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The cumulative distribution functions can be used as the basis for hysteresis models. Here it is de- scribed how, using only 3 parameters, including one representing the shape, hysteresis curves can be constructed using symmetric distribution functions. The model is useful in the interpretation of magnetic Barkhausen noise data. The model also has a clear physical meaning because it represents the distribution of coercivity inside the sample. An isotropic Stoner-Wohlfarth hysteresis was partially modelled by a three-parameter cumulative distribution function of Gaussian hysteresis for the 1st and 3rd quadrants. Asymmetric distributions will provide better hysteresis adjustment, but these are four- parameter models. [ABSTRACT FROM AUTHOR]

Purpose: The ETOP 10-16 BOOSTER study was a randomized phase II trial of osimertinib and bevacizumab therapy versus osimertinib therapy in patients with an acquired EGFR T790M mutation. The mechanisms of acquired resistance to osimertinib and bevacizumab have not been described previously., Experimental Design: Next-generation sequencing (Guardant360) was conducted in serial plasma samples. The association between ctDNA and efficacy outcomes was explored, and molecular alterations at progression were described., Results: A total of 136 patients (88% of 155 randomized) had plasma samples at baseline (68 per arm), 110 (71%) at week 9, and 65 (42%) at progression. In a multivariable model for progression-free survival (PFS), the treatment effect was found to differ by smoking status (interaction P = 0.046), with the effect of smoking also differing by baseline EGFR T790M (interaction P = 0.033), whereas both TP53 at baseline and the tissue EGFR exon 21 L858R mutation were significantly associated with worse PFS outcome. Smokers (current/former) without baseline EGFR T790M showed a significant improvement in PFS under combination treatment, albeit with small numbers (P = 0.015). Week-9 EGFR T790M clearance was associated with improved PFS in the osimertinib arm (P = 0.0097). Acquired EGFR C797S mutations were detected in 22% and 13% of patients in the combination and osimertinib arms, respectively., Conclusions: The differential effect of treatment by smoking was not explained by TP53 mutations or other molecular alterations examined. Molecular mechanisms of acquired resistance were detected, but no novel molecular alterations were identified in the combination arm., (©2024 American Association for Cancer Research.)

Background: Perioperative immunotherapy improves short-term outcomes in resectable non-small-cell lung cancer (NSCLC). We now report 5-year survival from the NADIM trial to assess its long-term benefit., Methods: NADIM was a multicentre, single-arm, phase 2 trial conducted across 18 hospitals in Spain. Patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had histologically or cytologically confirmed, treatment-naive, resectable stage IIIA NSCLC (American Joint Committee on Cancer, 7th edition criteria). The neoadjuvant treatment consisted of three cycles of intravenous paclitaxel (200 mg/m 2 ) and carboplatin (area under the curve 6 mg/mL per min) with nivolumab (360 mg). After surgery, 1 year of adjuvant treatment with intravenous nivolumab monotherapy was administered (240 mg every 2 weeks for 4 months, followed by 480 mg every 4 weeks for 8 months). The primary endpoint was 24-month progression-free survival, with 5-year progression-free survival and overall survival as secondary endpoints, assessed in the intention-to-treat population (ie, all patients who received neoadjuvant treatment). Toxicity profile was also assessed as a secondary endpoint. This trial is registered at ClinicalTrials.gov (NCT03081689) and is complete; this is the final report of the trial., Findings: Between April 26, 2017, and Aug 25, 2018, 51 patients were assessed for eligibility, of whom 46 comprised the intention-to-treat population (34 [74%] male and 12 [26%] female, median age 63 years [IQR 58-70]). Follow-up was concluded at 60 months (data cutoff July 11, 2023; median follow-up 60·0 months [IQR 60·0-60·0]). 5-year progression-free survival in the intention-to-treat population was 65·0% (95% CI 49·4-76·9), and overall survival was 69·3% (53·7-80·6). Disease progression occurred in 11 (24%) patients; 14 (30%) patients died, including nine (20%) from disease relapse and five (11%) from non-tumour-related causes. Treatment-related adverse events (TRAEs) of grade 3 or worse occurred in 14 (30%) of 46 patients during neoadjuvant treatment and in seven (19%) of 37 during adjuvant treatment. The most common grade 3 or worse TRAEs were increased lipase and febrile neutropenia (three [7%] each) during neoadjuvant treatment, and elevated serum lipase (four [7%]) and elevated serum amylase (three [8%]) during adjuvant treatment. Serious TRAEs included elevated serum lipase and neutropenia (one [2%] each) during neoadjuvant treatment, and elevated serum lipase (one [3%]) during adjuvant treatment. No treatment-related surgery delays, deaths, or unexpected long-term toxicities were reported., Interpretation: Perioperative chemoimmunotherapy showed a promising long-term benefit with no concerning safety data, reinforcing its use in resectable stage IIIA NSCLC., Funding: Bristol-Myers Squibb, Spanish Ministry of Science, Instituto de Salud Carlos III, European Union., Competing Interests: Declaration of interests MP reports non-financial support (reagents for T-cell receptor sequencing) from ThermoFisher Scientific; grants, consulting fees, and non-financial support from Bristol Myers Squibb, Roche, and AstraZeneca; and consulting fees from