Michael Sullivan

Background: Platinum-based chemotherapy is known to cause severe and debilitating hearing loss, but unlike cisplatin, the true incidence of carboplatin-induced hearing loss remains unclear. We evaluated functional hearing outcomes in children receiving carboplatin to determine the incidence and severity of ototoxicity. Procedure: We identified a large cohort of children with cancer treated with carboplatin and graded their audiograms using the SIOP ototoxicity scale. Patients with inadequate audiological follow-up, prior hearing loss, or exposure to cisplatin were excluded. Fisher’s exact test, logistic regression, and ROC analyses were performed to investigate associations of demographic, treatment, and exposure-related risk factors with incidence of hearing loss. Results: 200 patients were included, all of whom had been treated with carboplatin. Only nine (4.5%) patients developed clinically significant hearing loss (SIOP grade ≥2). Younger age at first exposure to carboplatin was the only significant predictor of hearing loss (OR = 0.7888, p=0.0241). Age ≤28 months was significantly associated with hearing loss (OR 12.37, p=0.0042). No other risk factors or exposures were statistically significant. Conclusions: Clinically significant carboplatin-associated hearing loss was uncommon (incidence 4.5%). We show that young age is the single-most important risk factor for hearing loss; of nine children who developed hearing loss, eight were aged ≤28 months. Children below this age have twelve-fold higher odds of developing hearing loss compared to those above this age (OR 12.37). These findings will allow physicians to provide more appropriate counselling to families regarding ototoxic risk and support intensified hearing surveillance in young children.

The 2021 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS5) is the sixth in a series of WHO classification systems published since 1979.¹ Built upon the WHO 2016 classification, the 2021 classification includes advanced molecular analysis to refine the diagnosis of CNS tumors and to assist with treatment stratification and treatment selection.¹ While lauded as a landmark in the integration of traditional morphological diagnosis with modern molecular and genomic classifiers,^2,3 the 2021 WHO “Blue Book” has been criticized as setting an unattainable standard for the pathological diagnosis of brain cancers, and for being beyond the limited resources and equitable reach of healthcare services in Low- and Middle-Income Countries (LMICs).^4,5

Improving the outcomes for children with cancer in low- and middle-income countries (LMICs) presents a great challenge for health care professionals and their health services. Many factors contribute to the poorer outcomes for childhood cancer in LMICs, including advanced disease at diagnosis, delays in referral and access to cancer care, and limited resources for the […]

Background: With more patients reaching survivorship, cardiovascular disease and its complications are posing an emerging problem for both oncologists and cardiologists [(1)](#ref-0001). There is a paucity of data on parent/carer or patient understanding of cardiotoxicity as a consequence of cancer therapy nor do we know the educational needs as identified by them. Objective: To determine the understanding of the long-term cardiac effects of therapy from a patient and carer perspective and what educational tools are seen as valuable. Method: This is a qualitative study using grounded theory and inductive thematic analysis. Participants were sampled from Australian Cardio-Oncology Registry Study at The Royal Children’s Hospital, Melbourne Australia and was HREC approved. Patient and parents/carers of children aged 1-18 years old who had been diagnosed with cancer were invited to participate. Semi-structured interviews were conducted via Zoom, with interviews being recorded and then transcribed to allow for thematic analysis. Findings: Twenty-one participants were recruited, with one participant being a young adult cancer survivor. A basic awareness of cardiac toxicity was expressed by all participants. Themes of feeling overwhelmed on diagnosis with poor information retention was common. Revisiting these conversations with preference for long-term side effects being discussed closer to end of treatment was highlighted as well as the provision of survivorship plans. Trust in primary physicians was a prominent theme, with most participants expressing desire to seek information from their treating team as well as hospital electronic resources. Conclusion: Better understanding of the educational needs of families of childhood cancer patients and survivors around cardiac risk and toxicity supports a family-centred approach to care.

PURPOSE: Hearing loss occurs in 50%-70% of children treated with cisplatin. Scientific efforts have led to the recent approval of a pediatric formula of intravenous sodium thiosulfate (STS) for otoprotection by the US Food and Drug Administration, the European Medicines Agency, and the Medicines and Health Regulatory Authority in the United Kingdom. To inform stakeholders regarding the clinical utility of STS, the current review summarizes available literature on the efficacy, pharmacokinetics (PK), and safety of systemic STS to minimize cisplatin-induced hearing loss (CIHL). DESIGN: A comprehensive narrative review is presented. RESULTS: Thirty-one articles were summarized. Overall, systemic STS effectively reduces CIHL in the preclinical and controlled clinical study settings, in both adults and children with cancer. The extent of CIHL reduction depends on the timing and dosing of STS in relation to cisplatin. Both preclinical and clinical data suggest that systemic STS may affect plasma platinum levels, but studies are inconclusive. Delayed systemic administration of STS, at 6 hours after the cisplatin infusion, does not affect cisplatin-induced inhibition of tumor growth or cellular cytotoxicity in the preclinical setting, nor affect cisplatin efficacy and survival in children with localized disease in the clinical setting. CONCLUSION: Systemic administration of STS effectively reduces the development and degree of CIHL in both the preclinical and clinical settings. More studies are needed on the PK of STS and cisplatin drug combinations, the efficacy and safety of STS in patients with disseminated disease, and the ability of STS to prevent further deterioration of pre-established hearing loss.

