Paediatric Integrated Cancer Service

Hospital standardised mortality ratio (HSMR) is a simple ratio that is plagued by sparsity, dimensionality, overdispersion, exclusions and controversy. Describe Hospital Outcome Prediction Equation V.7 (HOPE-7) methodology. State of Victoria (Australia), population 6.8 million. Multiphase process: (a) principal diagnoses aggregated into 406 clinical diagnosis groups (CDGs); (b) low case fatality rate (CFR<0.02%) CDGs set aside; (c) remaining CDGs ranked according to predicted risk; (d) final generalised linear model fitted to (75%) training dataset; (e) low-risk cases reinserted and allocated zero risk; (e) model performance in validation dataset assessed for calibration (Hosmer-Lemeshow goodness-of-fit (H10), Brier score, calibration plot), discrimination (area under the receiver operator characteristic (AUCROC) and area under the precision recall (AUCPRC) curves) and classification (dispersion value (φ), SD random effect (τ)). Ideal model: Brier score~0, H10 p value>0.05, AUCROC>0.80, AUCPRC>0.30, φ~1 and τ~0. Classification assessed by proportion of outlier CFR reclassified as inlier HSMR. 315 hospitals treated 12.97 million adult separations and 152 (48.3%) reported 63 806 in-hospital deaths, 0.49 (95% CI 0.48 to 0.50) per 100 separations. 10 722 principal diagnoses allocated to 198 non-significant CDGs, 45 low-risk CDGs (5.05 million cases) assigned zero risk and 163 significant CDGs aggregated to 20 risk ranks. Final model (development cohort 9.73 million) included demographic variables (age, birth sex, emergency, aged-care resident, hospital transfer, relationship status), one interaction term (emergency transfer) and 20 diagnosis-risk categories. Validation metrics (cohort 3.24 million): Brier score 0.015; H10 p value 0.09; AUCROC 0.90 (95% CI 0.87 to 0.92); AUCPRC 0.28 (95% CI 0.25 to 0.31); φ=4.31 and τ=0.24. Study hospitals generated 2192 hospital quarters with 2053 (95.7%) outlier CFR values, of which 1975 (96.2%) reclassified as HSMR inliers. HOPE-7 is a parsimonious and pragmatic HSMR model based on administrative data common to many jurisdictions that displayed satisfactory calibration, classification and discrimination metrics and addressed frequent HSMR limitations.

BackgroundLocal treatment of pelvic Ewing Sarcoma (EWS) is czhallenging due to complex anatomy and potential complications. Local therapy may be deferred to maintain chemotherapy dose-intensity, but the impact of this delay on outcomes remains unclear.Methods A systematic review using the PICO model evaluated whether delayed local therapy affects long-term outcomes in localized pelvic EWS. Ovid Medline, Ovid Embase, and Cochrane Central databases were searched through June 2024. Studies were screened by two independent reviewers for quantitative and qualitative data extraction.ResultsOf 1849 studies screened, eight eligible studies including 2618 patients were identified; none were pelvic-specific. When specified, 1–18% had pelvic primaries. All studies were retrospective with substantial heterogeneity in endpoints. Seven of eight studies indicated delayed local therapy was associated with reduced event-free survival (EFS) and/or overall survival (OS). In the largest study (Lin et al.) of 1319 EWS patients, delayed local therapy > 16 weeks was associated with significantly reduced OS (HR 1.41, CI 1.11–1.80, p = 0.005).Conclusion This systematic review highlights the importance of multidisciplinary coordinated care during initial chemotherapy to optimize local therapy timing, which may impact outcomes. Further studies are needed to assess timing significance, particularly for pelvic EWS.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00432-025-06286-8.