MSD and Takeda; outside the submitted work. EN reports grants from Roche, Pfizer, Bristol Myers Squibb, Merck, and Nanostring; consulting fees from Roche, Bristol Myers Squibb, Merck Sharpe & Dohme, Merck-Serono, Sanofi, Pfizer, Lilly, Amgen, Janssen, Daiichi-Sankyo, Boehringer-Ingelheim, AstraZeneca, Takeda, Sanofi, Pierre Fabre, Qiagen, and Bayer; payment of honoraria from Roche, Bristol Myers Squibb, Merck Sharpe & Dohme, Sanofi, Pfizer, Lilly, Amgen, Janssen, Daiichi-Sankyo, Boehringer-Ingelheim, AstraZeneca, Takeda, Sanofi, and Qiagen; support for attending meetings or travel from Takeda, MSD, Janssen, and Roche; and participation on advisory boards for Apollomics, Roche, and Pfizer. AI reports consulting fees from Pfizer, Amgen, and Astra Zeneca; payment for expert testimony from Bristol Myers Squibb, Roche, Pfizer, Astra Zeneca, and Takeda; support for attending meetings or travel from Roche, Takeda, and Pfizer; and participation on advisory boards for Roche and Bristol Myers Squibb. RG-C reports consulting fees from Bristol Myers Squibb, MSD, Roche, Pfizer, and AstraZeneca. MD reports consulting fees from AstraZeneca, Bristol Myers Squibb, MSD Oncology, Pfizer, Roche, and Takeda; and support for attending meetings or travel from AstraZeneca, MSD Oncology, Pfizer, and Takeda. BM reports consulting fees from Astra Zeneca and Amgen; payment or honoraria from Roche, Bristol Myers Squibb, and MSD; and support for attending meetings or travel from MSD and AstraZeneca. MM reports grants from Roche and Astra Zeneca; payment of honoraria from Roche, AstraZeneca, MSD, Pfizer, Helsinn, Cassen, Amgen, Janssen, Sanofi, Pierre Fabre, Bristol Myers Squibb, and Takeda; and support for attending meetings or travel from MSD, Roche, and AstraZeneca. DR-A reports honoraria for lectures from MSD, Roche, Bristol Myers Squibb, Novartis, Takeda, Lilly, and AstaZeneca; support for attending meetings or travel from Roche, MSD, Novartis, and Sanofi; and participation on advisory boards for Merck Sharpe & Dohme, Regeneron, Bristol Myers Squibb, GSK, and Lilly. AM-M reports consulting fees from AstraZeneca/MedImmune, Bristol Myers Squibb, F. Hoffmann La Roche, Merck Sharpe & Dohme, MSD Oncology, Pfizer, and Janssen; payment for expert testimony from AstraZeneca, MedImmune, Bristol Myers Squibb, and F. Hoffmann La Roche; support for attending meetings or travel from AstraZeneca, MedImmune, Bristol-Myers Squibb, F. Hoffmann La Roche, Merck Sharpe & Dohme, MSD Oncology, Pfizer, Janssen, and Lilly; and participation on advisory boards for AstraZeneca, MedImmune, Merck Sharpe & Dohme, F. Hoffmann La Roche, and Bristol-Myers Squibb. JdC reports consulting fees from AstraZeneca, Bristol Myers Squibb, Roche, MSD, Boehringer, Janssen, Lilly, Sanofi, Takeda, Pfizer, and GSK; support for attending meeting or travel from AstraZeneca, MSD, and Roche; participation on advisory boards for AstraZeneca, Bristol Myers Squibb, Roche, MSD, Glaxo, Janssen, and Gilea; and speaker's bureau fees from AstraZeneca/MedImmune, Bristol-Myers Squibb, F. Hoffmann La Roche, Merck Sharpe & Dohme, MSD Oncology, Pfizer, and Janssen. DG reports payment or honoraria from Astra Zeneca and Bristol Myers Squibb. VC reports consulting fees from Roche, AstraZeneca, MSD, Bristol Myers Squibb, Takeda, Sanofi, and Amgen; payment or honoraria from Roche, AstraZeneca, MSD, Bristol Myers Squibb, Takeda, SanofiI, and Amgen; and support for attending meetings or travel from AstraZeneca, Roche, MSD, and Takeda. RP reports payment or honoraria from Guardant Health and Pfizer; and support for attending meetings or travel from Merck Sharpe & Dohme; participation on an advisory board for AstraZeneca. AR reports payment or honoraria from Illumina, Health in Code, and ThermoFisher Scientific; support for attending meetings or travel from ThermoFisher Scientific, Bristol Myers Squibb Foundation, and Takeda; and advisory board participation for Takeda. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Loss of human leukocyte antigen (HLA) class I expression and loss of heterozygosity (LOH) are common events implicated in the primary resistance of non-small cell lung cancer (NSCLC) to immunotherapy. However, there is no data on perioperative chemoimmunotherapy (ChIO) efficacy or response mechanisms in the context of HLA class I defects., Methods: Baseline HLA class I tumor status (HLA-deficient (HLA-DEF) or HLA-proficient (HLA-PRO)) was determined by DNA LOH combined with immunohistochemistry for protein levels in tissue of 24 patients with NSCLC treated with perioperative nivolumab plus chemotherapy from NADIM trial (NCT03081689). We integrated HLA tumor status with molecular data (programmed death-ligand 1 (PD-L1), TMB, TCR repertoire, TILs populations, bulk RNA-seq, and spatial transcriptomics (ST)) and clinical outcomes (pathological response and survival data) to study the activity of perioperative ChIO considering HLA class I defects., Results: HLA-DEF tumors comprised 41.7% of analyzed tumors and showed a desert-like microenvironment at baseline, with lower PD-L1 levels and reduced immune infiltrate. However, perioperative ChIO induced similar complete pathological response (CPR) rates in both HLA-DEF and PRO tumors (50% and 60% respectively, p=0.670), as well as 3-year survival rates: Progression-free survival (PFS) and overall survival (OS) of 70% (95% CI 32.9% to 89.2%) for HLA-DEF, and PFS 71.4% (95% CI 40.6% to 88.2%) and OS 92.9% (95% CI 59.1% to 99.0%) for HLA-PRO (log-rank PFS p=0.909, OS p=0.137). Proof-of-concept ST analysis of a CPR HLA-DEF tumor after ChIO showed a strong immune response with tertiary lymphoid structures (TLS), CD4+T cells with HLA class II