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The EarlyCDT‐Lung test is a blood‐based autoantibody assay intended to identify high‐risk individuals for low‐dose computed tomography lung cancer screening. However, there is a paucity of evidence on the performance of the EarlyCDT‐Lung test in ever‐smokers. We conducted a nested case‐control study within two prospective cohorts to evaluate the risk‐discriminatory performance of the EarlyCDT‐Lung test using prediagnostic blood samples from 154 future lung cancer cases and 154 matched controls. Cases were selected from those who had ever smoked and had a prediagnostic blood sample <3 years prior to diagnosis. Conditional logistic regression was used to estimate the association between EarlyCDT‐Lung test results and lung cancer risk. Sensitivity and specificity of the EarlyCDT‐Lung test were calculated in all subjects and subgroups based on age, smoking history, lung cancer stage, sample collection time before diagnosis and year of sample collection. The overall lung cancer odds ratios were 0.89 (95% CI: 0.34‐2.30) for a moderate risk EarlyCDT‐Lung test result and 1.09 (95% CI: 0.48‐2.47) for a high‐risk test result compared to no significant test result. The overall sensitivity was 8.4% (95% CI: 4.6‐14) and overall specificity was 92% (95% CI: 87‐96) when considering a high‐risk result as positive. Stratified analysis indicated higher sensitivity (17%, 95% CI: 7.2‐32.1) in subjects with blood drawn up to 1 year prior to diagnosis. In conclusion, our study does not support a role of the EarlyCDT‐Lung test in identifying the high‐risk subjects in ever‐smokers for lung cancer screening in the EPIC and NSHDS cohorts. [ABSTRACT FROM AUTHOR]

Classification of pediatric T‐cell acute lymphoblastic leukemia (T‐ALL) patients into CIMP (CpG Island Methylator Phenotype) subgroups has the potential to improve current risk stratification. To investigate the biology behind these CIMP subgroups, diagnostic samples from Nordic pediatric T‐ALL patients were characterized by genome‐wide methylation arrays, followed by targeted exome sequencing, telomere length measurement, and RNA sequencing. The CIMP subgroups did not correlate significantly with variations in epigenetic regulators. However, the CIMP+ subgroup, associated with better prognosis, showed indicators of longer replicative history, including shorter telomere length (P = 0.015) and older epigenetic (P < 0.001) and mitotic age (P < 0.001). Moreover, the CIMP+ subgroup had significantly higher expression of ANTP homeobox oncogenes, namely TLX3, HOXA9, HOXA10, and NKX2‐1, and novel genes in T‐ALL biology including PLCB4, PLXND1, and MYO18B. The CIMP− subgroup, with worse prognosis, was associated with higher expression of TAL1 along with frequent STIL‐TAL1 fusions (2/40 in CIMP+ vs 11/24 in CIMP−), as well as stronger expression of BEX1. Altogether, our findings suggest different routes for leukemogenic transformation in the T‐ALL CIMP subgroups, indicated by different replicative histories and distinct methylomic and transcriptomic profiles. These novel findings can lead to new therapeutic strategies. In this study, an integrated methylomic, transcriptomic, and genomic analysis was performed to investigate the biology behind prognostically relevant DNA methylation (CIMP) subgroups in pediatric T‐cell acute lymphoblastic leukemia. We identified differentially expressed genes in the CIMP subgroups including known oncogenic drivers as well as novel genes in T‐ALL biology. Altogether, our findings suggest different routes for leukemogenic transformation in the T‐ALL CIMP subgroups, indicated by different replicative histories and distinct methylomic and transcriptomic profiles. [ABSTRACT FROM AUTHOR]

Traditionally, Sezary syndrome (SS) has been associated with few therapeutic options and poor prognosis, with 5-year disease-specific survival (DSS) less than one-third in historical cohorts. However, newer therapies and combinations are associated with impressive time-to-next-treatment (TTNT), particularly allogeneic stem-cell transplantation (AlloSCT) and combination therapies notably those including extracorporeal photopheresis. In this multicentre, international study, we explored the prognostic outcomes of 178 patients exclusively managed for SS, diagnosed between 2012 and 2020, and treated in the modern therapeutic era. In this cohort, 58 different therapies were delivered, with 13.5% of patients receiving AlloSCT. Long-term survival exceeded historical reports with 5-year DSS and OS of 56.4% and 53.4% respectively. In those receiving AlloSCT, prognosis was excellent: 5-year DSS and OS were 90.5% and 78.0% respectively. Confirming the results from the Cutaneous Lymphoma International Consortium (CLIC), LDH and LCT had significant prognostic impact. Unlike earlier studies, stage did not have prognostic impact; we speculate that greater relative benefit favours patients with extensive lymphomatous nodal disease (Stage IVA2) compared to historical reports. For patients ineligible for AlloSCT, the prognosis remains relatively poor (5-year DSS 51.4% and OS 49.6%), representing ongoing unmet needs for more effective novel agents and investigation of improved therapeutic combinations., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)