BackgroundPosaconazole is used to prevent and treat invasive fungal infections (IFIs) in immunocompromised children, including those undergoing cancer treatment or HSCT. Despite differences in pharmacokinetics and IFI epidemiology between children and adults, therapeutic targets established in adult studies are often applied to children.ObjectivesThis systematic review evaluated the correlation between serum posaconazole concentrations and clinical outcomes of IFI prophylaxis and treatment in children with malignancies or HSCT recipients.MethodsFour databases (Cochrane, Embase, MEDLINE and PubMed) were searched for studies involving children (≤18 years old) receiving cancer treatment or HSCT that reported posaconazole serum concentrations and treatment outcomes. Animal studies, those primarily in adult (>18 years old) populations, non-malignant conditions (excluding HSCT), case reports, letters, editorials, conference abstracts and narrative reviews were excluded. Bias was assessed using the Newcastle–Ottawa scale.ResultsNineteen studies were included: 12 reported outcomes of posaconazole prophylaxis; two of treatment; and five of both. For prophylaxis, breakthrough IFIs occurred in 1%–12% of children. All but one occurred with serum concentrations of ≤0.7 mg/L. For treatment, no clear association was observed between a trough concentration of >1.0 mg/L and treatment efficacy, with poor outcomes reported for serum concentrations ranging between 0.2 and 4.8 mg/L. Overall, quality of evidence was poor (medium to high risk of bias for 18 papers, low risk for 1 paper) and there was variation in IFI definitions across studies.ConclusionsThis review supports current recommendations for posaconazole prophylaxis in paediatric oncology and HSCT recipients. The absence of a clear correlation found between serum trough concentrations and treatment efficacy highlights the need for further studies to determine optimal therapeutic targets for treatment.

Chronic disseminated candidiasis (CDC) is a rare complication of immunosuppression. This review describes the presentation, management, and outcomes of CDC in pediatric patients with cancer or following hematopoietic cell transplant (HCT). PubMed, Embase, and Medline were searched identifying 32 studies, describing 95 cases of CDC. CDC occurred almost exclusively in patients with leukemia (91%), with only 5% occurring in lymphoma, 1% post HCT, and 3% in solid tumor. The most frequent presenting symptoms were fever (97%) and abdominal pain (45%), with lesions in liver in 63% and spleen in 54% (less common in kidney, lungs and skin/soft tissue). Of the 67 (71%) episodes with microbiological confirmation, Candida tropicalis (28%) was the most common causative species. Antifungal treatment durations varied from 14days to 28months. Additionally, 31 (33%) patients received an adjuvant therapy, the most common being corticosteroids. Mortality, directly attributable to CDC, occurred in nine (9%). There remains insufficient data to guide a unified approach to management.

ObjectivesLung complications occur commonly post‐haematopoietic stem cell transplant (HCT) in children and contribute significantly to mortality. The development of biomarkers predictive of post‐HCT lung complications may improve outcomes for these children. Therefore, the primary objective of this study was to identify pre‐transplant plasma biomarkers predictive of lung complications in children undergoing HCT.MethodsPlasma samples from 117 pre‐HCT patients were used to measure 78 soluble immune analytes, and extensive clinical metadata were retrospectively collected from the electronic medical record, including clinical characteristics of the post‐HCT lung complications.ResultsFirstly, we showed that the plasma cytokine signature of children undergoing HCT differed significantly between children depending on the indication for HCT (malignant vs non‐malignant). Secondly, we found that the plasma cytokine signature changed with the age of the patient. Thirdly, we showed that elevated pre‐HCT plasma levels of CXCL9 and Chitinase 3‐like 1, both induced by IFN‐γ, were predictive of post‐HCT lung complications in patients with a malignant indication for HCT [area under the curve (AUC): 0.70, P = 0.0007 and AUC: 0.68, P = 0.0016, respectively].ConclusionIn conclusion, we have identified two potential biomarkers of post‐HCT lung disease in paediatric patients and these require validation in future cohorts.

