Lung Squamous Cell Carcinoma mRNA Expression Subtypes Are Reproducible, Clinically Important, and Correspond to Normal Cell Types

Lung squamous cell carcinoma (SCC) is clinically and genetically heterogeneous and current diagnostic practices do not adequately substratify this heterogeneity. A robust, biologically-based SCC subclassification may describe this variability and lead to more precise patient prognosis and management. We sought to determine if SCC mRNA expression subtypes exist, are reproducible across multiple patient cohorts, and are clinically relevant

Correction: Molecular Subtypes in Head and Neck Cancer Exhibit Distinct Patterns of Chromosomal Gain and Loss of Canonical Cancer Genes

Head and neck squamous cell carcinoma (HNSCC) is a frequently fatal heterogeneous disease. Beyond the role of human papilloma virus (HPV), no validated molecular characterization of the disease has been established. Using an integrated genomic analysis and validation methodology we confirm four molecular classes of HNSCC (basal, mesenchymal, atypical, and classical) consistent with signatures established for squamous carcinoma of the lung, including deregulation of the KEAP1/NFE2L2 oxidative stress pathway, differential utilization of the lineage markers SOX2 and TP63, and preference for the oncogenes PIK3CA and EGFR. For potential clinical use the signatures are complimentary to classification by HPV infection status as well as the putative high risk marker CCND1 copy number gain. A molecular etiology for the subtypes is suggested by statistically significant chromosomal gains and losses and differential cell of origin expression patterns. Model systems representative of each of the four subtypes are also presented

Verteporfin photodynamic therapy cohort study: report 1: effectiveness and factors influencing outcomes.

PURPOSE: To compare the visual outcomes after verteporfin photodynamic therapy (VPDT) administered in routine clinical practice with those observed in the Treatment of Age-related macular degeneration with Photodynamic therapy (TAP) trials and to quantify the effects of clinically important baseline covariates on outcome. DESIGN: A prospective longitudinal study of patients treated with VPDT in 45 ophthalmology departments in the United Kingdom with expertise in the management of neovascular age-related macular degeneration (nAMD). PARTICIPANTS: Patients with wholly or predominantly classic choroidal neovascularization (CNV) of any cause with a visual acuity >or=20/200 in the eye to be treated. METHODS: Refracted best-corrected visual acuity (BCVA) and contrast sensitivity were measured in VPDT-treated eyes at baseline and subsequent visits. Eyes were retreated at 3 months if CNV was judged to be active. Baseline angiograms were graded to quantify the percentages of classic and occult CNV. Treated eyes were categorized as eligible or ineligible for TAP, or unclassifiable. MAIN OUTCOME MEASURES: Best-corrected visual acuity and contrast sensitivity during 1 year of follow-up after initial treatment. RESULTS: A total of 7748 treated patients were recruited. Data from 4043 patients with a diagnosis of nAMD were used in the present analysis. Reading center determination of lesion type showed that 87% were predominantly classic CNV. Eyes received 2.4 treatments in year 1 and 0.4 treatments in year 2. Deterioration of BCVA over 1 year was similar to that observed in the VPDT arms of the TAP trials and was not influenced by TAP eligibility classification. Best-corrected visual acuity deteriorated more quickly in current smokers; with increasing proportion of classic CNV, increasing age, and better baseline BCVA; and when the fellow eye was the better eye. CONCLUSIONS: Patients in the cohort who would have been eligible for the TAP trials demonstrated deterioration in BCVA similar to VPDT-treated TAP participants but with fewer treatments. Clinical covariates with a significant impact on BCVA outcomes were identified

The double layer sign is highly predictive of progression to exudation in age-related macular degeneration

PURPOSEThe presence of a double layer sign (DLS) and a shallow irregular RPE elevation (SIRE) were investigated using spectral domain-optical coherence tomography (SD-OCT) imaging to determine their ability to predict progression to exudative macular neovascularization (eMNV) in the unaffected fellow eyes (study eye) of participants with Age-Related Macular Degeneration (AMD) with newly diagnosed unilateral eMNV. DESIGNRetrospective, re-analysis of SD-OCT scans of study eyes from the Early detection of Neovascular AMD (EDNA) study with 3 years follow-up (FU). PARTICIPANTSThe EDNA study repository of SD-OCT scans was assessed for inclusion. Cases with incomplete datasets, low quality scans or exhibiting other pathology were excluded, which resulted in 459 eligible cases. METHODSSD-OCT volume scans of study eyes were graded for irregular elevation of the RPE (IE), length and height measurements made on the most affected B-scan. Eyes with heterogeneous reflectivity within the IE were classified as exhibiting the DLS. Eyes with DLS where the length of separation between RPE and Bruch's was equal or exceeded 1000 μm in length and less than 100 μm in height were sub-classified as SIRE. MAIN OUTCOME MEASURESHazard of progression to eMNV for DLS and SIRE RESULTS: Of the 459 eyes, 268 had IE in which 101 were DLS-like and 51 of these also fulfilled criteria for SIRE. Over the 3 years FU period, 104 (23%) eyes progressed to eMNV. After a follow up of 18 months, a significantly higher proportion of study eyes (p<0.001) with IE, DLS and SIRE developed eMNV compared with those without these features (IE: 17% vs no IE 6.3%; DLS: 23% vs no DLS 9.9%; SIRE: 22% vs no SIRE 11%). In the adjusted Cox regression models, a significantly greater hazard of progression (p<0.001) was associated with the presence of IE (adjHR, 3.01, 95%CI 1.88, 4.82), DLS (adjHR, 3.41, 95%CI 2.26, 5.14) or SIRE (adjHR, 2.83, 95%CI 1.68, 4.75). CONCLUSIONThe DLS is a highly sensitive predictor of progression to eMNV and the use of SIRE does not improve predictability