Impaired wound healing secondary to bevacizumab

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150555/1/iwj13139_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150555/2/iwj13139.pd

Evaluation of Negation and Uncertainty Detection and its Impact on Precision and Recall in Search

Radiology reports contain information that can be mined using a search engine for teaching, research, and quality assurance purposes. Current search engines look for exact matches to the search term, but they do not differentiate between reports in which the search term appears in a positive context (i.e., being present) from those in which the search term appears in the context of negation and uncertainty. We describe RadReportMiner, a context-aware search engine, and compare its retrieval performance with a generic search engine, Google Desktop. We created a corpus of 464 radiology reports which described at least one of five findings (appendicitis, hydronephrosis, fracture, optic neuritis, and pneumonia). Each report was classified by a radiologist as positive (finding described to be present) or negative (finding described to be absent or uncertain). The same reports were then classified by RadReportMiner and Google Desktop. RadReportMiner achieved a higher precision (81%), compared with Google Desktop (27%; p < 0.0001). RadReportMiner had a lower recall (72%) compared with Google Desktop (87%; p = 0.006). We conclude that adding negation and uncertainty identification to a word-based radiology report search engine improves the precision of search results over a search engine that does not take this information into account. Our approach may be useful to adopt into current report retrieval systems to help radiologists to more accurately search for radiology reports

AKT Inhibition in Solid Tumors With AKT1 Mutations.

Purpose AKT1 E17K mutations are oncogenic and occur in many cancers at a low prevalence. We performed a multihistology basket study of AZD5363, an ATP-competitive pan-AKT kinase inhibitor, to determine the preliminary activity of AKT inhibition in AKT-mutant cancers. Patients and Methods Fifty-eight patients with advanced solid tumors were treated. The primary end point was safety; secondary end points were progression-free survival (PFS) and response according to Response Evaluation Criteria in Solid Tumors (RECIST). Tumor biopsies and plasma cell-free DNA (cfDNA) were collected in the majority of patients to identify predictive biomarkers of response. Results In patients with AKT1 E17K-mutant tumors (n = 52) and a median of five lines of prior therapy, the median PFS was 5.5 months (95% CI, 2.9 to 6.9 months), 6.6 months (95% CI, 1.5 to 8.3 months), and 4.2 months (95% CI, 2.1 to 12.8 months) in patients with estrogen receptor-positive breast, gynecologic, and other solid tumors, respectively. In an exploratory biomarker analysis, imbalance of the AKT1 E17K-mutant allele, most frequently caused by copy-neutral loss-of-heterozygosity targeting the wild-type allele, was associated with longer PFS (hazard ratio [HR], 0.41; P = .04), as was the presence of coincident PI3K pathway hotspot mutations (HR, 0.21; P = .045). Persistent declines in AKT1 E17K in cfDNA were associated with improved PFS (HR, 0.18; P = .004) and response ( P = .025). Responses were not restricted to patients with detectable AKT1 E17K in pretreatment cfDNA. The most common grade ≥ 3 adverse events were hyperglycemia (24%), diarrhea (17%), and rash (15.5%). Conclusion This study provides the first clinical data that AKT1 E17K is a therapeutic target in human cancer. The genomic context of the AKT1 E17K mutation further conditioned response to AZD5363