PD-1 expression identifies proliferating malignant CLL B cells and is a potential biomarker of response to BTK inhibitor therapy.

Chronic lymphocytic leukemia (CLL) remains incurable despite treatment advances, and a major challenge is that biomarkers that predict response and resistance to current therapies are lacking. We report that activated and proliferating malignant CLL B cells in circulation express PD-1, a protein normally expressed in T cells. PD-1 expression is absent in circulating B cells from healthy controls and nonmalignant B cells from patients with CLL.

Defining the reliability of bladder scan in patients with obesity with postoperative urinary retention.

Background: Postoperative urinary retention warrants catheterization. A bladder scan helps check for postoperative urinary retention before catheterization. There is a paucity of data about its reliability in postoperative obese patients.

Bladder activity of different PSMA PET radioligands and impact of furosemide.

Background: Prostate-specific membrane antigen (PSMA) radioligands used for PET imaging of prostate cancer (PCa) have variable urinary excretion. The prostate bed region is an important site of disease localization where intense bladder activity may obscure lesion detection. We performed a comparative analysis of the bladder activity of different PSMA radioligands and investigated the impact of furosemide administration on bladder activity reduction.

Early-Phase Trial of IAP Antagonist Tolinapant and Definitive Radiation in Cisplatin-Ineligible Patients with Advanced Head and Neck Cancer.

Purpose: Tolinapant is an inhibitor of apoptosis protein antagonist that enhances apoptotic pathways. In preclinical studies, tolinapant + radiotherapy (RT) enhances antitumor immunity. We conducted an open-label, single-arm trial to evaluate the safety and feasibility of concurrent tolinapant and RT in cisplatin-ineligible patients with head and neck squamous cell carcinoma.

XL888 and pembrolizumab modulate the immune landscape of colorectal tumors in a phase Ib/II clinical trial.

We conducted a phase Ib/II clinical trial to evaluate the safety, feasibility, and clinical activity of combining pembrolizumab (anti-PD-1) with XL888 (Hsp90 inhibitor) in patients with advanced colorectal cancer (CRC). We hypothesized that this regimen would modulate soluble and cellular immune mediators and enhance clinical outcomes. The trial employed a 3 + 3 open-label design, with an expansion cohort at the recommended phase II dose (RP2D) in treatment-refractory, mismatch repair-proficient CRC patients.

Rurality Status and Cardiovascular Events/Survival in Older Men With Prostate Cancer.

Background: Rural areas have higher cardiovascular disease (CVD) incidence and age-adjusted mortality rates in the general population. However, the impact of rurality on CVD development and outcomes in patients with prostate cancer (PC) remains unclear.

Patients And Methods: This retrospective cohort study used the SEER-Medicare database to analyze males aged ≥65 years diagnosed with PC between 2009 and 2017.

Polo-like Kinase 1 Inhibitors Demonstrate In Vitro and In Vivo Efficacy in Preclinical Models of Small Cell Lung Cancer.

To investigate the preclinical efficacy and identify predictive biomarkers of polo-like kinase 1 (PLK1) inhibitors in small cell lung cancer (SCLC) models. We tested the cytotoxicity of selective PLK1 inhibitors (rigosertib, volasertib, and onvansertib) in a panel of SCLC cell lines. We confirmed the therapeutic efficacy of subcutaneous xenografts of representative cell lines and in four patient-derived xenograft models generated from patients with platinum-sensitive and platinum-resistant SCLC.

Characterisation of clinical response and transcriptional profiling of proliferating CD8 T cells in the blood of cancer patients after PD-1 monotherapy or combination therapy.

Objective: Immune checkpoint inhibitors (ICI) that block the programmed cell death 1 (PD-1) pathway have shown promise with limited benefit. We and others have shown in small patient cohorts that an early proliferative CD8 T-cell response in the blood may be predictive of clinical response. However, these studies lack detailed analyses and comparisons between monotherapy and combination therapies.

Diuresis During F-Flotufolastat (rhPSMA-7.3) PET/CT Improves Recurrence Detection After Prostatectomy: A Prospective Phase II Trial.

Radiopharmaceuticals targeting prostate-specific membrane antigen (PSMA) have emerged as a sensitive tool for PET imaging of prostate cancer (PCa) recurrence. Yet urinary bladder activity may obscure the visualization of prostate bed recurrence. Among the Food and Drug Administration-approved PSMA radiopharmaceuticals, F-flotufolastat (rhPSMA-7.

A registry-based approach for estimating county-level race disparities in breast cancer mortality: an analysis in Georgia.

Despite similar incidence rates, nationwide breast cancer mortality is 40% higher among non-Hispanic Black (NHB) than non-Hispanic White (NHW) women. The racial disparity persists even among women who have early-stage disease, prognostically favorable subtypes, or indicators of high socioeconomic status, and is not evenly distributed throughout the United States. Understanding geographic differences may provide additional insight into the drivers of the disparity.

Reducing Postoperative Opioid Use: A Comparison of Open Versus Ultrasound-Guided Regional Anesthesia for Patients Undergoing Open Pancreatoduodenectomy.

Background: Opioid crisis is a national issue with significant economic burden and marked increase in opioid-related deaths, particularly following surgical procedures. Reducing opioid requirements while maintaining effective analgesia is critically challenging, perioperatively. Multimodal drug regimens and guided regional anesthesia (RA) have been adopted to address this issue.

