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Background and objective Due in part to its effect on intraocular pressure (IOP) measurements, the assessment of central corneal thickness (CCT) is recognized as an essential part of the initial glaucoma assessment. The most widely utilized clinical technique to measure CCT is ultrasound pachymetry (USP). In recent years, many dedicated anterior-segment optical coherence tomography scanners (AS-OCTs) have been developed. Previous studies have compared CCT measurements between USP and various AS-OCTs. This study aimed to assess the degree of agreement between USP and CASIA2 (Tomey Corporation, Nagoya, Japan), a second-generation swept-source AS-OCT developed in Japan. Methodology The data on CCT screening measurements of 156 eyes (88 patients) performed over a period of three months, from January to March 2020, on glaucoma patients attending the Royal Hallamshire Hospital (RHH) in Sheffield, UK were collected retrospectively and statistically analyzed. Results The average age of the 88 patients included in the study was 66 years (range: 20-86 years). Our findings show that when compared to CASIA2 measurements, USP measurement of the CCT resulted in significantly thicker values (paired t-test: t=23.15,p<2.2 x 10-16). The average difference between the two methods was 19.98 ± 10.78 µm. It is hypothesized that this difference may be due in part to inaccurate probe placement during ultrasound probe measurement, resulting in thicker CCT values. Conclusion The observed difference may be clinically significant as it could induce clinical discrepancy in terms of perceived glaucoma risk in patients. Therefore, USP and CASIA2 should not be used interchangeably, and clinicians should take into account the significant difference between these methods.
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BACKGROUND: Better blood tests to elucidate the behaviour of metastatic castration-resistant prostate cancer (mCRPC) are urgently needed to drive therapeutic decisions. Plasma cell-free DNA (cfDNA) comprises normal and circulating tumour DNA (ctDNA). Low-pass whole-genome sequencing (lpWGS) of ctDNA can provide information on mCRPC behaviour. OBJECTIVE: To validate and clinically qualify plasma lpWGS for mCRPC. DESIGN, SETTING, AND PARTICIPANTS: Plasma lpWGS data were obtained for mCRPC patients consenting to optional substudies of two prospective phase 3 trials (FIRSTANA and PROSELICA). In FIRSTANA, chemotherapy-naïve patients were randomised to treatment with docetaxel (75 mg/m2) or cabazitaxel (20 or 25 mg/m2). In PROSELICA, patients previously treated with docetaxel were randomised to 20 or 25 mg/m2 cabazitaxel. lpWGS data were generated from 540 samples from 188 mCRPC patients acquired at four different time points (screening, cycle 1, cycle 4, and end of study). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: lpWGS data for ctDNA were evaluated for prognostic, response, and tumour genomic measures. Associations with response and survival data were determined for tumour fraction. Genomic biomarkers including large-scale transition (LST) scores were explored in the context of prior treatments. RESULTS AND LIMITATIONS: Plasma tumour fraction was prognostic for overall survival in univariable and stratified multivariable analyses (hazard ratio 1.75, 95% confidence interval 1.08-2.85; p = 0.024) and offered added value compared to existing biomarkers (C index 0.722 vs 0.709; p = 0.021). Longitudinal changes were associated with drug response. PROSELICA samples were enriched for LSTs (p = 0.029) indicating genomic instability, and this enrichment was associated with prior abiraterone and enzalutamide treatment but not taxane or radiation therapy. Higher LSTs were correlated with losses of RB1/RNASEH2B, independent of BRCA2 loss. CONCLUSIONS: Plasma lpWGS of ctDNA describes CRPC behaviour, providing prognostic and response data of clinical relevance. The added prognostic value of the ctDNA fraction over established biomarkers should be studied further. PATIENT SUMMARY: We studied tumour DNA in blood samples from patients with prostate cancer. We found that levels of tumour DNA in blood were indicative of disease prognosis, and that changes after treatment could be detected. We also observed a "genetic scar" in the results that was associated with certain previous treatments. This test allows an assessment of tumour activity that can complement existing tests, offer insights into drug response, and detect clinically relevant genetic changes.