White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer.
Alessandro LealNicole C T van GriekenDoreen N PalsgroveJillian PhallenJamie E MedinaCarolyn HrubanMark A M BroeckaertValsamo AnagnostouVilmos AdleffDaniel C BruhmJenna V CanzonieroJacob FikselMarianne NordsmarkFabienne A R M WarmerdamHenk M W VerheulDick Johan van SpronsenLaurens V BeerepootMaud M GeenenJohanneke E A PortieljeEdwin P M JansenJohanna van SandickElma Meershoek-Klein KranenbargHanneke W M van LaarhovenDonald L van der PeetCornelis J H van de VeldeMarcel VerheijRemond J A FijnemanRobert B ScharpfGerrit A MeijerAnnemieke CatsVictor E VelculescuPublished in: Nature communications (2020)
Liquid biopsies are providing new opportunities for detection of residual disease in cell-free DNA (cfDNA) after surgery but may be confounded through identification of alterations arising from clonal hematopoiesis. Here, we identify circulating tumor-derived DNA (ctDNA) alterations through ultrasensitive targeted sequencing analyses of matched cfDNA and white blood cells from the same patient. We apply this approach to analyze samples from patients in the CRITICS trial, a phase III randomized controlled study of perioperative treatment in patients with operable gastric cancer. After filtering alterations from matched white blood cells, the presence of ctDNA predicts recurrence when analyzed within nine weeks after preoperative treatment and after surgery in patients eligible for multimodal treatment. These analyses provide a facile method for distinguishing ctDNA from other cfDNA alterations and highlight the utility of ctDNA as a predictive biomarker of patient outcome to perioperative cancer therapy and surgical resection in patients with gastric cancer.
Keyphrases
- circulating tumor
- phase iii
- end stage renal disease
- cancer therapy
- open label
- clinical trial
- circulating tumor cells
- cell free
- chronic kidney disease
- double blind
- ejection fraction
- peritoneal dialysis
- phase ii
- patients undergoing
- single cell
- case report
- cell therapy
- prognostic factors
- drug delivery
- induced apoptosis
- gold nanoparticles
- loop mediated isothermal amplification
- quantum dots
- mesenchymal stem cells
- oxidative stress
- combination therapy
- placebo controlled
- cell death
- study protocol
- endoplasmic reticulum stress
- label free
- acute kidney injury
- smoking cessation
- liquid chromatography
- cell cycle arrest