Safety and Efficacy of Neoadjuvant Docetaxel and Radiotherapy in Localized High-Risk Prostate Cancer: Results From a Prospective Pilot Study.

Objectives: Approximately 15% of patients with localized prostate cancer are at high risk for disease recurrence. Many clinical trials have evaluated the impact of neoadjuvant therapy before radical prostatectomy with mixed results (NCT00321698).

Methods: This phase I/II clinical trial evaluated the tolerability and preliminary efficacy of neoadjuvant radiation therapy and docetaxel before prostatectomy in 25 men with high-risk prostate cancer.

Redefining Candidates for Deintensification in Locoregionally Advanced P16+ Oropharyngeal Cancer Based on Relative Risk.

Purpose: Randomized trials have found that patients with locoregionally advanced p16+ oropharyngeal squamous cell carcinoma (OPSCC) do not benefit from treatment deintensification, even among favorable risk groups. Although various methods have been used to identify candidates for treatment deintensification, the optimal approach is unknown.

Methods And Materials: We conducted a multi-institutional cohort study of 444 patients with previously untreated p16+ OPSCC undergoing definitive radiation therapy with or without systemic therapy between 2009 and 2022.

Reduced Nephrin Tyrosine Phosphorylation Enhances Insulin Secretion and Increases Glucose Tolerance With Age.

Background: Nephrin is a transmembrane protein with well-established signaling roles in kidney podocytes, and a smaller set of secretory functions in pancreatic β cells are implicated in diabetes. Nephrin signaling is mediated in part through its 3 cytoplasmic YDxV motifs, which can be tyrosine phosphorylated by high glucose and β cell injuries. Although in vitro studies demonstrate these phosphorylated motifs can regulate β cell vesicle trafficking and insulin release, in vivo evidence of their role in this cell type remains to be determined.

Optimized Atlas-Based Auto-Segmentation of Bony Structures from Whole-Body Computed Tomography.

Purpose: To develop and test a method for fully automated segmentation of bony structures from whole-body computed tomography (CT) and evaluate its performance compared with manual segmentation.

Methods And Materials: We developed a workflow for automatic whole-body bone segmentation using atlas-based segmentation (ABS) method with a postprocessing module (ABS) in MIM MAESTRO software. Fifty-two CT scans comprised the training set to build the atlas library, and 29 CT scans comprised the test set.

Identifying disparities in brachytherapy delivery for locally advanced cervical cancer.

Introduction: The standard of care for locally advanced cervical cancer is concurrent chemotherapy and external beam radiation therapy (EBRT) followed by a brachytherapy boost. Some studies show a decreased usage of brachytherapy in cervical cancer patients despite the standard of care and known survival advantage. This study aims to characterize the utilization of brachytherapy in Oregon and identify where disparities in treatment may exist.

Outcomes from a 3-fraction high-dose-rate brachytherapy regimen for patients with cervical cancer.

Purpose: To estimate local control, survival, and toxicity associated with a 3-fraction (3F) image-guided brachytherapy (IGBT) regimen compared to longer fraction (LF) for cervical cancer.

Methods: 150 patients treated between 2015-2020 with 3F (24Gy in 3 fractions) or LF (28..

Underutilization of brachytherapy for cervical cancer in the United States.

Brachytherapy is a critical component of the definitive management of cervical cancer and allows for the safe delivery of about half of the total effective radiation dose needed for optimal outcomes. Moreover, the dose distribution of brachytherapy is highly conformal, allowing for a therapeutic index currently unmatched by alternative techniques. However, a modern brachytherapy program requires special equipment, infrastructure, and procedural expertise.

Incomplete cisplatin regimens in chemoradiation and its effect on outcomes for locally advanced cervical cancer.

Objective: To identify factors associated with receipt of incomplete cisplatin during chemoradiation for locally advanced cervical cancer and its impact on outcomes.

Methods: Patients with locally advanced cervical cancer treated with chemoradiation at our institution between November 2015 and August 2020 were retrospectively identified. Patients who received ≤4 cycles were identified as the 'incomplete' cohort and those who received 5-6 cycles as the 'complete' cohort.

Sex Differences in Glomerular Protein Expression and Effects of Soy-Based Diet on Podocyte Signaling.

Background: Kidney disease is a major public health issue arising from loss of glomerular podocyte function, and there are considerable sex differences in its prognosis. Evidence suggests a renoprotective effect of estrogen and soy diet-derived phytoestrogens, although the molecular basis for this is poorly understood.

Objective: Here, we aim to assess sex differences in expression of key proteins associated with podocyte survival and determine the effects of dietary soy on glomerular and podocyte signaling.

Complementary Nck1/2 Signaling in Podocytes Controls Actinin-4-Mediated Actin Organization, Adhesion, and Basement Membrane Composition.

Background: Maintenance of the kidney filtration barrier requires coordinated interactions between podocytes and the underlying glomerular basement membrane (GBM). GBM ligands bind podocyte integrins, which triggers actin-based signaling events critical for adhesion. Nck1/2 adaptors have emerged as essential regulators of podocyte cytoskeletal dynamics.

Novel Therapies in Gynecologic Cancer.

During the past decade, considerable strides have been made in the understanding and treatment of gynecologic cancers. The advent of PARP inhibitors, antiangiogenic therapies, immunotherapy combinations, and targeted agents have altered the standard of care in ovarian, endometrial, and cervical cancers. However, continued advancement in the treatment of gynecologic cancers is critical.

Disparities in time to start of definitive radiation treatment for patients with locally advanced cervical cancer.

Background: Chemoradiation or radiation therapy alone are curative standards for patients with locally advanced cervical cancer.

