Publications by authors named "Jeffrey Ross"

Background And Purpose: Studies show a modest yield for image-guided biopsy of suspected vertebral osteomyelitis-discitis. Many studies evaluate factors to improve diagnostic yield, and few studies assess how biopsy results impact clinical management. We aim to evaluate the impact of biopsy results on clinical management in suspected vertebral osteomyelitis-discitis.

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Background: End-stage renal disease is a growing global health issue, disproportionately impacting low- and middle-income countries. While kidney transplantation remains the best treatment for end-stage renal disease, access to this treatment modality is limited by chronic donor organ shortages. To address this critical need, we are developing transplantable bioengineered kidney grafts.

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Introduction: Approximately 20% of patients living with colorectal cancer (CRC) have activating mutations in their tumors in the PIK3CA oncogene. Two or more activating mutations (multi-hit) for the PIK3CA allele increase PI3K⍺ signaling compared to single-point mutations, resulting in exceptional response to PI3K⍺ inhibition. We aimed to identify the prevalence of PIK3CA multi-hit mutations in metastatic CRC to identify patients who may benefit from PI3K inhibitors.

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Background: Tumors harboring two or more PIK3CA short variant (SV) ("multi-hit") mutations have been linked to improved outcomes with anti-PIK3CA-targeted therapies in breast cancer. The landscape and clinical implications of multi-hit PIK3CA alterations in clinically advanced prostate cancer (CAPC) remains elusive.

Objective: To evaluate the genomic landscape of single-hit and multi-hit PIK3CA genomic alterations in CAPC.

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Background And Objective: The 2024 US Food and Drug Administration approval of erdafitinib for the treatment of metastatic urothelial carcinoma (mUC) with FGFR3 alterations ushered in the era of targeted therapy for bladder cancer. In this review, we summarize the effects of FGFR pathway alterations in oncogenesis, clinical data supporting FGFR inhibitors in the management of bladder cancer, and the challenges that remain.

Methods: Original articles relevant to FGFR inhibitors in urothelial cancer between 1995 and 2024 were systematically identified in the PubMed and MEDLINE databases using the search terms "FGFR" and "bladder cancer".

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Background And Purpose: We aimed to evaluate GPT-4's ability to write radiology editorials and to compare these with human-written counterparts, thereby determining their real-world applicability for scientific writing.

Materials And Methods: Sixteen editorials from eight journals were included. To generate the AI-written editorials, the summary of 16 human-written editorials was fed into GPT-4.

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Background: Squamous cell carcinoma (SCC) of presumed lung origin (PLO) is now the second most frequent histologic subtype of non-small cell carcinoma after adenocarcinoma. The use of clinic-genomic correlation provided by comprehensive genomic profiling (CGP) can revise clinicopathologic diagnoses of presumed primary lung SCC (PLO-SCC) to diagnoses of metastatic SCC of cutaneous origin (C-SCC).

Design: A total of 10 146 samples of clinically advanced PLO-SCC (84% known Stage IV) passed QC metrics and were designated as PLO-SCCs by review of test requisition forms, clinical notes, and pathology reports.

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Microsatellite instability high (MSI-H) and mismatch repair deficient (dMMR) tumor status have been demonstrated to predict patient response to immunotherapies. We developed and validated a next-generation sequencing (NGS)-based companion diagnostic (CDx) to detect MSI-H solid tumors via a comprehensive genomic profiling (CGP) assay, FoundationOne®CDx (F1CDx). To determine MSI status, F1CDx calculates the fraction of unstable microsatellite loci across >2000 loci using a fraction-based (FB) analysis.

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Background: The effectiveness of the clinical outcome of CN (Cytoreductive Nephrectomy) in cases of mccRCC (Metastatic Clear Cell Renal cell Carcinoma) is still uncertain despite two trials, SURTIME and CARMENA. These trials, conducted with Sunitinib as the standard treatment, did not provide evidence supporting the use of CN.

Methods: We queried the NCDB for stage IV mccRCC patients between the years of 2004 to 2020, who received (immunotherapy) IO with or without nephrectomy.

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Article Synopsis
  • The study aimed to assess the effectiveness and safety of combining nivolumab with nab-paclitaxel as a pre-surgery treatment for patients with muscle-invasive bladder cancer (MIBC), followed by surgery and additional nivolumab therapy.
  • A total of 31 patients participated, with a significant portion experiencing severe treatment-related side effects; however, the treatment led to a notable pathologic complete response rate of 32.3% among those evaluated.
  • The findings indicate promising outcomes with an 89.8% event-free survival rate after 12 months, suggesting this combination therapy could enhance treatment options for these patients.
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  • Malignant phyllodes tumors (MPT) are rare breast cancers with a poor prognosis, prompting researchers to analyze their genomic characteristics and potential immunotherapy markers.
  • The study involved genomic profiling of 135 MPT cases, revealing that 69.6% were localized, with a median age of 54 and several patients demonstrating actionable mutations.
  • Findings indicate that routine genomic sequencing for metastatic MPT may improve treatment strategies and help in enrolling patients in clinical trials.
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Article Synopsis
  • There has been an increase in agents for treating bacillus Calmette-Guérin-unresponsive (BCG-U) non-muscle-invasive bladder cancer (NMIBC), and there is a pressing need for patient and therapy selection guidelines due to a lack of randomized trials.
  • A global expert committee developed recommendations through literature reviews and a voting process, refining these guidelines during a live meeting in August 2023, achieving over 75% agreement on the final recommendations.
  • No single optimal treatment exists for BCG-U patients; personalized treatment based on individual preferences, tumor characteristics, and available agent data is essential, with specific options recommended for carcinoma in situ and papillary-only tumors, and clinical trial participation encouraged.
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Purpose: Although both urachal (U) and nonurachal (NU) bladder adenocarcinomas (adenoCas) share several histologic similarities, they differ in location and sometimes in therapeutic options. We analyzed the differences in genomic alterations (GAs) between these tumor entities, with the aim of identifying potential therapeutic targets for clinical trials.

