Purpose: To assess the interreader variability of submillisievert CT for lung cancer screening in radiologists with various experience levels.
Method: Six radiologists with different degrees of clinical experience in radiology (range, 1-15 years), rated 100 submillisievert CT chest studies as either negative screening finding (no nodules, benign nodules, nodules <5 mm), indeterminate finding (nodules 5-10 mm), positive finding (nodules >10 mm). Each radiologist interpreted scans randomly ordered and reading time was recorded. Interobserver agreement was assessed with ak statistic. Reasons for differences in nodule classification were analysed on a case-by-case basis. Reading time was correlated with reader experience using Pearson correlation (r).
Results: The overall interobserver agreement between all readers was moderate (k = 0.454; p < 0.001). In 57 patients, all radiologists agreed on the differentiation of negative and indeterminate/positive finding. In 64 cases disagreement between readers led to different nodule classification. In 8 cases some readers rated the nodule as benign, whereas others scored the case as positive. Overall, disagreement in nodule classification was mostly due to failure in identification of target lesion (n = 40), different lesion measurement (n = 44) or different classification (n = 26). Mean overall reading time per scan was of 2 min 2 s (range: 7s-7 min 45 s) and correlated with reader-experience (r = -0.824).
Conclusions: Our study showed substantial interobserver variability for the detection and classification of pulmonary nodules in submillisievert CT. This highlights the importance for careful standardisation of screening programs with the objective of harmonizing efforts of involved radiologists across different institutions by defining and assuring quality standards.
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http://dx.doi.org/10.1016/j.ejrad.2019.108720 | DOI Listing |
Clin Cancer Res
January 2025
Moffitt Cancer Center, Tampa, Florida, United States.
Purpose: Therapeutic efficacy of KRASG12C(OFF) inhibitors (KRASG12Ci) in KRASG12C-mutant non-small cell lung cancer (NSCLC) varies widely. The activation status of RAS signaling in tumors with KRASG12C mutation remains unclear, as its ability to cycle between the active GTP-bound and inactive GDP-bound states may influence downstream pathway activation and therapeutic responses. We hypothesized that the interaction between RAS and its downstream effector RAF in tumors may serve as indicators of RAS activity, rendering NSCLC tumors with a high degree of RAS engagement and downstream effects more responsive to KRASG12Ci compared to tumors with lower RAS---RAF interaction.
View Article and Find Full Text PDFMol Biol Evol
January 2025
Shmunis School of Biomedicine and Cancer Research, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Bats have adapted to pathogens through diverse mechanisms, including increased resistance - rapid pathogen elimination, and tolerance - limiting tissue damage following infection. In the Egyptian fruit bat (an important model in comparative immunology) several mechanisms conferring disease tolerance were discovered, but mechanisms underpinning resistance remain poorly understood. Previous studies on other species suggested that elevated basal expression of innate immune genes may lead to increased resistance to infection.
View Article and Find Full Text PDFClin Cancer Res
January 2025
Istituti Fisioterapici Ospitalieri, Italy.
Background: The role of activating alterations in the MAPK pathway in predicting immunotherapy efficacy in lung squamous cell carcinoma (LSCC) patients is largely unknown. The aims of the randomized, phase II SQUINT trial were to assess the efficacy of nivolumab plus ipilimumab (NI) versus platinum-based chemotherapy plus nivolumab (N-CT) and to identify clinically available biomarkers of response to immunotherapy in patients with advanced or metastatic LSCC.
Methods: SQUINT was an open-label, randomized, parallel, non-comparative, phase II trial of NI versus N-CT in chemo-naïve, metastatic or recurrent LSCC adult patients.
Discov Nano
January 2025
Institute of Physiology II, University of Münster, Robert-Koch-Str. 27b, 48149, Münster, Germany.
Metastatic cancer cells undergo metabolic reprogramming, which involves changes in the metabolic fluxes, including endocytosis, nucleocytoplasmic transport, and mitochondrial metabolism, to satisfy their massive demands for energy, cell division, and proliferation compared to normal cells. We have previously demonstrated the ability of two different types of compounds to interfere with linchpins of metabolic reprogramming, Pitstop-2 and 1,6-hexanediol (1,6-HD). 1,6-HD disrupts glycolysis enzymes and mitochondrial function, enhancing reactive oxygen species production and reducing cellular ATP levels, while Pitstop-2 impedes clathrin-mediated endocytosis and small GTPases activity.
View Article and Find Full Text PDFInt J Colorectal Dis
January 2025
Department of Pathomorphology, Medical University of Gdańsk, Gdańsk, Poland.
Purpose: Liver and lung metastases demonstrate distinct biological, particularly immunological, characteristics. We investigated whether preoperative complete blood count (CBC) parameters, which may reflect the immune system condition, predict early dissemination to the liver and lungs in colorectal cancer (CRC).
Methods: In this retrospective single-centre study, we included 268 resected CRC cases with complete 2-year follow-up and analysed preoperative CBC for association with early liver or lung metastasis development.
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