The Landscape of Prostate Tumour Methylation.

Prostate cancer is characterized by profound heterogeneity in its clinical trajectory. While genomic heterogeneity has been well-characterized, epigenomic heterogeneity remains less understood. To fill this gap, we compiled 2,149 multi-ancestric prostate methylomes spanning normal tissue through localized disease of varying grades to poly-metastatic disease, most with multi-omic DNA and/or RNA characterization.

The Germline and Somatic Origins of Prostate Cancer Heterogeneity.

Newly diagnosed prostate cancers differ dramatically in mutational composition and lethality. The most accurate clinical predictor of lethality is tumor tissue architecture, quantified as tumor grade. To interrogate the evolutionary origins of prostate cancer heterogeneity, we analyzed 666 prostate tumor whole genomes.

Rates of long-term risk of revision and complications in total elbow arthroplasty in patients with rheumatoid arthritis: a propensity score-matched analysis.

Background: Rheumatoid arthritis (RA) poses unique challenges in total elbow arthroplasty (TEA) due to systemic inflammation. Previous studies suggest higher revision rates in RA patients after TEA, yet comprehensive investigations have not been conducted. We theorized that RA patients undergoing TEA would demonstrate a greater likelihood and risk of requiring revision procedures compared to those without RA.

The interplay between acute and late toxicity among patients receiving prostate radiotherapy: an individual patient data meta-analysis of six randomised trials.

Background: The association between acute and late toxicity following prostate radiotherapy has not been well studied using data from multiple randomised clinical trials and fractionation schedules. We aimed to characterise the relationship between acute and late genitourinary and gastrointestinal toxicity among patients receiving conventionally fractionated or moderately hypofractionated prostate radiotherapy.

Methods: This was an individual patient data meta-analysis that identified randomised phase 3 trials of conventionally fractionated or moderately hypofractionated prostate radiotherapy in the Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) Consortium that had individual-level acute and late toxicity data available and were available before Dec 1, 2023.

Future directions in the evaluation and management of newly diagnosed metastatic cancer.

There is much debate regarding optimal selection in patients with metastatic cancer who should undergo local treatment (surgery or radiation treatment) to the primary tumor and/or metastases. Additionally, the optimal treatment of newly diagnosed metastatic cancer is largely unclear. Current prognostication systems to best inform these clinical scenarios are limited, as all metastatic patients are grouped together as having Stage IV disease without further incorporation of patient and disease-specific covariates that significantly impact patient outcomes.

Urethra-sparing prostate cancer radiotherapy: Current practices and future insights from an international survey.

Purpose: In prostate cancer patients, high radiation doses to the urethra have been associated with an increased risk of severe genitourinary toxicity following dose-escalated radiotherapy. Urethra-sparing techniques have emerged as a promising approach to reduce urinary toxicity. This international survey aims to evaluate current global practices in urethra-sparing and explore future directions for the implementation of this technique in external beam radiotherapy (EBRT) for prostate cancer.

Patient-reported quality of life and adherence outcomes after integrating exclusive liquid meal replacement in patients with head and neck cancer undergoing chemoradiation: results from a phase II study.

Objectives: Preventing malnutrition during chemoradiation (CRT) for head and neck cancer is critical maximizing quality of life (QOL). We sought to assess patient-reported QOL outcomes after integrating exclusive liquid meal replacement with Soylent, a novel meal replacement agent, in patients with head and neck cancer undergoing CRT.

Methods: Patients undergoing definitive or adjuvant concurrent CRT for locally advanced head and neck cancer enrolled on our single-institution, prospective phase II protocol evaluating nutritional replacement with Soylent.

The Co-IMPACT Consortium: Integrating Prostate-specific Membrane Antigen Positron Emission Tomography and Radiotherapy in Prostate Cancer Care.

The Co-IMPACT consortium addresses knowledge gaps in prostate-specific membrane antigen positron emission tomography-guided radiotherapy for prostate cancer by establishing a global database (46 centres from 16 countries) to standardise and analyse data across four distinguished clinical scenarios. A collaborative model with the Advanced Prostate Cancer Consensus Conference aligns urgent clinical needs with actionable research insights.

Trends in surgical procedures for shoulder instability among patients with Ehlers-Danlos syndrome or joint hypermobility syndrome.

