ABSTRACT Ewing Sarcoma of the pelvis has poorer outcomes than other anatomical sites, with complex anatomy often precluding resection with wide margins. The role of postoperative radiotherapy (RT) in improving outcomes remains undefined. A systematic review using Medline, Embase and Cochrane databases (1972–April 2024) evaluated postoperative RT's impact on local recurrence, event‐free survival and overall survival. Twenty‐nine retrospective studies (21 to 296 patients) met inclusion criteria, with 28 rated good quality. Seven of 14 studies showed improved local control with postoperative RT. Ten studies reported consistent but non‐significant trends favoring postoperative RT for event‐free survival. Nineteen studies reported mixed overall survival findings; the Euro‐EWING 99 trial showed significantly improved 5‐year survival (72% vs. 47%, p = 0.024), while others showed conflicting results. Postoperative RT should be considered for high‐risk features including poor response to induction chemotherapy, large tumour volume (> 200 mL) and positive margins. Clinical trial participation should be encouraged. Trial Registration: PROSPERO registration number: CRD42021291665

AIMS:This study aimed to evaluate temporal trends in treatment patterns for localized soft tissue sarcomas (STSs) and identify factors associated with relapse-free survival (RFS) and overall survival (OS). METHODS:A retrospective cohort study was conducted using the Australian Comprehensive Cancer Outcomes and Research Database (ACCORD) and electronic health records from a high-volume sarcoma unit. Patients aged ≥18 years with grade 3, localized STS ≥5 cm diagnosed between 2013 and 2023 were included. The cohort was divided into two periods (2013-2017 and 2018-2023) to assess changes in treatment practices. Kaplan-Meier and Cox proportional hazards models evaluated RFS and OS. RESULTS:Among 202 patients, radiation use decreased in the late period (79% vs. 64%, p = 0.03), with a trend toward increased systemic therapy (8% vs. 16%, p = 0.13). Median RFS was 19 months (95% confidence interval [CI]: 14.9-26.0), with no significant difference between periods (hazard ratio [HR] 1.30, 95% CI: 0.93-1.82, p = 0.13). Median OS was 48 months (95% CI: 38.1-62.9), also showing no difference (HR 1.20, 95% CI: 0.80-1.78, p = 0.38). Radiotherapy improved RFS (HR 0.69, 95% CI: 0.49-0.98, p = 0.04) but not OS. Systemic therapy showed no RFS or OS benefit. Exploratory analyses identified age, tumor size, FDG-PET SUVmax, site, and Sarculator risk as prognostic factors. CONCLUSION:Treatment patterns evolved over time, reflecting emerging evidence, but no significant RFS or OS differences were observed. Further research is needed, including exploring prognostic factors like elevated baseline FDG-PET SUVmax.

Local 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. 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. Of 1849 studies screened, eight eligible studies including 2618 patients were identified; none were pelvic-specific. When specified, 1–18

Sarcomas are a heterogenous group of tumours that commonly carry poor prognosis with limited therapeutic options. Adolescents and young adults (AYAs) with sarcoma are a unique and understudied patient population that have only achieved modest survival gains compared to other groups. We present our institutional experience of AYAs with sarcoma who underwent comprehensive molecular profiling (CMP) via either large-panel targeted DNA sequencing or whole genome and transcriptome sequencing and evaluated the feasibility and clinical impact of this approach. Genomic variants detected were determined to be clinically relevant and actionable following evaluation by the Molecular Tumour Board. Clinicians provided feedback regarding the utility of testing three months after reporting. Twenty-five patients who were recruited for CMP are included in this analysis. The median time from consent to final molecular report was 45 days (interquartile range: 37–57). Potentially actionable variants were detected for 14 patients (56%), and new treatment recommendations were identified for 12 patients (48%). Pathogenic germline variants were identified in three patients (12%), and one patient had a change in diagnosis. The implementation of CMP for AYAs with sarcoma is clinically valuable, feasible, and should be increasingly integrated into routine clinical practice as technologies and turnaround times continue to improve.

