Publications by authors named "Sayegh N"

Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors, such as olaparib, talazoparib, rucaparib, and niraparib, comprise a therapeutic class that targets PARP proteins involved in DNA repair. Cancer cells with homologous recombination repair defects, particularly BRCA alterations, display enhanced sensitivity to these agents because of synthetic lethality induced by PARP inhibitors. These agents have significantly improved survival outcomes across various malignancies, initially gaining regulatory approval in ovarian cancer and subsequently in breast, pancreatic, and prostate cancers in different indications.

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Background: Enfortumab vedotin (EV) is a nectin-4-directed antibody and microtubule inhibitor conjugate indicated for patients with metastatic urothelial carcinoma (mUC) who have received prior platinum-based chemotherapy and PD-1/L1 inhibitors or are ineligible for cisplatin-containing regimens and have undergone at least 1 prior line of therapy. EV is also indicated in combination with pembrolizumab in the first-line setting. However, real-world effectiveness of EV based on treatment line and impact of prior therapy remains unclear.

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Olive mill wastewater (OMWW), a pollutant resulting from the olive oil industry, poses a serious ecological challenge due to its high pollution load. This effluent is highly concentrated in chemical oxygen demand (COD), which is 200 times higher than that of sewage wastewater. Moreover, OMWW is characterized by a strong acidity, high content of fatty matter, and high concentration of phenolic compounds.

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Background And Objectives: Intermittent androgen deprivation therapy (iADT) may result in measurable improvements in quality of life over continuous ADT in patients with advanced prostate cancer (aPC). Here, we studied time to castration and testosterone recovery in real-world patients with aPC undergoing iADT with relugolix.

Methods And Design: Eligibility criteria for this retrospective study were histologically confirmed through the diagnosis of aPC and initiation of iADT with relugolix.

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Background: Cabozantinib, a tyrosine kinase inhibitor (TKI), is a prevalent second-line (2 L) therapy and was approved for use after progression on TKIs. However, the 1 L treatment setting has changed since the approval of cabozantinib monotherapy in salvage therapy settings.

Objective: To assess the differential effectiveness of cabozantinib after prior progression on 1 L ipilimumab with nivolumab (IPI + NIVO) compared to programmed death receptor-1 (PD-1) or PD-1 ligand (PD-L1) inhibitors (PD1/L1i) with TKIs.

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Background: Bacillus cereus (B. cereus) is a Gram-positive, rod-shaped, motile organism, found in the environment and may exist in contaminated food sources such as reheated rice, vegetables and may lead to gastrointestinal symptoms after ingestion including diarrhea, nausea, and vomiting due to enterotoxigenic and emetic toxins. Non-gastrointestinal infections of have been reported in the literature, which include cutaneous and non-cutaneous infections in immunocompetent and immunocompromised individuals.

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Thromboembolic events (TE) are a common complication in patients with metastatic renal cell carcinoma (mRCC) and are associated with poorer clinical outcomes. However, the incidence of TE and clinical and genomic characteristics of patients with mRCC who develop this complication are poorly understood. Herein, we describe the incidence and clinical features of patients with mRCC with or without TE at our institution, and examine their association with the underlying genomic and transcriptomic characteristics of the tumor.

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Article Synopsis
  • Colorectal cancer is a major global health issue, often spreading to various organs, including rare cases of metastasis to the penis and scrotum from rectal adenocarcinoma.
  • A case study presents a patient who experienced severe complications, including infections and necrosis, requiring extensive surgical procedures alongside chemotherapy and radiotherapy.
  • The article highlights the unusual nature of peno-scrotal metastasis, emphasizing its symptoms, potential pathways of spread, and the importance of a comprehensive treatment approach for effective management.
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  • Targeted therapies for metastatic prostate cancer (mPC) and advanced urothelial carcinoma (aUC) have been approved to improve treatment outcomes based on tumor genomic testing.
  • This study evaluated trends and disparities in the utilization of next-generation sequencing (NGS) testing among patients with these cancers, analyzing data from healthcare records between 2015 and 2022.
  • The research found variations in NGS testing rates based on factors like race, socioeconomic status, and insurance type, highlighting the need to address these disparities in cancer care.
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  • Bone pain at diagnosis significantly impacts overall survival in patients with metastatic hormone-sensitive prostate cancer (MHSPC), with limited existing data on this relationship.
  • The analysis focused on data from a phase 3 clinical trial, SWOG-1216, involving patients diagnosed with MHSPC, comparing outcomes based on the presence or absence of baseline bone pain.
  • Out of 1279 participants, 23.5% reported baseline bone pain, revealing a need for further study on how pain influences survival outcomes and treatment effectiveness.
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Purpose: An increased BMI is linked to increased prostate adenocarcinoma incidence and mortality. Baseline tumor gene expression profiling (GEP) can provide a comprehensive picture of the biological processes related to treatment response and disease progression. We interrogate and validate the underlying differences in tumor GEP on the basis of BMI in patients with prostate adenocarcinoma.

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Background And Objective: It has been reported that patients with de novo metastatic castration-sensitive prostate cancer (dn-mCSPC) have worse prognosis and outcomes than those whose cancer relapses after prior local therapy (PLT-mCSPC). Our aim was to interrogate and validate underlying differences in tumor gene expression profiles between dn-mCSPC and PLT-mCSPC.

Methods: The inclusion criteria were histologically confirmed prostate adenocarcinoma and the availability of RNA sequencing data for treatment-naïve primary prostate tissue.

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Importance: The treatment paradigm for advanced urothelial carcinoma (aUC) has undergone substantial transformation due to the introduction of effective, novel therapeutic agents. However, outcomes remain poor, and little is known about current treatment approaches and attrition rates for patients with aUC.

