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ABSTRACT: We have recently witnessed an explosion in our understanding of melanoma. Knowledge of the molecular basis of melanoma and the successes of targeted therapies have pushed melanoma care to the precipice of a new era. Identification of significant pathways and oncogenes has translated to the development of targeted therapies, some of which have produced major clinical responses. In this review, we provide an overview of selected key pathways and melanoma oncogenes as well as the targeted agents and therapeutic approaches whose successes suggest the promise of a new era in melanoma and cancer therapy. Despite these advances, the conversion of transient remissions to stable cures remains a vital challenge. Continued progress towards a better understanding about the complexity and redundancy responsible for melanoma progression may provide direction for anti-cancer drug development.
The Journal of Pathology 01/2011; 223(2):241-50. · 6.32 Impact Factor
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ABSTRACT: Melanoma is one of the most aggressive and yet poorly understood of human malignancies. Advances in genomics has allowed a more nuanced understanding of the disease, moving beyond the traditional dysplastic nevus-to-melanoma model and identifying multiple divergent oncogenic pathways leading to melanoma. An understanding of the molecular mechanisms driving melanoma has opened the doors for the development of targeted therapeutic approaches. As we enter the era of personalized medicine, it will be critical for clinicians to both appreciate and be able to determine the molecular profile of their patients' melanoma because this profile will guide risk stratification, genetic counseling, and treatment customization. A review of the divergent pathways of melanoma development is presented here, with a particular emphasis on recently identified mutations, and their implications for patient care.
Seminars in cutaneous medicine and surgery 12/2010; 29(4):210-7. · 1.81 Impact Factor
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ABSTRACT: The purpose of this study was to prospectively assess the usefulness of computer-aided detection (CAD) in the interpretation of screening mammography and to provide the true sensitivity and specificity of this technique in a clinical setting.
Over a 26-month period, 5,016 screening mammograms were interpreted without, and subsequently with, the assistance of the iCAD MammoReader detection system. Data collected for actionable findings included dominant feature (calcification, mass, asymmetry, architectural distortion), detection method (radiologist only, CAD only, or both radiologist and CAD), BI-RADS assessment code, associated histopathology for those undergoing biopsy, and tumor stage for malignant lesions. The study population was cross-checked against an independent reference standard to identify false-negative cases.
Of the 5,016 cases, the recall rate increased from 12% to 14% with the addition of CAD. Of the 107 (2%) patients who underwent biopsy, 101 (94%) were prompted by the radiologist and six (6%) were prompted by CAD. Of the 124 biopsies performed on actionable findings in the 107 patients, findings in 79 (64%) were benign and in 45 (36%) were in situ or invasive carcinoma. Three study participants who were not recalled by the radiologist with the assistance of CAD developed cancer within 1 year of the screening mammogram and were considered to be false-negative cases. The radiologist detected 43 (90%) of the 48 total malignancies and 45 (94%) of the 48 malignancies with the assistance of CAD. CAD missed eight cancers that were detected by the radiologist, which presented as architectural distortions (n = 3), irregular masses (n = 4), and a circumscribed mass (n = 1). CAD detected two in situ cancers as a faint cluster of calcifications that had not been perceived by the radiologist and one mass that was dismissed by the radiologist, accounting for at least a 4.7% increase in cancer detection rate. Sensitivity of screening mammography with the use of CAD (94%) represented an absolute and relative 4% increase over the sensitivity of the radiologist alone (90%). Specificity of screening mammography with and without the use of CAD was 99%.
Routine use of CAD while interpreting screening mammograms significantly increases recall rates, has no significant effect on positive predictive value for biopsy, and can increase cancer detection rate by at least 4.7% and sensitivity by at least 4%. This study provides "true" values for sensitivity and specificity for use of CAD in interpretation of screening mammography as measured prospectively in the context of a working clinical setting.
American Journal of Roentgenology 01/2007; 187(6):1483-91. · 2.78 Impact Factor