Prognosis remains poor for patients with relapsed or refractory Ewing sarcoma, with limited treatment options after first-line therapy. Oral etoposide has efficacy in the paediatric setting; however, data are limited in adults. A retrospective analysis was conducted on 33 patients with relapsed or refractory Ewing sarcoma who completed at least one cycle of oral etoposide at the Peter MacCallum Cancer Centre from 2005 to 2020. The median age at diagnosis and first relapse was 21 and 23 years, respectively. All patients had prior exposure to intravenous etoposide. Nine patients (27%) had stable disease for at least 6 months, and six patients (18%) had a partial response. The clinical benefit rate was 45%. The median PFS was 3.6 months (95% CI: 1.7-5.5), and OS was 8.5 months (95% CI: 4.1-13.0). Despite prior exposure, oral etoposide demonstrated antitumour activity and durable responses in the relapsed or refractory setting for adult patients with Ewing sarcoma.

Abstract Background We present one of only seven reported cases of a catecholamine-secreting adrenal neuroblastoma in an adult. The case is used as a platform to discuss key biochemical, genomic and imaging considerations that are central to the successful, targeted management of catecholamine-secreting adrenal tumours. Case presentation A 63-year-old male was urgently reviewed at a tertiary hospital endocrinology outpatient clinic for a 12 cm right-sided adrenal incidentaloma. Plasma normetanephrine and 3-methoxytyramine levels were approximately 10 times the upper limit of normal at 9272 pmol/L (< 900) and 1023 pmol/L (< 110), respectively. The adrenal mass appeared to be inseparable from the liver on imaging, and thus was suspected to be an invasive malignant phaeochromocytoma. FDG positron emission tomography (PET)/CT demonstrated moderate to intense metabolic activity within the right adrenal mass. [68 Ga]Ga-DOTATATE (Ga-TATE) PET-CT demonstrated patchy, heterogenous somatostatin receptor (SSTR) expression in the adrenal lesion, at most Krenning 3 (intensity above liver). The patient underwent a right adrenalectomy and segment 6/7 liver resection. Histopathology revealed a 130 mm diameter neuroblastoma of the differentiating subtype with a low Mitosis-Karyorrhexis Index. There was lymphovascular invasion and tumour focally present at the resection margin, but no tumour in one periadrenal lymph node, and no tumour invasion in the adherent liver. Immunohistochemistry revealed ALK positivity (+ 3) and wild type ATRX. At nine months following adrenalectomy, the plasma normetanephrine level has reduced to 991 pmol/L (< 900). Post-operative GaTate PET/CT shows no definite abnormal SSTR-expressing lesions in the surgical bed or elsewhere. The patient has completed adjuvant radiotherapy and is a candidate for ALK-targeted therapy if required for recurrence in the future. Conclusions Neuroblastomas may be misdiagnosed as phaeochromocytomas given the ability to secrete catecholamines and similarities in radiological appearance. Differentiating neuroblastomas from phaeochromocytomas and paragangliomas (PPGL) is critical, but clinically difficult. Genomics are central for management; diagnosing ALK-positive neuroblastoma triggers consideration of ALK-targeted therapy, which is not relevant for PPGL. A critical eye is required for the accurate diagnosis and management of malignant adrenal incidentalomas.

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).

Purpose: Cancer and its treatments are known to compromise fertility in adolescents and young adults (AYAs). The emotional burden of possible infertility is reduced in those who receive supportive oncofertility care. In legal minors, provision of health care must consider the legal context and desire that AYAs have for autonomous decision-making, together with their competence to make health decisions. This has important implications for how oncofertility discussions may, or may not, involve parents. The aim of this study was to explore oncofertility decision-making and care experiences in a national Australian sample of AYA cancer patients and their parents. Methods: AYAs aged 15-25 years and parents were recruited from 17 cancer care sites and CanTeen Australia as part of a national AYA cancer care study. The cross-sectional survey included open-ended questions regarding oncofertility care experiences. We used reflexive thematic analysis to identify themes. Results: Data were available for 99 AYAs and 111 parents. Four themes were identified: emotional care needs; parent-AYA dynamics including AYA autonomy and agency; decision-making considerations including values and practicalities; and reflections on oncofertility care and follow-up. Both AYAs and parents placed importance on AYA autonomy in fertility decision-making, but many AYAs appreciated the role of parents in providing support and guidance throughout the process. Conclusion: Health care professionals are encouraged to autonomously engage AYAs around fertility decision-making, while concurrently offering opportunities that promote parental support. Better psychological support and follow-up oncofertility care are also needed.

