Prognostic Factors in Therapy Regimes of Breast Cancer Patients with Brain Metastases: A Retrospective Monocentric Analysis.

Breast cancer patients who develop brain metastases have a high mortality rate and a massive decrease in quality of life. Approximately 10-15% of all patients with breast cancer (BC) and 5-40% of all patients with metastatic BC develop brain metastasis (BM) during the course of the disease. However, there is only limited knowledge about prognostic factors in the treatment of patients with brain metastases in breast cancer (BMBC).

Phase I trial of ATR inhibitor elimusertib with FOLFIRI in advanced or metastatic gastrointestinal malignancies (ETCTN 10406).

Background: ATR is an apical DDR kinase activated at damaged replication forks. Elimusertib is an oral ATR inhibitor and potentiates irinotecan in human colorectal cancer models.

Methods: To establish dose and tolerability of elimusertib with FOLFIRI, a Bayesian Optimal Interval trial design was pursued.

Dose finding, bioavailability, and PK-PD of oral triapine with concurrent chemoradiation for locally advanced cervical cancer and vaginal cancer (ETCTN 9892).

Background: The addition of IV triapine to chemoradiation appeared active in phase I and II studies but drug delivery is cumbersome. We examined PO triapine with cisplatin chemoradiation.

Methods: We implemented a 3 + 3 design for PO triapine dose escalation with expansion, starting at 100 mg, five days a week for five weeks while receiving radiation with weekly IV cisplatin for locally advanced cervical or vaginal cancer.

The Value of Second-look Ultrasound and Mammography for Assessment and Biopsy of MRI-detected Breast Lesions.

Rationale And Objectives: Suspicious lesions detected in multiparametric breast MRI can be further analyzed with second-look ultrasound (SLUS) and/or mammography. This study aims to assess the value of second-look imaging in selecting the appropriate biopsy method for different lesion characteristics.

Materials And Methods: Between January 2021 and December 2023, 212 women underwent contrast-enhanced multiparametric breast MRI at 3 Tesla.

Quantitation of the DNA-dependent protein kinase inhibitor peposertib (M3814) and metabolite in human plasma by LC-MS/MS.

The DNA-dependent protein kinase (DNA-PK) is an abundant nuclear protein that mediates DNA double-strand break repair by nonhomologous end joining (NHEJ). As such, DNA-PK is critical for V(D)J recombination in lymphocytes and for survival in cells exposed to ionizing radiation and clastogens. Peposertib (M3814) is a small molecule DNA-PK inhibitor currently in preclinical and clinical development for cancer treatment.

Mitigation of Fetal Radiation Injury from Mid-Gestation Total-body Irradiation by Maternal Administration of Mitochondrial-Targeted GS-Nitroxide JP4-039.

Victims of a radiation terrorist event will include pregnant women and unborn fetuses. Mitochondrial dysfunction and oxidative stress are key pathogenic factors of fetal radiation injury. The goal of this preclinical study is to investigate the efficacy of mitigating fetal radiation injury by maternal administration of the mitochondrial-targeted gramicidin S (GS)-nitroxide radiation mitigator JP4-039.

Imaging for local recurrence of breast cancer.

Purpose: Isolated locoregional recurrence of breast cancer (ILRR) and contralateral breast cancer (CBC) affect up to 20% of all breast cancer (BC) patients in the first 20 years after primary diagnosis. Treatment options comprise surgical interventions and further systemic therapies depending on the histological subtype. Patients with hereditary breast or ovarian cancer (HBOC) undergo MRI, mammography, and ultrasound in the aftercare of BC, while non-HBOC (nHBOC) patients do not regularly receive MRI.

Preliminary Experience with Virtual Monoenergetic Imaging and Iodine Mapping in the Primary Staging of Endometrial Cancer.

This study investigated whether virtual monoenergetic images (VMIs) and iodine mapping based on dual-energy CT (DECT) provide advantages in the assessment of endometrial cancer. A dual-source DECT was performed for primary staging of histologically proven endometrioid adenocarcinoma in 21 women (66.8 ± 12.

Mitigation of Fetal Irradiation Injury from Mid-Gestation Total Body Radiation with Mitochondrial-Targeted GS-Nitroxide JP4-039.