Materials And Methods: Overall, 133 U and 328 NU adenoCas were analyzed.

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Article Synopsis
  • The CUPISCO trial is studying whether a new treatment approach called molecularly guided therapy (MGT) can help patients with a type of cancer called cancer of unknown primary (CUP) do better than the standard chemotherapy.
  • This trial involved 1,505 patients from 34 countries and focused on those who showed improvement after initial chemotherapy.
  • The goal is to see if using genomic profiling in deciding treatments can lead to better results in fighting cancer compared to the usual treatment options.
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Background: Male breast cancer (MaBC) has limited data on genomic alterations. We aimed to comprehensively describe and compare MaBC's genomics with female breast cancer's (FBC) across subtypes.

Methods: Using genomic data from Foundation Medicine, we categorized 253 MaBC into estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative (n = 210), ER-positive/HER2-positive (n = 22) and triple-negative (n = 20).

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  • Patients with acral and mucosal melanomas (A/M) have fewer treatment options and worse outcomes compared to those with cutaneous melanomas.
  • The study analyzed 156 melanoma cases and discovered new genomic alterations in A/M melanomas that could be targeted for treatment.
  • Key findings included unique alterations specific to A/M melanomas that respond to certain inhibitors, suggesting a need for tailored clinical testing and treatment strategies.
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Despite recent efforts to issue clinical guidelines outlining strategies to define the pathogenicity of genomic variants, there is currently no standardized framework for which to make these assertions. This review does not present a step-by-step methodology, but rather takes a holistic approach to discuss many aspects which should be taken into consideration when determining variant pathogenicity. Categorization should be curated to reflect relevant findings within the scope of the specific medical context.

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In this study, a mixed porcine-human bioengineered liver (MPH-BEL) was used in a preclinical setup of extracorporeal liver support devices as a treatment for a model of post-resection liver failure (PRLF). The potential for human clinical application is further illustrated by comparing the functional capacity of MPH-BEL grafts as assessed using this porcine PRLF model with fully human (FH-BEL) grafts which were perfused and assessed in vitro. BEL grafts were produced by reseeding liver scaffolds with HUVEC and primary porcine hepatocytes (MPH-BEL) or primary human hepatocytes (FH-BEL).

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Background: The treatment landscape for HR(+)HER2(-) metastatic breast cancer (MBC) is evolving for patients with ESR1 mutations (mut) and PI3K/AKT pathway genomic alterations (GA). We sought to inform clinical utility for comprehensive genomic profiling (CGP) using tissue (TBx) and liquid biopsies (LBx) in HR(+)HER2(-) MBC.

Methods: Records from a de-identified breast cancer clinicogenomic database for patients who underwent TBx/LBx testing at Foundation Medicine during routine clinical care at ~ 280 US cancer clinics between 01/2011 and 09/2023 were assessed.

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Background: The application of precision medicine in clinical practice implies a thorough evaluation of actionable genomic alterations to streamline therapeutic decision making. Comprehensive genomic profiling of tumor via next-generation sequencing (NGS) represents a great opportunity but also several challenges. During the 2023 San Raffaele Retreat, we aimed to provide expert recommendations for the optimal use of NGS in urothelial carcinoma (UC).

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Importance: Biliary tract cancers (BTCs) contain several actionable molecular alterations, including FGFR2, IDH1, ERBB2 (formerly HER2), and KRAS. KRAS allelic variants are found in 20% to 30% of BTCs, and multiple KRAS inhibitors are currently under clinical investigation.

Objectives: To describe the genomic landscape, co-sequence variations, immunophenotype, genomic ancestry, and survival outcomes of KRAS-mutated BTCs and to calculate the median overall survival (mOS) for the most common allelic variants.

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Article Synopsis
  • - The study examines genomic alterations (GA) in patients with urothelial bladder cancer (UBC), focusing on those with ERBB2 mutations and amplifications, and comparing them to patients with wild-type ERBB2.
  • - Findings show that 6.3% of UBC cases have short variant GAs in the ERBB2 extracellular domain, 2.7% in the kinase domain, and 9.1% show ERBB2 amplification, while 81.9% are ERBB2 wild-type.
  • - The analysis indicates that ERBB2-altered cases exhibit higher tumor mutational burden and specific genetic changes compared to wild-type ERBB2 cases, with notable associations found between various genetic markers
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Purpose: Isocitrate dehydrogenase ()/ genomic alterations (GA) occur in 20% of intrahepatic cholangiocarcinoma (iCCA); however, the immunogenomic landscape of mutated iCCA is largely unknown.

Methods: Comprehensive genomic profiling (CGP) was performed on 3,067 cases of advanced iCCA. Tumor mutational burden (TMB), PD-L1 expression (Dako 22C3), microsatellite instability (MSI), and genomic loss of heterozygosity (gLOH) as a surrogate marker for homologous recombination deficiency were examined.

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Article Synopsis
  • Extramammary Paget disease (EMPD) is a rare skin cancer often found on vulvar and penoscrotal areas, with its origin and how different types affect treatment still unclear.
  • The study aimed to analyze demographics, tumor traits, and treatment methods for various subtypes of EMPD, relying on data from multiple trusted medical databases.
  • Findings revealed that vulvar EMPD diagnoses are often delayed and have high recurrence rates (34%), while penoscrotal EMPD has a lower recurrence rate (14%) but more cases involve regional or distant spread.*
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