Background: Joint hypermobility syndrome (JHS) and Ehlers-Danlos Syndrome (EDS) are connective tissue disorders characterized by increased joint laxity, affecting musculoskeletal health and quality of life. In this study, we explored recent trends in surgical treatment of shoulder instability among patients with these disorders.

Methods: We searched the PearlDiver Mariner database, which includes deidentified US all-payer claims data from 2010 to 2020.

Pelvic Regional Control With 25 Gy in 5 Fractions in Stereotactic Radiation Therapy for High-Risk Prostate Cancer: Pooled Prospective Outcomes From the SHARP Consortium.

Purpose: To evaluate the efficacy of 25 Gy in 5 fractions (25 Gy/5#) prophylactic pelvic nodal irradiation for regional control during stereotactic radiation therapy (SBRT) for high-risk prostate cancer.

Methods And Materials: The multinational SHARP consortium database of patients treated with curative-intent prostate SBRT for high-risk prostate cancer was queried for prophylactic radiation therapy 25 Gy/5# to the pelvic lymph nodes. Details of Phoenix-defined biochemical failure and location of recurrence (local, regional, or distant) were extracted.

PSMA-PET/CT Findings in Patients With High-Risk Biochemically Recurrent Prostate Cancer With No Metastatic Disease by Conventional Imaging.

Importance: The phase 3 randomized EMBARK trial evaluated enzalutamide with or without leuprolide in high-risk nonmetastatic hormone-sensitive prostate cancer. Eligibility relied on conventional imaging, which underdetects metastatic disease compared with prostate-specific membrane antigen-positron emission tomography (PSMA-PET).

Objective: To describe the staging information obtained by PSMA-PET/computed tomography (PSMA-PET/CT) in a patient cohort eligible for the EMBARK trial.

Racial disparities in early postoperative proximal humerus fracture outcomes: Do minorities face longer operative times, extended hospital stays, and higher risks?

Background: Racial disparities in orthopedic surgery outcomes have been extensively documented, highlighting systemic biases in care. Proximal humerus fractures (PHFs), about 6% of all fractures, are rising, especially among the elderly. Despite the prevalence of PHFs, a research gap exists regarding racial disparities in postoperative complications and outcomes.

Magnetic Resonance Imaging Versus Computed Tomography Guidance for Stereotactic Body Radiotherapy in Prostate Cancer: 2-year Outcomes from the MIRAGE Randomized Clinical Trial.

It has been shown that magnetic resonance imaging (MRI) guidance versus computed tomography (CT) guidance for aggressive margin-reduction (AMR) for stereotactic body radiotherapy (SBRT) in prostate cancer reduces acute toxicity, but the longer-term benefits are unknown. We performed a secondary analysis of MIRAGE, a phase 3 randomized clinical trial of MRI-guided SBRT for prostate cancer, to determine whether AMR with MRI guidance significantly reduced 2-yr physician-scored or patient-reported toxic effects in comparison to CT guidance. The cumulative incidence of 2-yr physician-scored toxicity, defined as grade ≥2 genitourinary (GU) and gastrointestinal (GI) toxic effects according to Common Terminology Criteria for Adverse Events v4.

The Impact of Hormone Therapy on Inflammatory Bowel Disease in Transgender and Nonbinary Individuals.

Background: Inflammatory bowel disease (IBD) is a global healthcare problem that affects around 3 million people in the United States. Although the impact of gender-affirming hormone therapy (GAHT) on IBD severity has been studied in cisgender patients, there is currently no literature on the impact of exogenous hormone therapy (HT) in transgender and nonbinary (TGNB) individuals.

Methods: We conducted a retrospective chart review of TGNB adults diagnosed with IBD and treated with HT for gender dysphoria at Johns Hopkins Hospital (2015-2022).

Prior Local Therapy and First-Line Apalutamide in Patients With Nonmetastatic Castration-Resistant Prostate Cancer: A Secondary Analysis of the SPARTAN Randomized Clinical Trial.

Importance: Preclinical studies suggest that exposure to prostate-directed local therapy (LT) may influence the efficacy of subsequent systemic therapy including androgen receptor pathway inhibitors. However, there is insufficient clinical evidence to support this premise in patients with nonmetastatic castrate-resistant prostate cancer (nmCRPC).

Objective: To determine whether exposure to prior prostate-directed LT (radical prostatectomy [RP], radiation therapy [RT], or both) played any effect-modifying role in the treatment effect of apalutamide on metastasis-free survival (MFS) and overall survival (OS) in patients with nmCRPC.