Study objectiveMultidisciplinary meetings (MDMs) are increasingly implemented in complex care based on the principle that they lead to evidence-based treatment recommendations, foster adherence to clinical guidelines, induce better team performance and improve medical care. In oncofertility, the uncertain outcomes of fertility preservation procedures in children contribute to the complexity of decision-making. There is limited published information on the influence of MDMs on paediatric and adolescent oncofertility care.AimsTo describe the implementation, characteristics & outcomes of multidisciplinary meetings (MDMs) in a paediatric oncofertility setting.MethodsA retrospective medical records review of oncofertility MDMs held between April 2020 and March 2021 at the Royal Children's Hospital Melbourne. Inductive content analysis of the reasons for MDM was undertaken. MDM documentation was scored out of 24, according to a Victorian Paediatric Integrated Cancer Service quality assurance checklist for MDMs, (1)) which included consent for MDM, nature of attendees, quality of discussion and documentation.ResultsOf the 169 oncology patients treated at the Royal Children's Hospital between 1st April 2020 and 31st March 2021, MDMs were required for 40 patients (23.7%). The median number of clinical attendees was 10, and included craft groups from both paediatric and adult centres (oncology, oncofertility, gynaecology, clinical ethics, endocrinology, paediatric surgery, anaesthetics, haematology, fertility specialists and reproductive scientists). Fifty-four percent (n=22) of MDMs were for male patients (median age 8.4 [0.1-16.5] years) and 46% for females (n=18, median age 8.1[0.4-16.3] years). The commonest diagnoses presented at MDM were brain tumours (27.5%), leukemia (25%), and non malignant conditions (19.5%). Approximately 77% of all MDM patients were going to receive treatment that put them at high infertility risk and 62.5% had co-morbidities. MDMs included the following themes (i) likelihood of successful parenthood: disease progression, prognosis, neurocognitive decline; (ii) certainty or otherwise of planned treatment and infertility risks; (iii) mitigation of anaesthetic and surgical risks; (iv) ethical concerns; (v) organizational capacity and logistics in the face of covid restrictions or high dependent care between centres (vi) child and family of risks, expectations and their values regarding fertility preservation. In 87.5% of cases, it was deemed permissible to offer fertility preservation. The median score for the MDMs derived from the quality assurance checklist was 16.ConclussionMDMs acted as a valuable educational and communication tool improving situational awareness, building shared mental models, assisting with risk mitigation and oncofertility planning. Multidisciplinary meetings (MDMs) are increasingly implemented in complex care based on the principle that they lead to evidence-based treatment recommendations, foster adherence to clinical guidelines, induce better team performance and improve medical care. In oncofertility, the uncertain outcomes of fertility preservation procedures in children contribute to the complexity of decision-making. There is limited published information on the influence of MDMs on paediatric and adolescent oncofertility care. To describe the implementation, characteristics & outcomes of multidisciplinary meetings (MDMs) in a paediatric oncofertility setting. A retrospective medical records review of oncofertility MDMs held between April 2020 and March 2021 at the Royal Children's Hospital Melbourne. Inductive content analysis of the reasons for MDM was undertaken. MDM documentation was scored out of 24, according to a Victorian Paediatric Integrated Cancer Service quality assurance checklist for MDMs, (1)) which included consent for MDM, nature of attendees, quality of discussion and documentation. Of the 169 oncology patients treated at the Royal Children's Hospital between 1st April 2020 and 31st March 2021, MDMs were required for 40 patients (23.7%). The median number of clinical attendees was 10, and included craft groups from both paediatric and adult centres (oncology, oncofertility, gynaecology, clinical ethics, endocrinology, paediatric surgery, anaesthetics, haematology, fertility specialists and reproductive scientists). Fifty-four percent (n=22) of MDMs were for male patients (median age 8.4 [0.1-16.5] years) and 46% for females (n=18, median age 8.1[0.4-16.3] years). The commonest diagnoses presented at MDM were brain tumours (27.5%), leukemia (25%), and non malignant conditions (19.5%). Approximately 77% of all MDM patients were going to receive treatment that put them at high infertility risk and 62.5% had co-morbidities. MDMs included the following themes (i) likelihood of successful parenthood: disease progression, prognosis, neurocognitive decline; (ii) certainty or otherwise of planned treatment and infertility risks; (iii) mitigation of anaesthetic and surgical risks; (iv) ethical concerns; (v) organizational capacity and logistics in the face of covid restrictions or high dependent care between centres (vi) child and family of risks, expectations and their values regarding fertility preservation. In 87.5% of cases, it was deemed permissible to offer fertility preservation. The median score for the MDMs derived from the quality assurance checklist was 16. MDMs acted as a valuable educational and communication tool improving situational awareness, building shared mental models, assisting with risk mitigation and oncofertility planning. 1. Paediatric Integrated Cancer Service 2017, Multidisciplinary meeting framework: a guide for Victorian health services providing care to children and adolescents with cancer, Paediatric Integrated Cancer Service, Melbourne.