colocalization, and activated CD8+T cells., Conclusions: Our findings highlight the activity of perioperative ChIO, and the potential role of TLS and T-cell immune response, in NSCLC HLA-DEF tumors., Competing Interests: Competing interests: VC reports consulting fees from Roche, AstraZeneca, MSD, BMS, Takeda, Sanofi, Agmen; payment or honoraria from Roche, AstraZeneca, MSD, BMS, Takeda, Sanofi, Agmen, Janssen, Regeneron and Pfizer; and support for attending meetings and/or travel from Roche, AstraZeneca, MSD, and Takeda outside the submitted work. EN reports grants from Roche, BMS, Pfizer, and Merck Serono; consulting fees and payment or honoraria form Roche, BMS, MSD, Merck Serono, Sanofi, Pfizer, Lilly, Amgen, Janssen, Daiichi Sankyo, Boehringer Ingelheim, AstraZeneca, Takeda, Sanofi, Pierre Fabre, Qiagen; payment or honoraria from Bayer; and advisory board from MSD, Roche, Apollomics, Daiichi and Transgene outside the submitted work. AM-M reports consulting fees, payment or honoraria and support for attending meetings and/or travel from AstraZeneca/MedImmune, BMS, F Hoffmann-La Roche AG, MSD, MSD Oncology, Pfizer; Steering Committee Member of AstraZeneca/MedImmune; support for attending meetings and/or travel from Lilly; and advisory board from AstraZeneca/MedImmune, MSD, BMS, and F Hoffmann-La Roche AG outside the submitted work. AI reports consulting fees from Pfizer, Amgen, AstraZeneca, and Roche; payment form expert testimony form BMS, Roche, Pfizer, AstraZeneca, and Takeda; support for attending meetings and/or travel from Roche, Takeda, and Pfizer; and advisory abroad from Roche and BMS outside the submitted work. BM reports payment or honoraria from Roche, BMS, MSD, Boehringer Ingelheim, and Pfizer outside the submitted work. SV reports payment or honoraria from Merck GmbH, MSD, BMS, Takeda, AstraZeneca, and Roche; support for attending meetings and/or travel from OSE Immunotherapeutics, Roche, and GMS; and advisory board from Merck GmbH, Puma Biotech, Takeda, Ipsen, AbbVie, Roche, and AstraZeneca outside the submitted work. IBA reports payment or honoraria from AstraZeneca, BMS, Janssen Cilag, Lilly, MSD, Roche, Sanofi, and Takeda; as well as support for attending meetings and/or travel from MSD and AstraZeneca outside the submitted work. JdC reports consulting fees from AstraZeneca, BMS, Roche, MSD, Boehringer Ingelheim, Janssen, Lilly, Sanofi, Takeda, Pfizer, and Glaxo; payment or honoraria from AstraZeneca, BMS, Roche, MSD, Pfizer, Janssen, Takeda, and Sanofi; support for attending meetings and/or travel from AstraZeneca, MSD, and Roche; and advisory Board fees from AstraZeneca, BMS, Roche, MSD, Glaxo, Janssen, and Gilead outside the submitted work. MCo reports consulting fees from Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, Lilly, MSD, Takeda, Pfizer, Kyowa, Sanofi, and Janssen, as well as payment or honoraria from Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, Lilly, MSD, Takeda, Kyowa, Pierre Fabre, Novocure, Sanofi, and Janssen outside the submitted work. JM-L reports payment or honoraria from Roche, BMS, and EUSA Pharma, as well as support for attending meetings and/or travel from Roche outside the submitted work. MP reports consulting fees from BMS, AstraZeneca, MSD, Roche, Takeda. Support for attending meetings and/or travel and payment or honoraria from BMS, AstraZeneca, MSD, Roche, and Takeda outside the submitted work. No disclosures were reported by the other authors., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Immunotherapy-based treatments have demonstrated high efficacy in patients with advanced and locally advanced non-small-cell lung cancer (NSCLC). BRAF mutations affect a small but significant fraction of NSCLC. The efficacy of these therapies in this subgroup of patients is unknown., Materials and Methods: Plasma and tissue samples from 116 resectable stage IIIA/B NSCLC patients, included in NADIM and NADIM II clinical trials (NADIM cohort), and from a prospective academic cohort with 84 stage IV NSCLC patients (BLI-O cohort), were analyzed by next-generation sequencing., Results: The p.G464E, p.G466R, p.G466V, p.G469V, p.L597Q, p.T599I, p.V600E (n = 2) BRAF mutations, were identified in four (3.45 %) samples from the NADIM cohort, all of which were cases treated with neoadjuvant chemoimmunotherapy (CH-IO), and four (4.76 %) samples from the BLI-O cohort, corresponding to cases treated with first-line immunotherapy (n = 2) or CH-IO (n = 2). All these patients were alive and had no evidence of disease at data cut-off. Conversely, patients with BRAF wild-type (wt) tumors in the BLI-O cohort had a median progression-free survival (PFS) of 5.49 months and a median overall survival (OS) of 12.00 months (P-LogRank = 0.013 and 0.046, respectively). Likewise, PFS and OS probabilities at 36 months were 60.5 % and 76.1 % for patients with BRAF-wt tumors in the NADIM cohort. The pathological complete response (pCR) rate after neoadjuvant CH-IO in patients with BRAF-positive tumors (n = 4) was 100 %, whereas the pCR rate in the BRAF-wt population was 44.3 % (RR: 2.26; 95 % CI: 1.78-2.85; P < 0.001)., Conclusion: BRAF mutations may be a good prognostic factor for advanced and locally advanced NSCLC patients undergoing immunotherapy-based treatments., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M. Provencio declares consulting fees, payment for lectures, presentations or speakers bureaus and support for attending meetings and/or travel from BRISTOL-MYERS SQUIBB, Astra Zeneca, MSD, Roche, Takeda. This author has also declared that he have a pending patent (n° EP 22 382 701.5). R. Serna-Blasco declares to be in possession of a pending patent (n° EP 22 382 