The Validity Of Diagnostic Testing

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Author	4/5/2007 2:20:59 PM
gdpawel Registered User Location: Pennsylvania Joined: 4/22/2006 Posts: 57 Offline	The traditional criteria ever used to evaluate laboratory tests has been the predictive "accuracy" of the test. None of the available laboratory tests used in the selection of treatments for cancer patients have ever been tested for "efficacy." This includes estrogen receptor, progesterone receptor, Her2/neu, Oncotype DX, MammaPrint, EGFR amplification/mutation, immunohistochemical (IHC) staining for tumor classification, Cell Culture Assays, Bacterial Culture and Sensitivity Testing, CT, MRI and Pet Scans to measure tumor response to treatment. The only data supporting any of them relate to test "accuracy." Oncotype Dx and MammaPrint, laboratory tests, are a tool for the oncologist. The oncologist should take advantage of all the tools available to him/her to treat a patient. And since studies show that only 20-30% of patients do respond to chemotherapy that is available to them, there should be due consideration to looking at the advantage of molecular and cellular assay tests to the resistance that has been found to chemotherapy drugs. The MammPrint, looking at the expression of 70 genes linked to breast cancer, can accurately assess a patient's risk of recurrence or death. The correlations of this are vastly superior to those obtained with standard prognostic markers. The 70 genes in a woman's tumor analyzed by MammaPrint predict the 10-year survival of the patient at a significance level over three times greater than existing methods and with an accuracy level of 96.7% as determined by a study published in the New England Journal of Medicine. Existing methods can't distinguish the patients with a high risk for recurrence from those with low risk with comparable accuracy. This new gene expression profiling test enables the oncologist and breast surgeon to more accurately determine who should be treated. These tests have been shown to be superior over conventional assessment of risk of future metastatic disease, such as histological assessment of tumor aggressiveness (by grade). However, one gets more accurate information when using intact RNA isolated from "fresh" tissue than from using degraded RNA, which is present in paraffin-fixed tissues. These tests have enormous implications for the short-term future of cancer research in general, and is one of the truly great cancer breakthroughs of our time. The DNA microarray test will prove to be highly complementary to the parellel breakthrough efforts in targeted therapy through cell culture assays like the EGFRx™ Assay. For the vast majority of cancer patients, the cancer will not recur regardless of whether they receive chemotherapy. So they are exposed needlessly to the treatment, which can cause myelosuppression, mucositis, cardiac problems, peripheral neuropathy, central neurotoxicity, or leukemia. Doctors cannot tell, however, which patients need chemotherapy. These new genomic tests are supposed to tell physicians which cancer patients will benefit from chemotherapy and which ones do not need to be unnecessarily exposed to toxic chemotherapy cocktails. Because of this, there is a good portion of cancer patients that are either undertreated or overtreated because there was no adequate information on who will recur. The Oncotype DX and MammaPrint can enhance the ability to distinguish between low risk and high risk patients. However, these tests do not predict which patients will benefit from chemotherapy (i.e. which patients are chemosensitive). These tests don't do anything to indicate if chemotherapy would or would not be helpful for those patients at higher risk for recurrence, much less which chemotherapy would be most likely to be helpful. A genomic test can help to find out if a cancer patient will benefit from chemotherapy or not, and if they do, Cell Culture Assays can help see what treatments have the best oportunity of being successful. Patients in the high-risk group, who would benefit from chemotherapy can be pre-tested to see what treatments have the best opportunity of being successful, and offers a better chance of tumor response resulting in progression-free survival, while those in the lower-risk groups can be spared the unnecessary toxicity, particularly associated with ineffective treatment. Cell Culture Assays (like the EGFRx™ Assay) can report prospectively to a physician specifically which chemotherapy agent would benefit a high risk cancer patient by testing that patient’s "live" cancer cells. Drug sensitivity profiles differ significantly among cancer patients even when diagnosed with the same cancer. Knowing the drug sensitivity profile of a specific cancer patient allows the treating oncologists to prescribe chemotherapy that will be the most effective against the tumor cells of that patient. Every breast cancer patient should have her own unique chemotherapy trial based on consultation of pathogenic profiles and drug sensitivity testing data. Research and application of these tests are being encouraged by growing patient demands, scientific advances and medical ethics. These tests are not a luxury but an absolute necessity, and a powerful strategy that cannot be overlooked.
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Author	12/2/2007 2:02:43 AM
gdpawel Registered User Location: Pennsylvania Joined: 4/22/2006 Posts: 57 Offline	In chemotherapy selection, Gene and Protein testing examine a single process within the cell or a relatively small number of processes. The aim is to tell if there is a theoretical predisposition to drug response. Whole Cell Functional Profiling tests not only for the presence of genes and proteins but also for their functionality, for their interaction with other genes, proteins, and processes occurring within the cell, and for their response to anti-cancer drugs. Genes create the blueprints for the production of proteins within the cell. A protein is a molecule that makes a cell behave in a certain way. It does so by interacting with other proteins in a complex series of steps. The goal of Gene testing is to look for patterns of normal and abnormal gene expression which could suggest that certain proteins might or might not be produced within a cell. However, just because a gene is present it does not mean that an associated protein has been produced. Protein testing goes one step further by testing to see if the relevant protein actually has been produced. However, even Protein testing cannot tell us if a protein is functional or how it will interact with other proteins in the presence of anti-cancer drugs. Gene and Protein testing involve the use of dead, formaldehyde preserved cells that are never exposed to chemotherapy drugs. Gene and Protein tests cannot tells us anything about uptake of a certain drug into the cell or if the drug will be excluded before it can act or what changes will take place within the cell if the drug successfully enters the cell. Gene and Protein tests cannot discriminate among the activities of different drugs within the same class. Instead, Gene and Protein tests assume that all drugs within a class will produce precisely the same effect, even though from clinical experience, this is not the case. Nor can Gene and Protein tests tell us anything about drug combinations. "Whole Cell" Functional Tumor Cell Profiling tests living cancer cells. Functional Tumor Cell Profiling assesses the net result of all cellular processes, including interactions, occurring in real time when cancer cells actually are exposed to specific anti-cancer drugs. Functional Tumor Cell Profiling can discriminate differing anti-tumor effects of different drugs within the same class. Functional Profiling can also identify synergies in drug combinations. Gene and Protein tests are better suited for ruling out "inactive" drugs than for identifying "active" drugs. When considering a cancer drug which is believed to act only upon cancer cells that have a specific genetic defect, it is useful to know if a patient's cancer cells do or do not have precisely that defect. Although presence of a targeted defect does not necessarily mean that a drug will be effective, absence of the targeted defect may rule out use of the drug. Of course, this assumes that the mechanism of drug activity is known beyond any doubt, which is not always the case. Although Gene and Protein testing currently are limited in their reliability as clinical tools, the tests can be important in research settings such as in helping to identify rational targets for development of new anti-cancer drugs. As you can see, just selecting the right test to perform in the right situation is a very important step on the road to personalizing cancer therapy. * Edited 12/5/2007 5:25:53 AM UTC by gdpawel*
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Author

