Background: Glofitamab monotherapy induces durable remission in patients with relapsed or refractory diffuse large B-cell lymphoma after two or more previous therapies, but has not previously been assessed as a second-line therapy. We investigated the efficacy and safety of glofitamab plus gemcitabine-oxaliplatin (Glofit-GemOx) versus rituximab (R)-GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma.
Methods: The phase 3, randomised, open-label STARGLO trial was done at 62 centres in 13 countries in Asia and Australia, Europe, and North America.
Curr Opin Obstet Gynecol
August 2024
Purpose Of Review: Given the current political climate and the release of an updated version of the World Professional Association for Transgender Health's guidelines, this review assesses recent updates in the care of transgender and gender diverse (TGD) patients, specifically related to care provided by gynecologists.
Recent Findings: The number of people identifying as TGD and pursuing gender affirming care is increasing. Contraception for these patients is underdiscussed and high rates of pelvic pain and irregular bleeding were identified.
Public Health Pract (Oxf)
June 2024
Background: HPV (Human Papillomavirus) vaccination is a safe, effective method to prevent HPV-associated disease. Racial-ethnic disparities in HPV vaccination exist, which could lead to widening gaps in cervical cancer mortality. Provider discussion of HPV vaccination has been shown to be a primary factor for increasing vaccination rates.
View Article and Find Full Text PDFLung cancer continues to be the leading cause of cancer death in the United States. Despite recent advances, the five-year survival rate for lung cancer compared to other cancers still remains fairly low. The discovery of molecular targets for lung cancer is key to the development of new approaches and therapies.
View Article and Find Full Text PDFVulvar cancer incidence has been rising in recent years, possibly due to increasing exposure to human papillomavirus (HPV). We assessed incidence rates of HPV-associated and non-HPV-associated vulvar cancers diagnosed from 2001 to 2017 in the United States (US). Using population-based cancer registry data covering 99% of the US population, incidence rates were calculated and stratified by age, race/ethnicity, stage, geographic region, and histology.
View Article and Find Full Text PDFStudy Objective: To assess rates of and factors associated with complications and reoperation after myomectomy.
Design: Population-based cohort study.
Setting: All non-Veterans Affairs facilities in the state of California from January 1, 2005, to December 31, 2018.
Unlabelled: Endometriosis has a large impact on the lives of patients, affecting nearly 90% of women with chronic pelvic pain and infertility. Unfortunately, diagnosis for this condition is often delayed by an average of 7 years, with adolescent patients experiencing disproportionate delays. This is in part due to the use of an invasive procedure for primary diagnosis and limited access to subspecialty care.
View Article and Find Full Text PDFThe switch/sucrose non-fermentable (SWI/SNF) complex has a crucial role in chromatin remodelling and is altered in over 20% of cancers. Here we developed a proteolysis-targeting chimera (PROTAC) degrader of the SWI/SNF ATPase subunits, SMARCA2 and SMARCA4, called AU-15330. Androgen receptor (AR) forkhead box A1 (FOXA1) prostate cancer cells are exquisitely sensitive to dual SMARCA2 and SMARCA4 degradation relative to normal and other cancer cell lines.
View Article and Find Full Text PDFMulti-tyrosine kinase inhibitors (MTKIs) have thus far had limited success in the treatment of castration-resistant prostate cancer (CRPC). Here, we report a phase I-cleared orally bioavailable MTKI, ESK981, with a novel autophagy inhibitory property that decreased tumor growth in diverse preclinical models of CRPC. The anti-tumor activity of ESK981 was maximized in immunocompetent tumor environments where it upregulated expression through the interferon gamma pathway and promoted functional T cell infiltration, which resulted in enhanced therapeutic response to immune checkpoint blockade.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2021
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, employs two key host proteins to gain entry and replicate within cells, angiotensin-converting enzyme 2 (ACE2) and the cell surface transmembrane protease serine 2 (TMPRSS2). was first characterized as an androgen-regulated gene in the prostate. Supporting a role for sex hormones, males relative to females are disproportionately affected by COVID-19 in terms of mortality and morbidity.
View Article and Find Full Text PDFPurpose: The current standard-of-care for front-line therapy for acute myeloid leukaemia (AML) results in short-term and long-term toxicity, but still approximately 40% of children relapse. Therefore, there is a major need to accelerate the evaluation of innovative medicines, yet drug development continues to be adult-focused. Furthermore, the large number of competing agents in rare patient populations requires coordinated prioritisation, within the global regulatory framework and cooperative group initiatives.
