External Quality Assessment on Molecular Tumor Profiling with Circulating Tumor DNA-Based Methodologies Routinely Used in Clinical Pathology within the COIN Consortium.

BACKGROUND: Identification of tumor-derived variants in circulating tumor DNA (ctDNA) has potential as a sensitive and reliable surrogate for tumor tissue-based routine diagnostic testing. However, variations in pre(analytical) procedures affect the efficiency of ctDNA recovery. Here, an external quality assessment (EQA) was performed to determine the performance of ctDNA mutation detection work flows that are used in current diagnostic settings across laboratories within the Dutch COIN consortium (ctDNA on the road to implementation in The Netherlands). METHODS: Aliquots of 3 high-volume diagnostic leukapheresis (DLA) plasma samples and 3 artificial reference plasma samples with predetermined mutations were distributed among 16 Dutch laboratories. Participating laboratories were requested to perform ctDNA analysis for BRAF exon 15, EGFR exon 18-21, and KRAS exon 2-3 using their regular circulating cell-free DNA (ccfDNA) analysis work flow. Laboratories were assessed based on adherence to the study protocol, overall detection rate, and overall genotyping performance. RESULTS: A broad range of preanalytical conditions (e.g., plasma volume, elution volume, and extraction methods) and analytical methodologies (e.g., droplet digital PCR [ddPCR], small-panel PCR assays, and next-generation sequencing [NGS]) were used. Six laboratories (38%) had a performance score of >0.90; all other laboratories scored between 0.26 and 0.80. Although 13 laboratories (81%) reached a 100% overall detection rate, the therapeutically relevant EGFR p.(S752_I759del) (69%), EGFR p.(N771_H773dup) (50%), and KRAS p.(G12C) (48%) mutations were frequently not genotyped accurately. CONCLUSIONS: Divergent (pre)analytical protocols could lead to discrepant clinical outcomes when using the same plasma samples. Standardization of (pre)analytical work flows can facilitate the implementation of reproducible liquid biopsy testing in the clinical routine.

InterStim Sacral Neuromodulation and Botox Botulinum-A Toxin Intradetrusor Injections for Refractory Urge Urinary Incontinence: A Decision Analysis Comparing Outcomes Including Efficacy and Complications.

OBJECTIVE: : Overactive bladder is a common disease for which current pharmaceutical therapy is often unsatisfactory. Newer modalities, including Botox and InterStim, can be used when antimuscarinics fail. We compare InterStim and Botox using decision analysis. METHODS: : A Markov state transition decision analysis model was constructed using values for efficacy and complications from the literature. Overall utility was compared monthly. Multiple 1-way sensitivity analyses were performed. RESULTS: : For every month during the simulation, overall utility was higher for Botox than InterStim. After 54 months, cumulative utility was 3.86 versus 3.74, favoring Botox for an average yearly quality-adjusted life-year value of 0.86 versus 0.83. All differences were less than minimally important differences for utilities. Few meaningful thresholds were established supporting the robustness of the model. CONCLUSIONS: : Until appropriately powered randomized controlled trials are available, both InterStim and Botox are reasonable and effective strategies with similar outcomes.

High costs of urinary incontinence among women electing surgery to treat stress incontinence.

OBJECTIVE: To estimate costs for incontinence management, health-related quality of life, and willingness to pay for incontinence improvement in women electing surgery for stress urinary incontinence. METHODS: A total of 655 incontinent women enrolled in the Stress Incontinence Surgical Treatment Efficacy Trial, a randomized surgical trial. Baseline out-of-pocket costs for incontinence management were calculated by multiplying self-report of resources used (supplies, laundry, dry cleaning) by national resource costs (USD2,006). Health-related quality of life was estimated with the Health Utilities Index Mark 3. Participants estimated willingness to pay for 100% improvement in incontinence. Potential predictors of these outcomes were examined by using multivariable linear regression. RESULTS: Mean age was 52+/-10 years, and mean number of weekly incontinence episodes was 22+/-21. Mean and median (25%, 75% interquartile range) estimated personal costs for incontinence management among all women were USD14+/-USD24 and USD8 (interquartile range USD3, USD18) per week, and 617 (94%) women reported any cost. Costs increased significantly with incontinence frequency and mixed compared with stress incontinence. The mean and median Health Utilities Index Mark 3 scores were 0.73+/-0.25 and 0.84 (interquartile range 0.63, 0.92). Women were willing to pay a mean of USD118+/-USD132 per month for complete resolution of incontinence, and willingness to pay increased significantly with greater expected incontinence improvement, household income, and incontinent episode frequency. CONCLUSION: Urinary incontinence is associated with substantial costs. Women spent nearly USD750 per year out of pocket for incontinence management, had a significant decrement in quality of life, and were willing to pay nearly USD1,400 per year for cure.