NRG Oncology Updated International Consensus Atlas on Pelvic Lymph Node Volumes for Intact and Postoperative Prostate Cancer.

Purpose: In 2009, the Radiation Therapy Oncology Group (RTOG) genitourinary members published a consensus atlas for contouring prostate pelvic nodal clinical target volumes (CTVs). Data have emerged further informing nodal recurrence patterns. The objective of this study is to provide an updated prostate pelvic nodal consensus atlas.

Expression of the Androgen Receptor Governs Radiation Resistance in a Subset of Glioblastomas Vulnerable to Antiandrogen Therapy.

New approaches are needed to overcome intrinsic therapy resistance in glioblastoma (GBM). Because GBMs exhibit sexual dimorphism and are reported to express steroid hormone receptors, we reasoned that signaling through the androgen receptor (AR) could mediate therapy resistance in GBM, much as it does in AR-positive prostate and breast cancers. We found that nearly half of GBM cell lines, patient-derived xenografts (PDX), and human tumors expressed AR at the transcript and protein level-with expression levels overlapping those of primary prostate cancer.

Prostate-specific antigen kinetics and biochemical control following stereotactic body radiation therapy, high dose rate brachytherapy, and low dose rate brachytherapy: A multi-institutional analysis of 3502 patients.

Background And Purpose: Stereotactic body radiation therapy (SBRT), low dose rate brachytherapy (LDR-BT) and high dose rate brachytherapy (HDR-BT) are ablative-intent radiotherapy options for prostate cancer (PCa). These vary considerably in dose delivery, which may impact post-treatment prostate-specific antigen (PSA) patterns and biochemical control. We compared PSA kinetics between SBRT, HDR-BT, and LDR-BT, and assessed their relationships to biochemical recurrence-free survival (BCRFS).

The DNA methylation landscape of advanced prostate cancer.

Although DNA methylation is a key regulator of gene expression, the comprehensive methylation landscape of metastatic cancer has never been defined. Through whole-genome bisulfite sequencing paired with deep whole-genome and transcriptome sequencing of 100 castration-resistant prostate metastases, we discovered alterations affecting driver genes that were detectable only with integrated whole-genome approaches. Notably, we observed that 22% of tumors exhibited a novel epigenomic subtype associated with hypermethylation and somatic mutations in TET2, DNMT3B, IDH1 and BRAF.

An Angelman syndrome substitution in the HECT E3 ubiquitin ligase C-terminal Lobe of E6AP affects protein stability and activity.

Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by speech impairment, intellectual disability, ataxia, and epilepsy. AS is caused by mutations in the maternal copy of UBE3A located on chromosome 15q11-13. UBE3A codes for E6AP (E6 Associated Protein), a prominent member of the HECT (Homologous to E6AP C-Terminus) E3 ubiquitin ligase family.

Enrichment of the airway microbiome in people living with HIV with potential pathogenic bacteria despite antiretroviral therapy.

Background: Long-term antiretroviral therapy (ART) enables people living with HIV (PLW-HIV) to be healthier and live longer; though they remain at greater risk of pneumonia and chronic lung disease than the general population. Lung microbial dysbiosis has been shown to contribute to respiratory disease.

Methods: 16S-rRNA gene sequencing on the Miseq-platform and qPCR for typical respiratory pathogens were performed on sputum samples collected from 64 PLW-HIV (median blood CD4 count 676 cells/μL) and 38 HIV-negative participants.

Tumor Immune Microenvironment Clusters in Localized Prostate Adenocarcinoma: Prognostic Impact of Macrophage Enriched/Plasma Cell Non-Enriched Subtypes.

Background: Prostate cancer (PCa) is characterized by significant heterogeneity in its molecular, genomic, and immunologic characteristics.

Methods: Whole transcriptome RNAseq data from The Cancer Genome Atlas of prostate adenocarcinomas ( = 492) was utilized. The immune microenvironment was characterized using the CIBERSORTX tool to identify immune cell type composition.

Impact of Sequencing of Androgen Suppression and Radiation Therapy on Testosterone Recovery in Localized Prostate Cancer.

Purpose: We performed a secondary analysis of a phase 3 randomized trial to determine the influence of sequencing of radiation therapy and androgen deprivation therapy (ADT) on posttreatment testosterone recovery and implications of testosterone recovery on subsequent relapse.

Methods And Materials: Patients with localized prostate cancer with Gleason score ≤7, clinical stage T1b to T3a, and prostate-specific antigen <30 ng/mL were randomized to neoadjuvant and concurrent ADT for 6 months starting 4 months before prostate radiation therapy (NHT arm) or concurrent and adjuvant ADT for 6 months starting simultaneously with radiation therapy (CAHT arm). Full testosterone recovery (FTR) was defined as recovery of testosterone to >10.

Differences in the periodontal microbiome of successfully treated and persistent aggressive periodontitis.

Aims: The primary aim of this investigation was to analyse the periodontal microbiome in patients with aggressive periodontitis (AgP) following treatment.

Methods: Sixty-six AgP patients were recalled on average 7 years after completion of active periodontal treatment and had subgingival plaque samples collected and processed for 16S rRNA gene sequencing analyses.

Results: Of 66 participants, 52 showed persistent periodontal disease, while 13 participants were considered as "successfully treated AgP" (no probing pocket depths >4 mm) and 1 was fully edentulous.

Event-Free Survival, a Prostate-Specific Antigen-Based Composite End Point, Is Not a Surrogate for Overall Survival in Men With Localized Prostate Cancer Treated With Radiation.

