A genomic test can help to find out if a cancer patient will benefit from chemotherapy or not, and if they do (high risk patients), further pre-tests like cell culture assays can help see what treatments have the best opportunity of being successful. A cell culture assay measures the response of the tumor cells to drug exposure. Following this exposure, one of these assays measures both cell metabolism and cell morphology (Whole Cell Profiling). The integrated effect of the drugs on the whole cell, resulting in a cellular response to the drug, measuring the interaction of the entire genome.
Cell culture assay technology has been clinically validated for the selection of optimal chemotherapy regimens for individual patients. It is a laboratory analysis based on tumor tissue profiling that uses fresh human tumor biopsy or surgical specimen to determine which drugs or combinations of chemotherapeutic agents have the highest likelihood of response for individual cancer patients.
Individualized assay-directed therapy is based on the premise that each patient's cancer cells are unique and therefore will respond differently to a given treatment. This is in stark contrast to standard or empiric therapy, which chemotherapy for a specific patient is based on average population studies from prior clinical trials.
ASCO's 2004 position paper focused on an older cell-growth assay method and not on a newer cell-death method, which is the most relevant biological measure. Their panel made no attempt to distinguish cell-death from cell-growth techniques. Their conclusions simply did not apply to cell-death assays. In fact, cell-death assay results have consistently correlated with response, time to progression, and overall survival.
The ASCO paper focused solely on a lack of prospective, randomized clinical trials proving superior outcomes with assay-directed therapy, a standard not met by ER/PR testing, HER2 protein or gene analysis, or any other clinical test in cancer medicine, and has seldom been met by even the eimpiric chemotherapy treatments supported by ASCO. Were they to apply the standard measure of predictive test accuracy, the results of their analysis would have been much different and in favor of the use of cell-death assays in clinical practice.
This omission was so significant that Medicare contractor, National Heritage Insurance Company (NHIC) which spent six months reviewing everything about the cell culture assay, including all of the ASCO arguments, and upon reviewing all available information, approved Medicare coverage for the tests as Oncologic in Vitro Chemoresponse Assays. They made the courageous decision to reverse trend and noted that the ASCO paper had failed the consider any of the many studies which support the predictive accuracy of cell death-based in vitro chemosensitivity testing.
As part of this favorable coverage decision, NHIC carefully documented the historical progression of Medicare policy dating from the "colony assays" of the 1970's to the noncoverage-National Coverage Decision regarding "stem cell" assays (1980), to the 1999 National Medicare Coverage Advisory Committee review, to the initial coverage by NHIC in the late 2000, to the present comprehensive review, culminating in this favorable Local Coverage Decision.
The decision had been made that the assay is a perfectly appropriate medical service, worthy of coverage on a non-investigational basis. What is of particular significance is that they are finally abandoning the artificial distinction between "resistance" testing and "sensitivity" testing and are providing coverage for the whole FDA-approved kit.
Cell cuture assay tests based on cell-death have proven very effective in identifying novel treatment combinations for a variety of cancers. It is unfortunate that ASCO had not carried out studies to assess the value of cell-death assays, because they can and do accurately predict clinical outcomes and define novel chemotherapeutic synergies. In many cases, these same tests have induced highly durable remissions in patients whom current medical literature have deemed otherwise hopeless.
(Note) Medicare coverage is available for Chemosensitivity (Resistance) Testing for a tumor specimen from a Medicare patient obtained anywhere within the United States, but submitted for testing by one of the approved laboratories located within California.
The payment provided will be sufficiently realistic that all Medicare patients for whom this testing is indicated will be able to get it with only the routine 20% co-payment, as Medi-gap insurance secondaries are mandated to provide payment for co-pays for Medicare-approved services.