Clinical Validity of Circulating Tumor DNA as Prognostic and Predictive Marker for Personalized Colorectal Cancer Patient Management

Circulating tumor DNA (ctDNA) is a promising liquid biopsy (LB) marker to support clinical decisions in precision medicine. For implementation into routine clinical practice, clinicians need precise ctDNA level cutoffs for reporting residual disease and monitoring tumor burden changes during therapy. We clinically validated the limit of blank (LOB) and the limit of quantification (LOQ) of assays for the clinically most relevant somatic variants BRAF p.V600E and KRAS p.G12/p.G13 in colorectal cancer (CRC) in a study cohort encompassing a total of 212 plasma samples. We prove that residual disease detection using the LOB as a clinically verified cutoff for ctDNA positivity is in concordance with clinical evidence of metastasis or recurrence. We further show that tumor burden changes during chemotherapy and the course of disease are correctly predicted using the LOQ as a cutoff for quantitative ctDNA changes. The high potential of LB using ctDNA for accurately predicting the course of disease was proven by direct comparison to the routinely used carcinoembryonic antigen (CEA) as well as the circulating free DNA (cfDNA) concentration. Our results show that LB using validated ctDNA assays outperforms CEA and cfDNA for residual disease detection and the prediction of tumor burden changes

Additional educational needs in children born to mothers with epilepsy

OBJECTIVES—To examine the relative risks of additional educational needs (AENs) in children exposed to antiepileptic drug (AED) monotherapy and polytherapy regimes in utero.
METHODS—A retrospective survey of women between the ages of 16 to 40 registered at the Mersey Regional Epilepsy Clinic, who received a postal questionnaire concerning their experience of pregnancy and the subsequent schooling of live-born children.
RESULTS—721 (57%) women of the 1267 approached returned an adequately completed questionnaire; 330 (46%) had given birth to at least one live-born child. Information was collected on 594 children, 400 of whom were of school age (4-18). 150 (37.5%) had been exposed to monotherapy in utero, 74 (18.5%) were exposed to polytherapy, and 176 were not exposed to any AEDs. The odds ratio of AENs for all children exposed to AEDs in utero compared with those unexposed was 1.49 (95% confidence interval (95% CI) 0.83 -2.67). Odds ratios for AENs for each therapy subgroup compared with those unexposed were also calculated for all children. Those exposed to valproate monotherapy had an odds ratio of 3.4 (95% CI 1.63-7.10) by contrast with an odds ratio of 0.26 (95% CI 0.06- 1.15) for carbamazepine. Polytherapy including valproate had similarly high odds ratios for AENs compared with those unexposed of 2.51 ( 95% CI 1.04-6.07) versus the odds ratio of 1.51 ( 95% CI 0.56-4.07) for polytherapy excluding valproate.
CONCLUSIONS—Although the findings should be treated with caution, they suggest that monotherapy or polytherapy with valproate during pregnancy carries particular risks for the development of children exposed in utero.


Mapping European Association of Urology Guideline Practice Across Europe: An Audit of Androgen Deprivation Therapy Use Before Prostate Cancer Surgery in 6598 Cases in 187 Hospitals Across 31 European Countries

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