High transposable element expression in sarcomas is associated with increased immune infiltrates and improved outcomes including after immunotherapy.

Background: Response to immune checkpoint inhibition (ICI) in sarcomas is overall low and heterogeneous. Understanding determinants of ICI outcomes may improve efficacy and patient selection. Thus, we investigated whether the expression of transposable elements (TEs), which are epigenetically silenced and can stimulate antitumor immunity, influence ICI outcomes and immune infiltrates in common sarcoma subtypes.

Phase 1b/2 study evaluating safety, efficacy and immune effects of TLR9 agonist cavrotolimod with anti-PD-1 antibodies among patients with advanced solid tumors.

Background: There is an unmet need for novel immunotherapies to overcome immune evasion in patients with advanced skin cancers resistant to programmed death (PD)-1 / PD-ligand 1 (PD-L1) blockade. Cavrotolimod is a novel spherical nucleic acid configuration of a toll-like receptor 9 agonist oligonucleotide, designed to trigger innate and adaptive immune responses to tumors.

Patients And Methods: The safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of intratumoral cavrotolimod, first dosed alone and then in combination with anti-PD-1 antibodies (pembrolizumab or cemiplimab), were assessed in a combined Phase 1b/2 dose escalation/dose expansion study in patients with advanced skin cancers, including melanoma, Merkel cell carcinoma and cutaneous squamous cell carcinoma (www.

Circulating tumor DNA as a molecular biomarker in the phase II trial of imatinib plus binimetinib in patients with advanced gastrointestinal stromal tumors.

Purpose: This study investigated factors that affected ctDNA detection and ctDNA as a molecular biomarker in a phase II trial of imatinib and binimetinib in newly diagnosed advanced GIST, including patients exposed to imatinib within 4 weeks of trial enrollment.

Experimental Design: Plasma and tumor tissue samples were collected at baseline, on-treatment, and upon progression. DNAs extracted from plasma and tumor tissue were analyzed using genomic assays, MSK-ACCESS and MSK-IMPACT, respectively.

Phase II study of rucaparib and nivolumab in patients with leiomyosarcoma.

Background: Objective responses to immune checkpoint inhibitors (ICI) in leiomyosarcoma (LMS) are rare. Response rates may be increased by combination with other drugs known to promote immune infiltration, such as poly(ADP-ribose) polymerase (PARP) inhibitors, which have led to benefit in -altered uterine LMS. We therefore evaluated the combination of a PARP inhibitor, rucaparib, and the anti-programmed death receptor-1 monoclonal antibody, nivolumab, in patients with advanced LMS and investigated its effects on the tumor immune microenvironment.

ACR-368, a CHK1/2 Kinase Inhibitor, in Patients With Relapsed or Refractory Desmoplastic Small Round Cell Tumor: Phase I/II Trial Results.

Purpose: We hypothesized that ACR-368 (prexasertib) would be active in desmoplastic small round cell tumor (DSRCT) because of favorable responses in preclinical models.

Methods: Preclinical work identified ACR-368 activity in DSRCT, and a phase I/II trial of ACR-368 and irinotecan in patients 12 months and older with relapsed/refractory DSRCT was conducted. The primary objectives were determination of recommended phase II dose (RP2D) and best overall response rate (ORR) at the RP2D in DSRCT, with ≥3 of 16 responses considered promising.

Immunologic correlates in a CIC::DUX4 fusion-positive sarcoma responsive to dual immune checkpoint blockade.

CIC::DUX4 sarcoma (CDS) is a rare and aggressive subtype of soft tissue sarcoma with poor prognosis and limited treatment options. Immunotherapy has not been studied in this disease. To our knowledge, response to immune checkpoint blockade (ICB) has not been previously reported.

Plant-Based Meat Alternatives on the Island of Ireland: Changes in the Market and Comparisons with Conventional Meat.

The plant-based meat alternative (PBMA) market and consumer base on the island of Ireland (IOI) has grown rapidly in recent years. Therefore, this study compared the changes in PBMAs available on the IOI over time and the nutritional profiles of PBMAs with meat counterparts. Three online audits of PBMAs available in Tesco's and Sainsbury's in 2021/2022, 2022/2023 and 2023/2024 were conducted.

