The aim of our study is to evaluate the clinical efficacy of durvalumab in patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) or polymerase epsilon (POLE)-mutated metastatic or unresectable colorectal cancer (mCRC) who had disease progression after standard chemotherapy. This prospective, open-label, multicenter, phase II study enrolled patients with mCRC harboring MSI-H/dMMR or POLE mutations treated with at least one prior line of therapy. The participants received durvalumab (1500 mg) every 4 weeks intravenously. The primary endpoint was the objective response rate (ORR). Of the 33 patients, 30 had MSI-H/dMMR and 3 had POLE-mutated microsatellite stable (MSS) CRC. With a median follow-up duration of 11.2 months (95% confidence interval [CI]: 7.3-15.0), the ORR was 42.4% (95% CI: 25.5-60.8). Among three patients with POLE-mutated CRC, one patient who had an exonuclease domain mutation (EDM) achieved an objective response, but the others with mutations in the non-exonuclease domain had progressive disease. Overall, the median duration of response was not reached and 85.7% of the responses were ongoing at data cutoff. The progression-free survival rate of 12 months was 58.2% (95% CI: 39.0-73.1) and the 12-month overall survival rate was 68.3% (95% CI: 48.8-81.7). Grade 3 treatment-related adverse events occurred in 36.4% of the patients and were manageable. In conclusion, durvalumab showed promising clinical activity with encouraging response rates and satisfactory survival outcomes in mCRC patients with MSI-H/dMMR or POLE EDM. In patients with POLE-mutated mCRC, clinical response to durvalumab may be restricted to those with EDM.
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http://dx.doi.org/10.1002/ijc.33966 | DOI Listing |
Inorg Chem
January 2025
Department of Material and Environmental Chemistry, Arrhenius Laboratory, Stockholm University, SE-10691 Stockholm, Sweden.
Zinc oxide (ZnO) is a semiconductor with a wide range of applications, and often the properties are modified by metal-ion doping. The distribution of dopant atoms within the ZnO crystal strongly affects the optical and magnetic properties, making it crucial to comprehend the structure down to the atomic level. Our study reveals the dopant structure and its contents in Eu-doped ZnO nanosponges with up to 20% Eu-O clusters.
View Article and Find Full Text PDFRev Sci Instrum
January 2025
School of Electrical and Electronic Engineering, The University of Manchester, Manchester M13 9PL, United Kingdom.
Carbon fiber reinforced polymers (CFRPs) are widely used in fields such as aviation and aerospace. However, subtle defects can significantly impact the material's service life, making defect detection a critical priority. In this paper, delamination defects in CFRP are detected using line laser infrared thermography, and a defect characterization algorithm that combines differential thermography with a frequency-domain filter is proposed.
View Article and Find Full Text PDFJAMA Oncol
January 2025
Children's Wisconsin, Milwaukee.
Importance: Retrieval strategies for children, adolescents, and young adults with relapsed classic Hodgkin lymphoma (cHL) aim to maintain efficacy while minimizing long-term toxic effects. Children, adolescents, and young adults with low-risk, relapsed cHL may benefit from replacing high-dose chemotherapy and autologous stem cell transplant with less intensive involved-site radiotherapy (ISRT).
Objective: To evaluate a risk-stratified, response-adapted, transplant-free approach for treatment of children, adolescents, and young adults with low-risk relapsed cHL with nivolumab plus brentuximab vedotin (BV) followed by BV plus bendamustine for patients with suboptimal response and ISRT (30.
Eur J Emerg Med
September 2024
Department of Anaesthesiology and Intensive Care Medicine.
Background: Noncompressible truncal hemorrhage is a major contributor to preventable deaths in trauma patients and, despite advances in emergency care, still poses a big challenge.
Objectives: This study aimed to assess the clinical efficacy of trauma resuscitation care incorporating Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) compared to standard care for managing uncontrolled torso or lower body hemorrhage.
Methods: This study utilized a target trial design with a matched case-control methodology, emulating randomized 1 : 1 allocation for patients receiving trauma resuscitation care with or without the use of REBOA.
Arch Microbiol
January 2025
SLIIT, Malabe, Sri Lanka.
The development of new medicines with unique methods of antimicrobial action is desperately needed due to the emerging multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus. Therefore, antimicrobial peptoids have emerged as potential new antimicrobials. Thirteen peptoid analogues have been designed and synthesized via solid phase synthesis.
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