Medicine and Health Sciences Commons^™

Perspectives On Joint Eanm/Snmmi/Anzsnm Practice Guidelines/Procedure Standards For [18f]Fdg Pet/Ct Imaging During Immunomodulatory Treatments In Patients With Solid Tumors, E Lopci, R L Wahl, Et Al.

2020-Current year OA Pubs

Response assessment in the context of immunomodulatory treatments represents a major challenge for the medical imaging community and requires a multidisciplinary approach with involvement of oncologists, radiologists, and nuclear medicine specialists. There is evolving evidence that [

Immune Checkpoint Inhibitor Therapy And Outcomes From Sars-Cov-2 Infection In Patients With Cancer: A Joint Analysis Of Oncovid And Esmo-Cocare Registries, Alessio Cortellini, Gino M Dettorre, Et Al.

2020-Current year OA Pubs

BACKGROUND: As management and prevention strategies against COVID-19 evolve, it is still uncertain whether prior exposure to immune checkpoint inhibitors (ICIs) affects COVID-19 severity in patients with cancer.

METHODS: In a joint analysis of ICI recipients from OnCovid (NCT04393974) and European Society for Medical Oncology (ESMO) CoCARE registries, we assessed severity and mortality from SARS-CoV-2 in vaccinated and unvaccinated patients with cancer and explored whether prior immune-related adverse events (irAEs) influenced outcome from COVID-19.

FINDINGS: The study population consisted of 240 patients diagnosed with COVID-19 between January 2020 and February 2022 exposed to ICI within 3 months prior to COVID-19 …

Manufacturing-Dependent Change In Biological Activity Of The Tlr4 Agonist Gsk1795091 And Implications For Lipid A Analog Development, Neeltje Steeghs, Haeseong Park, Et Al.

2020-Current year OA Pubs

A phase I trial (NCT03447314; 204686) evaluated the safety and efficacy of GSK1795091, a Toll-like receptor 4 (TLR4) agonist, in combination with immunotherapy (GSK3174998 [anti-OX40 monoclonal antibody], GSK3359609 [anti-ICOS monoclonal antibody], or pembrolizumab) in patients with solid tumors. The primary endpoint was safety; other endpoints included efficacy, pharmacokinetics, and pharmacodynamics (PD). Manufacturing of GSK1795091 formulation was modified during the trial to streamline production and administration, resulting in reduced PD (cytokine) activity. Fifty-four patients received GSK1795091 with a combination partner; 32 received only the modified GSK1795091 formulation, 15 received only the original formulation, and seven switched mid-study from the original to …

Loneliness, Social Isolation, And Social Support In Older Adults With Active Cancer During The Covid-19 Pandemic, Katherine Clifton, Feng Gao, Joann Jabbari, Mary Van Aman, Patricia Dulle, Janice Hanson, Tanya M Wildes

2020-Current year OA Pubs

INTRODUCTION: The COVID-19 pandemic has had a considerable impact on mental health. The social distancing and stay-at-home orders have likely also impacted loneliness, social isolation, and social support. Older adults, particularly those with comorbidities such as cancer, have a greater potential to be impacted. Here we assessed loneliness, social isolation, and social support in older adults undergoing active cancer treatment during the pandemic.

MATERIALS AND METHODS: A mixed methods study in which quantitative data and qualitative response items were collected in parallel was conducted in 100 older adults with cancer. Participants completed a survey by telephone with a series of …

Pan-Cancer Analysis Reveals Recurrent Bcar4 Gene Fusions Across Solid Tumors, Andrew Nickless, Jin Zhang, Ghofran Othoum, Jace Webster, Matthew J Inkman, Emily Coonrod, Sherron Fontes, Emily B Rozycki, Christopher A Maher, Nicole M White

