Survival rates of children and young adolescents with CNS tumors improved in the Netherlands since 1990: A population-based study

Introduction Survival of children with central nervous system (CNS) tumors varies largely between countries. For the Netherlands, detailed population-based estimation of incidence, survival and mortality of pediatric CNS tumors are lacking but are needed to evaluate progress. Methods All CNS tumors diagnosed in patients <18 years during 1990-2017 were selected from the Netherlands Cancer Registry. Other than pilocytic astrocytomas, non-malignant tumors were included since 2000. Incidence and mortality trends were evaluated by Average Annual Percentage Change (AAPC). Changes over time in Five-year Observed Survival (5-year OS) were evaluated by Poisson regression models adjusted for follow-up time. Results Between 1990 and 2017, 2057 children were diagnosed with a malignant CNS tumor and 885 with a pilocytic astrocytoma. During 2000-17, 695 children were diagnosed with other non-malignant CNS tumors. Incidence rates of malignant tumors remained stable, while pilocytic astrocytomas and other non-malignant tumors increased by 2.0% and 2.4% per year, respectively. 5-year OS rates improved for all groups; however, improvement for malignant tumors was not constant over time. The contribution of malignant tumors located at the optic nerve tumors was 1% in 2000-09. However, shifting from pilocytic astrocytomas, increased to 6% in 2010-17, impacting survival outcomes for malignant tumors. Conclusion Survival rates of CNS tumors improved over time, but was not accompanied by a decreasing mortality rate. The observed temporary survival deterioration for malignant tumors appears to be related to changes in diagnostics and registration practices. Whether differences in treatment regimens contribute to this temporary decline in survival needs to be verified.

An Integrated Analysis of Tumor Purity of Common Central Nervous System Tumors in Children Based on Machine Learning Methods

Background: Tumor purity is defined as the proportion of cancer cells in the tumor tissue, and its effects on molecular genetics, the immune microenvironment, and the prognosis of children’s central nervous system (CNS) tumors are under-researched.Methods: We applied random forest machine learning, the InfiniumPurify algorithm, and the ESTIMATE algorithm to estimate the tumor purity of every child’s CNS tumor sample in several published pediatric CNS tumor sample datasets from Gene Expression Omnibus (GEO), aiming to perform an integrated analysis on the tumor purity of children’s CNS tumors.Results: Only the purity of CNS tumors in children based on the random forest (RF) machine learning method was normally distributed. In addition, the children’s CNS tumor purity was associated with primary clinical pathological and molecular indicators. Enrichment analysis of biological pathways related to the purity of medulloblastoma (MB) revealed some classical signaling pathways associated with MB biology and development-related pathways. According to the correlation analysis between MB purity and the immune microenvironment, three immune-related genes, namely, CD8A, CXCR2, and TNFRSF14, were negatively related to MB purity. In contrast, no significant correlation was detected between immunotherapy-associated markers, such as PD-1, PD-L1, and CTLA4; most infiltrating immune cells; and MB purity. In the tumor purity–related survival analysis of MB, ependymoma (EPN), and children’s high-grade glioma, we discovered a minor effect of tumor purity on the survival of the aforementioned pediatric patients with CNS tumors.Conclusion: Our purity pediatric pan-CNS tumor analysis provides a deeper understanding and helps with the clinical management of pediatric CNS tumors.

Development of a Semiautomated Search Tool to Identify Grading From Pathology Reports for Tumors of the CNS and Prostate Cancers

PURPOSE This study demonstrates the functionality of semiautomated algorithms to classify cancer-specific grading from electronic pathology reports generated from military treatment facilities. Two Perl-based algorithms are validated to classify WHO grade for tumors of the CNS and Gleason grades for prostate cancer. METHODS Case-finding cohorts were developed using diagnostic codes and matched by unique identifiers to obtain pathology records generated in the Military Health System for active duty service members from 2013 to 2018. Perl-based algorithms were applied to classify document-based pathology reports to identify malignant CNS tumors and prostate cancer, followed by a hand-review process to determine accuracy of the algorithm classifications. Inter-rater reliability, sensitivity, specificity, positive predictive values (PPVs), and negative predictive values were computed following abstractor adjudication. RESULTS The high PPV for the Perl-based algorithms to classify CNS tumors (PPV > 98%) and prostate cancer (PPV > 99%) supports this approach to classify malignancies for cancer surveillance operations, mediated by a hand-reviewed semiautomated process to increase sensitivity by capturing ungraded cancers. Early detection was pronounced where 33.6% and 50.7% of malignant records retained a CNS WHO grade of II or a Gleason score of 6, respectively. Sensitivity metrics met criteria (> 75%) for brain (79.9%, 95% CI, 73.0 to 85.7) and prostate (96.7%, 95% CI, 94.9 to 98.0) cancers. CONCLUSION Semiautomated, document-based text classification using Perl coding successfully leveraged identification of WHO and Gleason grades to classify pathology records for CNS tumors and prostate cancer. The process is recommended for data quality initiatives to support cancer reporting functions, epidemiology, and research.