BACKGROUND:Point-of-care decision support, embedded into electronic medical record (EMR) workflows, has the potential to improve efficiency, reduce unwarranted variation and improve patient outcomes. A clinical-facing best practice advisory (BPA) in the Epic EMR system was developed to identify children admitted with low-risk febrile neutropenia (FN) who should be considered for treatment at home after a brief inpatient stay. We evaluated the accuracy and impact of this BPA and identify areas for improvement.METHODS:The low-risk FN BPA was co-designed with key-stakeholders and implemented after a one-month testing phase. Mixed methodology was used to collect and analyse data. The sensitivity and positive predictive value of the BPA was calculated using FN episodes captured in a prospectively collected database. Overall effectiveness was defined as the proportion of alerts resulting in completion of a FN risk assessment flowsheet.RESULTS:Over the 12-month period 176 FN episodes were admitted. Overall, the alert had poor sensitivity (58%) and positive predictive value (75%), failing to trigger in 62 (35%) episodes. In the episodes where the alert did trigger, the alert was frequently dismissed by clinicians (76%) and the overall effectiveness was extremely low (3%). Manual review of each FN episode without a BPA identified important design limitations and incorrect workflow assumptions.DISCUSSION:Given the poor sensitivity and limited impact on clinician behaviour the low-risk BPA, in its current form, has not been an effective intervention at this site. While work is ongoing to enhance the accuracy of the BPA, alternative EMR workflows are likely required to improve the clinical impact.

Purpose: To understand how adolescents and young adults (AYAs) with cancer experience family and partner involvement in fertility preservation (FP) decision-making. Methods: As part of a nationally representative Australian cross-sectional study of 15-25-year olds with cancer, 196 participants (mean age 19.9 [standard deviation 3.2] years at diagnosis; 51% male) were surveyed regarding FP decision-making. Results: One hundred sixty-one (83%) participants reported discussion of potential effects of cancer and its treatment on fertility, of whom 57 (35%) did not undertake FP (51% of females; 19% of males). Parental involvement (mothers 62%, fathers 45%) in decision-making was considered helpful, including for 73% of 20-25-year olds with partners. Sisters and brothers were involved less often, yet rated helpful in 48% and 41% of cases, respectively. Older participants were more likely than younger ones to have involved partners (47% vs. 22%, p = 0.001) and less likely to have involved mothers (56% vs. 71%, p = 0.04) or fathers (39% vs. 55%, p = 0.04). Conclusion: This is the first quantitative study to explore family and partner involvement in AYA FP decision-making in both females and males in a nationally representative sample. Parents are important resources who commonly assist AYAs with these complex decisions. Although many AYAs will be the main decision-makers when it comes to FP, particularly as AYAs mature, these data suggest that resources and support should be available for and inclusive of parents, partners, and siblings.

