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Opportunity and Pitfalls in Cancer Prediction, Prognosis and Prevention. Richard Simon, D.Sc. Chief, Biometric Research Branch National Cancer Institute http://brb.nci.nih.gov. Kinds of Biomarkers. Prognostic biomarkers
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Richard Simon, D.Sc.
Chief, Biometric Research Branch
National Cancer Institute
Most prognostic factor studies use a heterogeneous convenience sample of patients based on tissue availability. Often the patients have been previously treated with various types of chemotherapy and so it is not possible to focus the analysis on patients who would have such good prognosis with only local surgery/xrt that chemotherapy is not needed.
To discover a marker or signature predictive of survival or disease-free survival benefit of treatment T relative to control C, you should ideally examine specimens from patients in a randomized clinical trial comparing T to C
Because of the long time between first mutation and clinical diagnosis of human solid tumors, there would seem to be great opportunity for early detection
Most studies of early detection markers are based on a convenience sample of diagnostic tumor tissue from cancer patients and non cancer tissue from controls.
“With the appropriate informatic analyses and experimental design, the depth and breadth of sequencing available on the next-generation platforms will provide the tools to reconstruct clonal interrelationships of cancer cell populations, with relevance to identifying and tracking subpopulations of cells responsible for drug resistance, invasion, metastasis, and relapse, as well as annotating the genuinely initiating genetic lesions.”
Cross validation is only valid if the test set is not used in any way in the development of the model. Using the complete set of samples to select genes violates this assumption and invalidates cross-validation.
In order to bridge the valley of death new approaches to cancer research are needed