Methods and algorithms for aiding in the detection of cancer

Abstract

A method of data interpretation from a multiplex cancer assay is described. The aggregate normalized score from the assay is transformed to a quantitative risk score quantifying a human subject's increased risk for the presence of cancer as compared to the known prevalence of the cancer in the population before testing the subject.

What is claimed is: 
     
         1 . A method of determining a risk level for the presence of a cancer in an asymptomatic human subject relative to a population, comprising:
 measuring at least one cancer marker in a sample from the human subject and normalizing measured values, wherein the at least one cancer marker is from a panel of markers associated with the presence of the cancer;   summing each normalized value to obtain a composite score; and,   matching the composite score to a predetermined risk score, whereby the risk level for the presence of the cancer in an asymptomatic human subject has been determined.   
     
     
         2 . The method of  claim 1 , wherein the cancer is selected from lung cancer, kidney cancer, breast cancer, bile duct cancer, bone cancer, pancreatic cancer, cervical cancer, colon cancer, colorectal cancer, gallbladder cancer, liver or hepatocellular cancer, ovarian cancer, testicular cancer, lobular carcinoma, prostate cancer, and skin cancer or melanoma. 
     
     
         3 . The method of  claim 1 , wherein the cancer is lung cancer. 
     
     
         4 . The method of  claim 1 , wherein the panel of markers comprise two of more markers selected from CEA, CA125, Cyfra 21-1, Pro-GRP, anti-NY-ESO-1, anti-p53, anti-Cyclin E2 and anti-MAPKAPK3. 
     
     
         5 . The method of  claim 1 , wherein the normalizing comprises determining the multiple of median (MoM) score for each marker. 
     
     
         6 . The method of  claim 1 , wherein the predetermined risk score is obtained from a grouping of a stratified human subject population comprising at least three risk categories wherein each risk category comprises a risk score correlated to a range of composite scores. 
     
     
         7 . The method of  claim 1 , wherein the predetermined risk score is determined from retrospective clinical samples. 
     
     
         8 . The method of  claim 6 , wherein the risk category further comprises a risk identifier. 
     
     
         9 . The method of  claim 8 , wherein the risk identifier is selected from low risk, intermediate-low risk, intermediate risk, intermediate-high risk and highest risk. 
     
     
         10 . The method of  claim 1 , wherein the predetermined risk score is obtained from a risk categorization table comprising a risk value correlated to a range of composite scores. 
     
     
         11 . The method of  claim 1 , further comprising weighting the measured values of the markers. 
     
     
         12 . The method of  claim 1 , wherein the risk score is provided to a physician as the human subject's increased risk of having the presence of the cancer relative to a rate of having the cancer in a same cohort before testing. 
     
     
         13 . A method of assessing the likelihood that a patient has lung cancer relative to a population comprising the steps of:
 (i) obtaining a fluid sample from said patient;   (ii) measuring the levels of multiple biomarkers in said sample;   (iii) calculating a composite score from said biomarker measurements;   (iv) comparing said patient composite score to the composite scores of persons known to be at a high and a low risk for lung cancer; and   (v) determining the level of risk of the patient for having lung cancer relative to the population.   
     
     
         14 . The method of  claim 13 , wherein the patient and the population are over age 50 and have had a history of smoking cigarettes. 
     
     
         15 . The method of  claim 14 , wherein the smoking history comprises at least about a 20 pack year smoking history. 
     
     
         16 . The method of  claim 13 , wherein the multiple biomarkers comprise two of more markers selected from CEA, CA125, Cyfra 21-1, Pro-GRP, anti-NY-ESO-1, anti-p53, anti-Cyclin E2 and anti-MAPKAPK3. 
     
     
         17 . The method of  claim 13 , wherein the composite score of the patient is compared to the composite score of patients in at least three categories comprising those at high, intermediate, and low risk. 
     
     
         18 . The method of  claim 13 , wherein the composite score of the patient is compared to the composite score of patients in at least five categories comprising those at highest, intermediate high risk, intermediate risk, intermediate low risk, and low risk. 
     