MPC-8 Serum anti-zinc finger FYVE domain-containing protein 21 (ZFYVE21) autoantibody as a novel biomarker for oligodendroglioma IDH-mutant and 1p/19q co-deletion

Background: Glioma is one of the most challenging diseases to cure, and it would be beneficial to discover new serum biomarkers for early diagnosis. Moreover, zinc finger FYVE domain-containing protein 21 (ZFYVE21) was a regulator of tumor invasion and migration. In this study, we examined the levels of serum anti-ZFYVE21 antibodies in patients with glioma. Methods: This is a multicenter observational prospective study to discover a novel serum autologous antibody marker. We analyzed 286 pre-surgically collected sera of CNS tumors and compared them to healthy donors(HD). Bacterially expressed glutathione-S-transferase-fused ZFYVE21 protein was purified, and its antibody levels were measured by amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA). Results: The anti-ZFYVE21 antibody levels were significantly elevated in patients with gliomas (P<0.001) than those in HD, instead of patients with other CNS tumors. Among gliomas, the highest sensitivity was observed for oligodendroglioma containing IDH mutation and 1p/19q co-deletion to HD (sensitivity: 72.00%, specificity: 67.71%, AUC: 0.7565, P<0.0001), while there is no significance in astrocytoma containing only IDH mutation. In comparing 1p/19q co-deleted oligodendroglioma with IDH-mutated astrocytoma, the sensitivity and specificity were 50% and 100%, respectively. Conclusion: Serum anti-ZFYVE21 antibodies might be a novel diagnostic marker distinguishing 1p/19q co-deleted oligodendroglioma from IDH-mutant astrocytoma.

AURKA gene polymorphisms and central nervous system tumor susceptibility in Chinese children

Introduction Central nervous system (CNS) tumors comprise 15–20% of all malignancies occurring in childhood and adolescence. Previous researches have shown that overexpression and amplification of the AURKA gene could induce multiple human malignancies, with which the connection of CNS tumor susceptibility has not been extensively studied. Material and methods In this study, we assessed whether and to what extent AURKA gene single nucleotide polymorphisms (SNPs) (rs1047972 C > T, rs2273535 T > A, rs8173 G > C) were associated with CNS tumor susceptibility, based on a case–control analysis in 191 CNS tumor patients and 248 controls. We determined this correlation using odds ratios (ORs) and 95% confidence intervals (CIs). Results AURKA gene rs8173 G > C exhibited a crucial function to CNS tumor susceptibility fall-off (GC/CC vs. GG: adjusted OR = 0.68, 95% CI = 0.46–0.998, P = 0.049). In addition, the combined effect of lowering the risk of developing CNS tumors was more pronounced in carriers with 3 protective genotypes than others (adjusted OR = 0.55, 95% CI = 0.31–0.98, P = 0.044). Further stratification analysis illustrated that the existence of rs8173 GC/CC and three protective genotypes lowered CNS tumor risk in some subgroups. Conclusions Our research suggested that the AURKA gene rs8173 G > C could significantly reduce CNS tumor susceptibility in Chinese children. More functional experiments are needed to explore the role of the AURKA gene rs8173 G > C.

Epidemiology of Brain and Other CNS Tumors

Purpose of Review Brain and other central nervous system (CNS) tumors, while rare, cause significant morbidity and mortality across all ages. This article summarizes the current state of the knowledge on the epidemiology of brain and other CNS tumors. Recent Findings For childhood and adolescent brain and other CNS tumors, high birth weight, non-chromosomal structural birth defects and higher socioeconomic position were shown to be risk factors. For adults, increased leukocyte telomere length, proportion of European ancestry, higher socioeconomic position, and HLA haplotypes increase risk of malignant brain tumors, while immune factors decrease risk. Summary Although no risk factor accounting for a large proportion of brain and other CNS tumors has been discovered, the use of high throughput “omics” approaches and improved detection/measurement of environmental exposures will help us refine our current understanding of these factors and discover novel risk factors for this disease.