Olaparib and Radiotherapy Induce Type I Interferon- and CD8+ T Cell-Dependent Sensitization to Immunotherapy in Pancreatic Cancer.

PARP inhibitors sensitize pancreatic ductal adenocarcinoma (PDAC) to radiation by inducing DNA damage and replication stress. These mechanisms also have the potential to enhance radiation-induced type I interferon (T1IFN)-mediated antitumoral immune responses. We hypothesized that the PARP inhibitor olaparib would also potentiate radiation-induced T1IFN to promote antitumor immune responses and sensitization of otherwise resistant PDAC to immunotherapy.

Development of a RIPK1 degrader to enhance antitumor immunity.

The scaffolding function of receptor interacting protein kinase 1 (RIPK1) confers intrinsic and extrinsic resistance to immune checkpoint blockades (ICBs) and emerges as a promising target for improving cancer immunotherapies. To address the challenge posed by a poorly defined binding pocket within the intermediate domain of RIPK1, here we harness proteolysis targeting chimera (PROTAC) technology to develop a RIPK1 degrader, LD4172. LD4172 exhibits potent and selective RIPK1 degradation both in vitro and in vivo.

Systematic Review of the Comparative Studies of Image-guided Thermal Ablation, Stereotactic Radiosurgery, and Sublobar Resection for Treatment of High-Risk Patients with Stage I Non-Small Cell Lung Cancer.

The Clinical Practice Standards Committee of the American Association for Thoracic Surgery assembled an expert panel and conducted a systematic review of the literature detailing studies directly comparing treatment options for high-risk patients with stage I non-small cell lung cancer (NSCLC). A systematic search was performed to identify publications comparing outcomes following image-guided thermal ablation (IGTA), stereotactic ablative radiotherapy (SABR), and sublobar resection-the main treatment options applicable to high-risk patients with stage I NSCLC. There were no publications detailing completed randomized controlled trials comparing these treatment options.

Systematic Review of Stereotactic Ablative Radiotherapy (SABR)/ Stereotactic Body Radiation Therapy (SBRT) for Treatment of High-Risk Patients with Stage I Non-Small Cell Lung Cancer.

Stereotactic ablative radiotherapy (SABR) has emerged as an alternative, non-surgical treatment for high-risk patients with stage I non-small cell lung cancer (NSCLC) with increased use over time. The American Association for Thoracic Surgery (AATS) Clinical Practice Standards Committee (CPSC) assembled an expert panel and conducted a systematic review of the literature evaluating the results of SABR, which is also referred to as stereotactic body radiation therapy (SBRT) or stereotactic radiosurgery (SRS), prior to developing treatment recommendations for high-risk patients with stage I NSCLC based on expert consensus. Publications detailing the findings of 16 prospective studies of SABR and 14 retrospective studies of SABR for the management of early-stage lung cancer in 54 697 patients were identified by systematic review of the literature with further review by members of our expert panel.

Systematic Review of Sublobar Resection for Treatment of High-Risk Patients with Stage I Non-Small Cell Lung Cancer.

Sublobar resection offers a parenchymal-sparing surgical alternative to lobectomy and includes wedge resection and segmentectomy. Sublobar resection has been historically utilized in high-risk patients with compromised lung function; however, the technique is becoming more prevalent for normal-risk patients with peripheral lung tumors < 2 cm. In this article, we summarize the technique of sublobar resection, the importance of surgical margins and lymph node sampling, patient selection, perioperative complications, outcomes, and the impact of sublobar resection on the quality of life.

In vitro hydrolysis of areca nut xenobiotics in human liver.

Areca nut (AN) is a substance of abuse consumed by millions worldwide, in spite of established oral and systemic toxicities associated with its use. Previous research demonstrates methyl ester alkaloids in the AN, such as arecoline and guvacoline, exhibit mood-altering and toxicological effects. Nonetheless, their metabolism has not been fully elucidated in humans.

Treatment Selection for the High-risk Patient with Stage I Non-Small Cell Lung Cancer: Sublobar Resection, Stereotactic Ablative Radiotherapy or Image-guided Thermal Ablation?

Objective: A significant proportion of patients with stage I non-small cell lung cancer (NSCLC) are considered at high risk for complications or mortality after lobectomy. The American Association for Thoracic Surgery (AATS) previously published an expert consensus document detailing important considerations in determining who is at high risk. The current objective was to evaluate treatment options and important factors to consider during treatment selection for these high-risk patients.

Systematic Review of Image-guided Thermal Ablation for Treatment of High-Risk Patients with Stage I Non-Small Cell Lung Cancer.

Image-guided thermal ablation (IGTA) applied to pulmonary pathology is an alternative to surgery in high-risk patients with stage I non-small cell lung cancer (NSCLC). Its application to lung neoplasm was first introduced in 2001 and has been implemented to treat metastatic disease to the lung or in select medically inoperable patients with peripheral stage I NSCLC. IGTA may also be an alternative to treat stage I NSCLC in non-operable patients with interstitial lung disease in whom a radiation modality is deemed too high risk.

The Importance of Pulmonary Nodule Features in the Selection of Treatment for the High-risk Patient with Stage I Non-Small Cell Lung Cancer.

Objective: The American Association for Thoracic Surgery (AATS) Clinical Practice Standards Committee (CPSC) previously published important considerations in determining who is at high risk for complications or mortality after lobectomy. Sublobar resection, stereotactic ablative radiotherapy, or image-guided thermal ablation is typically considered when the risks associated with lobectomy are high. The current objective was to evaluate important lung-nodule-related factors to consider during treatment selection for high-risk patients with stage I non-small cell lung cancer (NSCLC).