Purpose: International data demonstrate association between clinical trial participation and reduced cancer mortality. Adolescents and young adults (AYA) have low clinical trial enrollment rates. We established a program to understand local barriers and develop targeted solutions that lead to greater AYA clinical trial participation. Methods: A steering committee (SC) with expertise in adult and pediatric oncology, research ethics, and consumer representation was formed. The SC mapped barriers related to AYA trial access and established working groups (WGs) around three themes. Results: The Regulatory Awareness WG identified a lack of understanding of processes that support protocol approval for clinical trials across the AYA age range. A guideline to raise awareness was developed. The Access WG identified challenges for young adults (18-25 years) to access a pediatric hospital to enroll in a pediatric trial. A procedure was developed to streamline applications for access. The first six applications using this procedure have been successful. The Availability WG identified lack of pediatric-adult oncology reciprocal relationships as a barrier to awareness of open trials, and future collaboration. An AYA Craft Group Framework was established to grow relationships within tumor streams across institutions; two craft groups are now operating locally. An additional achievement was a successful request to the Therapeutic Goods Administration for Australian adoption of the Food and Drug Administration Guidance on Considerations for the Inclusion of Adolescent Patients in Adult Oncology Clinical Trials. Conclusion: This multipronged approach to improving AYA clinical trial access has relevance for other health environments. Our knowledge products are available as an online toolkit.

ImportanceSpitz nevi are benign melanocytic neoplasms that classically present in childhood. Isolated Spitz nevi have been associated with oncogenic gene fusions in approximately 50% of cases. The rare agminated variant of Spitz nevi, thought to arise from cutaneous genetic mosaicism, is characterized by development of clusters of multiple lesions in a segmental distribution, which can complicate surgical removal. Somatic single-nucleotide variants in the HRAS oncogene have been described in agminated Spitz nevi, most of which were associated with an underlying nevus spilus. The use of targeted medical therapy for agminated Spitz nevi is not well understood.ObservationsA girl aged 30 months presented with facial agminated Spitz nevi that recurred rapidly and extensively after surgery. Owing to the morbidity of further surgery, referral was made to a molecular tumor board. The patient's archival nevus tissue was submitted for extended immunohistochemical analysis and genetic sequencing. Strong ROS1 protein expression was identified by immunohistochemistry. Consistent with this, analysis of whole-genome sequencing data revealed GOPC-ROS1 fusions. These results indicated likely benefit from the oral tyrosine kinase inhibitor crizotinib, which was administered at a dosage of 280 mg/m2 twice daily. An excellent response was observed in all lesions within 5 weeks, with complete flattening after 20 weeks.Conclusions and RelevanceGiven the response following crizotinib treatment observed in this case, the kinase fusion was believed to be functionally consequential in the patient's agminated Spitz nevi and likely the driver mutational event for growth of her nevi. The repurposing of crizotinib for GOPC-ROS1 Spitz nevi defines a new treatment option for these lesions, particularly in cases for which surgery is relatively contraindicated.

