Publications by authors named "Herbst R"

Public-private partnerships (PPPs) in cancer research have emerged as a pivotal model in the development of strategies to rapidly advance therapeutic innovations. The collaboration between public entities, such as government agencies and research institutions, and private entities, including pharmaceutical and biotechnology companies, as well as nonprofit organizations, brings together diverse expertise, resources, and perspectives to address the challenges of efficient drug development and equitable care delivery. This synergy has the potential to accelerate the translation of basic research findings into tangible clinical applications.

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Background: Cancer immunotherapy has revolutionized melanoma treatment, but the high number of non-responders still emphasizes the need for improvement of therapy. One potential avenue for enhancing anti-tumor treatment is through the modulation of coagulation and platelet activity. Both have been found to play an important role in the tumor microenvironment, tumor growth and metastasis.

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  • Patients with multiple myeloma and soft-tissue plasmacytoma (STP) have a poor prognosis, despite new treatments and bone marrow transplants.
  • A study of 120 STP patients showed a 67% rate of partial response to first-line treatment, with median progression-free survival (PFS) of 10.5 months and overall survival (OS) of 24.5 months.
  • Secondary STP and organ involvement were identified as significant negative factors affecting PFS and OS, highlighting the need for customized treatment strategies, including immunotherapies.
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Background: Prompt follow-up for positive depression screen results is important in providing high-quality care for adolescents. We sought to improve follow-up within 30 days for adolescents (≥12 years) with Patient Health Questionnaire-9 scores ≥10, or those with a positive question 9, from 25% to 40%.

Methods: We conducted a quality improvement project at 6 primary care locations serving ∼33,300 patients (70% Black, 7.

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Although many pediatric clinicians have familiarity with motivational interviewing (MI), they may have limited awareness of how it can benefit mental and behavioral health assessment and management. This article describes the spirit, tasks, and skills of MI. Cases illustrate the application of MI to common presentations of mental health concerns in pediatric primary care.

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  • Lung cancer is a significant public health challenge with ongoing difficulties in prevention, diagnosis, and treatment, prompting a review of current research and management strategies.
  • Experts from various fields collaborated to discuss ways to enhance lung cancer care, emphasizing the importance of tobacco cessation, early detection, and addressing treatment side effects.
  • Effective lung cancer management requires global cooperation, better education, improved access to care and trials, and a focus on personalized treatment through innovative research.
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  • Dual immune checkpoint blockade (ICB) using CTLA4 and PD-(L)1 inhibitors shows improved anti-tumor effectiveness and immune toxicity compared to PD-(L)1 inhibitors alone in advanced non-small-cell lung cancer (NSCLC) patients.
  • Patients with mutations in STK11 and/or KEAP1 genes benefit more from the combination treatment compared to those receiving only PD-(L)1 inhibitors, as shown in the POSEIDON trial.
  • The loss of KEAP1 serves as a strong predictor for the success of dual ICB, as it leads to a more favorable outcome by changing the tumor's immune environment to better engage CD4 and CD8 T cells for anti-tumor activity. *
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Purpose: To determine the optimal daunorubicin dose and number of 7 + 3 induction cycles in newly diagnosed AML, this randomized controlled trial compared a once daily dose of 60 mg/m with 90 mg/m daunorubicin in the first 7 + 3 induction and one versus two cycles of 7 + 3 induction.

Patients And Methods: Patients age 18-65 years with newly diagnosed AML were randomly assigned to 60 versus 90 mg/m daunorubicin once daily plus cytarabine. Patients with marrow blasts below 5% on day 15 after first induction were randomly assigned to receive a second induction cycle or no second induction cycle.

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  • Researchers studied patients with advanced skin cancer (melanoma) to see how well they responded to a special treatment called immune checkpoint inhibition (ICI).
  • They found that only about 8% of patients responded quickly to the treatment, while others had slower responses or did not respond at all.
  • Despite the quick responders showing some improvement, they didn’t live longer or have better outcomes than those who responded later to the treatment.
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Non-small cell lung cancer (NSCLC) accounts for 85 % of all lung cancers. In NSCLC, 10-20 % of Caucasian patients and 30-50 % of Asian patients have tumors with activating mutations in the Epidermal Growth Factor Receptor (EGFR). A high percentage of these patients exhibit favorable responses to treatment with tyrosine kinase inhibitors (TKI).

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Following the onset of the "Iron Swords" war, Israel's National Emergency Medical Organization Magen David Adom (MDA) implemented a program designed to prevent post-traumatic sequelae among its teams. 'Team debriefing' is at the core of the program, which also includes primary, secondary, and tertiary prevention carried out regularly to preclude psychological harm to employees and volunteers. Apart from the initial team debriefings, MDA's enhanced prevention program includes several other components and stages.

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Introduction: Squamous cell cancer (SqCC) is a lung cancer subtype with few targeted therapy options. Molecular characterization, that is, by next-generation sequencing (NGS), is needed to identify potential targets. Lung Cancer Master Protocol Southwest Oncology Group S1400 enrolled patients with previously treated stage IV or recurrent SqCC to assess NGS biomarkers for therapeutic sub-studies.

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Background: Melanomas lacking mutations in BRAF, NRAS and NF1 are frequently referred to as "triple wild-type" (tWT) melanomas. They constitute 5-10 % of all melanomas and remain poorly characterized regarding clinical characteristics and response to therapy. This study investigates the largest multicenter collection of tWT-melanomas to date.