701.5). E. Nadal declares Grants or contracts from Roche, Pfizer, Bristol-Myers Squibb and Merck Serono; consulting fees from Roche, Bristol Myers Squibb, Merck Sharp Dohme, Merck-Serono, Sanofi, Pfizer, Lilly, Janssen, AMGEN, Daiichi-Sankyo, Boehringer-Ingelheim, AstraZeneca, Takeda, Sanofi, Pierre Fabre, Qiagen, and Bayer; payment for lectures, presentations or speakers bureaus from Roche, Bristol Myers Squibb, Merck Sharp Dohme, Merck-Serono, Sanofi, Pfizer, Lilly, Janssen, Amgen, Boehringer-Ingelheim, AstraZeneca, Takeda, Sanofi, Pierre Fabre and Qiagen; support for attending meetings and/or travel from Roche, Takeda and Pfizer; and Participation on data safety Monitoring board or advisory board from Roche, Apollomics and MSD. M.P. Diz Taín declares Payment or honoraria for lectures, presentations or speakers bureaus from BRISTOL-MYERS SQUIBB, Astra-Zeneca, Roche, MSD, Takeda, Pfizer and Amgen; support for attending meetings and/or travel from BRISTOL-MYERS SQUIBB, Roche, MSD and Takeda; Participation on a Data Safety Monitoring Board or Advisory Board from BRISTOL-MYERS SQUIBB, Astra-Zeneca, and Boehringer Ingelheim; and other financial or non-financial interests from Astra-Zeneca, Roche, Mirati, and Pfizer. B. Massuti declares consulting fees and support for attending meetings and/or travel from Bristol-Myers Squibb, Takeda, Merck Sharpe and Dohme. J.L. González Larriba declares consulting fees from MSD, Janssen Cilag, Bristol Myers Squibb, Boehringer Ingelheim, and AMGEN; Payment or honoraria for lectures, presentations or speakers bureaus from MSD, Astra Zeneca, Roche, Pfizer, Janssen-Cilag, Novartis, Astella Pharma, and Bristol-Myers Squibb; Support for attending meetings and/or travel from MSD, Takeda, Bristol-Myers Squibb, Roche, Pfizer, and Janssen-Cilag. A. Insa declares Payment or honoraria for lectures, presentations or speakers bureaus from AMGEN, Bristol-Myers Squibb, Roche, and Takeda; Support for attending meetings and/or travel from Roche, Pfizer, and MSD; Participation on a Data Safety Monitoring Board or Advisory Board from Astra Zeneca, Sanofi, and Pfizer. A. Sánchez-Hernández declares Payment or honoraria for lectures, presentations or speakers bureaus from Roche, Lilly, MSD, Sanofi, Astra Zeneca, Janssen, Takeda, Merck, Novartis, Pfizer, and Bristol-Myers Squibb; Support for attending meetings and/or travel from Roche, Sanofi, MSD Takeda, Janssen, Pfizer, and Bristol-Myers Squibb. R. García-Campelo declares Grants or contracts from Bristol-Myers Squibb, Astra Zeneca, and MSC; consulting fees from Roche, Bristol-Myers Squibb, MSD, Sanofi, Takeda, Pfizer, Regeneron, AMGEN, and Astra Zeneca. J. Rogado declares Payment or honoraria for lectures, presentations or speakers bureaus from Roche, Astra Zeneca, MSD, MERCK, Ferrer, Persan Farma, Fresenius Kabi, and Sanofi; Support for attending meetings and/or travel from Roche, MSD, Bristol-Myers Squibb, Astra Zeneca, and Lilly; Participation on a Data Safety Monitoring Board or Advisory Board from Fresenius Kabi, MSD, Sanofi. A. Martínez-Martí declares consulting fees from AstraZeneca/MedImmune, Bristol-Myers Squibb, F. Hoffmann La Roche AG, MSD, and Pfizer; Payment or honoraria for lectures, presentations, speakers bureaus from AstraZeneca/MedImmune, Bristol-Myers Squibb, F. Hoffmann La Roche AG, MSD, MSD, and Pfizer; Payment for expert testimony from AstraZeneca/MedImmune; Support for attending meetings and/or travel from AstraZeneca/MedImmune, Bristol-Myers Squibb, F. Hoffmann La Roche AG, MSD, Pfizer, and Lilly; Participation on a Data Safety Monitoring Board or Advisory Board from AstraZeneca/MedImmune, MSD, F. Hoffmann La Roche, Bristol-Myers Squibb. J. Bosch-Barrera declares consulting fees from Sanofi and Roche; Payment or honoraria for lectures, presentations or speakers bureaus from Roche, Bristol-Myers Squibb, Astra Zeneca, and Pfizer; Support for attending meetings and/or travel from Takeda and MSD. R. Bernabé-Caro declares an investigational grant Roche; Payment or honoraria for lectures, presentations, speakers bureaus from Roche, Bristol-Myers Squibb, Pfizer, MSD, Amgen, Takeda, and Astra Zeneca; Participation on a Data Safety Monitoring Board or Advisory Board from Takeda, Roche, Bristol-Myers Squibb, and Astra Zeneca. J. de Castro Carpeño declares consulting from fees Astra Zeneca, Bristol Myers Squibb, Hoffmann- La Roche, MSD, Boehringer Ingelheim, Janssen, Lilly, Sanofi, Takeda, Pfizer, and Glaxo; Payment or honoraria for lectures, presentations, speakers bureaus from Astra Zeneca, Bristol Myers Squibb, Hoffmann- La Roche, MSD, Pfizer, Janssen, Takeda, and Sanofi; Support for attending meetings and/or travel from Astra Zaneca, MSD, and Hoffmann- La Roche; Participation on a Data Safety Monitoring Board or Advisory Board from Astra Zeneca, Bristol Myers Squibb, Hoffmann- La Roche, MSD, Glaxo, Janssen, Gilead, and Sanofi. N. Reguart declares Payment or honoraria for lectures, presentations or speakers bureaus from MSD, Bristol Myers Squibb, Roche, Boehringer Ingelheim, Guardant Health, Bayer, Merck, Pfizer, Takeda, Novartis, Astra-Zeneca, Janssen Oncology, Sanofi, Eli Lilly, and Amgen; Support for attending meetings and/or travel from Roche, Takeda, and MSD. M. Dómine declares consulting fees and Payment or honoraria for lectures, presentations or speakers bureaus from Astra Zeneca, Bristol-Myers Squibb, MSD, Pfizer, Roche, and Takeda; Support for attending meetings and/or travel from Astra Zeneca, MSD, Pfizer, and Takeda. M. Majem declares Grants or contracts from Roche and Astra Zeneca; Payment or honoraria for lectures, presentations or speakers bureaus from Roche, Astra Zeneca, MSD, Pfizer, Helsinn, Cassen, AMGEN, Janssen, Sanofi, Pierre