     
         19 . A method of determining a risk level for the presence of lung cancer in an asymptomatic human subject relative to a population, comprising:
 measuring a panel of markers in a human subject;   determining a multiple of median (MoM) score for each marker;   summing the MoM score to obtain a composite score for each human subject, quantifying the increased risk for the presence of the cancer for the human subject as a risk score, wherein the composite score is matched to a risk category of a grouping of stratified human subject populations wherein each risk category comprises a multiplier indicating increased likelihood of having the lung cancer correlated to a range of composite scores; and,   providing a risk score for the human subject, whereby the quantified increased risk for the presence of the lung cancer in an asymptomatic human subject has been determined.   
     
     
         20 . The method of  claim 19 , wherein the panel of markers is selected wherein the panel of markers comprise two of more markers selected from CEA, CA125, Cyfra 21-1, Pro-GRP, anti-NY-ESO-1, anti-p53, anti-Cyclin E2 and anti-MAPKAPK3. 
     
     
         21 . The method of  claim 19 , wherein the panel of markers is selected from CEA, CA125, Cyfra 21-1, anti-NY-ESO-1, anti-p53 and anti-MAPKAPK3. 
     
     
         22 . The method of  claim 19 , wherein the sample is blood, blood serum, blood plasma, or some part thereof. 
     
     
         23 . The method of  claim 19 , wherein the grouping of a stratified human subject population, the multiplier indicating increased likelihood of having the cancer and the range of composite scores are determined from retrospective clinical samples of a population. 
     
     
         24 . The method of  claim 19 , wherein the risk category further comprises a risk identifier. 
     
     
         25 . The method of  claim 24 , wherein the risk identifier is selected from low risk, intermediate-low risk, intermediate risk, intermediate-high risk and highest risk. 
     
     
         26 . The method of  claim 19 , wherein calculating the multiplier indicating increased likelihood of having the cancer for each risk category comprises stratifying the human cohort based on retrospective MoM scores and weighting a known prevalence of the cancer in the cohort by a positive predictive score for each stratified population. 
     
     
         27 . The method of  claim 19 , wherein the grouping of a stratified human subject population comprises at least three risk categories wherein the multiplier indicating increased likelihood of having cancer is about 2 or greater. 
     
     
         28 . The method of  claim 19 , wherein the grouping of a stratified human subject population comprises at least two risk categories wherein the multiplier indicating increased likelihood of having cancer is about 5 or greater. 
     
     
         29 . The method of  claim 19 , wherein the human subject is aged 50 years or older and has a history of smoking tobacco. 
     
     
         30 . A method of determining a quantified increased risk for the presence of lung cancer in an asymptomatic human subject, comprising:
 measuring at least one cancer marker in a sample from the human subject, wherein the human subject is at least 50 years of age or older and has a history of smoking tobacco and wherein the at least one cancer marker is selected from CEA, CA125, Cyfra 21-1, Pro-GRP, anti-NY-ESO-1, anti-p53, anti-Cyclin E2 and anti-MAPKAPK3;   determining a multiple of median (MoM) score for each marker measured in the sample;   summing the MoM score to obtain a composite score for each human subject, quantifying the increased risk for the presence of the lung cancer for the human subject as a risk score, wherein the composite score is matched to one of at least three risk categories of a grouping of stratified human subject populations wherein each risk category comprises a multiplier indicating increased likelihood of having the lung cancer correlated to a range of composite scores; and,   providing a risk score for the human subject, whereby the quantified increased risk for the presence of the lung cancer in an asymptomatic human subject has been determined.   
     
     
         31 . The method of  claim 30 , wherein the panel of markers is selected from CEA, CA125, Cyfra 21-1, anti-NY-ESO-1, anti-p53 and anti-MAPKAPK3. 
     
     
         32 . The method of  claim 30 , wherein the sample is blood, blood serum, blood plasma, or a component thereof. 
     
     
         33 . The method of  claim 30 , wherein the composite score of the human subject is compared to the composite score of human subjects in at least three risk categories comprising those at high, intermediate, and low risk. 
     