BackgroundIn 2018, Palliative Care Australia issued a report outlining nine standards which intended to guide and support the delivery of high-quality palliative care in Australia. Standard 8 encouraged services to structurally integrate quality improvement into their care provision.1 The changing patient demographic marked by increasingly older patients affected by chronic disease and the growing variety of interventions available contribute to increasing complexity in palliative care.2 Quality improvement seeks to address these emerging complexities and the knowledge gaps that exist. Its aim is to improve and develop service provision by identifying best practice in the care of individuals affected by life-limiting illness.2 3ObjectivesThe quality and safety audit tool was introduced to improve palliative care service provision at Austin Health, a tertiary metropolitan public hospital in Victoria.MethodsThe tool is utilised in fortnightly meetings attended by clinicians across the palliative care service. Contributing teams include the palliative care ward, consults, clinic, and outreach service. Aligned with the National Consensus Statement: Essential elements for safe and high-quality end-of-life care, fifteen ‘Quality Alerts’ form the framework used to systematically identify patient cases that warrant discussion.4 These ’Quality Alerts’ reflect the multidimensionality of palliative care and cover areas such as quality of death, challenging symptom management, family distress, voluntary assisted dying requests, care dissatisfaction, complex case management, service partnership issues and referrals for interventional procedures and outcomes. These cases and issues are then reviewed during these meetings, where actionable outcomes are documented and taken forwards by allocated clinicians. This process allows for internal ‘peer review’ to occur, demonstrating both successes in care and areas for improvement.2 Providing a safe and approachable environment in which to explore these cases is essential to its efficacy.ResultsThis framework prompts regular dialogue about patient care and service provision, providing a space for clinicians to reflect and debrief. It has translated into service-wide benefits including the strengthening of interdepartmental relationships, furthering collaboration with community services, complex case discussions, identifying education and research opportunities, policy/guideline development and quality improvement projects. Further to this, it has and continues to create tangible outcomes for patients and carers with complex specialist palliative care needs. Collectively, it embeds a culture of quality and safety into local palliative care provision.ConclusionThe use of a quality and safety audit tool in a hospital-based palliative care service can drive quality improvement to support the delivery of high-quality palliative care to optimise patient outcomes.ReferencesPalliative Care Australia. National palliative care standards 5th edn; 2018.Higginson IJ, Hocaoglu MB. Clinical audit, quality improvement, and safety in palliative medicine. In: Oxford Textbook of Palliative Medicine. Sixth. Oxford University Press; 2021. p. 1335–50.Kamal AH, Nicolla JM, Power S. Quality improvement pearls for the palliative care and hospice essional. Journal of Pain and Symptom Management. 2017 Nov;54(5):758–65.Australian Commission on Safety and Quality in Health Care. National consensus statement: essential elements for safe and high-quality end-of-life care. 2023.

Fever and infection are an important complication of childhood cancer therapy. Most research and guideline development has focussed on febrile neutropenia, with a paucity directed at non-neutropenic fever (NNF). We describe the clinical presentation, management and outcomes of NNF in children with cancer, and externally validate the Esbenshade Vanderbilt (EsVan) clinical decision rules (CDR) to predict bacteraemia. Using a prospective database, retrospective data were collected on consecutive NNF episodes (fever ≥38.0°C and absolute neutrophil count >1.0cells/mm3 ). Sensitivity, specificity and area under the receiver operator characteristic curve (AUC-ROC) of the CDR were compared to derivation study. There were 203 NNF episodes occurring in 125 patients. Severe sepsis was uncommon (n=2, 1%) and bacteraemia occurred in 10 (4.9%, 95% confidence interval [CI]: 2.7%-8.8%) episodes. A confirmed or presumed bacterial infection requiring antibiotics occurred in 31 (15%) patients. Total 202 (99%) episodes received at least one dose of intravenous broad-spectrum antibiotic and 141 (70%) episodes were admitted to hospital. Six (3%) episodes required intensive care unit (ICU)-level care and there were no infection-related deaths. The EsVan 1 rule had an AUC-ROC of 0.67, 80% were identified as low risk, and sensitivity and specificity were 50% and 81.5%, respectively, for a risk threshold of 10%. Serious infection and adverse outcome are uncommon in children with NNF. Many children did not have a bacterial cause of infection identified, but were still treated with broad-spectrum antibiotics and admitted to hospital. National clinical practice guidelines should be developed for this important cohort to enable risk stratification and optimise antibiotic management. Further research is required to determine appropriateness of EsVan CDR in our cohort.