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68% of all respondents did not test for NTM prior to initiating macrolide monotherapy, despite guidelines recommending testing. The perceived risk of and screening for NTM varied among countries. CONCLUSIONS The study demonstrates that physicians understand the risk of NTM-LD and associated morbidity in patients with bronchiectasis; however, a minority do not perceive that NTM-LD significantly affects mortality. Greater awareness of the need to test for NTM infection before initiating macrolide monotherapy for bronchiectasis is essential due to potential emergence of drug-resistant NTM. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.The full British Thoracic Society (BTS) guideline for the use of long-term macrolides in adults with respiratory disease is published in Thorax. The following is a summary of the recommendations and good practice points. The sections referred to in the summary refer to the full guideline. The appendices are available in the full guideline and online appendices are available on the BTS website. This is the first BTS guideline to use the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach as part of the process of guideline development and the guideline was used to pilot the new methodology. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Gastrointestinal adenocarcinomas (GIAC) of the tubular GI tract including esophagus, stomach, colon, and rectum comprise most GI cancers and share a spectrum of genomic features. However, the unified epigenomic changes specific to GIAC are poorly characterized. Using 907 GIAC samples from The Cancer Genome Atlas, we applied mathematical algorithms to large-scale DNA methylome and transcriptome profiles to reconstruct transcription factor (TF) networks and identify a list of functionally hyperactive master regulator (MR) TF shared across different GIAC. The top candidate HNF4A exhibited prominent genomic and epigenomic activation in a GIAC-specific manner. A complex interplay between the HNF4A promoter and three distal enhancer elements was coordinated by GIAC-specific MRTF including ELF3, GATA4, GATA6 and KLF5; HNF4A also self-regulated its own promoter and enhancers. Functionally, HNF4A promoted cancer proliferation and survival by transcriptional activation of many downstream targets, including HNF1A and factors of Interleukin signaling, in a lineage-specific manner. Overall, our study provides new insights into the GIAC-specific gene regulatory networks and identifies potential therapeutic strategies against these common cancers. Copyright ©2020, American Association for Cancer Research.PURPOSE To identify a predictive biomarker of sorafenib for HCC personalized therapy. EXPERIMENTAL DESIGN The patients treated with or without sorafenib after HCC recurrence from multi-centers were matched with propensity score matching analysis. The expression levels of FLT3 in HCC specimens of the matched patients (n=276) were analyzed by immunohistochemistry. The optimal cutoff point of FLT3 levels for overall survival (OS) was defined via Cutoff Finder. Fasoracetam Subgroup analysis of OS was employed to investigate the association between FLT3 levels and sorafenib benefit. The predictive value was assessed via Cox regression models with an interaction term. HCC and para-tumoral normal tissues were used to investigate the expression and CNV of FLT3. PDX models were used to confirm the association between FLT3 levels and sorafenib response. RESULTS HCC patients with high FLT3 levels exhibited a superior OS upon sorafenib treatment. High FLT3 levels were predictive of sorafenib benefit in term of OS (p of interaction=0.00006). Copy number losses and decreased expression of FLT3 in HCC were detected in about 64% of patients. Moreover, the PDXs derived from tumors with high FLT3 levels also displayed a better response to sorafenib. CONCLUSIONS Sorafenib may be able to delay tumor progression in FLT3-High HCC patients. This potential biomarker needs to be further validated in independent cohorts prior to helping stratify patients for precision therapy in advanced HCC. Copyright ©2020, American Association for Cancer Research.PURPOSE Drug induced interstitial lung disease (DILD) is a rare, but potentially fatal toxicity. Clinical and radiological features of DILD in the early experimental setting are poorly described. EXPERIMENTAL DESIGN 2499 consecutive advanced cancer patients on phase I clinical trials were included. DILD was identified by a dedicated radiologist and investigators, categorized per internationally recognized radiological patterns and graded per CTCAE and the Royal Marsden Hospital DILD score. Clinical and radiological features of DILD were analysed. RESULTS 60 patients overall (2.4%) developed DILD. Median time to onset of DILD was 63 days (range 14-336 days). 45% of patients who developed DILD were clinically asymptomatic. Incidence was highest in patients receiving drug conjugates (7.4%), followed by inhibitors of the PI3K/AKT/mTOR pathway (3.9%). Commonest pattern seen was hypersensitivity pneumonitis (33.3%), followed by non-specific interstitial pneumonia (30%) and cryptogenic organising pneumonia (26.7%). A higher DILD score (OR 1.47, 95% CI 1.19-1.81, p less then 0.001) and the pattern of DILD (OR 5.83 for acute interstitial pneumonia, 95% CI 0.38-90.26, p=0.002) were significantly associated with a higher CTCAE grading. The only predictive factor for an improvement in DILD was an interruption of treatment (OR 0.05, 95% CI 0.01-0.35, p=0.01). CONCLUSIONS DILD in early phase clinical trials is a toxicity of variable onset, with diverse clinical and radiological findings. Radiological findings precede clinical symptoms. The extent of the affected lung parenchyma, scored by the RMH DILD score, correlates with clinical presentation. Most events are low grade, and improve with treatment interruption which should be considered early. Copyright ©2020, American Association for Cancer Research.