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This study investigated whether adjuvant treatments in stage III cutaneous melanoma (CM) influenced patterns of recurrence. Patients with primary (n = 1033) or relapsed CM (n = 350) who received adjuvant therapies with Nivolumab (N), Pembrolizumab (P), or Dabrafenib and Trametinib (D + T) were extracted from the prospective multicenter real-world skin cancer registry ADOReg. Endpoints were progression-free survival (PFS), distant metastasis-free survival (DMFS), organ-specific DMFS, and overall survival (OS).

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Recently, low human epidermal growth factor receptor 2 (HER2) protein expression has been proposed as a predictive biomarker for response to the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) in metastatic breast cancer. HER2 expression in non-small cell lung cancer (NSCLC) patients has never been carefully measured, and little is known about the frequency of cases with unamplified but detectable levels of the protein. Although some HER2-targeted therapies have been studied in NSCLC patients, they have been restricted to those with genomic ERBB2 gene alterations, which only represent relatively rare cases of NSCLC.

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  • Screening for gene mutations in melanoma has become standard practice, with identified mutations impacting prognosis in metastatic uveal melanoma, while their significance in non-uveal melanoma is still unclear.
  • A study analyzing 2,650 melanoma cases found mutations in 129 samples, highlighting differences in the prevalence and types of mutations between uveal and non-uveal melanomas.
  • Unlike uveal melanomas, where mutations are linked to worse outcomes, mutations in non-uveal melanomas are mostly seen as "passenger mutations" with little impact on prognosis or treatment effectiveness.
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Clinical trials are essential for advancing oncology treatment strategies and have contributed significantly to the decline in cancer mortality rates over the past decades. Traditional explanatory trials, focused on establishing intervention efficacy in ideal settings, often lack generalizability and may not reflect real-world patient care scenarios. Furthermore, increasing complexity in cancer clinical trial design has led to challenges such as protocol deviations, slow enrollment leading to lengthened durations of trial, and escalating costs.

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A coordinated and complex interplay of signals between motor neurons, skeletal muscle cells, and Schwann cells controls the formation and maintenance of neuromuscular synapses. Deficits in the signaling pathway for building synapses, caused by mutations in critical genes or autoantibodies against key proteins, are responsible for several neuromuscular diseases, which cause muscle weakness and fatigue. Here, we describe the role that four key genes, , , , and , play in this signaling pathway, how an understanding of their mechanisms of action has led to an understanding of several neuromuscular diseases, and how this knowledge has contributed to emerging therapies for treating neuromuscular diseases.

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For cancer clinical trials that require central confirmation of tumor genomic profiling, exhaustion of tissue from standard-of-care testing may prevent enrollment. For Lung-MAP, a master protocol that requires results from a defined centralized clinical trial assay to assign patients to a therapeutic substudy, we developed a process to repurpose existing commercial vendor raw genomic data for eligibility: genomic data reanalysis (GDR). Molecular results for substudy assignment were successfully generated for 369 of the first 374 patients (98.

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  • Osimertinib targets and inhibits the epidermal growth factor receptor (EGFR) in cancer cells, leading to cell death and reduced tumors, making it a key treatment for EGFR-mutated non-small cell lung cancer (NSCLC).
  • The ADAURA study compared the effects of osimertinib to a placebo in patients with surgically removed early-stage (IB-IIIA) EGFR-mutated NSCLC, showing that those on osimertinib had longer disease-free survival.
  • Recent results reveal that osimertinib significantly improves overall survival, with a 51% lower risk of death for patients treated with it compared to the placebo group.
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Background: While many molecular assays can detect mutations at low tumor purity and variant allele frequencies, complex biomarkers such as tumor mutational burden (TMB), microsatellite instability (MSI), and genomic loss of heterozygosity (gLOH) require higher tumor purity for accurate measurement. Scalable, quality-controlled, tissue-conserving methods to increase tumor nuclei percentage (TN%) from tumor specimens are needed for complex biomarkers and hence necessary to maximize patient matching to approved therapies or clinical trial enrollment. We evaluated the clinical utility and performance of precision needle-punch enrichment (NPE) compared with traditional razor blade macroenrichment of tumor specimens on molecular testing success.

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Background: Pembrolizumab has a manageable safety profile as described in its label, which was primarily based on 2799 patients who participated in clinical trials for melanoma or non-small cell lung cancer. Here, we evaluated the safety of pembrolizumab in a broader population of patients from 31 advanced cancer clinical trials across 19 cancer types.

Methods: Safety was analyzed in patients who received at least one dose of pembrolizumab (200 mg every 3 weeks [Q3W], 10 mg/kg Q2W or Q3W, or 2 mg/kg Q3W).

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In metastatic urothelial cancer (mUC), cisplatin versus carboplatin leads to durable disease control in a subset of patients. The IMvigor130 trial reveals more favorable effects with atezolizumab combined with gemcitabine and cisplatin (GemCis) versus gemcitabine and carboplatin (GemCarbo). This study investigates the immunomodulatory effects of cisplatin as a potential explanation for these observations.

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  • * Multi-omics analyses of blood and tissue samples from a clinical trial revealed that higher immune scores correlate with better responses to ICIs, while certain immune cells, like regulatory T cells, negatively impact survival.
  • * Variations in immune cell density and proximity to tumor cells influence survival outcomes, and soluble proteins found in the blood could serve as indicators for treatment effectiveness and overall survival in SqNSCLC patients.
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Objective: Pediatric primary care is a promising setting in which to deliver preventive behavioral health services to young children and their families. Integrated behavioral health care models typically emphasize treatment rather than prevention. This pilot study examined the efficacy of an integrated behavioral health preventive (IBH-P) intervention delivered by psychologists and focused on supporting parenting in low-income mothers of infants as part of well-child visits in the first 6 months of life.

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