2020-Current year OA Pubs

UNLABELLED: Chromosomal rearrangements often result in active regulatory regions juxtaposed upstream of an oncogene to generate an expressed gene fusion. Repeated activation of a common downstream partner-with differing upstream regions across a patient cohort-suggests a conserved oncogenic role. Analysis of 9,638 patients across 32 solid tumor types revealed an annotated long noncoding RNA (lncRNA), Breast Cancer Anti-Estrogen Resistance 4 (BCAR4), was the most prevalent, uncharacterized, downstream gene fusion partner occurring in 11 cancers. Its oncogenic role was confirmed using multiple cell lines with endogenous BCAR4 gene fusions. Furthermore, overexpressing clinically prevalent BCAR4 gene fusions in untransformed cell lines was sufficient …

Phase Ib Study Of Eprenetapopt (Apr-246) In Combination With Pembrolizumab In Patients With Advanced Or Metastatic Solid Tumors, H Park, Et Al.

2020-Current year OA Pubs

BACKGROUND: We conducted a phase I, multicenter, open-label, dose-finding, and expansion study to determine the safety and preliminary efficacy of eprenetapopt (APR-246) combined with pembrolizumab in patients with advanced/metastatic solid tumors (ClinicalTrials.gov NCT04383938).

PATIENTS AND METHODS: For dose-finding, requirements were non-central nervous system primary solid tumor, intolerant to/progressed after ≥1 line of treatment, and eligible for pembrolizumab; for expansion: (i) gastric/gastroesophageal junction tumor, intolerant to/progressed after first-line treatment, and no prior anti-programmed cell death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy; (ii) bladder/urothelial tumor, intolerant to/progressed after first-line cisplatin-based chemotherapy, and no prior anti-PD-1/PD-L1 therapy; (iii) non-small-cell lung cancer (NSCLC) with …

Efficacy Of A Smartphone-Based Care Support Programme In Improving Post-Traumatic Stress In Families With Childhood Cancer: Protocol Of A Randomised Controlled Trial, Jun Ma, Han-Zhu Qian, Yueyang Peng, Yali Xiang, Minghua Yang, Jessica Hahne, Can Gu

2020-Current year OA Pubs

INTRODUCTION: Diagnosis and treatment represent distressing experiences for the families of children with cancer. Psychosocial challenges are faced by these families in China because of limited health services and resources for psychosocial oncology care. Effective interventions tailored to the knowledge level and cultural values of this population are needed. The goal of this study is to evaluate a smartphone-based care support (SBCS) programme for the families of children with cancer in China.

METHODS AND ANALYSIS: A parallel randomised controlled trial will be conducted to examine the efficacy of an evidence-based and culturally tailored SBCS programme for the families of children …

Implementation Of A Provider-Focused Intervention For Maximizing Human Papillomavirus (Hpv) Vaccine Uptake In Young Cancer Survivors Receiving Follow-Up Care In Pediatric Oncology Practices: Protocol For A Cluster-Randomized Trial Of The Hpv Protect Intervention, Wendy Landier, Smita Bhatia, Joshua S Richman, Paula D Campos Gonzalez, Brooke Cherven, Veronica Chollette, Jamie Aye, Sharon M Castellino, Maria M Gramatges, Susan Lindemulder, Thomas B Russell, Lucie M Turcotte, Graham A Colditz, Melissa B Gilkey, James L Klosky

2020-Current year OA Pubs

BACKGROUND: Childhood cancer survivors are at high risk for developing new cancers (such as cervical and anal cancer) caused by persistent infection with the human papillomavirus (HPV). HPV vaccination is effective in preventing the infections that lead to these cancers, but HPV vaccine uptake is low among young cancer survivors. Lack of a healthcare provider recommendation is the most common reason that cancer survivors fail to initiate the HPV vaccine. Strategies that are most successful in increasing HPV vaccine uptake in the general population focus on enhancing healthcare provider skills to effectively recommend the vaccine, and reducing barriers faced by …

A Case Study Of Adapting A Health Insurance Decision Intervention From Trial Into Routine Cancer Care, Miles E Charles, Lindsay M Kuroki, Ana A Baumann, Rachel G Tabak, Aimee James, Krista Cooksey, Mary C Politi