Unlabelled: Victims of a radiation terrorist event will include pregnant women and unborn fetuses. Mitochondrial dysfunction and oxidative stress are key pathogenic factors of fetal irradiation injury. The goal of this preclinical study is to investigate the efficacy of mitigating fetal irradiation injury by maternal administration of the mitochondrial-targeted gramicidin S (GS)- nitroxide radiation mitigator, JP4-039.

Breast lesion morphology assessment with high and standard b values in diffusion-weighted imaging at 3 Tesla.

Introduction: With increasing spatial resolution, diffusion-weighted imaging (DWI) may be suitable for morphologic lesion characterization in breast MRI - an area that has traditionally been occupied by dynamic contrast-enhanced imaging (DCE). This investigation compared DWI with b values of 800 and 1600 s/mm to DCE for lesion morphology assessment in high-resolution breast MRI at 3 Tesla.

Material And Methods: Multiparametric breast MRI was performed in 91 patients with 93 histopathologically proven lesions (31 benign, 62 malignant).

Tumor cell p38 inhibition to overcome immunotherapy resistance.

Patients with tumors that do not respond to immune-checkpoint inhibition often harbor a non-T cell-inflamed tumor microenvironment, characterized by the absence of IFN-γ-associated CD8 T cell and dendritic cell activation. Understanding the molecular mechanisms underlying immune exclusion in non-responding patients may enable the development of novel combination therapies. p38 MAPK is a known regulator of dendritic and myeloid cells however a tumor-intrinsic immunomodulatory role has not been previously described.

Artificial-intelligence-enhanced synthetic thick slabs versus standard slices in digital breast tomosynthesis.

Objectives: Digital breast tomosynthesis (DBT) can provide additional information over mammography, albeit at the cost of prolonged reading time. This study retrospectively investigated the impact of reading enhanced synthetic 6 mm slabs instead of standard 1 mm slices on interpretation time and readers performance in a diagnostic assessment centre.

Methods: Three radiologists (R1-3; 6/4/2 years of breast imaging experience) reviewed 111 diagnostic DBT examinations.

Diffusion-weighted Breast MRI at 3 Tesla: Improved Lesion Visibility and Image Quality with a Combination of Water-excitation and Spectral Fat Saturation.

Rationale And Objectives: In breast MRI with diffusion-weighted imaging (DWI), fat suppression is essential for eliminating the dominant lipid signal. This investigation evaluates a combined water-excitation-spectral-fatsat method (WEXfs) versus standard spectral attenuated inversion recovery (SPAIR) in high-resolution 3-Tesla breast MRI.

Materials And Methods: Multiparametric breast MRI with 2 echo-planar DWI sequences was performed in 83 patients (50.

Potential of employing a quantum iterative reconstruction algorithm for ultra-high-resolution photon-counting detector CT of the hip.

Introduction: This study investigated the image quality of a new quantum iterative reconstruction algorithm (QIR) for high resolution photon-counting CT of the hip.

Methods: Using a first-generation photon-counting CT scanner, five cadaveric specimens were examined with ultra-high-resolution protocols matched for radiation dose. Images were post-processed with a sharp convolution kernel and five different strength levels of iterative reconstruction (QIR 0 - QIR 4).

Tin-filtered 100 kV Ultra-low-dose Abdominal CT for Calculi Detection in the Urinary Tract: A Comparative Study of 510 Cases.

Objectives: For detection of urinary calculi, unenhanced low-dose computed tomography is the method of choice, outperforming radiography and ultrasound. This retrospective monocentric study aims to compare a clinically established, dedicated low-dose imaging protocol for detection of urinary calculi with an ultra-low-dose protocol employing tin prefiltration at a standardized tube voltage of 100 kVp.

Methods: Two study arms included a total of 510 cases.

Phantom study for comparison between computed tomography- and C-Arm computed tomography-guided puncture applied by residents in radiology.

Purpose: Comparison of puncture deviation and puncture duration between computed tomography (CT)- and C-arm CT (CACT)-guided puncture performed by residents in training (RiT).

Methods: In a cohort of 25 RiTs enrolled in a research training program either CT- or CACT-guided puncture was performed on a phantom. Prior to the experiments, the RiT's level of training, experience playing a musical instrument, video games, and ball sports, and self-assessed manual skills and spatial skills were recorded.

Dasatinib and dexamethasone followed by hematopoietic cell transplantation for adults with Ph-positive ALL.

