ABSTRACT
Genomic tumour profiling informs targeted treatment options. Entrectinib is a tyrosine kinase inhibitor with efficacy in NTRK fusion-positive (-fp) solid tumours and ROS1-fp non-small cell lung cancer. FoundationOne® Liquid CDx (F1L CDx), a non-invasive in vitro next-generation sequencing (NGS)-based diagnostic, detects genomic alterations in plasma circulating tumour DNA (ctDNA). We evaluated the clinical validity of F1L CDx as an aid in identifying patients with NTRK-fp or ROS1-fp tumours and assessed the genomic landscape pre- and post-entrectinib treatment. Among evaluable pre-treatment clinical samples (N = 85), positive percentage agreements between F1L CDx and clinical trial assays (CTAs) were 47.4% (NTRK fusions) and 64.5% (ROS1 fusions); positive predictive value was 100% for both. The objective response rate for CTA+ F1L CDx+ patients was 72.2% in both cohorts. The median duration of response significantly differed between F1L CDx+ and F1L CDx- samples in ROS1-fp (5.6 vs. 17.3 months) but not NTRK-fp (9.2 vs. 12.9 months) patients. Fifteen acquired resistance mutations were detected. We conclude that F1L CDx is a clinically valid complement to tissue-based testing to identify patients who may benefit from entrectinib and those with acquired resistance mutations associated with disease progression.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Benzamides , Carcinoma, Non-Small-Cell Lung/genetics , Genomics , Humans , Indazoles , Lung Neoplasms/genetics , Protein-Tyrosine Kinases/genetics , Proto-Oncogene Proteins/geneticsABSTRACT
PURPOSE: To test an anecdotally reported cataract grading system predictive of a 20/50 visual threshold in cataract-induced vision loss using cobalt blue light. SETTING: Hennepin County Medical Center, Minneapolis, Minneapolis VA Medical Center, Minneapolis, and Regions Hospital, St. Paul, Minnesota, USA. METHODS: Four observers evaluated pure nuclear cataracts using a standardized cobalt-blue-light protocol. Observers graded a nuclear cataract as positive if the posterior capsule was visualized with cobalt blue light and negative if the posterior capsule was not visualized. Results of the grading were compared with cataract-induced vision loss in an attempt to establish a threshold for lost visual acuity in grading cataracts with cobalt blue light. The study design was prospective observation of a cohort with a visually significant cataract. RESULTS: This study did not show a clear visual acuity threshold for cataract-induced vision loss using a standardized cobalt-blue-light protocol. Overall, 26.3% (95% confidence interval, 13.4-40.2) of all 20/40 or less dense nuclear cataracts had visible posterior capsules using cobalt blue light, with good estimated interobserver agreement. CONCLUSIONS: Although cobalt blue light is selectively absorbed by yellow pigment in an aging nuclear cataract, its ability to predict visual acuity loss due to lens opacity was limited.
Subject(s)
Cataract/classification , Diagnostic Techniques, Ophthalmological , Light , Vision Disorders/diagnosis , Aged , Aged, 80 and over , Cataract/physiopathology , Cobalt , Female , Humans , Lens Capsule, Crystalline/pathology , Lens Nucleus, Crystalline/physiopathology , Male , Middle Aged , Prospective Studies , Sensory Thresholds/physiology , Vision Disorders/physiopathology , Visual Acuity/physiologyABSTRACT
We report a case of unilateral erythropsia lasting 1 week that occurred 18 years after cataract extraction and intraocular lens (IOL) implantation. The unaffected eye was pseudophakic and had an IOL with ultraviolet (UV) light protection; the affected eye had an IOL without UV light protection.
Subject(s)
Cataract Extraction , Lens Implantation, Intraocular , Postoperative Complications , Vision Disorders/etiology , Aged , Coated Materials, Biocompatible , Humans , Male , Pseudophakia/etiology , Pseudophakia/physiopathology , Ultraviolet Rays , Vision Disorders/physiopathologyABSTRACT
PURPOSE: To identify the major soluble proteins from human vitreous, and to establish a baseline for comparison of vitreous samples from eyes with various diseases. DESIGN: Laboratory investigation. METHODS: Normal vitreous was obtained from eight human donor eyes and from eight eyes of patients undergoing diabetic vitrectomy. Vitreous specimens were subjected to SDS-PAGE and MALDI-TOF-MS analysis. Six specific antibodies were used to identify proteins using Western blot. Four proteins were localized within ocular tissue in a normal donor eyebank eye. RESULTS: We found eight distinct bands on SDS-PAGE in normal vitreous and two additional bands (hemoglobin) in eyes with diabetic retinopathy. Proteins were identified using MALDI-TOF-MS and confirmed by Western blot. We established a quantitative analysis of relative protein concentrations of undiluted vitreous. Immunohistochemistry localized selected proteins within the posterior segment layers. CONCLUSIONS: We present a normal human vitreous protein profile using current technologies and provide a baseline for comparison to ocular disease states. Tissue distribution of vitreous proteins may help to elucidate more specific protein function.