Purpose: Recently, we have shown that metastasis-free survival is a strong surrogate for overall survival (OS) in men with intermediate- and high-risk localized prostate cancer and can accelerate the evaluation of new (neo)adjuvant therapies. Event-free survival (EFS), an earlier prostate-specific antigen (PSA)-based composite end point, may further expedite trial completion.

Methods: EFS was defined as the time from random assignment to the date of first evidence of disease recurrence, including biochemical failure, local or regional recurrence, distant metastasis, or death from any cause, or was censored at the date of last PSA assessment.

Clinical Applications of Molecular Biomarkers in Prostate Cancer.

There is clinically relevant molecular heterogeneity in prostate cancer (PCa), but this biological diversity has had only a minimal impact on clinical practice. Treatment outcomes in patients with localised PCa are often highly variable, even among patients stratified to the same risk group or disease state based on standard clinical and pathological parameters. In recent years, the development of gene panels has provided valuable data on the differential expression of genes in patients with PCa.

Cost-Effectiveness of Metastasis-Directed Therapy in Oligorecurrent Hormone-Sensitive Prostate Cancer.

Purpose: Oligorecurrent prostate cancer has historically been treated with indefinite androgen deprivation therapy (ADT), although many patients and providers opt to defer this treatment at the time of recurrence given quality-of-life and/or comorbidity considerations. Recently, metastasis-directed therapy (MDT) has emerged as a potential intermediary between surveillance and immediate continuous ADT. Simultaneously, advanced systemic therapy in addition to ADT has also been shown to improve survival in metastatic hormone-sensitive disease.

Transcriptomic Heterogeneity of Gleason Grade Group 5 Prostate Cancer.

Gleason grade group (GG) 5 prostate cancer has been associated with an aggressive natural history, and retrospective data support a role for treatment intensification. However, clinical outcomes remain heterogeneous in this cohort, and intensified treatments carry an increased risk of adverse events. We sought to explore the transcriptomic heterogeneity of GG 5 tumors by querying transcriptomic data from the tumors of 2138 patients with GG 5 disease who underwent prostatectomy.

Radiation-Induced Insufficiency Fractures After Pelvic Irradiation for Gynecologic Malignancies: A Systematic Review.

Purpose: To identify and define the incidence, risk factors, clinical characteristics, and treatment approaches to pelvic insufficiency fractures (PIFs) that develop as a consequence of pelvic radiation therapy for gynecologic malignancies.

Materials And Methods: A systematic literature review (PubMed and Embase indexed from January 1, 1980, to May 1, 2020) of studies describing PIFs that result from radiation therapy for gynecologic malignancies. A random-effects model weighted by the inverse variance was used to calculate the pooled crude incidence, actuarial incidence, and proportion of symptomatic PIFs, and to evaluate the relationship between PIF incidence and various risk factors.

Transcriptional profiling identifies an androgen receptor activity-low, stemness program associated with enzalutamide resistance.

The androgen receptor (AR) antagonist enzalutamide is one of the principal treatments for men with castration-resistant prostate cancer (CRPC). However, not all patients respond, and resistance mechanisms are largely unknown. We hypothesized that genomic and transcriptional features from metastatic CRPC biopsies prior to treatment would be predictive of de novo treatment resistance.

Addition of Androgen-Deprivation Therapy or Brachytherapy Boost to External Beam Radiotherapy for Localized Prostate Cancer: A Network Meta-Analysis of Randomized Trials.

Purpose: In men with localized prostate cancer, the addition of androgen-deprivation therapy (ADT) or a brachytherapy boost (BT) to external beam radiotherapy (EBRT) have been shown to improve various oncologic end points. Practice patterns indicate that those who receive BT are significantly less likely to receive ADT, and thus we sought to perform a network meta-analysis to compare the predicted outcomes of a randomized trial of EBRT plus ADT versus EBRT plus BT.

Materials And Methods: A systematic review identified published randomized trials comparing EBRT with or without ADT, or EBRT (with or without ADT) with or without BT, that reported on overall survival (OS).

Changes in prostate-specific antigen at the time of prostate cancer diagnosis after Medicaid expansion in young men.

Background: The objective of this study was to determine the effect of Medicaid expansion under the Patient Protection and Affordable Care Act (January 1, 2014) on the epidemiology of high-risk prostate-specific antigen (PSA) levels (≥20 ng/mL) at the time of prostate cancer (PCa) diagnosis. The authors hypothesized that better access to care would result in a reduction of high-risk features at diagnosis.

Methods: A retrospective cohort study was performed of 122,324 men aged <65 years who were diagnosed with PCa within the National Cancer Database.

Management of gastrointestinal perforation related to radiation.

Perforation of gastrointestinal (GI) tract is a rare, but serious complication of abdominopelvic irradiation, and it can even occur several years after radiotherapy. As one of the symptoms of radiation enteropathy, it shares common features with other chronic complications and has its own characteristic at the same time. It has been reported that some systematic therapies, such as sorafenib and bevacizumab, could add the risk of radiation-induced GI perforation.

Prostate Cancer Radiation Therapy Recommendations in Response to COVID-19.

Purpose: During a global pandemic, the benefit of routine visits and treatment of patients with cancer must be weighed against the risks to patients, staff, and society. Prostate cancer is one of the most common cancers radiation oncology departments treat, and efficient resource utilization is essential in the setting of a pandemic. Herein, we aim to establish recommendations and a framework by which to evaluate prostate radiation therapy management decisions.