Precision-guided treatment in high-risk pediatric cancers.

Recent research showed that precision medicine can identify new treatment strategies for patients with childhood cancers. However, it is unclear which patients will benefit most from precision-guided treatment (PGT). Here we report consecutive data from 384 patients with high-risk pediatric cancer (with an expected cure rate of less than 30%) who had at least 18 months of follow-up on the ZERO Childhood Cancer Precision Medicine Program PRecISion Medicine for Children with Cancer (PRISM) trial. A total of 256 (67%) patients received PGT recommendations and 110 (29%) received a recommended treatment. PGT resulted in a 36% objective response rate and improved 2-year progression-free survival compared with standard of care (26% versus 12%; P = 0.049) or targeted agents not guided by molecular findings (26% versus 5.2%; P = 0.003). PGT based on tier 1 evidence, PGT targeting fusions or commenced before disease progression had the greatest clinical benefit. Our data show that PGT informed by comprehensive molecular profiling significantly improves outcomes for children with high-risk cancers. ClinicalTrials.gov registration: NCT03336931.

Late effects and treatment related morbidity associated with treatment of neuroblastoma patients in a tertiary paediatric centre.

BACKGROUND: Survival of neuroblastoma patients has improved over recent decades, but chronic health issues and treatment related late effects cause significant morbidity in survivors. AIMS: We aimed to describe late effects and long-term toxicity in neuroblastoma patients treated at a tertiary, paediatric institution in Australia. METHODS & RESULTS: Patients with neuroblastoma treated primarily at The Children's hospital at Westmead were eligible for inclusion. Retrospective analysis of 65 (45 with high-risk and 20 with non-high-risk disease) neuroblastoma patients were performed via medical record review. Approximately 60% of patients were >5 years from diagnosis and termed the "full effects cohort" who had a range of medical and psychosocial late effects analysed through descriptive means. The remaining 26 patients who had not yet reached 5 years post treatment had audiometry analysis only. Of the 65 patients, 72% were alive at last follow-up. The median length of follow-up was 7 years from diagnosis amongst survivors. Therapy was according to contemporary protocols for neuroblastoma and ranged from standard cytotoxic therapies to intensive multimodal regimens and/or experimental therapy depending on risk group/relapse status. Of the 39 full effects cohort, 85% suffered from at least one late effect. Late effects were common in the endocrine, dental and audiometry domains with 38%, 49% and 72% of patients affected in these areas, respectively. Neuro-cognitive domains were also notably affected with 46% of patients suffering a deficit. Two thirds of survivors were disease free at last follow-up. CONCLUSION: Survivors of high-risk neuroblastoma suffer from a range of chronic illnesses, which lead to morbidity and affect quality of life of survivors.

Spectrum of Disease in Children Treated for Tuberculosis at a Tertiary Children's Hospital in Australia.

BACKGROUND: Tuberculosis (TB) notification rates in Australia have plateaued at a low level, but the pediatric disease burden remains poorly described. Child cases provide a marker of recent transmission and present unique diagnostic challenges. METHODS: We performed an audit of all children (<18 years of age) treated for TB at the Children's Hospital at Westmead, Sydney, Australia from January 2008 to December 2011. Demographics, clinical presentation, diagnostics, disease profile, treatment, and outcome were reviewed. RESULTS: A total of 25 children were treated for TB: 15 had microbiologically confirmed TB; 7 were diagnosed on clinical grounds; and in 3, an alternate diagnosis was established (2 bacille Calmette-Guérin disease and 1 atypical mycobacterial infection). Of the 22 TB cases, 21 had a history of immigration or travel to a TB-endemic country and 4 reported recent contact with a TB source case within Australia. Isolated intrathoracic TB was documented in 16 (72%) cases. Symptoms on presentation included the following: lethargy, weakness, or malaise (75%); fever (73%); and cough (64%). Among the 15 children with microbiologically confirmed TB, 11 (73%) were positive by culture and 11 of 13 (85%) by polymerase chain reaction test. Tuberculin skin test was positive (≥10 mm) in 80% (16 of 20) of cases, and interferon-gamma release assay was positive in 87% (13 of 15) of cases. All children received directly observed therapy and recovered. CONCLUSIONS: This series demonstrates the broad spectrum of disease with which pediatric TB cases present and the need for ongoing vigilance. A more comprehensive review of pediatric TB cases throughout Australia would be informative.