American Radium Society Appropriate Use Criteria for the Workup and Treatment of Local Intraprostatic Recurrence of Prostate Cancer Following Definitive Radiotherapy.

Background And Objective: Local intraprostatic radiorecurrence of prostate cancer (IPR-PC) can be associated with an aggressive natural history and impact long-term disease-specific survival. While appropriate local salvage intervention can be curative, best practices for workup and local salvage of intraprostatic recurrence are poorly defined. The American Radium Society (ARS) Genitourinary Appropriate Use Criteria Committee sought to develop evidence-based recommendations to address this gap.

Testosterone Recovery Following Androgen Suppression and Prostate Radiotherapy (TRANSPORT): A Pooled Analysis of Five Randomized Trials from the Meta-Analysis of Randomized Trials in Cancer of the Prostate (MARCAP) Consortium.

Background And Objective: Time to testosterone recovery (TR) following androgen deprivation therapy (ADT) with gonadotropin-releasing hormone agonists varies widely. We evaluate TR kinetics and the oncological impact of an effective castration period in patients receiving definitive radiotherapy and ADT for prostate cancer.

Methods: We obtained individual patient data from randomized controlled trials of radiotherapy with ADT and prospectively collected serial testosterone data from the MARCAP Consortium.

Molecular Hallmarks of Prostate-specific Membrane Antigen in Treatment-naïve Prostate Cancer.

Background And Objective: We characterized tumor prostate-specific membrane antigen (PSMA) levels as a reflection of cancer biology and treatment sensitivities for treatment-naïve prostate cancer.

Methods: We first correlated PSMA positron emission tomography (PET) maximum standardized uptake values (SUVmax) in primary prostate cancer with tumor FOLH1 (PSMA RNA abundance) to establish RNA as a proxy (n = 55). We then discovered and validated molecular pathways associated with PSMA RNA levels in two large primary tumor cohorts.

Systematic review and recommendations for re-irradiation for intraprostatic radiorecurrent prostate cancer after definitive radiation therapy.

Purpose: Intraprostatic recurrence (IRR) of prostate cancer after radiation therapy is increasingly identified. Our objective was to review the literature to determine the optimal workup for identifying IRR, the management options, and practical considerations for the delivery of re-irradiation as salvage local therapy.

Methods: We performed a systematic review of available publications and ongoing studies on the topics of IRR, with a focus on salvage re-irradiation.

Effect of concomitant medications on treatment response and survival in non-metastatic castrate resistant prostate cancer: Exploratory analysis of the SPARTAN trial.

Background: We performed an exploratory analysis of the SPARTAN trial to determine whether concomitant exposure to several classes of commonly prescribed medications influenced the effect of apalutamide on overall survival (OS) and metastasis-free survival (MFS) in patients with non-metastatic castration-resistant prostate cancer (nmCRPC).

Patients And Methods: SPARTAN was a phase III randomized controlled trial in which nmCRPC patients were randomly assigned in a 2:1 ratio to receive androgen deprivation therapy with or without apalutamide. We focused on 5 commonly prescribed classes of medications: metformin, statins, angiotensin converting enzyme inhibitors (ACEI), acetylsalicylic acid (ASA), and proton pump inhibitors (PPI) based on a plausible biological and clinical rationale.

Local salvage therapies in patients with radio-recurrent prostate cancer following external beam radiotherapy: a systematic review and meta-analysis.

Introduction: To date, radio-recurrent prostate cancer (PCa) ranks as the fourth most common urological malignancy when considering the number of men with localized PCa who undergo radiation treatment and subsequently experience a biochemical recurrence. This systematic review aimed to summarize available evidence about the outcomes of local salvage strategies in patients with local PCa recurrence following primary external-beam radiation therapy (EBRT).

Methods: We conducted a comprehensive bibliographic search on MEDLINE, Scopus, and Web of Science Core Collection databases in October 2023 to identify studies published in the last 20 years evaluating outcomes of local salvage procedures in patients with locally radio-recurrent PCa following EBRT.

The Proteogenomics of Prostate Cancer Radioresistance.

Unlabelled: Prostate cancer is frequently treated with radiotherapy. Unfortunately, aggressive radioresistant relapses can arise, and the molecular underpinnings of radioresistance are unknown. Modern clinical radiotherapy is evolving to deliver higher doses of radiation in fewer fractions (hypofractionation).