International and national oncofertility networks, including the US‐led Oncofertility Consortium, FertiProtekt, and the Danish Network, have played pivotal roles in advancing the discipline of oncofertility over the last decade. Many other countries lack a shared approach to pediatric oncofertility health service delivery. This study aims to describe baseline oncofertility practices at Australian New Zealand Children's Haematology/Oncology Group centers in 2019–2021, describe binational priorities for care, and propose a 5‐year action plan for best practice to be implemented by the newly formed Australian New Zealand Consortium in Children, Adolescents, and Young Adults (CAYA) Oncofertility (ANZCO).

Background: Intra-arterial chemotherapy (IAC) is increasingly used in managing patients with retinoblastoma. In Australia, IAC is primarily used as a globe-salvage treatment when primary treatment has failed. Methods: A retrospective, single-institution study conducted on consecutive children treated with IAC at the Royal Children’s Hospital, Victoria, Australia between September 2009 to January 2021. Results: Using the Intraocular Classification of Retinoblastoma (ICRB), 16 eyes of 14 children classified as group A (n=1), Group B (n=3), Group D (n=10), or Group E (n=2) were treated with IAC. All but one child received IAC as secondary treatment for relapsed or refractory disease. Successful catheterisation of the ophthalmic artery was achieved in 37/46 (80.4%) procedures. A systemic complication occurred in one child (n=1): radiological evidence of a watershed infarct. Local complications of IAC included conjunctival injection (n=1), forehead rash (n=1), sixth cranial nerve palsy (n=2), ptosis (n=2), hemi-retinal ischaemia (n=1), choroidal ischaemia (n=1), retinal detachment (n=2), and choroidal neovascularisation (n=1). Regional extra-ocular disease occurred in one child. No child had distant metastatic disease and no child died. The overall globe salvage rate was 8/16 (50%): Group A (n=1, 100%), group B (n=2, 66.6%), Group D (n=5, 50%), group E (n=0, 0%). Kaplan Meier analysis of ocular survival following treatment with IAC was 75%, 68% and 53% for 6 months, 1 year and 2 years, respectively. Conclusions: Our experience demonstrates that IAC can be a useful treatment modality for refractory retinoblastoma in globe salvage, with an acceptable side-effect profile.

Development of portable Raman instrumentation over the past two decades has expanded in-field application of the method in areas including forensics, minerology, and plant pathology. Recently, Raman spectroscopy has attracted the interest of researchers from these fields because of its minimal interference from water and significant reduction of equipment costs. In this paper we demonstrate a hyperspectral Raman system capable of identifying minerals using very short integration times suitable for fast scanning of mining cores. Hyperspectral scans showed strong local Raman features of the known minerals in the core samples measured.

PURPOSE: The global pediatric oncology clinical research landscape, particularly in Central and South America, Africa, and Asia, which bear the highest burden of global childhood cancer cases, is less characterized in the literature. Review of how existing pediatric cancer clinical trial groups internationally have been formed and how their research goals have been pursued is critical for building global collaborative research and data-sharing efforts, in line with the WHO Global Initiative for Childhood Cancer.METHODS: A narrative literature review of collaborative groups performing pediatric cancer clinical research in each continent was conducted. An inventory of research groups was assembled and reviewed by current pediatric cancer regional and continental leaders. Each group was narratively described with identification of common structural and research themes among consortia.RESULTS: There is wide variability in the structure, history, and goals of pediatric cancer clinical trial collaborative groups internationally. Several continental regions have longstanding endogenously-formed clinical trial groups that have developed and published numerous adapted treatment regimens to improve outcomes, whereas other regions have consortia focused on developing foundational database registry infrastructure supported by large multinational organizations or twinning relationships.CONCLUSION: There cannot be a one-size-fits-all approach to increasing collaboration between international pediatric cancer clinical trial groups, as this requires a nuanced understanding of local stakeholders and resources necessary to form partnerships. Needs assessments, performed either by local consortia or in conjunction with international partners, have generated productive clinical trial infrastructure. To achieve the goals of the Global Initiative for Childhood Cancer, global partnerships must be sufficiently granular to account for the distinct needs of each collaborating group and should incorporate grassroots approaches, robust twinning relationships, and implementation science.