 Likewise, anti-angiogenesis drugs, which work by preventing new blood vessel formation in order to stall tumor growth, cannot be tested by tissue culture. 

<b>So the chemosensitivity tests cannot always predict that the tumor will respond to the chemotherapy drug.</b> The current prediction accuracy is about 60% to 69%... meaning that approximately 2/3 of the tumors designated as ''sensitive'' to a chemotherapy drug will respond to that drug. BUT the response could be a partial response or stable disease, not necessarily a complete remission. AND it does not indicate how long the response will last. 

<b>LMS tumors are not homogeneous,</b> like jello, they are heterogeneous like beef stew. They are not made up of identical cancer cells throughout, but have groups of cells with differing mutations.  <b>Often in leiomyosarcoma, clones or colonies of cells resistant to the chemotherapy agent occur</b>, and the tumor then becomes composed of these cells during treatment [because the sensitive cells are being killed off], and resistant to the chemotherapy agent. Or the testing might have been done on one metastasis, but when the chemotherapy is carried out, one or more of the other remaining metastases might not be sensitive to this chemo agent. <b>The metastases may have come from different cells in the original tumor, and may have different chemosensitivities.</b>  So a short-time clinical usefulness of sensitivity tests has been reported, but whether this will be useful in LMS longterm survival is much less likely because of the development of resistance and the lack of really effective agents to choose from. <b>However, the elimination of some chemotherapy agents because of the likelihood that they will be ineffective, is useful.</b>  And if a tumor shows marked chemoresistance to most or all chemotherapy agents, other methods than chemotherapy, like ablative, antiangiogenesis or vaccine or immunological methods would probably be worth exploring.

<b>Tumor cell heterogeneity poses significant problems in the clinical use of chemosensitivity assays.</b> Tumors are not homogeneous cells of one cell line.  They are heterogeneous [all the cells are not the same].  See the section on "de-differentiation".  The question arises as to whether a single biopsy specimen is representative of a patient's disease. In one study, evidence of tumor heterogeneity was sought by comparing chemosensitivity responses between: 1) different portions of a single tumor, 2) a primary and a metastatic biopsy taken from a patient on the same day, and 3) different metastases from a patient taken on the same day. The results demonstrated the presence of considerably different responses to chemotherapy among different tumors from the same patient, and even within the same tumor. The reported discrepancies of in vitro and in vivo sensitivity may be due to such heterogeneity among tumors. 

<b>Extreme Drug Resistance Testing: But if a drug can't stop tissue culture growth in a test tube, with all the best conditions for it to work... then it is a good bet that the drug will not stop the tumor growth in a live body.</b> The accuracy of prediction of drug ineffectiveness is reportedly 91% to 97%... meaning that over 90% of the drugs that are designated as useless for the tumor, will indeed be useless. Since there is a lifetime limit on the amount of radiation and chemotherapy that one can have*, avoidance of useless chemotherapy agents is worthwhile. The elimination of ineffective drugs is an issue of crucial importance because the side effects of chemotherapy agents are severe. [*The development of life-threatening myelodysplasia syndromes, and subsequent cancers of the blood or bone marrow, is a well known effect of multiple chemotherapy treatments.] 

Where there are cases of tumors that are very sensitive to chemotherapy agents, the use of chemosensitivity testing can indeed lengthen lifespan, and even predict/contribute to longterm remission. 

But where effective agents are not available, and only short term partial responses the rule rather than the exception, the major benefit from chemosensitivity testing of the standard chemotherapy agents will be avoidance of the useless ones. With LMS, none of the chemotherapy agents is very effective against the cancer, some or the entire tumor becomes resistant, and then response is variable. So there is no marked increase in survival when chemosensitivity testing is used late in the course of the disease. In vitro chemosensitivity/extreme resistance testing may prevent the administration of ineffective chemotherapy. It might also be useful in investigational work with new drugs, to see whether they might be effective against LMS. Whether it will make a difference in long term survival when used early, in chemotherapy-naive patients, is not known. 

To optimize the patient's chance of survival and to justify related toxicities, the chemo regimen should be individualized and based on the patient's extreme drug resistance profiles, to avoid treatment with ineffective drugs and their associated toxic side effects. In several cancers, there is noted benefit in using the testing to help decide chemotherapy regimens. The major limitation in the treatment of leiomyosarcoma is the lack of availability of effective agents for treatment. 

In order to have this testing done, live tumor cells must be obtained through surgery or laparoscopic biopsy. At least one to two grams of fresh biopsy tissue is needed to perform the tests, and placed in a special kit [obtained in advance from the lab.]  A gram of tissue is a cube of approximately one cm [3/8 inch] on a side.  Needle or core biopsies will not provide enough tissue.  Laparoscopic biopsies and initial or follow up surgery is an excellent time to obtain a specimen for testing, even when chemotherapy is not planned, as tumor tissue may not be available later on when the information may be needed. The surgeon and/or the pathologist prepare the specimen and arrange for it to be sent.

The tests should never be used as a reason to deny giving chemotherapy. If there is a proven effective therapy that has not yet been tried, it would perhaps be unwise to let assay results determine that this therapy should not be used. However, if a person is not able to undergo aggressive regimens, the tests can help to choose less toxic drugs that might be effective. If resistance occurs to a chemotherapy agent, the tests can help to identify a different agent that MIGHT work. If clinical trials are under consideration, these tests can identify the specific clinical trial in which the odds for success are the greatest. 

<b>The tests reveal, but cannot alter, an individual tumor's resistance to drugs. Not every patient will respond to an assay-favored drug, and there is no guarantee that a drug will be found that shows activity against the cancer cells of a particular patient.

I cannot emphasize enough how the number of toxic treatments is limited because of cumulative bone marrow effects, how the LMS is radio and chemo resistant. You need to get the best chance you can.</b>