2020-Current year OA Pubs

OBJECTIVE: This study adapted Improving Cancer Patients' Insurance Choices (I Can PIC), an intervention to help cancer patients navigate health insurance decisions and care costs. The original intervention improved knowledge and confidence making insurance decisions, however, users felt limited by choices provided in insurance markets. Using decision trees and frameworks to guide adaptations, we modified I Can PIC to focus on using rather than choosing health insurance. The COVID-19 pandemic introduced unforeseen obstacles, prompting changes to study protocols. As a result, we allowed users outside of the study to use I Can PIC (> 1050 guest users) to optimize public …

Feasibility And Sensitivity Study Of Radiomic Features In Photoacoustic Imaging Of Patient-Derived Xenografts, Lorena Escudero Sanchez, Emma Brown, Leonardo Rundo, Stephan Ursprung, Evis Sala, Sarah E Bohndiek, Ignacio Xavier Partarrieu

2020-Current year OA Pubs

Photoacoustic imaging is an increasingly popular method of exploring the tumour microenvironment, which can provide insight into tumour oxygenation status and potentially treatment response assessment. Currently, the measurements most commonly performed on such images are the mean and median of the pixel values of the tumour volumes of interest. We investigated expanding the set of measurements that can be extracted from these images by adding radiomic features. In particular, we found that Skewness was sensitive to differences between basal and luminal patient derived xenograft cancer models with an [Formula: see text] of 0.86, and that it was robust to variations …

Potentiation Of Combined P19arf And Interferon-Beta Cancer Gene Therapy Through Its Association With Doxorubicin Chemotherapy, Ruan F V Medrano, Thiago A Salles, Rafael Dariolli, Fernanda Antunes, Valker A Feitosa, Aline Hunger, João P P Catani, Samir A Mendonça, Rodrigo E Tamura, Marlous G Lana, Elaine G Rodrigues, Bryan E Strauss

2020-Current year OA Pubs

Balancing safety and efficacy is a major consideration for cancer treatments, especially when combining cancer immunotherapy with other treatment modalities such as chemotherapy. Approaches that induce immunogenic cell death (ICD) are expected to eliminate cancer cells by direct cell killing as well as activation of an antitumor immune response. We have developed a gene therapy approach based on p19Arf and interferon-β gene transfer that, similar to conventional inducers of ICD, results in the release of DAMPS and immune activation. Here, aiming to potentiate this response, we explore whether association between our approach and treatment with doxorubicin (Dox), a known inducer …

The Role Of Natural Products And Their Multitargeted Approach To Treat Solid Cancer, Naoshad Muhammad, Darksha Usmani, Mohammad Tarique, Huma Naz, Mohammad Ashraf, Ramesh Raliya, Shams Tabrez, Torki A Zughaibi, Ahdab Alsaieedi, Israa J Hakeem, Mohd Suhail

2020-Current year OA Pubs

Natural products play a critical role in the discovery and development of numerous drugs for the treatment of various types of cancer. These phytochemicals have demonstrated anti-carcinogenic properties by interfering with the initiation, development, and progression of cancer through altering various mechanisms such as cellular proliferation, differentiation, apoptosis, angiogenesis, and metastasis. Treating multifactorial diseases, such as cancer with agents targeting a single target, might lead to limited success and, in many cases, unsatisfactory outcomes. Various epidemiological studies have shown that the steady consumption of fruits and vegetables is intensely associated with a reduced risk of cancer. Since ancient period, plants, …

Dcs At The Center Of Help: Origins And Evolution Of The Three-Cell-Type Hypothesis, Renee Wu, Kenneth M Murphy