Patient-reported outcomes after CAR T-cell therapy in patients with hematological malignancies.

The remarkable improvement in survival among individuals with hematological malignancies receiving chimeric antigen receptor (CAR) T-cell therapy has highlighted the growing unmet need to incorporate patient-centered assessments in management guidelines for these patients. That CAR T-cell therapy is associated with unique toxicities and relatively high symptom burden in the first few weeks after cell infusion is well known. Magnifying the patient's voice by using patient-reported outcomes (PROs) might support personalized intervention in the acute-care setting, optimize the use of medical resources, improve satisfaction with therapy, and enhance survival benefit.

A commissioning protocol for portal imaging-based radiotherapy in vivo dosimetry systems.

Background And Purpose: With the availability of commercial electronic portal imaging detector-based in vivo dosimetry (EPID-based IVD) solutions, many radiotherapy departments are adopting this technology. However, comprehensive commissioning guidance is lacking. This study aims to provide a protocol for testing the accuracy and sensitivity of EPID-based IVD systems.

Unlocking Intracellular Oncology Targets: The Unique Role of Antibody-Based T-Cell Receptor Mimic (TCRm) Therapeutics in T-Cell Engagers (TCEs) and Antibody-Drug Conjugates (ADCs).

Effectively targeting intracellular tumor-associated proteins presents a formidable challenge in oncology, as they are traditionally considered inaccessible to conventional antibody-based therapies and CAR-T cell therapies. However, recent advancements in antibody engineering have revolutionized this field, offering promising new strategies to combat cancer. This review focuses on the innovative use of T-cell receptor mimic (TCRm) antibodies within the therapeutic frameworks of T-cell engagers (TCE) and antibody-drug conjugates (ADCs).

Standard or Extended Lymphadenectomy for Muscle-Invasive Bladder Cancer.

Background: Whether extended lymphadenectomy is associated with improved disease-free and overall survival, as compared with standard lymphadenectomy, among patients with localized muscle-invasive bladder cancer undergoing radical cystectomy is unclear.

Methods: We randomly assigned, in a 1:1 ratio, patients with localized muscle-invasive bladder cancer of clinical stage T2 (confined to muscle) to T4a (invading adjacent organs) with two or fewer positive nodes (N0, N1, or N2) to undergo bilateral standard lymphadenectomy (dissection of lymph nodes on both sides of the pelvis) or extended lymphadenectomy involving removal of common iliac, presciatic, and presacral nodes. Randomization was performed during surgery and stratified according to the receipt and type of neoadjuvant chemotherapy, tumor stage (T2 vs.

Insights from a multiscale framework on metabolic rate variation driving glioblastoma multiforme growth and invasion.

Non-physiological levels of oxygen and nutrients within the tumors result in heterogeneous cell populations that exhibit distinct necrotic, hypoxic, and proliferative zones. Among these zonal cellular properties, metabolic rates strongly affect the overall growth and invasion of tumors. Here, we report on a hybrid discrete-continuum (HDC) mathematical framework that uses metabolic data from a biomimetic two-dimensional (2D) in-vitro cancer model to predict three-dimensional (3D) behaviour of in-vitro human glioblastoma (hGB).

Data-Driven Cutoff Selection for the Patient Health Questionnaire-9 Depression Screening Tool.

Importance: Test accuracy studies often use small datasets to simultaneously select an optimal cutoff score that maximizes test accuracy and generate accuracy estimates.

Objective: To evaluate the degree to which using data-driven methods to simultaneously select an optimal Patient Health Questionnaire-9 (PHQ-9) cutoff score and estimate accuracy yields (1) optimal cutoff scores that differ from the population-level optimal cutoff score and (2) biased accuracy estimates.

Design, Setting, And Participants: This study used cross-sectional data from an existing individual participant data meta-analysis (IPDMA) database on PHQ-9 screening accuracy to represent a hypothetical population.

Cyclin D1-negative mantle cell lymphoma.

Cyclin D1-negative mantle cell lymphoma (MCL) is regarded as a B-cell neoplasm that has morphologic and immunophenotypic findings indistinguishable from typical MCL. These neoplasms lack cyclin D1 overexpression by immunohistochemistry and t(11;14)(q13;q32)/IGH::CCND1. Since cyclin D1-negative MCL was first recognized by gene expression profiling in 2003, there has been diagnostic confusion regarding this entity, mostly attributable to a lack of diagnostic tools to recognize these neoplasms in most clinical laboratories.

Treatment of Invasive Pulmonary Aspergillosis and Preventive and Empirical Therapy for Invasive Candidiasis in Adult Pulmonary and Critical Care Patients. An Official American Thoracic Society Clinical Practice Guideline.

Background: The incidence of invasive fungal infections is increasing in immune-competent and immune-compromised patients. An examination of the recent literature related to the treatment of fungal infections was performed to address two clinical questions. First, in patients with proven or probable invasive pulmonary aspergillosis, should combination therapy with a mold-active triazole plus echinocandin be administered vs.

PIT-1/SF-1 co-expression in pituitary neuroendocrine tumors (PitNETs) with comprehensive review of the literature: How should we best characterize these neoplasms?

The nomenclature and classification of neuroendocrine tumors of the anterior pituitary have undergone significant change over the last few years. Despite the updated classification system as devised by the World Health Organization, some tumors do not fit neatly into the currently defined categories. The most common tumor type not defined by the updated guidelines is a pituitary neuroendocrine tumor with co-expression of SF-1 and PIT-1.