Publications by authors named "Nghiem P"

Article Synopsis
  • - PDEMA, previously known as CCPDMA, allows for complete histologic visualization of tumor margins, which helps in accurately removing cancerous tissue while preserving healthy tissue.
  • - It is the preferred treatment method by NCCN for certain skin cancers due to its high cure rates, with Mohs micrographic surgery being the most common PDEMA technique used in the U.S.
  • - The article discusses the differences between Mohs and Tubingen PDEMA techniques, emphasizing the importance of collaboration between surgeons and pathologists, and includes a step-by-step Tubingen protocol with visual aids.
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Background: Antibodies blocking programmed death (PD)-1 or its ligand (PD-L1) have revolutionized cancer care, but many patients do not experience durable benefits. Novel treatments to stimulate antitumor immunity are needed in the PD-(L)1 refractory setting. The stimulator of interferon genes (STING) protein, an innate sensor of cytoplasmic DNA, is a promising target with several agonists in development.

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Article Synopsis
  • * It was previously thought that CLL suppresses the immune system and allows MCC to develop, but new findings suggest that MCC may actually help CLL persist.
  • * The research indicates that a factor produced by MCC, known as macrophage migration inhibitory factor (MIF), stimulates certain receptors that help maintain CLL, and this might explain why patients' blood cell counts normalize after MCC treatment.
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Merkel cell carcinoma (MCC) incidence has risen to approximately 3,000 cases annually in the USA. Although anti-programmed cell death (ligand) 1 (PD-(L)1) agents are now the first-line treatment for advanced MCC, approximately 50% of such patients do not persistently benefit. In PD-(L)1-refractory cases, ipilimumab (anti-cytotoxic T lymphocyte antigen-4) is often added; however, the extent of the clinical benefit of this combination is controversial.

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Purpose: Merkel cell carcinoma (MCC) is an aggressive skin cancer with a 40% recurrence rate, lacking effective prognostic biomarkers and surveillance methods. This prospective, multicenter, observational study aimed to evaluate circulating tumor DNA (ctDNA) as a biomarker for detecting MCC recurrence.

Methods: Plasma samples, clinical data, and imaging results were collected from 319 patients.

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Purpose: Avelumab (anti-PD-L1) became the first approved treatment for metastatic Merkel cell carcinoma (mMCC) based on results from the phase II JAVELIN Merkel 200 trial. In this study, we report exploratory biomarker analyses from the trial.

Patients And Methods: Patients with mMCC (n = 88) with or without prior first-line chemotherapy received avelumab 10 mg/kg every 2 weeks.

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Although immune check-point inhibitors (CPIs) revolutionized treatment of Merkel cell carcinoma (MCC), patients with CPI-refractory MCC lack effective therapy. More than 80% of MCC express T-antigens encoded by Merkel cell polyomavirus, which is an ideal target for T-cell receptor (TCR)-based immunotherapy. However, MCC often repress HLA expression, requiring additional strategies to reverse the downregulation for allowing T cells to recognize their targets.

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Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer with a high risk of metastasis. The development of anti-PD-1/PD-L1 immunotherapy has improved outcomes for advanced MCC, yet about 50% of such patients do not achieve durable responses. This study analyzed the effects of age and body mass index (BMI) on immunotherapy response in 183 advanced MCC patients from a single-center longitudinal database.

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Article Synopsis
  • - The JAVELIN Merkel 200 study showed that avelumab, an anti-PD-L1 antibody, is effective as a first-line treatment for metastatic Merkel cell carcinoma (mMCC), leading to its approval and inclusion in treatment guidelines.
  • - In the study, 116 patients were followed for an average of 54.3 months, revealing a median overall survival of 20.3 months and a 4-year survival rate of 38%, with rates differing between PD-L1 positive and negative tumors.
  • - Results suggest that avelumab offers significant long-term survival benefits compared to traditional chemotherapy, reinforcing its status as a standard treatment option for mMCC.
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Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer with a high risk of recurrence and metastasis. Regular surveillance through physical exams and imaging studies is crucial for the timely detection of recurrences. MCC patients who produce antibodies to the Merkel cell polyomavirus oncoprotein may benefit from antibody testing in addition to routine imaging surveillance for the early detection of disease recurrence.

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Merkel cell carcinoma (MCC) is a highly immunogenic skin cancer primarily induced by Merkel cell polyomavirus, which is driven by the expression of the oncogenic T antigens (T-Ags). Blockade of the programmed cell death protein-1 (PD-1) pathway has shown remarkable response rates, but evidence for therapy-associated T-Ag-specific immune response and therapeutic strategies for the nonresponding fraction are both limited. We tracked T-Ag-reactive CD8+ T cells in peripheral blood of 26 MCC patients under anti-PD1 therapy, using DNA-barcoded pMHC multimers, displaying all peptides from the predicted HLA ligandome of the oncoproteins, covering 33 class I haplotypes.