Fabre, Bristol-Myers Squibb, and Takeda; Support for attending meetings and/or travel from Astra Zeneca, MSD, and Roche. A. Estival declares Payment or honoraria for lectures, presentations or speakers bureaus from MSD, Pharmamar, Astra Zeneca, Takeda, Roche, and GSK; Support for attending meetings and/or travel from MSD, Boehringer Ingelheim, and Pharmamar; Participation on a Data Safety Monitoring Board or Advisory Board from Roche and MSD. A. López Martín declares Payment or honoraria for lectures, presentations, speakers bureaus from GSK, Bristol-Myers Squibb, and Astra Zeneca; Support for attending meetings and/or travel from Pfizer and Takeda. M. A. Sala González declares Payment or honoraria for lectures, presentations or speakers bureaus from Takeda and Roche; Support for attending meetings and/or travel from Roche and PharmaMar. M. Cobo declares consulting fees from Novartis, Roche, Astra Zeneca, Bristol-Myers Squibb, Boehringer-Ingelheim, MSD, Lilly, Takeda, Pfizer, Kyowa, Sanofi, and Jansen. Payment or honoraria for lectures, presentations or speakers bureaus from Novartis, Astra Zeneca Boehringer-Ingelheim, Bristol-Myers Squibb, Roche, Lilly, MSD, Takeda, Kyowa, Pierre-Fabre, Novocure, Sanofi, and Jansen. I. Barneto declares Payment or honoraria for lectures, presentations or speakers bureaus from Bristol-Myers Squibb, Astra Zeneca, MSD, Takeda, AMGEN, and Novartis; Support for attending meetings and/or travel from MSD and Astra Zeneca; Participation on a Data Safety Monitoring Board or Advisory Board from Sanofi. V. Calvo declares consulting fees from Roche, Astra Zeneca, MSD, Bristol-Myers Squibb, Takeda, Sanofi, and AMGEN; Payment or honoraria for lectures, presentations or speakers bureaus from Roche, Astra Zeneca, MSD, Bristol-Myers Squibb, Takeda, Pfizer, and Janssen; Support for attending meetings and/or travel from Astra Zeneca, Roche, and Takeda. A. Collazo declares Payment or honoraria for lectures, presentations or speakers bureaus from Astra Zeneca and Janssen; Support for attending meetings and/or travel from MSD and Takeda. A. Romero declares consulting fees from Takeda; Payment or honoraria for lectures, presentations or speakers bureaus from Illumina, Health in code, and Thermofisher. Support for attending meetings and/or travel from Thermofisher Scientific. Bristol Myers Squibb Foundation, and Takeda; the author also declares a pending patent (n° EP 22 382 701.5). The rest of the authors declare no potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The use of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs), such as lorlatinib, for the treatment of patients with ALK gene rearrangement (or ALK-positive) non-small cell lung cancer (NSCLC) has been shown to improve the overall survival and quality of life of these patients. However, lorlatinib is not exempt from potential adverse events. Adequate monitoring and management of these adverse events are critical for increasing patient adherence to lorlatinib, thereby maximizing the benefits of treatment and minimizing the risks associated with treatment discontinuation. Considering that the adverse events of lorlatinib can affect different organs and systems, the participation of a multidisciplinary team, including cardiologists, neurologists, internal medicine specialists, and oncology pharmacists, is needed. This article presents specific and pragmatic strategies for identifying and treating the most relevant adverse events associated with lorlatinib in patients with advanced ALK-positive NSCLC based on the clinical experience of a multidisciplinary panel of experts., (© 2024. The Author(s).)

Purpose: Transcriptomic subtyping holds promise for personalized therapy in extensive-stage small cell lung cancer (ES-SCLC). In this study, we aimed to assess intratumoral transcriptomic subtype diversity and to identify biomarkers of long-term chemoimmunotherapy benefit in human ES-SCLC., Experimental Design: We analyzed tumor samples from 58 patients with ES-SCLC enrolled in two multicenter single-arm phase IIIb studies evaluating frontline chemoimmunotherapy in Spain: n = 32 from the IMfirst trial and n = 26 from the CANTABRICO trial. We used the GeoMx Digital Spatial Profiler system to perform multi-region transcriptomic analysis. For subtype classification, we performed hierarchical clustering using the relative expression of ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P), and YAP1 (SCLC-Y)., Results: Subtype distribution was found to be similar between bothcohorts, except for SCLC-P, which was not identified in the CANTABRICO&#95;DSP cohort. A total of 44% of the patients in both cohorts had tumors with multiple coexisting transcriptional subtypes. Transcriptional subtypes or subtype heterogeneity was not associated with outcomes. Most potential targets did not show subtype-specific expression. Consistently in both cohorts, tumors from patients with long-term benefit (time to progression ≥12 months) contained an IFNγ-dominated mRNA profile, including enhanced capacity for antigen presentation. Hypoxia and glycolytic pathways were associated with resistance to chemoimmunotherapy., Conclusions: This work suggests that intratumoral heterogeneity, inconsistent association with outcome, and unclear subtype-specific target expression might be significant challenges for subtype-based precision oncology in SCLC. Preexisting IFNγ-driven immunity and mitochondrial metabolism seem to be correlates of long-term efficacy in this study, although the absence of a chemotherapy control arm precludes concluding that these are predictive features specific for immunotherapy., (©2024 American Association for Cancer Research.)

