Sir Peter MacCallum Department of Oncology - Theses
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ItemFever and neutropenia in children with cancer: optimising clinical research and the delivery of care in Australia( 2017)Fever and neutropenia (FN) is the most common complication of childhood cancer treatment. Management traditionally involves hospital admission for antibiotics until resolution of fever and recovery of neutrophil count. However, children with FN are a heterogeneous group with varying risk of severe infection, and this approach over treats up to half of all episodes where risk of serious complications is low. Unlike FN management for adults, formal low-risk treatment strategies for children are not routinely employed. In Australia, little is known about the aetiology and management of FN in children and clinical decision rules (CDRs), designed to predict infection, have not been validated. These factors remain a critical barrier to implementing ambulatory-care programs for children with low-risk FN in this country. Such programs are safe, improve quality of life (QoL) and reduce healthcare expenditures. The overall aims of this thesis were to optimise clinical paediatric FN research; to advance our understanding of the assessment and management of FN in children with cancer in Australia; and to facilitate treatment that is tailored to the patient’s risk of infection. Each project addresses important evidence gaps, namely the absence of standardised paediatric FN research outcomes and definitions, the lack of a contemporary evaluation of FN management in Australia and the limited use of risk-based treatment algorithms. To optimise clinical paediatric FN research, Delphi survey methodology was used to achieve consensus on a set of core variables and outcomes that should be reported in all FN studies. This is the first time a paediatric-specific FN research framework has been developed and is the result of an international collaboration. Standardised FN research outcomes will reduce heterogeneity between studies, minimise reporting bias and enable research results to be compared, contrasted and combined. To advance our understanding of the management of FN in Australia, a national practice survey was conducted. There was clear evidence of heterogeneity in assessment, risk stratification and treatment of children with FN. The survey identified critical knowledge gaps and deviations from best practice, and the results will be used to inform guidelines, education and low-risk program implementation strategies. It also highlighted the necessity for validation studies to determine which CDRs are most appropriate for use in Australia. A series of studies were conducted to facilitate FN treatment that is tailored to the risk of infection. In a retrospective study, seven CDRs were validated, of which two exhibited the most clinically meaningful results. The accompanying economic evaluation highlights opportunities for substantial healthcare savings by reducing length of stay (LOS) for low-risk patients. The systematic review and meta-analysis of the predictive ability of novel biomarkers found that marked heterogeneity between studies limits firm conclusions, and further research is required. This thesis has addressed key evidence gaps and contributed new knowledge that will optimise clinical FN research and the delivery of FN care to children with cancer. It has informed the national Australian Predicting Infectious ComplicatioNs in Children with Cancer (PICNICC) project that will prospectively validate CDRs, identify novel biomarkers and evaluate the cost and QoL associated with standard FN treatment. It has also established a collaborative network that will ensure FN research continues in this country and results are translated into practice.