ABSTRACT
We conducted integrative somatic-germline analyses by deeply sequencing 864 cancer-associated genes, complete genomes and transcriptomes for 300 mostly previously treated children and adolescents/young adults with cancer of poor prognosis or with rare tumors enrolled in the SickKids Cancer Sequencing (KiCS) program. Clinically actionable variants were identified in 56% of patients. Improved diagnostic accuracy led to modified management in a subset. Therapeutically targetable variants (54% of patients) were of unanticipated timing and type, with over 20% derived from the germline. Corroborating mutational signatures (SBS3/BRCAness) in patients with germline homologous recombination defects demonstrates the potential utility of PARP inhibitors. Mutational burden was significantly elevated in 9% of patients. Sequential sampling identified changes in therapeutically targetable drivers in over one-third of patients, suggesting benefit from rebiopsy for genomic analysis at the time of relapse. Comprehensive cancer genomic profiling is useful at multiple points in the care trajectory for children and adolescents/young adults with cancer, supporting its integration into early clinical management.
Subject(s)
Neoplasms , Young Adult , Adolescent , Humans , Child , Neoplasms/drug therapy , Neoplasms/genetics , Mutation , Genomics , Transcriptome/genetics , Homologous RecombinationABSTRACT
OBJECTIVE: The aim of the study was to declare a call to action to improve mental health in the workplace. METHODS: We convened a public health summit and assembled an Advisory Council consisting of experts in the field of occupational health and safety, workplace wellness, and public policy to offer recommendations for action steps to improve health and well-being of workers. RESULTS: The Advisory Council narrowed the list of ideas to four priority projects. CONCLUSIONS: The recommendations for action include developing a mental health in the workplace (1) "how to" guide, (2) scorecard, (3) recognition program, and (4) executive training.
