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Temporal changes in childhood cancer incidence and survival by stage at diagnosis in Australia, 2000–2017

The Toronto Paediatric Cancer Stage Guidelines are a compendium of staging systems developed to facilitate collection of consistent and comparable data on stage at diagnosis for childhood cancers by cancer registries.

Reproducible Bioinformatics Analysis Workflows for Detecting IGH Gene Fusions in B-Cell Acute Lymphoblastic Leukaemia Patients

B-cell acute lymphoblastic leukaemia (B-ALL) is characterised by diverse genomic alterations, the most frequent being gene fusions detected via transcriptomic analysis (mRNA-seq). Due to its hypervariable nature, gene fusions involving the Immunoglobulin Heavy Chain (IGH) locus can be difficult to detect with standard gene fusion calling algorithms and significant computational resources and analysis times are required. We aimed to optimize a gene fusion calling workflow to achieve best-case sensitivity for IGH gene fusion detection.

A multi-institutional retrospective pooled outcome analysis of molecularly annotated pediatric supratentorial ZFTA-fused ependymoma

ZFTA-RELA (formerly known as c11orf-RELA) fused supratentorial ependymoma has been recognized as a novel entity in the 2016 WHO classification of CNS tumors and further defined in the recent 2021 edition.

FDA-approved disulfiram as a novel treatment for aggressive leukemia

Acute leukemia continues to be a major cause of death from disease worldwide and current chemotherapeutic agents are associated with significant morbidity in survivors. While better and safer treatments for acute leukemia are urgently needed, standard drug development pipelines are lengthy and drug repurposing therefore provides a promising approach.

Protocol for delivery of intraoperative immunotherapy to mice by surgical debulking of subcutaneous tumors

Pre-clinical studies developing novel therapies to prevent cancer recurrence require appropriate surgical models. Here, we present a protocol for surgical debulking of subcutaneous tumors in mice, which allows for intraoperative application of immunotherapy-loaded biomaterials. 

Insights into the Clinical, Biological and Therapeutic Impact of Copy Number Alteration in Cancer

Copy number alterations (CNAs), resulting from the gain or loss of genetic material from as little as 50 base pairs or as big as entire chromosome(s), have been associated with many congenital diseases, de novo syndromes and cancer. It is established that CNAs disturb the dosage of genomic regions including enhancers/promoters, long non-coding RNA and gene(s) among others, ultimately leading to an altered balance of key cellular functions.

Population-level 5-year event-free survival for children with cancer in Australia

Event-free survival considers other adverse events in addition to mortality. It therefore provides a more complete understanding of the effectiveness and consequences of treatment than standard survival measures, but is rarely reported at the population level for childhood cancer.

The critical role of the bone marrow stromal microenvironment for the development of drug screening platforms in leukemia

Extensive research over the past 50 years has resulted in significant improvements in survival for patients diagnosed with leukemia. Despite this, a subgroup of patients harboring high-risk genetic alterations still suffer from poor outcomes. There is a desperate need for new treatments to improve survival, yet consistent failure exists in the translation of in vitro drug development to clinical application.

Pharmacokinetics of PEGasparaginase in Infants with Acute Lymphoblastic Leukemia

PEGasparaginase is known to be a critical drug for treating pediatric acute lymphoblastic leukemia (ALL), however, there is insufficient evidence to determine the optimal dose for infants who are less than one year of age at diagnosis. This international study was conducted to identify the pharmacokinetics of PEGasparaginase in infants with newly diagnosed ALL and gather insight into the clearance and dosing of this population.

Presence of onco-fetal neighborhoods in hepatocellular carcinoma is associated with relapse and response to immunotherapy

Onco-fetal reprogramming of the tumor ecosystem induces fetal developmental signatures in the tumor microenvironment, leading to immunosuppressive features. Here, we employed single-cell RNA sequencing, spatial transcriptomics and bulk RNA sequencing to delineate specific cell subsets involved in hepatocellular carcinoma  relapse and response to immunotherapy.