IDH1/2 Mutations in Cancer: Unifying Insights and Unlocking Therapeutic Potential for Chondrosarcoma.

Chondrosarcomas, a rare form of bone sarcomas with multiple subtypes, pose a pressing clinical challenge for patients with advanced or metastatic disease. The lack of US Food and Drug Administration (FDA)-approved medications underscores the urgent need for further research and development in this area. Patients and their families face challenges as there are no systemic therapeutic options available with substantial effectiveness.

Histology-Specific Clinical Trial of Lenvatinib and Pembrolizumab in Patients with Sarcoma.

Purpose: Survival of patients with metastatic sarcoma remains poor, and there is a pressing need for new therapies. Most sarcoma subtypes are not responsive to immune checkpoint inhibition alone. Lenvatinib, a multireceptor tyrosine kinase inhibitor targeting tumor vasculature, has an immunomodulatory activity that contributes to its antitumor effects.

What factors are associated with infant hearing aid use? A parent survey using the Theoretical Domains Framework.

Objective: Hearing aid use is lowest in 0-3-year-olds with hearing loss, placing spoken language development at risk. Existing interventions lack effectiveness and are typically not based on a theoretically driven, comprehensive understanding of the factors influencing infant hearing aid use. The present study is the first to address this gap in understanding.

The approach to developing Ireland's first national health protection strategy and lessons learnt, December 2021 to October 2022.

The COVID-19 pandemic highlighted the importance of strengthening health protection worldwide. To address this as a public health priority in Ireland, between December 2021 and October 2022 the first national Health Protection Strategy (2022-2027) for the Irish Health Service Executive (HSE) was developed. We describe the approach taken to develop a first national health protection strategy for Ireland, and highlight the key lessons learned.

A Single-Arm Phase 2 Trial of Trametinib in Patients with Locally Advanced or Metastatic Epithelioid Hemangioendothelioma.

Purpose: Epithelioid hemangioendothelioma (EHE) is a rare vascular cancer with pathogenic TAZ-CAMTA1 (calmodulinbinding transcription activator 1) operating as an oncogenic driver through activation of the MAPK pathway. Trametinib is an inhibitor of MEK, a critical kinase in the MAPK pathway. We sought to evaluate the effect of trametinib in patients with EHE.

Pegylated Liposomal Doxorubicin Causes Kidney-limited Thrombotic Microangiopathy.

A definite causal link between pegylated liposomal doxorubicin (PLD) and kidney-limited thrombotic microangiopathy (TMA) remains unestablished. Here, we report 2 cases of PLD-induced kidney-limited TMA, 1 in a patient with myxofibrosarcoma and the other in a patient with liposarcoma. The 2 patients received a high cumulative dose of PLD, and both presented with a rise in serum creatinine and proteinuria.

Immune-related Adverse Events after Immune Checkpoint Blockade-based Therapy Are Associated with Improved Survival in Advanced Sarcomas.

Unlabelled: The association between immune-related AEs (irAE) and outcome in patients with sarcoma is not known. We retrospectively reviewed a cohort of patients with advanced sarcoma treated with immune checkpoint blockade (ICB)-based therapy. Association of irAEs with survival was assessed using a Cox regression model that incorporated irAE occurrence as a time-dependent covariate.

Novel Genomic Risk Stratification Model for Primary Gastrointestinal Stromal Tumors (GIST) in the Adjuvant Therapy Era.

Purpose: Traditional risk stratification schemes in gastrointestinal stromal tumors (GIST) were defined in the pre-imatinib era and rely solely on clinicopathologic metrics. We hypothesize that genomic-based risk stratification is prognostically relevant in the current era of tyrosine kinase inhibitor (TKI) therapeutics.

Experimental Design: Comprehensive mutational and copy-number profiling using MSK-IMPACT was performed.

Adolescent binge drinking in the West of Ireland: associated risk and protective factors.

Background: Alcohol is a leading cause of morbidity and mortality worldwide. Adolescence is when alcohol use typically begins. Harmful patterns of alcohol consumption, such as binge drinking, may emerge during adolescence and become established.

