Invasive Fungal Infection in Childhood Embryonal Brain Tumour Treatment: A 10-year Review

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Abstract

Background

Invasive fungal infection (IFI) is well recognised in children with acute leukaemia and allogeneic haematopoietic stem-cell transplantation but is poorly characterised in children with brain tumours. Children receiving intensive therapy for embryonal brain tumours (EBTs) have multiple potential risk exposures including corticosteroids, central venous access, neurosurgical devices, mucosal injury and myelosuppressive chemotherapy with, in selected protocols, autologous stem-cell rescue.

Methods

We performed a single-centre retrospective cohort study of children aged 0–18 years treated for EBTs between 2015-2025. IFIs were classified as proven, probable, possible, or modified possible using EORTC/MSGERC and TERIFIC criteria. Clinical characteristics, treatment exposures, timing, microbiology and outcomes were described. IFI prevalence was calculated using exact binomial confidence intervals. Exploratory Cox proportional hazards analyses assessed associations with clinical and treatment factors.

Results

Seventy-seven patients were included. Fourteen patients experienced 15 IFI episodes, giving a patient-level IFI prevalence of 18.2% (95% CI, 10.3– 28.6%). Proven or probable IFI occurred in seven patients (9.1%; 95% CI, 3.7–17.8%). Nine episodes had microbiological evidence. Non-mould pathogens predominated, accounting for six of nine identified pathogens. Treatment on ACNS0334/ACNS0333 was associated with a lower hazard of proven/probable IFI compared with SJMB12 (HR 0.062; 95% CI, 0.002–0.78; p=0.031). Two patients had chemotherapy delays exceeding one month, one had persistent infection at 12 months; no deaths were directly attributed to IFI. Three patients received antifungal prophylaxis.

Conclusion

Rates of IFI following intensive embryonal brain tumour therapy were comparable to those in other high-risk oncology populations. Local consideration of antifungal prophylaxis is warranted.

Key Points

  • Among children receiving intensive therapy for embryonal brain tumours, 18.2% developed an IFI of any category and 9.1% developed proven or probable IFI.

  • Non-mould infections predominated, accounting for 6/9 mycologically identified episodes (67%).

  • Importance of the Study

    Invasive fungal infection (IFI) risk is poorly described during paediatric brain tumour treatment. Incidence has not previously been reported in embryonal brain tumours despite these children having multiple risk exposures including corticosteroids, central venous access, neurosurgical devices, mucosal injury and myelosuppressive chemotherapy with, in selected protocols, autologous stem-cell rescue. Our study addresses this gap by describing IFI incidence, timing and microbiology during intensive EBT therapy, in a denominator-defined cohort. Our findings help identify EBT treatment as a potentially under-recognised setting for IFIs and support prospective evaluation of risk-stratified prevention strategies.

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