Introduction: Recent advances in the treatment of locally advanced NSCLC have led to changes in the standard of care for this disease. For the selection of the best approach strategy for each patient, it is necessary the homogenization of diagnostic and therapeutic interventions, as well as the promotion of the evaluation of patients by a multidisciplinary oncology team., Objective: Development of an expert consensus document with suggestions for the approach and treatment of locally advanced NSCLC leaded by Spanish Lung Cancer Group GECP., Methods: Between March and July 2023, a panel of 28 experts was formed. Using a mixed technique (Delphi/nominal group) under the guidance of a coordinating group, consensus was reached in 4 phases: 1. Literature review and definition of discussion topics 2. First round of voting 3. Communicating the results and second round of voting 4. Definition of conclusions in nominal group meeting. Responses were consolidated using medians and interquartile ranges. The threshold for agreement was defined as 85% of the votes., Results: New and controversial situations regarding the diagnosis and management of locally advanced NSCLC were analyzed and reconciled based on evidence and clinical experience. Discussion issues included: molecular diagnosis and biomarkers, radiologic and surgical diagnosis, mediastinal staging, role of the multidisciplinary thoracic committee, neoadjuvant treatment indications, evaluation of response to neoadjuvant treatment, postoperative evaluation, and follow-up., Conclusions: Consensus clinical suggestions were generated on the most relevant scenarios such as diagnosis, staging and treatment of locally advanced lung cancer, which will serve to support decision-making in daily practice., (© 2024. The Author(s).)

Glioblastoma (GB) is a devastating tumor of the central nervous system characterized by a poor prognosis. One of the best-established predictive biomarker in IDH-wildtype GB is O6-methylguanine-DNA methyltransferase (MGMT) methylation (mMGMT), which is associated with improved treatment response and survival. However, current efforts to monitor GB patients through mMGMT detection have proven unsuccessful. Small extracellular vesicles (sEVs) hold potential as a key element that could revolutionize clinical practice by offering new possibilities for liquid biopsy. This study aimed to determine the utility of sEV-based liquid biopsy as a predictive biomarker and disease monitoring tool in patients with IDH-wildtype GB. Our findings show consistent results with tissue-based analysis, achieving a remarkable sensitivity of 85.7% for detecting mMGMT in liquid biopsy, the highest reported to date. Moreover, we suggested that liquid biopsy assessment of sEV-DNA could be a powerful tool for monitoring disease progression in IDH-wildtype GB patients. This study highlights the critical significance of overcoming molecular underdetection, which can lead to missed treatment opportunities and misdiagnoses, possibly resulting in ineffective therapies. The outcomes of our research significantly contribute to the field of sEV-DNA-based liquid biopsy, providing valuable insights into tumor tissue heterogeneity and establishing it as a promising tool for detecting GB biomarkers. These results have substantial implications for advancing predictive and therapeutic approaches in the context of GB and warrant further exploration and validation in clinical settings., (© 2024. The Author(s).)

Glioblastoma (GBM) is the most lethal and common malignant primary brain tumor in adults. An important feature that supports GBM aggressiveness is the unique composition of its extracellular matrix (ECM). Particularly, fibronectin plays an important role in cancer cell adhesion, differentiation, proliferation, and chemoresistance. Thus, herein, a hydrogel with mechanical properties compatible with the brain and the ability to disrupt the dynamic and reciprocal interaction between fibronectin and tumor cells was produced. High-molecular-weight hyaluronic acid (HMW-HA) functionalized with the inhibitory fibronectin peptide Arg-Gly-Asp-Ser (RGDS) was used to produce the polymeric matrix. Liposomes encapsulating doxorubicin (DOX) were also included in the hydrogel to kill GBM cells. The resulting hydrogel containing liposomes with therapeutic DOX concentrations presented rheological properties like a healthy brain. In vitro assays demonstrated that unmodified HMW-HA hydrogels only caused GBM cell killing after DOX incorporation. Conversely, RGDS-functionalized hydrogels displayed per se cytotoxicity. As GBM cells produce several proteolytic enzymes capable of disrupting the peptide-HA bond, we selected MMP-2 to illustrate this phenomenon. Therefore, RGDS internalization can induce GBM cell apoptosis. Importantly, RGDS-functionalized hydrogel incorporating DOX efficiently damaged GBM cells without affecting astrocyte viability, proving its safety. Overall, the results demonstrate the potential of the RGDS-functionalized hydrogel to develop safe and effective GBM treatments.

Introduction Our department conducted a retrospective cohort study to compare the efficacy of continuous glucose monitoring devices versus capillary blood glucose in the glycemic control of inpatient type 2 diabetes on intensive insulin therapy in a Portuguese hospital. The use of continuous glucose monitoring devices was associated with improved glycemic control, including an increased number of glucose readings within target range and reduced hyperglycemic events, being safe concerning hypoglycemias. This is the cost-effectiveness analysis associated with these results. Aim The primary objective was to compare the cost-effectiveness of achieving glycemic control, defined as the number of patients within glycemic goals, between groups. Secondary endpoints included cost-effectiveness analyses of each time in range goal, and each percentual increment in time in range. Methods We defined each glycemic goal as: "readings within range (70-180 mg/dL) >70%", "readings below range (below 70 mg/dL) <4%", "severe hypoglycemia (below 54 mg/dL) <1%", "readings above range (above 180 mg/dL) <25%", "very high glycemic readings (above 250 mg/dL) <5%". Results Continuous glucose monitoring showed lower median cost per effect for the primary outcome (€11.1 vs. €34.9/patient), with lower cost for readings in range (€7.8 vs. €11.6/patient) and for both readings above range goals ("above 180mg/dL": €7.4 vs. €9.9/patient, and "above 250mg/dL": €6.9 vs. €17.4/patient). Conclusions There are no published data regarding the cost-effectiveness of continuous glucose monitoring devices in inpatient settings. Our results show that continuous glucose monitoring devices were associated with an improved glycemic control, at a lower cost, and endorse the feasibility of incorporating these devices into hospital settings, presenting a favorable cost-effective option compared to capillary blood glucose., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Veríssimo et al.)