     
         34 . The method of  claim 30 , wherein the composite score of the human subject is compared to the composite score of human subjects in at least five categories comprising those at highest, intermediate high risk, intermediate risk, intermediate low risk, and low risk. 
     
     
         35 . The method of  claim 30 , wherein the risk score is provided to a physician as the human subject's increased risk of having the presence of the cancer relative to a population before testing. 
     
     
         36 . The method of  claim 30 , wherein calculating the multiplier indicating increased likelihood of having the cancer for each risk category comprises stratifying the human cohort based on retrospective MoM scores and weighting a known prevalence of the cancer in the cohort by a positive predictive score for each stratified population. 
     
     
         37 . The method of  claim 30 , wherein the history of smoking tobacco comprises smoking at least 20 packs a year. 
     
     
         38 . A grouping of a stratified human subject cohort used to assess a risk level for the presence of a cancer in an asymptomatic human subject relative to a population, comprising:
 at least three risk categories, wherein each risk category comprises a risk score, a risk identifier and a range of composite scores,   wherein a human subject's risk score is determined by comparing the human subject's calculated composite score to the range of composite scores which are correlated to a predetermined risk score.   
     
     
         39 . The grouping of a stratified human subject cohort of  claim 38 , wherein the risk identifier is selected from low risk, intermediate-low risk, intermediate risk, intermediate-high risk and highest risk. 
     
     
         40 . The grouping of a stratified human subject cohort of  claim 38 , wherein risk score comprises a multiplier indicating increased likelihood of having the cancer calculated for each risk category comprising stratifying the human population based on retrospective MoM scores and weighting a known prevalence of the cancer in the cohort by a positive predictive score for each stratified population. 
     
     
         41 . The grouping of stratified human subject populations of  claim 38 , wherein the composite scores are a sum of multiple of median (MoM) scores determined from a panel of markers for the cancer. 
     
     
         42 . The grouping of stratified human subject populations of  claim 38 , wherein the range of composite scores are derived from retrospective clinical samples. 
     
     
         43 . The grouping of stratified human subject populations of  claim 38 , wherein the groupings are in a form selected from a table form, a software application, a computer program, and an excel spreadsheet. 
     
     
         44 . The grouping of stratified human subject populations of  claim 38 , wherein the cancer is lung cancer and the range of composite scores were generated by measuring a panel of markers from retrospective clinical samples, wherein the panel of markers is selected from CEA, CA125, Cyfra 21-1, Pro-GRP, anti-NY-ESO-1, anti-p53, anti-Cyclin E2 and anti-MAPKAPK3. 
     
     
         45 . The grouping of stratified human subject populations of  claim 38 , wherein the measured marker values were further normalized and summed to generate the range of composite scores. 
     
     
         46 . A kit for use to assess a risk level for the presence of a cancer in an asymptomatic human subject relative to a population, comprising:
 reagents for measuring at least one cancer marker in a sample from the human subject;   a risk categorization table; and   an algorithm for determining a composite score for each sample and correlating to a predetermined risk score of the Risk Categorization Table, whereby the risk level for the presence of the cancer in an asymptomatic human subject relative to a population has been determined.   
     
     
         47 . The kit of  claim 46 , wherein the risk categorization table and algorithm are in a form of a software application, computer program or paper instructions for calculating the risk level of the presence of cancer in the human subject relative to a population. 
     
     
         48 . The kit of  claim 46 , wherein the cancer is selected from lung cancer, kidney cancer, breast cancer, bile duct cancer, bone cancer, pancreatic cancer, cervical cancer, colon cancer, colorectal cancer, gallbladder cancer, liver or hepatocellular cancer, ovarian cancer, testicular cancer, lobular carcinoma, prostate cancer, and skin cancer or melanoma. 
     
     
         49 . The kit of  claim 46 , wherein the cancer is lung cancer. 
     
     
         50 . The kit of  claim 46 , wherein the reagents are selected from antigens and antibodies for measuring biomarkers.