Post-remission strategies after dasatinib-corticosteroid induction in adult Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) are not well studied. We evaluated dasatinib and dexamethasone induction then protocol-defined post-remission therapies, including hematopoietic cell transplantation (HCT). Adults (N = 65) with Ph-positive ALL received dasatinib-dexamethasone induction, methotrexate-based central nervous system (CNS) prophylaxis, reduced-intensity conditioning (RIC) allogeneic HCT, autologous HCT, or chemotherapy alone, and dasatinib-based maintenance.

Evaluation of the pharmacokinetic drug-drug interaction potential of iohexol, a renal filtration marker.

Purpose: Carboplatin dose is calculated based on kidney function, commonly estimated with imperfect creatinine-based formulae. Iohexol is used to measure glomerular filtration rate (GFR) and allows calculation of a more appropriate carboplatin dose. To address potential concerns that iohexol administered during a course of chemotherapy impacts that therapy, we performed in vitro and in vivo pharmacokinetic drug-drug interaction evaluations of iohexol.

Phase 1 study of the Aurora kinase A inhibitor alisertib (MLN8237) combined with the histone deacetylase inhibitor vorinostat in lymphoid malignancies.

Alisertib, an Aurora kinase A inhibitor, was evaluated in a Phase 1 study in combination with the histone deacetylase inhibitor vorinostat, in patients with relapsed/refractory lymphoid malignancies ( = 34; NCT01567709). Patients received alisertib plus vorinostat in 21-day treatment cycles with escalating doses of alisertib following a continuous or an intermittent schedule. All dose-limiting toxicities (DLTs) were hematologic and there were no study-related deaths.

Quantitation of paclitaxel, and its 6-alpha-OH and 3-para-OH metabolites in human plasma by LC-MS/MS.

We have developed a high performance liquid chromatography mass spectrometry method for quantitating paclitaxel and its 6-alpha-OH and 3-para-OH metabolites in 0.1 mL human plasma. After MTBE liquid-liquid extraction, chromatographic separation was achieved with a Phenomenex synergy polar reverse phase (4 μm, 2 mm × 50 mm) column and a gradient of 0.

A window-of-opportunity clinical trial of dasatinib in women with newly diagnosed endometrial cancer.

Objective: To determine the extent of dasatinib uptake and effect on Src kinase activity in tumor, normal adjacent tissue, and blood in newly diagnosed endometrial cancer patients.

Methods: Dasatinib was dosed at 100 or 200 mg PO BID at 32 and 8 h preoperatively. Blood and tissue were collected pre-treatment and at surgery to assess active (pY419) and total Src protein (pharmacodynamics [PD]) and pharmacokinetics (PK).

Evaluation of Biodistribution of Sulforaphane after Administration of Oral Broccoli Sprout Extract in Melanoma Patients with Multiple Atypical Nevi.

Broccoli sprout extract containing sulforaphane (BSE-SFN) has been shown to inhibit ultraviolet radiation-induced damage and tumor progression in skin. This study evaluated the toxicity and potential effects of oral BSE-SFN at three dosages. Seventeen patients who each had at least 2 atypical nevi and a prior history of melanoma were randomly allocated to 50, 100, or 200 μmol oral BSE-SFN daily for 28 days.

A phase-1 study of dasatinib plus all-trans retinoic acid in acute myeloid leukemia.

Src family kinases (SFKs) are hyperactivated in acute myeloid leukemia (AML). SFKs impede the retinoic acid receptor, and SFK inhibitors enhance all-trans retinoic acid (ATRA)-mediated cellular differentiation in AML cell lines and primary blasts. To translate these findings into the clinic, we undertook a phase-I dose-escalation study of the combination of the SFK inhibitor dasatinib and ATRA in patients with high-risk myeloid neoplasms.

Liquid chromatography-tandem mass spectrometric assay for the quantitation of the novel radiation protective agent and radiation mitigator JP4-039 in murine plasma.

JP4-039 radio-protects prior to, and radio-mitigates after ionizing radiation by neutralizing reactive oxygen species. We developed and validated an LC-MS/MS assay for the quantitation of JP4-039 in murine plasma. Methanol protein precipitation of 50μL plasma was followed by isocratic reverse phase chromatography for a 6min run time, and electrospray positive mode ionization mass spectrometric detection.