4/5/2007 2:20:59 PM

gdpawel
Registered User

Location: Pennsylvania
Joined: 4/22/2006
Posts: 57
Offline

The traditional criteria ever used to evaluate laboratory tests has been the predictive "accuracy" of the test. None of the available laboratory tests used in the selection of treatments for cancer patients have ever been tested for "efficacy." This includes estrogen receptor, progesterone receptor, Her2/neu, Oncotype DX, MammaPrint, EGFR amplification/mutation, immunohistochemical (IHC) staining for tumor classification, Cell Culture Assays, Bacterial Culture and Sensitivity Testing, CT, MRI and Pet Scans to measure tumor response to treatment. The only data supporting any of them relate to test "accuracy."

Oncotype Dx and MammaPrint, laboratory tests, are a tool for the oncologist. The oncologist should take advantage of all the tools available to him/her to treat a patient. And since studies show that only 20-30% of patients do respond to chemotherapy that is available to them, there should be due consideration to looking at the advantage of molecular and cellular assay tests to the resistance that has been found to chemotherapy drugs.

The MammPrint, looking at the expression of 70 genes linked to breast cancer, can accurately assess a patient's risk of recurrence or death. The correlations of this are vastly superior to those obtained with standard prognostic markers.

The 70 genes in a woman's tumor analyzed by MammaPrint predict the 10-year survival of the patient at a significance level over three times greater than existing methods and with an accuracy level of 96.7% as determined by a study published in the New England Journal of Medicine.

Existing methods can't distinguish the patients with a high risk for recurrence from those with low risk with comparable accuracy. This new gene expression profiling test enables the oncologist and breast surgeon to more accurately determine who should be treated.

These tests have been shown to be superior over conventional assessment of risk of future metastatic disease, such as histological assessment of tumor aggressiveness (by grade). However, one gets more accurate information when using intact RNA isolated from "fresh" tissue than from using degraded RNA, which is present in paraffin-fixed tissues.

These tests have enormous implications for the short-term future of cancer research in general, and is one of the truly great cancer breakthroughs of our time. The DNA microarray test will prove to be highly complementary to the parellel breakthrough efforts in targeted therapy through cell culture assays like the EGFRx™ Assay.

