Citations

PURPOSE This study aimed to investigate the clinicomolecular profiles and the efficacy of human epidermal growth factor receptor 2 (HER2)-targeted therapy in HER2 -amplified biliary tract cancer (BTC). METHODS This study was an international collaboration that used combined data from the prospective SCRUM-Japan GOZILA and MONSTAR-SCREEN in Japan and retrospective reviews in the United States; patients with advanced BTC who had received systemic therapy were included. The clinicomolecular profiles were evaluated in an exploratory cohort, whereas the efficacy of HER2-targeted therapy was assessed in a biomarker-selected cohort. RESULTS Of the 439 patients in the exploratory cohort, 43 (10%) had HER2 amplification. The frequencies of coalterations were higher in patients with HER2 amplification versus patients without HER2 amplification including HER2 mutations (26% v 5%, P < .001), TP53 mutations (84% v 61%, P = .003), and BRAF amplification (9% v 2%, P = .030). There were no KRAS mutations identified in patients with HER2- amplified BTC. No significant difference in overall survival (OS) was observed between patients with and without HER2 amplification (median, 17.7 v 16.9 months; hazard ratio [HR], 0.95 [95% CI, 0.65 to 1.40]). Of the 60 patients with HER2 -amplified BTC in the biomarker-selected cohort (43 from Japan and 17 from the United States), the OS was significantly longer in 29 patients who received HER2-targeted therapy than in those who did not receive HER2-targeted therapy (median, 24.3 v 12.1 months; HR, 0.39 [95% CI, 0.23 to 0.82]). Multivariate analysis identified HER2-targeted therapy as an independent prognostic factor for OS (HR, 0.29 [95% CI, 0.14 to 0.58]; P < .001). CONCLUSION HER2 amplification was found in 10% of advanced BTC and was not identified as an independent prognostic factor for OS. Patients with HER2 -amplified BTC derive significant benefit from HER2-targeted therapy.

Abstract Chimeric antigen receptor T (CART) cell therapy is an innovative form of immunotherapy that has shown remarkable and long-term responses in patients with B-cell malignancies. Over the years, the field has made significant progress in our understanding of the successes and challenges associated with CART cell therapy. In this review, we provide an overview of the current state of CART cell therapy in the clinic. We detail current challenges including patient access, CART-associated toxicity, tumor heterogeneity, CART cell trafficking, the tumor microenvironment, and different CART cell fates. With each challenge, we review lessons learned, potential solutions and outline areas for future development. Finally, we discuss how the field of engineered cell therapy is moving into the treatment of solid tumors and other diseases beyond cancer.

Abstract ZUMA-8 evaluated the safety of brexucabtagene autoleucel (brexu-cel), a CD19-directed autologous chimeric antigen receptor (CAR) T-cell immunotherapy, for patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL). Patients with ≥2 prior lines of therapy (including a Bruton tyrosine kinase inhibitor) underwent leukapheresis, optional bridging therapy, and conditioning chemotherapy (fludarabine/cyclophosphamide) before infusion of 1 × 106 (cohort 1) or 2 × 106 (cohort 2) anti-CD19 CAR T cells per kg. Patients in cohort 3 (low tumor burden), and cohort 4A (postibrutinib) received 1 × 106 cells per kg. Fifteen patients, median age of 63 years (range, 52-79), were treated in cohorts 1 (n = 6), 2 (n = 3), 3 (n = 3), and 4A (n = 3). Median follow-up was 24.3 months. One dose-limiting toxicity was observed in cohort 3 (grade 4 cytokine release syndrome). Grade ≥3 neurologic events occurred in 3 patients (20%). Seven of 15 patients responded (overall response rate, 47%; complete response [CR], 7%), including all 3 patients in cohort 3 (1 with CR). CAR T-cell expansion occurred in 4 patients (27%), with an apparent weak inverse correlation with absolute lymphocyte count before apheresis. Brexu-cel had no new safety signals in R/R CLL. CAR T-cell expansion and responses occurred in patients with low tumor burden. This trial was registered at www.clinicaltrials.gov as #NCT03624036.

Frequently overlooked yet clinically significant, the urachus can exhibit a diverse range of pathologic conditions, which can pose a diagnostic challenge at imaging for the radiologist and which require a thorough understanding of urachal embryogenesis.