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Article Synopsis
  • Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the degeneration of motor neurons, and recent research indicates that inflammation-triggered upregulation of the p53 protein is linked to ALS in both familial and sporadic cases.
  • The study shows that treatment with interferon-gamma (IFNγ) leads to severe aggregation of the TDP-43 protein in motor neurons, activating the p53 pathway and causing neuronal dysfunction.
  • Additionally, IFNγ exposure increases expression of programmed death-ligand 1 (PD-L1) in motor neurons, potentially contributing to ALS progression, and the findings point to possible immunotherapeutic targets for treating sporadic ALS.
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Merkel cell carcinoma is a skin cancer often driven by Merkel cell polyomavirus (MCPyV) with high rates of response to anti-PD-1 therapy despite low mutational burden. MCPyV-specific CD8 T cells are implicated in anti-PD-1-associated immune responses and provide a means to directly study tumor-specific T cell responses to treatment. Using mass cytometry and combinatorial tetramer staining, we find that baseline frequencies of blood MCPyV-specific cells correlated with response and survival.

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Understanding cancer immunobiology has been hampered by difficulty identifying cancer-specific T cells. Merkel cell polyomavirus (MCPyV) causes most Merkel cell carcinomas (MCCs). All patients with virus-driven MCC express MCPyV oncoproteins, facilitating identification of virus (cancer)-specific T cells.

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The NCCN Guidelines for Merkel Cell Carcinoma (MCC) provide recommendations for diagnostic workup, clinical stage, and treatment options for patients. The panel meets annually to discuss updates to the guidelines based on comments from expert review from panel members, institutional review, as well as submissions from within NCCN and external organizations. These NCCN Guidelines Insights focus on the introduction of a new page for locally advanced disease in the setting of clinical node negative status, entitled "Clinical N0 Disease, Locally Advanced MCC.

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Purpose: The role of postoperative radiation therapy (PORT) in early stage Merkel cell carcinoma (MCC) is controversial. We analyzed the role of PORT in preventing local recurrences (LR) among patients with low-risk, pathologic stage I MCC based on the location of the primary tumors: head/neck (HN) versus non-HN sites.

Methods And Materials: One hundred forty-seven patients with MCC were identified that had "low risk" disease (pathologic T1 primary tumor, negative microscopic margins, negative pathologic node status, no immunosuppression or prior systemic therapy).

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Approximately 50% of Merkel cell carcinoma (MCC) patients facing this highly aggressive skin cancer initially respond positively to PD-1-based immunotherapy. Nevertheless, the recurrence of MCC post-immunotherapy emphasizes the pressing need for more effective treatments. Recent research has highlighted Cyclin-dependent kinases 4 and 6 (CDK4/6) as pivotal cell cycle regulators gaining prominence in cancer studies.

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Importance: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer. Of the patients who develop MCC annually, only 4% are younger than 50 years.

Objective: To identify genetic risk factors for early-onset MCC via genomic sequencing.

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Background: Merkel cell carcinoma (MCC) recurs in 40% of patients. In addition to stage, factors known to affect recurrence risk include: sex, immunosuppression, unknown primary status, age, site of primary tumor, and time since diagnosis.

Purpose: Create a multivariable model and web-based calculator to predict MCC recurrence risk more accurately than stage alone.

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Basal cell carcinoma (BCC) is the most common form of skin cancer in the United States. Due to the high frequency, BCC occurrences are not typically recorded, and annual rates of incidence can only be estimated. Current estimated rates are 2 million Americans affected annually, and this continues to rise.

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Purpose: Merkel cell carcinoma (MCC) is a highly immunogenic skin cancer. Although essentially all MCCs are antigenic through viral antigens or high tumor mutation burden, MCC has a response rate of only approximately 50% to PD-(L)1 blockade suggesting barriers to T-cell responses. Prior studies of MCC immunobiology have focused on CD8 T-cell infiltration and their exhaustion status, while the role of innate immunity, particularly myeloid cells, in MCC remains underexplored.

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Background: Merkel cell carcinoma (MCC) is often treated with surgery and postoperative radiation therapy (PORT). The optimal time to initiate PORT (Time-to-PORT [ttPORT]) is unknown.

Purpose: We assessed if delays in ttPORT were associated with inferior outcomes.

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Background: Optimal duration of treatment (DoT) with immune checkpoint inhibitors (ICI) in metastatic cancers remains unclear. Many patients, especially those without radiologic complete remission, develop progressive disease after ICI discontinuation. Extending DoT with ICI may potentially improve efficacy outcomes but presents major logistical and cost challenges with standard frequency dosing (SFD).

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