Safety and efficacy of pembrolizumab, radiation therapy, and surgery versus radiation therapy and surgery for stage III soft tissue sarcoma of the extremity (SU2C-SARC032): an open-label, randomised clinical trial.

Background: Approximately half of patients with localised, high-risk soft tissue sarcoma of the extremity develop metastases. We aimed to assess whether the addition of pembrolizumab to preoperative radiotherapy and surgery would improve disease-free survival.

Methods: We completed an open-label, randomised clinical trial in patients with grade 2 or 3, stage III undifferentiated pleomorphic sarcoma or dedifferentiated or pleomorphic liposarcoma of the extremity and limb girdle.

Integrated Epigenetic and Transcriptomic Analysis Identifies DNA Methylation Signature of Malignant Peripheral Nerve Sheath Tumor Progression and Metastasis.

Purpose: Sarcomas are a complex group of highly aggressive and metastatic tumors with over 100 distinct subtypes. Because of their diversity and rarity, it is challenging to generate multisarcoma signatures that are predictive of patient outcomes.

Materials And Methods: Here, we identify a DNA methylation signature for progression and metastasis of numerous sarcoma subtypes using multiple epigenetic and genomic patient data sets.

Objective Responses in Metastatic Pleomorphic Rhabdomyosarcoma Treated with Combination of Doxorubicin and Pembrolizumab: A Case Series.

Introduction: Pleomorphic rhabdomyosarcoma is a rare subtype of rhabdomyosarcoma, a soft tissue sarcoma with skeletal muscle differentiation. Although rhabdomyosarcoma is typically seen in the pediatric population, the pleomorphic variant most frequently presents in adulthood and is characteristically aggressive with no currently established treatment regimen in the setting of metastatic disease. There has been growing interest in the application of immune checkpoint inhibitors alongside conventional chemotherapeutic agents in the treatment of pleomorphic rhabdomyosarcoma.

T* Imaging Assessment of Neoadjuvant Radiation Therapy Combined With Pharmacological Ascorbate in Extremity Soft-Tissue Sarcomas: A Pilot Study.

Background: Extremity soft-tissue sarcomas (STS) are commonly treated with neoadjuvant radiation therapy followed by surgical resection. However, the pathological near-complete response rate is low (9-25%). Noninvasive imaging assessment that predicts treatment response before and during treatment is desirable to optimize treatment regimens.

PRT543, a protein arginine methyltransferase 5 inhibitor, in patients with advanced adenoid cystic carcinoma: An open-label, phase I dose-expansion study.

Objectives: Currently, no systemic treatments are approved for patients with recurrent and/or metastatic (R/M) adenoid cystic carcinoma (ACC). PRT543, a protein arginine methyltransferase 5 inhibitor that downregulates NOTCH1 and MYB signalling in tumours, is a potential candidate for R/M ACC treatment. We report the safety, tolerability and preliminary efficacy of PRT543 in a dose-expansion cohort of patients with R/M ACC.

Exploring the Dorian Gray Trait: Unveiling the Complexities of Perceived Aging and Self-Image.

The concept of the "Dorian Gray Trait," inspired by Oscar Wilde's renowned literary work, delves into the intricate interplay between self-perception, the fear of aging, and the pursuit of eternal youth. This article explores the psychological dimensions of this trait, wherein individuals harbor an intense preoccupation with maintaining their youthful appearance, often at the cost of their overall well-being. By examining the underlying factors that drive this phenomenon, including societal pressures and personal anxieties, we aim to shed light on the broader implications for mental health and self-image.

Topiramate Monotherapy for Civilian Posttraumatic Stress Disorder: A Controlled Pilot Study.

