Publications by authors named "Shawn Malone"

Article Synopsis
  • - Abiraterone acetate, apalutamide, darolutamide, and enzalutamide are androgen receptor axis-targeted therapies (ARATs) used to treat prostate cancer, often alongside oral antithrombotic therapies, which may lead to significant drug-drug interactions.
  • - A multidisciplinary expert panel used a modified electronic Delphi process to reach consensus on which ARAT/antithrombotic pairs should be monitored and how to manage these interactions, ultimately recommending avoiding 11 pairs and modifying therapy for 8 others.
  • - This process underscores the need for more research into the clinical outcomes of ARAT and antithrombotic interactions while providing clinicians with actionable guidance for safer therapeutic choices. *
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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.

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Article Synopsis
  • Androgen-deprivation therapy (ADT) is a common treatment for advanced prostate cancer but can lead to significant side effects, prompting guidelines for routine testing to monitor these effects.
  • A study analyzed data from older men in Ontario, Canada, revealing that adherence to testing guidelines was notably low, with only 11.9% of patients receiving all recommended tests within the first year of ADT.
  • The research highlights a need for further investigation into the factors preventing adherence to these recommendations, as most patients are not adequately monitored for potential treatment-related health issues.
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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.

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Intraosseous meningiomas are a rare subtype of meningiomas representing approximately 2% of all cases. They can confound a diagnosis of other bone lesions including metastatic tumors. We present a case of a patient with prostate cancer who on staging workup was suspected to have a skull metastasis.

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Purpose: Early PSA response has been found to be prognostic of outcomes in metastatic hormone sensitive prostate cancer. We performed a secondary analysis of the TITAN trial to determine if early PSA response was predictive of treatment efficacy in metastatic hormone sensitive prostate cancer patients.

Materials And Methods: Early PSA response was defined as achieving a PSA level of ≤ 0.

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Purpose: We present long-term outcomes from a phase 3 randomized controlled trial that compared helical tomotherapy with 3-dimensional conformal radiation therapy (3D-CRT) in the treatment of high-risk prostate cancer.

Methods And Materials: Newly diagnosed patients with high-risk prostate cancer were randomly allocated to receive radical radiation therapy (RT) using 3D-CRT or helical tomotherapy. In both arms, patients received an initial dose of 46 Gy in 23 fractions to the prostate and pelvic lymph nodes, followed by an additional boost to the prostate of 32 Gy in 16 fractions.

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Article Synopsis
  • A clinical trial called RADICALS-HD studied the effects of adding short-course androgen deprivation therapy (ADT) to postoperative radiotherapy in patients with localized prostate cancer after surgery.
  • It involved 1480 patients, examining how ADT impacts metastasis-free survival compared to radiotherapy alone, and measured outcomes like distant metastasis and overall survival.
  • The trial aimed to see if combining ADT with radiotherapy could improve the 10-year metastasis-free survival rate, potentially increasing it from 80% to 86%.
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Article Synopsis
  • The study investigates the effectiveness and optimal duration of androgen deprivation therapy (ADT) combined with postoperative radiotherapy for patients with localized prostate cancer following radical prostatectomy.
  • A randomised controlled trial, RADICALS-HD, compared short-course ADT (6 months) to long-course ADT (24 months) among participants who met specific criteria, including PSA levels and absence of metastatic disease.
  • The primary outcome measured was metastasis-free survival, with the trial aiming to determine if longer ADT duration leads to better survival rates, involving over 1,500 patients from 2008 to 2015.
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Background And Objective: The utility of prostate radiotherapy (RT) is unclear in men with metastatic hormone-sensitive prostate cancer (mHSPC) receiving intensified systemic therapy with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPIs). We performed a network meta-analysis of randomized controlled trials (RCTs) to investigate the role of prostate RT in low-volume mHSPC.

Methods: Bibliographic databases and conference proceedings were searched through July 2023 for RCTs evaluating the addition of ARPIs or prostate RT to standard of care (SOC) systemic therapy, defined as ADT or ADT plus docetaxel, for the initial treatment of mHSPC.

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Article Synopsis
  • There's a meeting called the Canadian Consensus Forum (CCF3) where doctors talked about how to manage prostate cancer (PCa) better.
  • They discussed important topics like treatment options and how to test for the disease using new technology.
  • The doctors agreed on more than half of the questions discussed, helping to guide future treatment and research to improve care for patients with prostate cancer.
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Purpose: It is unclear whether exposure to commonly prescribed medications influences survival and treatment response in patients with de novo high-risk metastatic prostate cancer (mPCa) treated with androgen receptor pathway inhibitors (ARPIs).