Introduction: RET inhibitors with impressive overall response rates are now available for patients with NSCLC, yet the identification of RET fusions remains a difficult challenge. Most guidelines encourage the upfront use of next-generation sequencing (NGS), or alternatively, fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction (RT-PCR) when NGS is not possible or available. Taken together, the suboptimal performance of single-analyte assays to detect RET fusions, although consistent with the notion of encouraging universal NGS, is currently widening some of the clinical practice gaps in the implementation of predictive biomarkers in patients with advanced NSCLC., Methods: This situation prompted us to evaluate several RET assays in a large multicenter cohort of RET fusion-positive NSCLC (n = 38) to obtain real-world data. In addition to RNA-based NGS (the criterion standard method), all positive specimens underwent break-apart RET FISH with two different assays and were also tested by an RT-PCR assay., Results: The most common RET partners were KIF5B (78.9%), followed by CCDC6 (15.8%). The two RET NGS-positive but FISH-negative samples contained a KIF5B(15)-RET(12) fusion. The three RET fusions not identified with RT-PCR were AKAP13(35)-RET(12) , KIF5B(24)-RET(9) and KIF5B(24)-RET(11) . All three false-negative RT-PCR cases were FISH-positive, exhibited a typical break-apart pattern, and contained a very high number of positive tumor cells with both FISH assays. Signet ring cells, psammoma bodies, and pleomorphic features were frequently observed (in 34.2%, 39.5%, and 39.5% of tumors, respectively)., Conclusions: In-depth knowledge of the advantages and disadvantages of the different RET testing methodologies could help clinical and molecular tumor boards implement and maintain sensible algorithms for the rapid and effective detection of RET fusions in patients with NSCLC. The likelihood of RET false-negative results with both FISH and RT-PCR reinforces the need for upfront NGS in patients with NSCLC., Competing Interests: Dr. Conde has received research funding from Eli Lilly, 10.13039/100004325AstraZeneca, and 10.13039/100011033ThermoFisher Scientific; and honoraria from Pfizer, Roche, AstraZeneca, Janssen, and Eli Lilly. Dr. Hernandez has received research funding from Eli Lilly, AstraZeneca, and ThermoFisher Scientific, and honoraria from Pfizer, Roche, AstraZeneca, ThermoFisher Scientific, and Eli Lilly. Mr. Alonso has received research funding from AstraZeneca, and honoraria from Pfizer, Roche, and AstraZeneca. Dr. Jimenez has received honoraria from Roche. Dr. Garrido has received research grants from 10.13039/100002429Amgen, AstraZeneca, Blueprint, 10.13039/100002491Bristol-Myers Squibb, Boehringer Ingelheim, 10.13039/501100002973Daiichi-Sankyo, 10.13039/100004330GlaxoSmithKline, 10.13039/100005565Janssen, IO Biotech, Eli Lilly, 10.13039/100009947Merck Sharp & Dohme, 10.13039/100004337Roche, Takeda; and honoraria from AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, GlaxoSmithKline, Janssen, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi, Takeda, Medscape, and Touch Medical. Dr. Clave has received honoraria from AstraZeneca, Pfizer, Roche, Eli Lilly, and Takeda. Dr. Arriola has received honoraria from AstraZeneca, Boehringer Ingelheim, Pfizer, Roche/Genentech, Eli Lilly and Company, Novartis, Takeda, Merck Sharp & Dohme, Bayer, and Bristol Myers Squibb. Dr. Esteban-Rodriguez has received honoraria from AstraZeneca, Pfizer, and Merck Sharp & Dohme. Dr. De Castro has received honoraria from AstraZeneca, Bristol Myers Squibb, Hoffmann- La Roche, Merck Sharp and Dohme, Boehringer-Ingelheim, Janssen, Eli Lilly, Sanofi, Takeda, Pfizer, Glaxo, and Gilead. Dr. Sansano has received honoraria from F. Hoffmann La Roche AG, Merck Sharp & Dohme, Pfizer, Takeda, AstraZeneca, and Boehringer Ingelheim. Dr. Felip has received honoraria from AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Eli Lilly, F. Hoffmann – La Roche, Gilead, Glaxo Smith Kline, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Peervoice, Pfizer, Regeneron, Sanofi, Takeda, Turning Point, and Touch Oncology. Dr. Rojo has received research funding from 10.13039/100004337Roche, AstraZeneca, Menarini, 10.13039/100004336Novartis, 10.13039/100004334Merck, Merck Sharp & Dohme, Bristol-Myers Squibb, 10.13039/100004319Pfizer, GlaxoSmithKline, Palex, Amgen, 10.13039/100004322Agilent, and Janssen, and honoraria from Roche, AstraZeneca, Menarini, Novartis, Merck, Merck Sharp & Dohme, Bristol-Myers Squibb, Pfizer, GlaxoSmithKline, Palex, Amgen, Agilent, Janssen. Dr. Dómine has received honoraria from AstraZeneca, Boehringer Ingelheim, Pfizer, Roche/Genentech, Takeda, Merck Sharp & Dohme, and Bristol Myers Squibb. Dr. Abdulkader has received honoraria from AstraZeneca, Eli Lilly, Pfizer, Roche, Merck Sharp & Dohme, Bristol Myers Squibb, Takeda, and Agilent Technologies S.A. Dr. Garcia-Gonzalez has received honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Roche, Sanofi, Pierre Fabre, Eli Lilly, Pfizer, and Takeda. Dr. Teixido has received honoraria from Novartis, AstraZeneca, Roche, Merck Sharp Dohme, Pfizer, Janssen, Eli Lilly, and, Bristol Myers Squibb. Dr. Reguart has received honoraria from Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer, Guardant, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi, and Takeda. Dr. Insa has received honoraria from Roche, Bristol Myers Squibb, Sanofi, Pfizer, Boehringer Ingelheim, AstraZeneca, Takeda, Bayer, Merck Sharp & Dohme, and Eli Lilly. Dr. Mancheño has received honoraria from Roche, AstraZeneca, and Pfizer. Dr. Palanca has received honoraria from Roche Pharma, Pfizer, Amgen, AstraZeneca, Takeda, Eli Lilly, and Janssen. Dr. Juan-Vidal has received honoraria from Boehringer Ingelheim, Bristol Myers Squibb, Merck Sharp & Dohme, Roche/Genetech, AstraZeneca, Pfizer, Eli Lilly, and Takeda. Dr. Baixeras has received honoraria from AstraZeneca and Eli Lilly. Dr. Nadal has received research funding from Roche, Pfizer, Bristol-Myers Squibb and Merck Serono, and honoraria from Roche, Bristol Myers Squibb, Merck Sharp Dohme, Merck Serono, Sanofi, Pfizer, Eli Lilly, Janssen, Amgen, Daiichi-Sankyo, Boehringer Ingelheim, AstraZeneca, Takeda, Sanofi, Pierre Fabre, Qiagen, Janssen, and Bayer. Dr. Calles has received research funding from Merck Sharp & Dome, and honoraria from AstraZeneca, Boehringer