To assess the efficacy, safety, and tolerability of topiramate for the treatment of posttraumatic stress disorder (PTSD) in civilians. This 12-week double-blind, randomized, placebo-controlled study enrolled 72 outpatients (aged 19-64 years) with a diagnosis of non-combat-related PTSD and a score ≥ 50 on the Clinician-Administered PTSD Scale (CAPS). The primary efficacy endpoint, percent change in total CAPS score, and secondary efficacy measures were assessed by analysis of covariance.

Malignant Tourette's Syndrome in an Adult on Deep Brain Stimulation Presenting With Rhabdomyolysis.

Tourette's syndrome (TS) patients experiencing severe tics and behavioral disturbances can have a rare complication called rhabdomyolysis (RML), which is characterized by the breakdown of muscle tissue. The occurrence of RML poses a significant physical and emotional risk to patients with TS by impacting the quality of life and in some cases causing severe damage. In this case report, we present the first documented case of RML resulting from severe tics in an adult with a diagnosis of TS.

Magnetic Resonance Imaging of Iron Metabolism with T2* Mapping Predicts an Enhanced Clinical Response to Pharmacologic Ascorbate in Patients with GBM.

Purpose: Pharmacologic ascorbate (P-AscH-) is hypothesized to be an iron (Fe)-dependent tumor-specific adjuvant to chemoradiation in treating glioblastoma (GBM). This study determined the efficacy of combining P-AscH- with radiation and temozolomide in a phase II clinical trial while simultaneously investigating a mechanism-based, noninvasive biomarker in T2* mapping to predict GBM response to P-AscH- in humans.

Patients And Methods: The single-arm phase II clinical trial (NCT02344355) enrolled 55 subjects, with analysis performed 12 months following the completion of treatment.

A Rare Presentation of Narcolepsy With Cataplexy After Vaccines in a Genetically Susceptible Elderly Woman: A Case Report.

Observing cataplexy episodes during an office visit is extremely rare as they are usually triggered by laughter or emotional stress. Narcolepsy usually occurs in the younger population. We report a case of a 65-year-old Caucasian female with a past medical history of obesity who developed excessive daytime sleepiness, fatigue, and sleep attacks five weeks after getting influenza and pneumococcal vaccines.

Gaps in Adolescent and Young Adult Cancer Education in Oncology Fellowship Training.

Adolescents and young adults (AYAs, 15-39 years) with cancer experience disparities in care and outcomes compared with older/younger patients. AYAs receive care from medical and pediatric oncologists, however, little is known about the extent of training fellows receive. This needs assessment evaluating current AYA oncology (AYA-O) education in pediatric and medical oncology fellowship programs to identify knowledge gaps for curricular development.

Radiology Gets Chatty: The ChatGPT Saga Unfolds.

As artificial intelligence (AI) continues to evolve and mature, it is increasingly finding applications in the field of healthcare, particularly in specialties like radiology that are data-heavy and image-focused. Language learning models (LLMs) such as OpenAI's Generative Pre-trained Transformer-4 (GPT-4) are new in the field of medicine and there is a paucity of literature regarding the possible utilities of GPT-4 given its novelty. We aim to present an in-depth exploration of the role of GPT-4, an advanced language model, in radiology.

CDK4/6-MEK Inhibition in MPNSTs Causes Plasma Cell Infiltration, Sensitization to PD-L1 Blockade, and Tumor Regression.

Purpose: Malignant peripheral nerve sheath tumors (MPNST) are lethal, Ras-driven sarcomas that lack effective therapies. We investigated effects of targeting cyclin-dependent kinases 4 and 6 (CDK4/6), MEK, and/or programmed death-ligand 1 (PD-L1) in preclinical MPNST models.

Experimental Design: Patient-matched MPNSTs and precursor lesions were examined by FISH, RNA sequencing, IHC, and Connectivity-Map analyses.

Serotonin Syndrome with Monotherapy of Low-Dose Sertraline in an Adult Patient with Autism Spectrum Disorder.