Methods: We performed a secondary analysis of the LATITUDE trial to determine whether receipt of concomitant medications influenced the effect of abiraterone acetate and prednisone, in addition to androgen deprivation therapy (ADT), on overall survival (OS) and prostate cancer-specific mortality (PCSM) in patients with de novo mPCa. We focused on 7 commonly prescribed classes of medications: metformin, statins, proton pump inhibitors (PPIs), cyclooxygenase 2 (COX-2) inhibitors, aspirin, acetaminophen, and NSAIDs (nonselective COX inhibitors).

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Renal cell carcinoma (RCC) is an uncommon malignancy whose incidence has been increasing over the past few decades, posing treatment challenges for elderly or infirm patients who are not surgical candidates. Stereotactic ablative radiotherapy (SABR) has emerged as a promising non-invasive treatment modality for RCC. The high dose-per-fraction used in SABR overcomes some of the mechanisms of radioresistance that has hindered the effective treatment of RCC with conventional radiotherapy.

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Hemangiomas can arise anywhere in the body. While vertebral hemangiomas are common, atypical hemangiomas with paraspinal and epidural extension are rare. We present a case of a patient who presented with persistent cough and anorexia from a paravertebral hemangioma that invaded the adjacent vertebrae and neural foramen causing moderate spinal canal stenosis.

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Purpose: Trigeminal neuralgia (TN) can be treated on the CyberKnife system using two different treatment delivery paths: the general-purpose full path corrects small rotations, while the dedicated trigeminal path improves dose fall-off but does not allow rotational corrections. The study evaluates the impact of uncorrected rotations on brainstem dose and the length of CN5 (denoted as L) covered by the prescription dose.

Methods And Materials: A proposed model estimates the delivered dose considering translational and rotational delivery errors for TN treatments on the CyberKnife system.

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South Africa's PrEP programming has primarily focused on men who have sex with men and other key populations through dedicated clinical and outreach services. However, data shows that the pool of men vulnerable to contracting HIV extends beyond this group, including men who have sex only with women and who do not identify as gay. The aim of this pilot study was to assess acceptability of PrEP among this subset of men who are at risk of HIV acquisition in South Africa and to describe the demographic and behavioral characteristics of male PrEP users as well as their experience of PrEP use.

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Purpose: Pelvic radiation therapy may lead to decreased bone mineral density (BMD) and increased risk of fracture that could be of particular concern in patients with prostate cancer who also receive androgen deprivation therapy (ADT). We performed an exploratory analysis of a randomized, double-masked, placebo-controlled trial to determine whether exposure to prior pelvic external beam radiation therapy (XRT) affects BMD and risk of fracture in patients with prostate cancer treated with ADT.

Methods And Materials: Patients with nonmetastatic prostate cancer aged ≥70 years or <70 years with low BMD (T-score < -1) or osteoporotic fracture who had been receiving ADT for ≥12 months were randomly assigned to receive densoumab or placebo every 6 months for 3 years.

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Purpose: The synergy of combining androgen receptor-signaling inhibition (ARSI) to radiotherapy (RT) in prostate cancer has been largely attributed to non-homologous end joining (NHEJ) inhibition. However, this mechanism is unlikely to explain recently observed trial results that demonstrated the sequencing of ARSI and RT significantly impacts clinical outcomes, with adjuvant ARSI following RT yielding superior outcomes to neoadjuvant/concurrent therapy. We hypothesized this is driven by differential effects on AR-signaling and alternative DNA repair pathway engagement based on ARSI/RT sequencing.

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Purpose: After cessation of androgen deprivation therapy (ADT), testosterone gradually recovers to supracastrate levels (> 50 ng/dL). After this, rises in prostate-specific antigen (PSA) are often seen. However, it remains unknown whether early PSA kinetics after testosterone recovery are associated with subsequent biochemical recurrence (BCR).

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We investigated whether inter-patient variation in the dynamic trajectory of hemoglobin (Hb), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), and prostate-specific antigen (PSA) can prognosticate overall survival (OS) in de novo mHSPC. This is a secondary analysis of the LATITUDE trial in which high-risk de novo mHSPC patients were randomly assigned to receive either androgen deprivation therapy (ADT) plus abiraterone or ADT plus placebo. We used a five-fold cross-validated joint model approach to determine the association of temporal changes in the serological markers with OS.

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