Objective: To investigate factors that influence time to initiation of chemoradiation or radiation and the subsequent impact of time to treatment on recurrence and survival outcomes.

Methods: Patients with locally advanced cervical cancer treated with definitive chemoradiation or radiation at our institution between November 2015 and August 2020 were retrospectively identified.

Advances in immunotherapy for cervical cancer: recent developments and future directions.

There is an unmet need for novel therapies to improve clinical outcomes for patients with locally advanced, recurrent, or metastatic cervical cancer. Most cases of cervical cancer are driven by infection with human papillomavirus (HPV), which uses multiple mechanisms to avoid immune surveillance. Several classes of agents have been developed that seek to activate the immune system in order to overcome this resistance and improve treatment outcomes.

Validation of NRG Oncology's prognostic nomograms for oropharyngeal cancer in the Veterans Affairs database.

Background: To test whether nomograms developed by NRG Oncology for oropharyngeal squamous cell carcinoma (OPSCC) patients could be validated in an independent population-based sample.

Methods: The authors tested nomograms for estimating progression-free survival (PFS) and overall survival (OS) in patients from the Veterans Health Administration with previously untreated locoregionally advanced OPSCC, diagnosed between 2008 and 2017, managed with definitive radiotherapy with or without adjuvant systemic therapy. Covariates were age, performance status, p16 status, T/N category, smoking history, education history, weight loss, marital status, and anemia.

Bias Reduction through Analysis of Competing Events (BRACE) Correction to Address Cancer Treatment Selection Bias in Observational Data.

Purpose: Cancer treatments can paradoxically appear to reduce the risk of noncancer mortality in observational studies, due to residual confounding. Here we introduce a method, Bias Reduction through Analysis of Competing Events (BRACE), to reduce bias in the presence of residual confounding.

Experimental Design: BRACE is a novel method for adjusting for bias from residual confounding in proportional hazards models.

Design and Validation of an Automated Dilator Prototype for the Treatment of Radiation Induced Vaginal Injury.

Vaginal stenosis (VS) is a common late complication of radiation injury caused by cervical cancer radiotherapy. It is characterized by the narrowing or shortening of the vaginal canal, which is often detrimental to patient quality of life. To address this public health problem, an expandable vaginal dilator was designed for the prevention of VS in cervical cancer survivors.

Improved Prognosis of Treatment Failure in Cervical Cancer with Nontumor PET/CT Radiomics.

Radiomics has been applied to predict recurrence in several disease sites, but current approaches are typically restricted to analyzing tumor features, neglecting nontumor information in the rest of the body. The purpose of this work was to develop and validate a model incorporating nontumor radiomics, including whole-body features, to predict treatment outcomes in patients with previously untreated locoregionally advanced cervical cancer. We analyzed 127 cervical cancer patients treated definitively with chemoradiotherapy and intracavitary brachytherapy.

Positron Emission Tomography-Guided Bone Marrow-Sparing Radiation Therapy for Locoregionally Advanced Cervix Cancer: Final Results From the INTERTECC Phase II/III Trial.

Purpose: To test effects of positron emission tomography (PET)-based bone marrow-sparing (BMS) image-guided intensity modulated radiation therapy (IG-IMRT) on efficacy and toxicity for patients with locoregionally advanced cervical cancer.

Methods And Materials: In an international phase II/III trial, patients with stage IB-IVA cervical carcinoma were treated with either PET-based BMS-IG-IMRT (PET-BMS-IMRT group) or standard image-guided IMRT (IMRT group), with concurrent cisplatin (40 mg/m weekly), followed by brachytherapy. The phase II component nonrandomly assigned patients to PET-BMS-IMRT or standard IMRT.

Standardized Uptake Value Illuminates Tumor Inflammation and Treatment Response.

Maximum standardized uptake value (SUV) on PET imaging is prognostic in cervical cancer. It was recently demonstrated that low pretreatment SUV is associated with superior prognosis and is correlated with decreased inflammatory signaling and myeloid-derived cell infiltration into the tumor microenvironment, potentially identifying susceptibility to targeted therapies..

Immunotherapy and radiation therapy sequencing: State of the data on timing, efficacy, and safety.

Radiation therapy exerts a tumoricidal local effect as well as both local and systemic immunomodulation. Immune checkpoint blockade has become a widely used treatment modality across cancer types with a rapidly growing list of agents and US Food and Drug Administration-approved indications. Moreover, there may be synergy between radiation therapy and immune checkpoint blockade.

Comparison of Hematologic Toxicity and Bone Marrow Compensatory Response in Head and Neck vs. Cervical Cancer Patients Undergoing Chemoradiotherapy.

Hematologic toxicity is a critical problem limiting treatment delivery in cancer patients undergoing concurrent chemoradiotherapy. However, the extent to which anatomic variations in radiation dose limit chemotherapy delivery is poorly understood. A unique natural experiment arises in patients with head and neck and cervical cancer, who frequently undergo identical chemotherapy but receive radiation to different regions of the body.

A Multi-atlas Approach for Active Bone Marrow Sparing Radiation Therapy: Implementation in the NRG-GY006 Trial.

Purpose: Sparing active bone marrow (ABM) can reduce acute hematologic toxicity in patients undergoing chemoradiotherapy for cervical cancer, but ABM segmentation based on positron emission tomography/computed tomography (PET/CT) is costly. We sought to develop an atlas-based ABM segmentation method for implementation in a prospective clinical trial.

Methods And Materials: A multiatlas was built on a training set of 144 patients and validated in 32 patients from the NRG-GY006 clinical trial.