Limited transmission of SARS-CoV-2 in schools in Ireland during the 2020-2021 school year.

BackgroundThe role of schools in SARS-CoV-2 transmission has been a debated topic since the beginning of the COVID-19 pandemic.AimTo examine SARS-CoV-2 transmission in all schools in Ireland during the 2020-21 school year.MethodsIn a national descriptive cross-sectional study, we investigated PCR-confirmed cases of COVID-19 among students (aged < 20 years) and staff (aged ≥ 20 years) who attended school during their infectious period to identify school close contacts.

A Phase II Study of Epacadostat and Pembrolizumab in Patients with Advanced Sarcoma.

Purpose: Epacadostat, an indole 2,3 dioxygenase 1 (IDO1) inhibitor, proposed to shift the tumor microenvironment toward an immune-stimulated state, showed early promise in melanoma but has not been studied in sarcoma. This study combined epacadostat with pembrolizumab, which has modest activity in select sarcoma subtypes.

Patients And Methods: This phase II study enrolled patients with advanced sarcoma into five cohorts including (i) undifferentiated pleomorphic sarcoma (UPS)/myxofibrosarcoma, (ii) liposarcoma (LPS), (iii) leiomyosarcoma (LMS), (iv) vascular sarcoma, including angiosarcoma and epithelioid hemangioendothelioma (EHE), and (v) other subtypes.

Distinct IDH1/2-associated Methylation Profile and Enrichment of and Mutations Distinguish Dedifferentiated Chondrosarcoma from Conventional Chondrosarcoma.

Unlabelled: Dedifferentiated chondrosarcoma (DDCS) is a rare high-grade chondrosarcoma characterized by a well-differentiated chondrosarcoma (WDCS) component that abruptly transitions to a high-grade, noncartilaginous sarcomatous component. To date, the molecular pathogenesis of DDCS and its distinction from conventional chondrosarcoma remain poorly understood. By targeted sequencing, we examined the mutational and copy-number profiles of 18 DDCS, including macrodissected WDCS components, compared with 55 clinically sequenced conventional chondrosarcomas.

Lessons from inter-disciplinary collaboration to mitigate SARS-CoV-2 transmission in schools, Ireland, 2020/2021, to inform health systems and multisectoral recovery.

Introduction: School closures associated with the COVID-19 pandemic resulted in the loss of educational and social supports for up to 1,000,000 students in Ireland and disproportionately affected students from lower socio-economic backgrounds. For the 2020/2021 school year, multisectoral and interdisciplinary "Schools Teams" were established within Public Health departments to maintain in-person education by minimizing transmission of SARS-CoV-2 in schools. This study aimed to describe this model and explore the experiences of Schools Team members in the East of Ireland to identify factors that influenced effective working that can be sustained in the context of health systems and multisectoral recovery.

Psychological support for healthcare workers during the COVID-19 pandemic: a mixed methods study involving support providers.

Healthcare staff represent a high-risk group for mental health difficulties as a result of their role during the COVID-19 pandemic. A number of wellbeing initiatives have been implemented to support this population, but remain largely untested in terms of their impact on both the recipients and providers of supports. To examine the experience of staff support providers in delivering psychological initiatives to healthcare staff, as well as obtain feedback on their perceptions of the effectiveness of different forms of support.

NCCN Guidelines® Insights: Gastrointestinal Stromal Tumors, Version 2.2022.

Gastrointestinal stromal tumors (GIST) are the most common type of soft tissue sarcoma that occur throughout the gastrointestinal tract. Most of these tumors are caused by oncogenic activating mutations in the KIT or PDGFRA genes. The NCCN Guidelines for GIST provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with these tumors.

Management of pelvic sarcoma.

Pelvic sarcomas are a rare and heterogenous group of tumors divided into two groups: soft tissue sarcomas and bone sarcomas. Soft tissue sarcomas of the pelvis include most commonly liposarcoma, leiomyosarcoma, gastrointestinal stromal tumors, malignant peripheral nerve sheath tumors, and solitary fibrous tumors. Bone sarcomas of the pelvis most commonly include osteosarcoma and chondrosarcoma.