BioMed

Introduction: Current treatments for patients with stage III non-small-cell lung cancer (NSCLC) are not sufficiently personalized, resulting in suboptimal outcomes and high mortality rates. The Developing Circulating and Imaging Biomarkers Towards Personalized Radiotherapy in Lung Cancer (VIGILANCE) study employs innovative health technologies to collect a range of clinical data and features. This includes longitudinal analyses of cell-free and circulating tumor DNA from blood samples and radiomic features extracted from standard-of-care imaging. Additionally, patient-reported outcome measures will be collected to capture patients’ symptoms and quality of life. This will provide invaluable insight into the patient experience during and after radiotherapy. We aim to evaluate whether the data, including patient-reported outcomes, can serve as biomarkers to refine treatment strategies, improve post-treatment follow-up and provide patients with realistic outcome predictions. Key endpoints include the following: (1) assessing whether baseline ctDNA status and its early on-treatment dynamics can identify patients with radioresistant disease who could benefit from treatment intensification; (2) determining whether post-radiotherapy ctDNA clearance can predict benefit from consolidation durvalumab, potentially sparing ctDNA-negative patients from unnecessary immunotherapy; and (3) developing integrated models combining novel ctDNA and radiomic biomarkers to distinguish between radiation fibrosis and tumor recurrence and to predict survival. We adopt a pragmatic approach by recruiting patients receiving standard-of-care treatments in a real-world setting. In addition, most of the clinical data is already routinely collected in our center, except for the blood tests for cell-free and circulating tumor DNA analysis. Methods and analysis: This is a single-center, prospective, exploratory, longitudinal, follow-up study, recruiting patients with stage III NSCLC undergoing standard-of-care curative-intent radiotherapy (with or without systemic therapy). Data collection spans from baseline to during radiotherapy and is extended up to 1 year following radiotherapy. The longitudinal analysis aims to describe and characterize dynamic changes in the collected features and assess their utility as prognostic and response biomarkers. Trial registration number: NCT06086574.

Background and Clinical Significance: Primary Cutaneous Cribriform Apocrine Carcinoma (PCCAC) is a rare, inert low-grade cutaneous malignancy that is diagnosed on histopathologic assessment. PCCAC usually presents in middle-aged adults as a solitary, subcutaneous nodule on the extremities. Characterized by anastomosing tubules and solid/cribriform nests of atypical epithelial cells generating a sieve-like display, the tumor is a histopathological variant of apocrine metaplasia of the skin. PCCAC also follows characteristic staining patterns. It is important to distinguish PCCAC from other similar histological variants, which may hold more grievous indications. Case Presentation: A 47-year-old female presented with an enlarging, itchy growth of several months on her back. On physical exam, an indurated pink, nontender papule of 8 mm on the left lateral side wall was noted. Histopathology demonstrated a well-circumscribed, pandermal tumor composed of anastomosing solid and cribriform nests, tubules, and cords of mildly atypical, eosinophilic epithelial cells forming a glandular lumina. An immunohistochemical study revealed the tumoral epithelium to express CK7, CK5/6, BER-EP4, CD117 (C-kit), and S100. Positive EMA and CEA staining highlighted intratumoral glandular ductal differentiation and apocrine secretion. Immunohistochemical stains for CK20, GATA-3, and p63 were negative. Conclusions: We present this case to distinguish the histological attributes of PCCAC and help differentiate it from more concerning visceral metastatic malignancies. We follow with a narrative review of the histopathologic differential for PCCAC and feature reconciliation of corresponding staining patterns reported in the literature.

Background/Objectives: Bacteriophages are considered promising alternatives for the treatment of multidrug-resistant (MDR) Pseudomonas aeruginosa infections. Methods: Five bacteriophages with lytic activity against MDR P. aeruginosa were isolated from lake and sewage samples and characterized for their biological properties, host range, and efficacy in biofilm and in vitro infection models. Results: The phages displayed broad host ranges, producing zones of lysis in 40–53% of MDR isolates. The average burst size was 112 ± 70 PFU per cell. All phages, either individually or in combination, inhibited biofilm formation and were capable of disrupting preformed biofilms. While treatment with single phages led to bacterial regrowth, the cocktail of all five phages achieved complete bacterial lysis with no regrowth observed. In an in vitro wound and burn infection model, the phage cocktail significantly enhanced cell proliferation and promoted healing. Transmission electron microscopy (TEM) analysis identified phage PA2 as a Myovirus based on its morphology. Conclusions: The phage isolates demonstrated strong activity in multiple in vitro models, effectively targeting both planktonic and biofilm-associated P. aeruginosa. Notably, the five-phage combination prevented the emergence of bacterial resistance, supporting its potential as a biocontrol strategy against MDR P. aeruginosa.