Precision-guided treatment in high-risk pediatric cancers.
Loretta M S LauDong Anh K Khoung-QuangChelsea MayohMarie WongPaulette BarahonaPamela AjuyahAkanksha SenapatiSumanth NagabushanAlexandra SherstyukAnn-Kristin AltekoesterNoemi A Fuentes-BolanosVeronica YeungAshleigh SullivanNatacha OmerYonatan DiamondSophie JessopLauren BattagliaNataliya ZhukovaLujing CuiAngela LinAndrew J GiffordEmmy D G FleurenLuciano Dalla-PozzaAndrew S MooreSeong-Lin KhawDavid D EisenstatNicholas G GottardoPaul J WoodHeather TappFrank AlvaroGeoffrey McCowageWayne NichollsJordan R HansfordNeevika ManoharanRishi Sury KotechaMarion K MateosRichard B LockVanessa TyrrellMichelle HaberToby N TrahairMark J CowleyPaul G EkertGlenn M MarshallDavid S ZieglerPublished in: Nature medicine (2024)
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.
Keyphrases
- childhood cancer
- young adults
- end stage renal disease
- chronic kidney disease
- newly diagnosed
- healthcare
- ejection fraction
- clinical trial
- prognostic factors
- free survival
- papillary thyroid
- randomized controlled trial
- peritoneal dialysis
- quality improvement
- electronic health record
- metabolic syndrome
- single cell
- single molecule
- replacement therapy
- adipose tissue
- data analysis
- phase ii
- chronic pain