane bagasse, as compared with only fungal pretreatment. Enzymatic pretreatments need only hours to enhance pulping and paper properties, compared with the weeks necessary for fungal treatments. Higher pulp yields were obtained compared with the fungal pretreatments. Enzymatic pretreatment reduced the energy consumption in a proportion similar to that of C. subvermispora fungal pretreatment and increased the pulp tensile index compared with the normal TMP and CTMP pulps, although the tensile strength was somewhat lower than that for pulps from C. subvermispora fungal pretreatment before CTMP processing. An advantage of enzymatic pretreatment is that brightness is increased compared with normal TMP and CTMP processes, whereas fungal pretreatments reduce the brightness.