View Article and Find Full Text PDFObjective: To evaluate the cost-effectiveness of the addition of chemotherapy or abiraterone to androgen deprivation.
Methods: We developed an analytical model to determine the cost-effectiveness of the addition of docetaxel or abiraterone versus androgen deprivation therapy alone. Direct and indirect costs were included in the model.
In recent years, quantum mechanical/molecular mechanical (QM/MM) methods have emerged that are designed specifically for chemical reactions in water. Despite the many advances, a remaining problem is that the patchwork of QM and MM descriptions changes the solvent structure. In a solvent as intricately connected as water, such structural changes can alter a chemical process even across large distances.
View Article and Find Full Text PDFBackground: Vemurafenib, a selective inhibitor of BRAF kinase, is approved for the treatment of adult stage IIIc/IV BRAF V600 mutation-positive melanoma. We conducted a phase I, open-label, dose-escalation study in pediatric patients aged 12-17 years with this tumor type (NCT01519323).
Procedure: Patients received vemurafenib orally until disease progression.
Background: Non-Hodgkin lymphoma (NHL) is a relatively common malignancy in pediatric patients; however, a small subgroup have unusual lymphoma subtypes for the pediatric population.
Procedure: The Children's Oncology Group Rare and Cutaneous NHL registry's (protocol ANHL 04B1) main objectives were to determine the pathologic, biologic, and clinical features of rare and cutaneous pediatric NHL and establish a bank of centrally reviewed tissue specimens. We report the clinical data, treatment data, and outcome for rare pediatric NHL.
Inactivation of the LKB1 tumor suppressor is a frequent event in non-small cell lung carcinoma (NSCLC) leading to the activation of mTOR complex 1 (mTORC1) and sensitivity to the metabolic stress inducer phenformin. In this study, we explored the combinatorial use of phenformin with the mTOR catalytic kinase inhibitor MLN0128 as a treatment strategy for NSCLC bearing comutations in the LKB1 and KRAS genes. NSCLC is a genetically and pathologically heterogeneous disease, giving rise to lung tumors of varying histologies that include adenocarcinomas and squamous cell carcinomas (SCC).
View Article and Find Full Text PDFObjective: To identify features associated with multisystem involvement and therapeutic failure in patients with skin Langerhans cell histiocytosis (LCH).
Study Design: We reviewed medical records of 71 consecutive patients with LCH with skin involvement evaluated at Texas Children's Hospital and analyzed clinical features, laboratory results, and the presence of circulating cells with the BRAF-V600E mutation with respect to initial staging and clinical outcomes.
Results: Skin disease in patients older than 18 months of age at diagnosis was associated with the presence of multisystem disease (OR, 9.
Langerhans cell histiocytosis (LCH) is a myeloproliferative disorder characterized by lesions composed of pathological CD207(+) dendritic cells with an inflammatory infiltrate. BRAFV600E remains the only recurrent mutation reported in LCH. In order to evaluate the spectrum of somatic mutations in LCH, whole exome sequencing was performed on matched LCH and normal tissue samples obtained from 41 patients.
View Article and Find Full Text PDFLangerhans cell histiocytosis (LCH) is a clonal disorder with elusive etiology, characterized by the accumulation of CD207(+) dendritic cells (DCs) in inflammatory lesions. Recurrent BRAF-V600E mutations have been reported in LCH. In this study, lesions from 100 patients were genotyped, and 64% carried the BRAF-V600E mutation within infiltrating CD207(+) DCs.
View Article and Find Full Text PDFBackground: Existing therapies for recurrent or refractory histiocytoses, including Langerhans cell histiocytosis (LCH), juvenile xanthogranuloma (JXG), and Rosai-Dorfman disease (RDD), have limited effectiveness. We report our experience with using clofarabine as therapy in children with recurrent or refractory histiocytic disorders, including LCH (11 patients), systemic JXG (4 patients), and RDD (3 patients).
Methods: Patients treated with clofarabine for LCH, JXG, or RDD by Texas Children's Hospital physicians or collaborators between May 2011 and January 2013 were reviewed for response and toxicity.