For the vast majority of cancer patients, the cancer will not recur regardless of whether they receive chemotherapy. So they are exposed needlessly to the treatment, which can cause myelosuppression, mucositis, cardiac problems, peripheral neuropathy, central neurotoxicity, or leukemia. Doctors cannot tell, however, which patients need chemotherapy. These new genomic tests are supposed to tell physicians which cancer patients will benefit from chemotherapy and which ones do not need to be unnecessarily exposed to toxic chemotherapy cocktails.

Because of this, there is a good portion of cancer patients that are either undertreated or overtreated because there was no adequate information on who will recur. The Oncotype DX and MammaPrint can enhance the ability to distinguish between low risk and high risk patients. However, these tests do not predict which patients will benefit from chemotherapy (i.e. which patients are chemosensitive).

These tests don't do anything to indicate if chemotherapy would or would not be helpful for those patients at higher risk for recurrence, much less which chemotherapy would be most likely to be helpful. A genomic test can help to find out if a cancer patient will benefit from chemotherapy or not, and if they do, Cell Culture Assays can help see what treatments have the best oportunity of being successful.

Patients in the high-risk group, who would benefit from chemotherapy can be pre-tested to see what treatments have the best opportunity of being successful, and offers a better chance of tumor response resulting in progression-free survival, while those in the lower-risk groups can be spared the unnecessary toxicity, particularly associated with ineffective treatment.

Cell Culture Assays (like the EGFRx™ Assay) can report prospectively to a physician specifically which chemotherapy agent would benefit a high risk cancer patient by testing that patient’s "live" cancer cells. Drug sensitivity profiles differ significantly among cancer patients even when diagnosed with the same cancer. Knowing the drug sensitivity profile of a specific cancer patient allows the treating oncologists to prescribe chemotherapy that will be the most effective against the tumor cells of that patient.

Every breast cancer patient should have her own unique chemotherapy trial based on consultation of pathogenic profiles and drug sensitivity testing data. Research and application of these tests are being encouraged by growing patient demands, scientific advances and medical ethics. These tests are not a luxury but an absolute necessity, and a powerful strategy that cannot be overlooked.

profile private message

Author

12/2/2007 2:02:43 AM

gdpawel
Registered User

Location: Pennsylvania
Joined: 4/22/2006
Posts: 57
Offline

In chemotherapy selection, Gene and Protein testing examine a single process within the cell or a relatively small number of processes. The aim is to tell if there is a theoretical predisposition to drug response.

Whole Cell Functional Profiling tests not only for the presence of genes and proteins but also for their functionality, for their interaction with other genes, proteins, and processes occurring within the cell, and for their response to anti-cancer drugs.

Genes create the blueprints for the production of proteins within the cell. A protein is a molecule that makes a cell behave in a certain way. It does so by interacting with other proteins in a complex series of steps.

The goal of Gene testing is to look for patterns of normal and abnormal gene expression which could suggest that certain proteins might or might not be produced within a cell. However, just because a gene is present it does not mean that an associated protein has been produced.

Protein testing goes one step further by testing to see if the relevant protein actually has been produced. However, even Protein testing cannot tell us if a protein is functional or how it will interact with other proteins in the presence of anti-cancer drugs.

Gene and Protein testing involve the use of dead, formaldehyde preserved cells that are never exposed to chemotherapy drugs. Gene and Protein tests cannot tells us anything about uptake of a certain drug into the cell or if the drug will be excluded before it can act or what changes will take place within the cell if the drug successfully enters the cell.

Gene and Protein tests cannot discriminate among the activities of different drugs within the same class. Instead, Gene and Protein tests assume that all drugs within a class will produce precisely the same effect, even though from clinical experience, this is not the case. Nor can Gene and Protein tests tell us anything about drug combinations.

"Whole Cell" Functional Tumor Cell Profiling tests living cancer cells. Functional Tumor Cell Profiling assesses the net result of all cellular processes, including interactions, occurring in real time when cancer cells actually are exposed to specific anti-cancer drugs. Functional Tumor Cell Profiling can discriminate differing anti-tumor effects of different drugs within the same class. Functional Profiling can also identify synergies in drug combinations.

Gene and Protein tests are better suited for ruling out "inactive" drugs than for identifying "active" drugs. When considering a cancer drug which is believed to act only upon cancer cells that have a specific genetic defect, it is useful to know if a patient's cancer cells do or do not have precisely that defect.

Although presence of a targeted defect does not necessarily mean that a drug will be effective, absence of the targeted defect may rule out use of the drug. Of course, this assumes that the mechanism of drug activity is known beyond any doubt, which is not always the case.

Although Gene and Protein testing currently are limited in their reliability as clinical tools, the tests can be important in research settings such as in helping to identify rational targets for development of new anti-cancer drugs.

As you can see, just selecting the right test to perform in the right situation is a very important step on the road to personalizing cancer therapy. *** Edited 12/5/2007 5:25:53 AM UTC by gdpawel***

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The Validity Of Diagnostic Testing