Withdrawal Statement The authors have withdrawn the manuscript because the data it contained has been updated. Consequently, they request that this work should not be cited as a reference for any projects to ensure the use of the most current information. For any questions or further clarifications, readers are encouraged to contact the corresponding author directly

Introduction: Despite significant advancements in COVID-19 treatment and prevention, immunocompromised individuals, particularly those with hematological malignancies, remain at high risk for severe infection and suboptimal vaccine response. Pre-exposure prophylaxis strategies for these vulnerable populations have been limited. Monoclonal antibodies, proteins designed to target specific antigens, offer a promising preventive solution for individuals unable to mount a sufficient immune response to vaccination. However, there is a critical unmet need to establish clear patient selection criteria for pre-exposure prophylaxis with monoclonal antibodies in these groups. This consensus statement explores recent research to address this gap, outlining profiles of patients most likely to benefit from monoclonal antibody-based prophylaxis. Methodology: The consensus statement was developed through a rigorous process, utilizing a pre-Delphi search method and a modified Delphi technique to gather expert opinions. This approach ensured a comprehensive and informed consensus among experts in the field. Initially, nine distinct patient categories requiring pre-exposure prophylaxis with monoclonal antibodies were identified. Through iterative rounds of expert feedback, discussion, and refinement, these nine categories were expanded and subdivided into twelve more specific groups of hematological malignancies and immunocompromised disorders. This refinement aimed to better capture the diverse patient profiles requiring prophylaxis, providing a more detailed framework for the targeted administration of monoclonal antibodies. Results: The study resulted in the panel members agreeing on nine categories for the use of monoclonal antibodies in COVID-19 prevention for high-risk patients. Achieving consensus among experts is crucial as it reflects the collective validation of evidence-based recommendations that can be reliably applied in clinical practice. A 100% agreement was reached for HIV and AIDS, underscoring the unanimous recognition of the vulnerability of this group to severe COVID-19 outcomes. Similarly, 96% agreement was reached for patients on immunomodulatory drugs (IMiDs), and 90.5% for those with hematological diseases, highlighting strong expert support for prophylaxis in these categories. Immunodeficiencies and renal conditions garnered 86% agreement, indicating broad, although slightly more varied, expert consensus on these groups. Lastly, 80% of the panel supported patients with solid organ cancer, liver conditions, rare neurological disorders, and severe life-limiting neuro-disabilities, reflecting recognition of their elevated risk despite more diverse opinions for these categories. Conclusion: This consensus statement offers healthcare professionals in the UAE a clear, evidence-based framework for the use of monoclonal antibodies in preventing COVID-19 among patients with hematological malignancies and immunocompromised conditions. By outlining specific patient categories, the statement provides a practical guide that enables clinicians to make informed decisions about pre-exposure prophylaxis, ensuring that high-risk individuals receive timely and appropriate protection. The consensus not only enhances the ability of healthcare providers to identify and prioritize at-risk populations, but also optimizes patient outcomes by streamlining preventive measures in clinical practice. In addition, these findings lay the groundwork for future research and the development of standardized protocols, ultimately improving the management of vulnerable populations in the ongoing fight against COVID-19.

Abstract Rationale Stereotactic body radiation therapy (SBRT) represents an effective therapeutic strategy for early-stage non–small cell lung cancer (NSCLC); however, local and systemic recurrences represent ongoing challenges. Computed tomography (CT) radiomics-based risk models can potentially be used to predict the risk of local recurrence on pretreatment CT scans. Objective Development of a radiomics model to predict local recurrence after SBRT in patients with NSCLC. Methods This single-institution study includes a retrospective case-control training set (20 patients with local recurrence and 40 control subjects) and an independent validation set (198 consecutive cases) of patients with early-stage NSCLC treated with SBRT. Tumors were semiautomatically segmented, and 102 quantitative radiomic features, including texture, landscape, spatial, nodule shape, and nodule surface features, were extracted. These features were included in three separate multivariable models to predict the risk of recurrence on the basis of pre-SBRT, post-SBRT, and the difference between the pre-SBRT and post-SBRT scans (Delta model). The pre-SBRT model was subsequently validated in an independent validation set. Results Thirteen independent variables were selected for the models using the Boruta algorithm. The sensitivity, specificity, and area under the curve of the pre-SBRT, post-SBRT, and Delta models were 85%, 90%, and 0.91; 85%, 92.5%, and 0.92; and 85%, 92.5%, and 0.94, respectively. The pre-SBRT model was validated in the independent validation set (area under the curve, 0.89; confidence interval, 0.83–0.92), because this model was believed to be the most useful to assist in individualized treatment planning. Conclusions Radiomic analysis facilitated the development of three high-performing models predicting local recurrence using either pre-SBRT CT, post-SBRT CT, or the change between these two. We successfully validated the most clinically relevant model, the pre-SBRT model. Although this model needs further validation, it may facilitate individualized surveillance, treatment planning, and selection of adjuvant therapy.