Purpose: While central nervous system (CNS) tumors account for only 10% of adolescent and young adult (AYA) cancers, they are the leading cause of cancer death in this age group. Using national data for Australia, we describe the presentation, treatment, and survival for AYAs diagnosed with CNS tumors. Methods: A population-based study of 15-24 year-olds diagnosed with CNS tumors (low- and high-grade glioma [LGG, HGG], medulloblastoma [MB], primitive neuroectodermal tumors [PNET], ependymoma [EP]) or other (e.g., low-grade neuronal tumor) between 2007 and 2012. Clinical details were extracted from hospital medical records for each patient. Treatment centers were classified as pediatric or adult services. Results: Two hundred seventy-five patients (129 LGG, 77 HGG, 23 MB, 10 PNET, 19 EP, 17 other) were identified, with 17% treated at pediatric hospitals. Symptoms (headache [53%], nausea [31%]) were present for a median of 3 weeks before consulting a health professional. Of LGG patients, 15% had radiotherapy (RT) and 12% chemotherapy (CT). Of HGG patients, 81% had RT and 75% CT. All MB and PNET were managed with surgery, and 74% of MB and 80% of PNET had both RT and CT. Treatment did not differ by treatment center type. Five-year survival for LGG and EP was over 80%, but was 42% for HGG and 20% for PNET. Conclusions: This national, population-based study indicates similar treatment for AYA patients with CNS tumors between pediatric and adult services. Poor outcomes for HGG and PNET patients highlight the need for clinical trials of novel approaches for these tumors.

Introduction Home-based treatment of febrile neutropenia (FN) in children with cancer with oral or intravenous antibiotics is safe and effective. There are limited data on the economic impact of this model of care. We evaluated the cost-effectiveness of implementing an FN programme, incorporating home-based intravenous antibiotics for carefully selected patients, in a tertiary paediatric hospital. Methods A decision analytic model was constructed to compare costs and outcomes of the home-based FN programme, with usual in-hospital treatment with intravenous antibiotics. The programme included a clinical decision rule to stratify patients by risk for severe infection and home-based eligibility criteria using disease, chemotherapy and patient-level factors. Health outcomes (quality of life) and probabilities of FN risk classification and home-based eligibility were based on prospectively collected data between 2017 and 2019. Patient-level costs were extracted from hospital administrative records. Cost-effectiveness was expressed as the incremental cost per quality-adjusted life year (QALY). Findings The mean health care cost of home-based FN treatment in low-risk patients was Australian dollars (A$) 7765 per patient compared to A$20,396 for in-hospital treatment (mean difference A$12,632 [95% CI: 12,496-12,767]). Overall, the home-based FN programme was the dominant strategy, being more effective (0.0011 QALY [95% CI: 0.0011-0.0012]) and less costly. Results of the model were most sensitive to proportion of children eligible for home-based care programme. Conclusion Compared to in-hospital FN care, the home-based FN programme is cost-effective, with savings arising from cheaper cost of caring for children at home. These savings could increase as more patients eligible for home-based care are included in the programme.

Background Home-based management of low-risk febrile neutropenia (FN) is safe, improves quality of life and reduces healthcare expenditure. A formal low-risk paediatric program has not been implemented in Australia. We aimed to describe the implementation process and evaluate the clinical impact. Method This prospective study incorporated three phases: implementation, intervention and evaluation. A low-risk FN implementation toolkit was developed, including a care-pathway, patient information, home-based assessment and educational resources. The program had executive-level endorsement, a multidisciplinary committee and a nurse specialist. Children with cancer and low-risk FN were eligible to be transferred home with a nurse visiting daily after an overnight period of observation for intravenous antibiotics. Low-risk patients were identified using a validated decision rule, and suitability for home-based care was determined using disease, chemotherapy and patient-level criteria. Plan-Do-Study-Act methodology was used to evaluate clinical impact and safety. Results Over 18 months, 292 children with FN were screened: 132 (45%) were low-risk and 63 (22%) were transferred to home-based care. Compared with pre-implementation there was a significant reduction in in-hospital median LOS (4.0 to 1.5 days,p < 0.001) and 291 in-hospital bed days were saved. Eight (13%) patients needed readmission and there were no adverse outcomes. A key barrier was timely screening of all patients and program improvements, including utilising the electronic medical record for patient identification, are planned. Conclusion This program significantly reduces in-hospital LOS for children with low-risk FN. Ongoing evaluation will inform sustainability, identify areas for improvement and support national scale-up of the program.