Ingelheim, Pfizer, Roche/Genentech, Eli Lilly and Company, Novartis, Takeda, Merck Sharp & Dohme, and Bristol Myers Squibb. Dr. Martin has received honoraria from Daiichi-Sankyo and Pfizer. Dr. Salas has received honoraria from Boehringer Ingelheim, Pfizer, and Merck Sharp & Dohme. Dr. Provencio has received honoraria from AstraZeneca, Boehringer Ingelheim, Pfizer, Roche/Genentech, Takeda, Merck Sharp & Dohme, and Bristol Myers Squibb. Dr. Massuti has received research funding from Bristol Myers Squibb, and honoraria from Bristol Myers Squibb, Roche, Janssen, Merck Sharp & Dohme, and AstraZeneca. Dr. Majem has received research funding from 10.13039/100002429Amgen Inc., AstraZeneca, Bristol Myers Squibb, and Roche, and honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Kyowa Kyrin, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche, Sanofi, and Takeda. Dr. Paz-Ares has received research funding from Merck Sharp & Dohme, AstraZeneca, Pfizer, and Bristol-Myers Squibb, and honoraria from Eli Lilly, Merck Sharp & Dohme, Roche, Pharmamar, Merck, AstraZeneca, Novartis, Servier, Amgen, Pfizer, Sanofi, Bayer, Bristol-Myers Squibb, Mirati, GlaxoSmithKline, Janssen, Takeda, and Mirati. Dr. Lopez-Rios has received research funding from Eli Lilly, AstraZeneca, Roche, Pfizer, and ThermoFisher Scientific, and honoraria from Abbvie, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, Janssen, Eli Lilly, Merck Sharp & Dohme, Merck, Pfizer, Roche, Sanofi, Takeda, and Thermo Fisher. The remaining authors declare no conflict of interest., (© 2024 The Authors.)

The incidence and mortality of lung cancer in women are rising, with both increasing by 124% between 2003 and 2019. The main risk factor for lung cancer is tobacco use, but indoor radon gas exposure is one of the leading causes in nonsmokers. The most recent evidence demonstrates that multiple factors can make women more susceptible to harm from these risk factors or carcinogens. For this consensus statement, the Association for Lung Cancer Research in Women (ICAPEM) invited a group of lung cancer experts to perform a detailed gender-based analysis of lung cancer. Clinically, female patients have different lung cancer profiles, and most actionable driver alterations are more prevalent in women, particularly in never-smokers. Additionally, the impact of certain therapies seems to be different. In the future, it will be necessary to carry out specific studies to improve the understanding of the role of certain biomarkers and gender in the prognosis and evolution of lung cancer., (© 2023. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Objective: To analyze possible changes in body composition in elderly individuals with combat sports as an intervention., Methods: This study is characterized as a systematic review and meta-analysis. The PRISMA criteria were followed, and the study was registered in PROSPERO under the number CRD42023392613. The databases used were MEDLINE (via PubMed), Scopus, SPORTDiscus, Web of Science, and Science Direct. The risk of bias and methodological quality were assessed using Robins-I, Cochrane, and Testex tools., Results: Of the 126 publications found, 9 studies were included (5 controlled and randomized studies and 4 intervention studies). Of these studies, 6 provided data for the meta-analysis. A total of 126 publications were found and, the studies included in this systematic review had an average of 51 weeks, 3 times a week, and 50 min per session. In the results presented by the meta-analysis the variable body fat showed a reduction (SMD: -0.11; 95% CI: -0.99 to 0.09; p = 0.02; I2 = 0%)., Conclusion: Combat sports showed an improvement in the body composition of the elderly, with a reduction in the percentage of body fat., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The long non-coding RNA HOX transcript antisense intergenic RNA ( HOTAIR ) is associated with oncogenic features in bladder cancer and is predictive of poor clinical outcomes in patients diagnosed with this disease. In this study, we evaluated the impact of the HOTAIR single nucleotide polymorphisms rs920778 and rs12826786 on bladder cancer risk and survival. This case-control study included 106 bladder cancer patients and 199 cancer-free controls. Polymorphisms were evaluated through PCR-restriction fragment length polymorphism. The odds ratio and 95% confidence intervals were tested using univariable and multivariable logistic regressions. The effects on patient survival were evaluated using the log-rank test and Cox regression models. Our data showed that the HOTAIR rs920778 and rs12826786 genetic variants are not associated with the risk of developing bladder cancer. Nevertheless, survival analyses suggested that the HOTAIR rs920778 TT genotype and rs12826786 CC genotype are associated with increased survival in male bladder cancer patients and in patients, both male and female, who have primary tumors with a pathological stage of pT2. Together, these results suggest that, despite not being associated with bladder cancer risk, HOTAIR rs920778 and rs12826786 polymorphisms might represent new prognostic factors in this type of cancer. This is particularly important as these polymorphisms might be easily evaluated in bladder cancer patients in a minimally invasive manner to better predict their clinical outcomes.

Background: Fecal occult blood tests (FOBT) are inappropriately used in patients with melena, hematochezia, coffee ground emesis, iron deficiency anemia, and diarrhea. The use of FOBT for reasons other than screening for colorectal cancer is considered low-value and unnecessary., Methods: Quality Improvement Project that utilized education, Best Practice Advisory (BPA) and modification of order sets in the electronic health record (EHR). The interventions were done in a sequential order based on the Plan-Do-Study-Act (PDSA) method. An annotated run chart was used to analyze the collected data., Results: Education and Best Practice Advisory within the EHR led to significant reduction in the use of FOBT in the ED. The interventions eventually led to a consensus and removal of FOBT from the order set of the EHR for patients in the ED and hospital units., Conclusions: The use of electronic BPA, education and modification of order sets in the EHR can be effective at de-implementing unnecessary tests and procedures like FOBT in the ED and hospital units., (© 2024 Greater Baltimore Medical Center.)