Serotonin syndrome, also known as serotonin toxicity, is associated with increased serotonergic activity in the central and the peripheral nervous system. The symptoms can range from mild to potentially life threatening. Given the widespread use of serotonergic agents, the number of cases is on the rise.

The Impact of TSC-1 and -2 Mutations on Response to Therapy in Malignant PEComa: A Multicenter Retrospective Analysis.

Background: Perivascular epithelioid cell neoplasms (PEComas) are a diverse family of mesenchymal tumors with myomelanocytic differentiation that disproportionately affect women and can be associated with tuberous sclerosis (TS). Although mTOR inhibition is widely used as first-line treatment, it is unclear what genomic alterations exist in these tumors and how they influence the response to therapy.

Methods: This was a multicenter study conducted at five sites within the US.

Alliance A071401: Phase II Trial of Focal Adhesion Kinase Inhibition in Meningiomas With Somatic Mutations.

Purpose: Patients with progressive or recurrent meningiomas have limited systemic therapy options. Focal adhesion kinase (FAK) inhibition has a synthetic lethal relationship with loss. Given the predominance of mutations in meningiomas, we evaluated the efficacy of GSK2256098, a FAK inhibitor, as part of the first genomically driven phase II study in recurrent or progressive grade 1-3 meningiomas.

Patient reported quality of life in young adults with sarcoma receiving care at a sarcoma center.

Background: Sarcomas are a diverse group of neoplasms that vary greatly in clinical presentation and responsiveness to treatment. Given the differences in the sites of involvement, rarity, and treatment modality, a multidisciplinary approach is required. Previous literature suggests patients with sarcoma suffer from poorer quality of life (QoL) especially physical and functional wellbeing.

Augmenting chemotherapy with low-dose decitabine through an immune-independent mechanism.

The DNA methyltransferase inhibitor decitabine has classically been used to reactivate silenced genes and as a pretreatment for anticancer therapies. In a variation of this idea, this study explores the concept of adding low-dose decitabine (DAC) following administration of chemotherapy to bolster therapeutic efficacy. We find that addition of DAC following treatment with the chemotherapy agent gemcitabine improves survival and slows tumor growth in a mouse model of high-grade sarcoma.

Pharmacological ascorbate as a novel therapeutic strategy to enhance cancer immunotherapy.

Pharmacological ascorbate (i.e., intravenous infusions of vitamin C reaching ~ 20 mM in plasma) is under active investigation as an adjuvant to standard of care anti-cancer treatments due to its dual redox roles as an antioxidant in normal tissues and as a prooxidant in malignant tissues.

Detection of Ferritin Expression in Soft Tissue Sarcomas With MRI: Potential Implications for Iron Metabolic Therapy.

Background: Cancer cells often have altered iron metabolism relative to non-malignant cells with increased transferrin receptor and ferritin expression. Targeting iron regulatory proteins as part of a cancer therapy regimen is currently being investigated in various malignancies. Anti-cancer therapies that exploit the differences in iron metabolism between malignant and non-malignant cells (e.

Olutasidenib (FT-2102) in patients with relapsed or refractory IDH1-mutant glioma: A multicenter, open-label, phase Ib/II trial.

Background: Olutasidenib (FT-2102) is a highly potent, orally bioavailable, brain-penetrant and selective inhibitor of mutant isocitrate dehydrogenase 1 (IDH1). The aim of the study was to determine the safety and clinical activity of olutasidenib in patients with relapsed/refractory gliomas harboring an IDH1R132X mutation.

Methods: This was an open-label, multicenter, nonrandomized, phase Ib/II clinical trial.

Epigenetic modulation in sensitizing metastatic sarcomas to therapies and overcoming resistance.

Sarcomas are a class of rare malignancies of mesenchymal origin with a heterogeneous histological spectrum. They are classically associated with poor outcomes, especially once metastasized. A path to improving clinical outcomes may be made through modifying the epigenome, where a variety of sarcomas demonstrate changes that contribute to their oncogenic phenotypes.