Detection and treatment of disease exhibiting disease cell heterogeneity and systems and methods for communicating test results

Abstract

This disclosure provides, among other things, methods for generating and applying therapeutic interventions. The methods involve, for example, (a) sequencing polynucleotides from cancer cells from a subject; (b) identifying and quantifying somatic mutations in the polynucleotides; (c) developing a profile of tumor heterogeneity in the subject indicating the presence and relative quantity of a plurality of the somatic mutations in the polynucleotides, wherein different relative quantities indicates tumor heterogeneity; and (d) determining a therapeutic intervention for a cancer exhibiting the tumor heterogeneity, wherein the therapeutic intervention is effective against a cancer having the profile of tumor heterogeneity determined.

What is claimed is: 
     
         1 . A method of treating a subject having cancer, the method comprising:
 using a database to identify one or more effective therapeutic interventions for the subject having the cancer, which cancer comprises one or more somatic alterations detected by sequencing a plurality of tagged polynucleotides that comprise molecular barcodes to generate a set of sequencing reads, wherein the plurality of tagged polynucleotides is derived from cell-free nucleic acid (cfDNA) molecules from the subject and wherein the one or more somatic alterations are identified from the set of sequencing reads, and wherein the database comprises, for each of a plurality of subjects comprising at least 50 subjects having the cancer, tumor genomic testing data comprising (i) one or more of the somatic alterations from cfDNA samples collected at two or more time intervals per subject, (ii) one or more therapeutic interventions administered to each of the subjects at one or more times and (iii) efficacy of the therapeutic interventions; and,   administering to the subject the one or more identified effective therapeutic interventions, thereby treating the subject having the cancer.   
     
     
         2 . The method of  claim 1 , wherein the plurality of subjects comprises at least 500 or at least 5000 subjects. 
     
     
         3 . The method of  claim 1 , wherein the tumor genomic testing data further comprises somatic alterations from tissue samples, cell-free ribonucleic acid (cfRNA), or circulating tumor cells. 
     
     
         4 . The method of  claim 1 , wherein relative frequencies of detected genetic variants are used to classify treatment efficacy. 
     
     
         5 . The method of  claim 1 , wherein treatment response per patient is collected and classified quantitatively through additional testing. 
     
     
         6 . The method of  claim 1 , comprising classifying effectiveness of treatment using a classification algorithm. 
     
     
         7 . The method of  claim 6 , wherein the classification algorithm comprises linear regression processes, binary decision trees, artificial neural networks, discriminant analyses, logistic classifiers, and/or support vector classifiers. 
     
     
         8 . The method of  claim 1 , wherein identified therapeutic interventions are stratified by efficacy. 
     
     
         9 . The method of  claim 1 , wherein quantitative bounds on predicted therapeutic interventions efficacy or lack thereof are reported. 
     
     
         10 . The method of  claim 1 , wherein the therapeutic interventions use information of predicted tumor genomic evolution or acquired resistance mechanisms in similar patients in response to treatment. 
     
     
         11 . The method of  claim 1 , wherein the database comprises other clinically relevant information comprising CT scans, MM scans, ultrasound scans, bone scans, PET scans, bone marrow tests, barium X-rays, endoscopies, lymphangiograms, intravenous urograms (IVU), IV pyelograms (IVP), lumbar punctures, cystoscopy, immunological tests, and/or cancer marker tests. 
     
     
         12 . The method of  claim 1 , wherein the database comprises other clinically relevant information comprising weight, adverse effects, histological testing, blood testing, radiographic information, prior treatments, and/or cancer type. 
     
     
         13 . The method of  claim 1 , wherein the database comprises other clinically relevant information comprising results of laboratory tests, medical imaging data, and/or medical procedures directed to diagnosing the condition, providing a prognosis, monitoring the progression of the disease, determining relapse or remission, or combinations thereof. 
     
     
         14 . The method of  claim 13 , wherein the laboratory tests comprise analysis of genetic variants, metabolic panel, and/or complete blood count. 
     
     
         15 . The method of  claim 1 , wherein the one or more identified effective therapeutic interventions are effective against a tumor exhibiting tumor heterogeneity. 
     
     
         16 . The method of  claim 1 , wherein the one or more identified effective therapeutic interventions comprise administering, in combination or in series, a plurality of drugs. 
     
     
         17 . The method of  claim 16 , wherein each drug is relatively more effective against a cancer presenting with a different one of somatic mutations that occur at different relative frequency. 
     
     
         18 . The method of  claim 16 , wherein a drug that is relatively more effective against a cancer presenting with a somatic mutation occurring at higher relative frequency is administered in a higher amount. 
     
     
         19 . The method of  claim 16 , wherein the drugs are delivered at doses that are stratified to reflect relative amounts of variants in DNA from the subject. 
     
     
         20 . A method of treating a subject having cancer, the method comprising:
 selecting the subject having the cancer, which cancer comprises one or more somatic alterations detected by sequencing a plurality of tagged polynucleotides that comprise molecular barcodes to generate a set of sequencing reads, wherein the plurality of tagged polynucleotides is derived from cell-free nucleic acid (cfDNA) molecules from the subject and wherein the one or more somatic alterations are identified from the set of sequencing reads; and,   administering to the subject one or more effective therapeutic interventions identified using a database to identify the one or more effective therapeutic interventions for the subject having the cancer, wherein the database comprises, for each of a plurality of subjects comprising at least 50 subjects having the cancer, tumor genomic testing data comprising (i) one or more of the somatic alterations from cfDNA samples collected at two or more time intervals per subject, (ii) one or more therapeutic interventions administered to each of the subjects at one or more times and (iii) efficacy of the therapeutic interventions, thereby treating the subject having the cancer.