ABSTRACT
Uveal melanoma (UM) metastasises in ~50% of patients, most frequently to the liver. Surveillance imaging can provide early detection of hepatic metastases; however, guidance regarding UM patient risk stratification for surveillance is unclear. This study compared sensitivity and specificity of four current prognostic systems, when used for risk stratification for surveillance, on patients treated at the Liverpool Ocular Oncology Centre (LOOC) between 2007-2016 (n = 1047). It found that the Liverpool Uveal Melanoma Prognosticator Online III (LUMPOIII) or Liverpool Parsimonious Model (LPM) offered greater specificity at equal levels of sensitivity than the American Joint Committee on Cancer (AJCC) system or monosomy 3 alone, and suggests guidance to achieve 95% sensitivity and 51% specificity (i.e., how to detect the same number of patients with metastases, while reducing the number of negative scans). For example, 180 scans could be safely avoided over 5 years in 200 patients using the most specific approach. LUMPOIII also offered high sensitivity and improved specificity over the AJCC in the absence of genetic information, making the result relevant to centres that do not perform genetic testing, or where such testing is inappropriate or fails. This study provides valuable information for clinical guidelines for risk stratification for surveillance in UM.
ABSTRACT
New approaches to drug discovery are unlocking enormous therapeutic potential residing in cancer-specific molecules. Brachyury is emerging as an exciting new drug target for the rare bone cancer chordoma. Here, recent advances targeting Brachyury in chordoma are discussed and how these might open doors to the targeting of other, more common cancer types.
Subject(s)
Antineoplastic Agents/pharmacology , Biomarkers, Tumor/antagonists & inhibitors , Bone Neoplasms/drug therapy , Chordoma/drug therapy , Fetal Proteins/antagonists & inhibitors , T-Box Domain Proteins/antagonists & inhibitors , Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/analysis , Biomarkers, Tumor/metabolism , Bone Neoplasms/diagnosis , Bone Neoplasms/pathology , Chordoma/diagnosis , Chordoma/pathology , Computer Simulation , Crystallography, X-Ray , Drug Discovery , Fetal Proteins/analysis , Fetal Proteins/metabolism , Fetal Proteins/ultrastructure , Humans , Models, Molecular , Protein Domains , T-Box Domain Proteins/analysis , T-Box Domain Proteins/metabolism , T-Box Domain Proteins/ultrastructureABSTRACT
Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy with a well recognized propensity for aggressive bone erosions. In some individuals, however, periarticular bone mineralization is maintained, and there is often associated new bone formation with periostitis and frank ankylosis; thus PsA manifests, in different individuals, reciprocal patterns of joint pathology suggesting a disorder of bone remodeling. Recent key scientific advances will be briefly reviewed including T cell, B cell, human leukocyte antigen associations; and the importance of neoangiogenesis, vascularity, and adhesion molecules in conjunction with inflammatory infiltrates and cytokine expression. Finally, the mechanisms of abnormal bone remodeling are discussed, including mediators of osteoclastogenesis such as RANK ligand and molecular signaling pathways including Dickkop-1 and bone morphogenetic proteins. Although much has been learned about the pathogenesis of PsA, much remains to be defined regarding the mechanisms linking synovial biology and immunopathology to different disease outcomes. Identifying key differentiating factors between the diverse PsA phenotypes, correlating findings with the rapidly advancing field of ultrasound image acquisition, and delineating the cellular and molecular mechanisms of abnormal bone remodeling in combination should enable the development of improved prognostic algorithms. This in turn should facilitate the targeting of expensive (about pound10k/patient/year) and potentially toxic yet effective biologics to patients most in need.