2020-Current year OA Pubs

Last year was the 10th anniversary of Ralph Steinman's Nobel Prize awarded for his discovery of dendritic cells (DCs), while next year brings the 50th anniversary of that discovery. Current models of anti-viral and anti-tumor immunity rest solidly on Steinman's discovery of DCs, but also rely on two seemingly unrelated phenomena, also reported in the mid-1970s: the discoveries of "help" for cytolytic T cell responses by Cantor and Boyse in 1974 and "cross-priming" by Bevan in 1976. Decades of subsequent work, controversy, and conceptual changes have gradually merged these three discoveries into current models of cell-mediated immunity against viruses and …

Joint Eanm/Snmmi/Anzsnm Practice Guidelines/Procedure Standards On Recommended Use Of [18f]Fdg Pet/Ct Imaging During Immunomodulatory Treatments In Patients With Solid Tumors Version 1.0, E Lopci, R J Hicks, A Dimitrakopoulou-Strauss, L Dercle, A Iravani, R D Seban, C Sachpekidis, O Humbert, O Gheysens, A W J M Glaudemans, W Weber, R L Wahl, A M Scott, N Pandit-Taskar, N Aide

2020-Current year OA Pubs

PURPOSE: The goal of this guideline/procedure standard is to assist nuclear medicine physicians, other nuclear medicine professionals, oncologists or other medical specialists for recommended use of [

METHODS: In a cooperative effort between the EANM, the SNMMI and the ANZSNM, clinical indications, recommended imaging procedures and reporting standards have been agreed upon and summarized in this joint guideline/procedure standard.

CONCLUSIONS: The field of immuno-oncology is rapidly evolving, and this guideline/procedure standard should not be seen as definitive, but rather as a guidance document standardizing the use and interpretation of [

PREAMBLE: The European Association of Nuclear Medicine (EANM) is a …

First-In-Human, Open-Label, Phase 1/2 Study Of The Monoclonal Antibody Programmed Cell Death Protein-1 (Pd-1) Inhibitor Cetrelimab (Jnj-63723283) In Patients With Advanced Cancers, Enriqueta Felip, Daniel Morgensztern, Et Al.

2020-Current year OA Pubs

PURPOSE: To assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of cetrelimab (JNJ-63723283), a monoclonal antibody programmed cell death protein-1 (PD-1) inhibitor, in patients with advanced/refractory solid tumors in the phase 1/2 LUC1001 study.

METHODS: In phase 1, patients with advanced solid tumors received intravenous cetrelimab 80, 240, 460, or 800 mg every 2 weeks (Q2W) or 480 mg Q4W. In phase 2, patients with melanoma, non-small-cell lung cancer (NSCLC), and microsatellite instability-high (MSI-H)/DNA mismatch repair-deficient colorectal cancer (CRC) received cetrelimab 240 mg Q2W. Response was assessed Q8W until Week 24 and Q12W thereafter.

RESULTS: In phase 1, 58 patients …

Phase 1b Trial Of Anti-Vegf/Pdgfr Vorolanib Combined With Immune Checkpoint Inhibitors In Patients With Advanced Solid Tumors, Nusayba A Bagegni, Haeseong Park, Katlyn Kraft, Maura O-Toole, Feng Gao, Saiama N Waqar, Lee Ratner, Daniel Morgensztern, Siddhartha Devarakonda, Manik Amin, Maria Q Baggstrom, Chris Liang, Giovanni Selvaggi, Andrea Wang-Gillam

2020-Current year OA Pubs

PURPOSE: Vorolanib is a multi-target tyrosine kinase inhibitor with anti-angiogenic properties. This study aimed to evaluate the tolerability, safety and efficacy of vorolanib when added to checkpoint inhibitors (CPIs) in patients with advanced solid tumors.

METHODS: We conducted a phase 1b study of vorolanib (300 or 400 mg orally once daily) plus pembrolizumab or nivolumab using a standard 3 + 3 design to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). The endpoints included safety, toxicity and objective response rate, according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1).