Objectives: To delineate evolving treatment patterns and attrition rates in patients with aUC using a US-based patient-level sample.

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Introduction: Gastric outlet obstruction presents with a range of symptoms which include abdominal pain, early satiety, weight loss and vomiting caused obstruction secondary to tumors from outside the gastrointestinal tract or due to motility disorders. Bladder cancer is rarely associated with Gastric outlet obstruction. It usually presents with painless hematuria and urinary symptoms.

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Background: Current tobacco smoking is independently associated with decreased overall survival (OS) among patients with metastatic renal cell carcinoma (mRCC) treated with targeted monotherapy (VEGF-TKI). Herein, we assess the influence of smoking status on the outcomes of patients with mRCC treated with the current first-line standard of care of immune checkpoint inhibitor (ICI)-based regimens.

Materials And Methods: Real-world data from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were collected retrospectively.

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Background And Objective: The impact of time of metastasis onset with respect toprimary renal cell carcinoma (RCC) diagnosis on survival outcomes is not well characterized in the era of immune checkpoint inhibitor (ICI)-based combinations. Herein, we assessed differences in clinical outcomes between synchronous and metachronous metastatic RCC (mRCC).

Methods: Data for patients with mRCC treated with first-line ICI-based combination therapies between 2014 and 2023 were retrospectively collected.

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Introduction: Rechallenge with antibodies targeting programmed cell death protein-1 or its ligand (PD-1/L1) after discontinuation or disease progression in solid tumors following a prior PD-1/L1 treatment is often practiced in clinic. This study aimed to investigate if adding PD-1/L1 inhibitors to cabozantinib, the most used second-line treatment in real-world patients with metastatic clear cell renal cell carcinoma (mccRCC), offers additional benefits.

Methods: Using de-identified patient-level data from a large real-world US-based database, patients diagnosed with mccRCC, who received any PD-1/L1-based combination in first-line (1L) setting, followed by second-line (2L) therapy with either cabozantinib alone or in combination with PD-1/L1 inhibitors were included.

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Article Synopsis
  • Androgen deprivation therapy intensification (ADTi) has improved survival for patients with metastatic hormone-sensitive prostate cancer (mHSPC), but its effects on later stages of metastatic castration-resistant prostate cancer (mCRPC) are not well understood.
  • A study analyzed 387 patients with mCRPC to compare outcomes based on their prior treatment with intensified versus nonintensified ADT in the mHSPC setting.
  • Results indicated that patients who received ADTi were younger and presented with more aggressive disease features, but they had worse progression-free survival (4.8 months vs. 8.4 months) and overall survival (21.3 months vs. 33.1 months) compared
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Introduction: Cystitis glandularis is a proliferative disease of the bladder epithelium usually presenting in the setting of chronic inflammation, characterized by the formation of glands in the bladder mucosa and submucosa. Intestinal metaplasia is a described process in cystitis glandularis characterized by the presence of intestinal cells and mucin production which is rare as compared to cystitis glandularis.

Case Presentation: We present a case of cystitis glandularis with intestinal metaplasia located in the bladder and concomitantly in the prostatic urethra.

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Somatic or germline homologous recombination repair (HRR) pathway gene mutations are commonly detected in prostate cancer, especially in advanced disease, and are associated with response to poly (ADP-ribose) polymerase (PARP) inhibitors. In this study, we evaluated whether histological patterns are predictive of HRR pathway gene mutations. The study population comprised 130 patients with advanced prostate carcinoma who underwent comprehensive genomic profiling (CGP) of tumor tissue at a CLIA-certified laboratory.

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Compared to the urban population, patients in rural areas face healthcare disparities and experience inferior healthcare-related outcomes. To compare the healthcare quality metrics and outcomes between patients with advanced genitourinary cancers from rural versus urban areas treated at a tertiary cancer hospital, in this retrospective study, eligible patients with advanced genitourinary cancers were treated at Huntsman Cancer Institute, an NCI-Designated Comprehensive Cancer Center in Utah. Rural-urban commuting area codes were used to classify the patients' residences as being in urban (1-3) or rural (4-10) areas.

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Article Synopsis
  • - The study investigates how the timing of metastasis (synchronous vs metachronous) affects survival outcomes in patients with newly diagnosed metastatic castration-resistant prostate cancer (mCRPC) who have not been previously treated with androgen receptor pathway inhibitors (ARPIs).
  • - Findings indicate that patients with synchronous metastasis had a significantly shorter median overall survival (26 months) compared to those with metachronous metastasis (38.7 months), although median progression-free survival was similar for both groups.
  • - The results suggest that synchronous metastasis is a key factor linked to shorter overall survival, highlighting the need for further validation and potential changes in patient management and clinical trial designs.
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For about a decade, poly [ADP ribose] polymerases (PARP) inhibitors have been used almost exclusively to treat tumours that are deficient in one of the BRCA genes. In advanced prostate cancer, which is largely driven by the activity of the androgen receptor (AR), accumulating preclinical evidence has suggested an interplay between the AR and PARP, which could be therapeutically exploited independently of defects in the tumour's DNA homologous recombination repair (HRR) machinery. This includes the regulation of HRR genes by the AR, a mutual influence between the activities of PARP and the AR, and the co-localisation of BRCA2 to the retinoblastoma gene in the human genome.

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Background: Androgen receptor (AR) gene alterations, as detected by circulating tumor cell-free DNA (cfDNA) genomic profiling, have been shown to emerge after a variable duration of androgen signaling inhibition. AR alterations were associated with inferior outcomes on treatment with androgen receptor pathway inhibitors (ARPI) in the first line metastatic castration-resistant prostate cancer (mCRPC) setting in a phase 2 trial. Here in, we assessed the impact of these AR alterations on survival outcomes in a real-world patient population of mCRPC experiencing disease progression on an ARPI.

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