Mechanism of enhancing chemotherapy efficacy in pancreatic ductal adenocarcinoma with paricalcitol and hydroxychloroquine.

Pancreatic ductal adenocarcinoma (PDAC) has a minimal (<15%) 5-year existence, in part due to resistance to chemoradiotherapy. Previous research reveals the impact of paricalcitol (P) and hydroxychloroquine (H) on altering the lysosomal fusion, decreasing stromal burden, and triggering PDAC to chemotherapies. This investigation aims to elucidate the molecular properties of the H and P combination and their potential in sensitizing PDAC to gemcitabine (G).

Investigating interaction effects of social risk factors and exposure to air pollution on pediatric lymphoma cancer in Georgia, United States.

Childhood cancer constitutes a major cause of death in children. In a recent study of the Georgia Cancer Registry, joint exposures to environmental and social/behavioral stressors were associated with spatial clustering of lymphomas and reticuloendothelial neoplasms among the 159 counties in Georgia, USA. The present study aims to further investigate these associations on a more granular level.

Fifteen-Year Experience of a Single Institution: Outcomes for Early-Stage Hodgkins Lymphoma Comparing Chemotherapy Alone Versus Combined Modality Therapy.

Purpose: Doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy is the current standard treatment for early-stage Hodgkins lymphoma (HL). The use of consolidative radiation therapy (RT) in addition to chemotherapy may lead to better survival rates but is controversial because of concerns about long-term toxicity. The aim of this study is to compare outcomes of patients receiving ABVD chemotherapy alone (CTX alone) versus ABVD with consolidative RT (CMT).

Divergence of variant antibodies following SARS-CoV-2 booster vaccines in myeloma and impact of hybrid immunity.

Hematological malignancies are associated with an increased risk of complications during SARS-CoV-2 infections. Primary series or monovalent booster vaccines reduce disease severity, hospitalization, and death among multiple myeloma patients. We characterized virus-neutralizing and spike-binding antibody profiles following monovalent (WA1) or bivalent (WA1/BA.

Pre-operative stereotactic radiosurgery and peri-operative dexamethasone for resectable brain metastases: a two-arm pilot study evaluating clinical outcomes and immunological correlates.

Enhancing the efficacy of immunotherapy in brain metastases (BrM) requires an improved understanding of the immune composition of BrM and how this is affected by radiation and dexamethasone. Our two-arm pilot study (NCT04895592) allocated 26 patients with BrM to either low (Arm A) or high (Arm B) dose peri-operative dexamethasone followed by pre-operative stereotactic radiosurgery (pSRS) and resection (n= 13 per arm). The primary endpoint, a safety analysis at 4 months, was met.

Radiomic Analysis of Treatment Effect for Patients with Radiation Necrosis Treated with Pentoxifylline and Vitamin E.

Background: The combination of oral pentoxifylline (Ptx) and vitamin E (VitE) has been used to treat radiation-induced fibrosis and soft tissue injury. Here, we review outcomes and perform a radiomic analysis of treatment effects in patients prescribed Ptx + VitE at our institution for the treatment of radiation necrosis (RN).

Methods: A total of 48 patients treated with stereotactic radiosurgery (SRS) had evidence of RN and had MRI before and after starting Ptx + VitE.

Intraoperative radiation therapy for early-stage breast cancer.

Background: Intraoperative radiotherapy (IORT) offers more convenience compared to external beam radiotherapy (EBRT) following breast-conserving surgery for early-stage breast cancer. This study describes the implementation of IORT at a metropolitan academic cancer center.

Methods: Demographics, tumor characteristics, margin status, adjunct EBRT, and cosmetic results were retrospectively analyzed in patients undergoing BCS with IORT.

PD-L1 deglycosylation promotes its nuclear translocation and accelerates DNA double-strand-break repair in cancer.

Resistance to radiotherapy is a major barrier during cancer treatment. Here using genome-scale CRISPR/Cas9 screening, we identify CD274 gene, which encodes PD-L1, to confer lung cancer cell resistance to ionizing radiation (IR). Depletion of endogenous PD-L1 delays the repair of IR-induced DNA double-strand breaks (DSBs) and PD-L1 loss downregulates non-homologous end joining (NHEJ) while overexpression of PD-L1 upregulates NHEJ.

Initial experience and patient tolerance of proton stereotactic body radiotherapy.

Purpose: To review our initial experience with proton-based SBRT to evaluate the planning outcomes and initial patient tolerance of treatment.

Patients And Methods: From Sep. 2019 to Dec.

Prospective investigation of amino acid transport and PSMA-targeted positron emission tomography for metastatic lobular breast carcinoma.

Purpose: To explore the feasibility of imaging amino-acid transport and PSMA molecular pathways in the detection of metastatic breast invasive lobular carcinoma (ILC) and if there is superior detection compared to standard-of-care imaging [computed tomography (CT)/bone scan, or F-FDG positron-emission-tomography (PET)-CT].

Methods: 20 women with de-novo or suspected metastatic ILC underwent two PET-CT scans with F-fluciclovine and Ga-PSMA-11 on separate days. Uptake per patient and in 3 regions per patient - ipsilateral axillary lymph node (LN), extra-axillary LN (ipsilateral supraclavicular or internal mammary), or distant sites of disease - was compared to standard-of-care imaging (CT/bone scan in 13 patients and F-FDG PET-CT in 7 patients).