RESULTS: …

Prospectively Defined Patterns Of Apobec3a Mutagenesis Are Prevalent In Human Cancers, Rachel A Deweerd, Eszter Németh, Ádám Póti, Nataliya Petryk, Chun-Long Chen, Olivier Hyrien, Dávid Szüts, Abby M Green

2020-Current year OA Pubs

Mutational signatures defined by single base substitution (SBS) patterns in cancer have elucidated potential mutagenic processes that contribute to malignancy. Two prevalent mutational patterns in human cancers are attributed to the APOBEC3 cytidine deaminase enzymes. Among the seven human APOBEC3 proteins, APOBEC3A is a potent deaminase and proposed driver of cancer mutagenesis. In this study, we prospectively examine genome-wide aberrations by expressing human APOBEC3A in avian DT40 cells. From whole-genome sequencing, we detect hundreds to thousands of base substitutions per genome. The APOBEC3A signature includes widespread cytidine mutations and a unique insertion-deletion (indel) signature consisting largely of cytidine deletions. This …

Oncodb: An Interactive Online Database For Analysis Of Gene Expression And Viral Infection In Cancer, Gongyu Tang, Minsu Cho, Xiaowei Wang

2020-Current year OA Pubs

Large-scale multi-omics datasets, most prominently from the TCGA consortium, have been made available to the public for systematic characterization of human cancers. However, to date, there is a lack of corresponding online resources to utilize these valuable data to study gene expression dysregulation and viral infection, two major causes for cancer development and progression. To address these unmet needs, we established OncoDB, an online database resource to explore abnormal patterns in gene expression as well as viral infection that are correlated to clinical features in cancer. Specifically, OncoDB integrated RNA-seq, DNA methylation, and related clinical data from over 10 000 …

A Comparison Of 64cu-Labeled Bi-Terminally Pegylated A20fmdv2 Peptides Targeting Integrin Ανβ6, Truc T Huynh, Sreeja Sreekumar, Cedric Mpoy, Buck E Rogers

2020-Current year OA Pubs

Expression of epithelial-specific integrin α

In And Out: Leishmania Metastasis By Hijacking Lymphatic System And Migrating Immune Cells, Baijayanti Jha, Marta Reverte, Catherine Ronet, Florence Prevel, Florence D Morgenthaler, Chantal Desponds, Lon-Fye Lye, Katherine L Owens, Leonardo Scarpellino, Lalit Kumar Dubey, Amélie Sabine, Tatiana V Petrova, Sanjiv A Luther, Stephen M Beverley, Nicolas Fasel

2020-Current year OA Pubs

The lymphatic system plays a crucial role in mounting immune response against intracellular pathogens, and recent studies have documented its role in facilitating tumor dissemination linked largely with cancer cells. However, in mucocutaneous leishmaniasis (MCL) caused by

Positive Predictive Value Of Erbb2 Copy Number Gain By Tissue Or Circulating Tumor Dna Next-Generation Sequencing Across Advanced Cancers, Ami N Shah, Ashwin Sunderraj, Brian Finkelman, Sharlene H See, Andrew A Davis, Lorenzo Gerratana, Firas Wehbe, Neelima Katam, Deva Mahalingam, William J Gradishar, Amir Behdad, Luis Blanco, Massimo Cristofanilli

2020-Current year OA Pubs

BACKGROUND: The correlation of ERBB2 copy number gain (CNG) from tissue or circulating tumor DNA (ctDNA) by next-generation sequencing (NGS) with standard HER2 tissue evaluation is not well understood.

MATERIALS AND METHODS: We retrospectively identified patients with ERBB2 CNG on commercial NGS. We described their clinical-pathologic features and calculated the positive predictive value (PPV) of ERBB2 CNG by NGS for HER2-positivity by IHC and FISH testing.

RESULTS: 176 patients had NGS revealing an ERBB2 CNG (112 by tumor tissue and 91 by ctDNA). The cancer subtypes with the most cases with ERBB2 CNG by NGS were breast (

CONCLUSIONS: ERBB2 …