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Has anyone heard of Dr. Grace in New York City? He is doing work with patients targeting chemotherapy specifically based on lab tests that identify which chemos work with your specific tumor. He is not covered by my sister's insurance but I have a strong recommendation from a friend. Just curious if this site has any information.
Many thanks.
Targeted therapy Cancer Taxol Surgery Hysterectomy Avastin Aromasin Breast cancer Ovarian cancer Chemotherapy Lung cancer Luminal Metformin
No, but I would like more information. I will try to research.
Tgen is based here in Phoenix, they specialize in this research. They are based in the Virginia Piper Center.
I will get you some more information on them tomorrow.
GOD BLESS
Scott
Dr. William R. Grace is a board certified practicing medical oncologist who for nearly two decades was an academic oncologist as Chief of Medical Oncology and Cancer Research at St. Vincent's Hospital and Medical Center of Manhattan. He has utilized cell culture assays in the management of his cancer patients since 1995.
He has co-authored over twenty publications in immunology and cancer research and has had extensive clinical experience in both the older (clonogenic) and newer (apoptotic) cell culture assays.
He believes it is unethical not to use cell culture assay testing in his practice. It is a real credit to oncologists like Dr. Grace who utilize cell culture assays in their management of their cancer patients.
William R. Grace, M.D., P.C.
Oncology and Hematology
36 Seventh Avenue, Suite 511
New York, New York 10011
Telephone (212) 675-6826
Thanks for sharing your info there Gregory - knew you'd have the inside story on this one! xxxGGC
Dear Gregory,
As our resident expert in this area, do you know of any other doctors who are using assays or if there is a professional list somewhere that we can refer to?
chloemom
I do not consider myself an expert. I leave that up to the average medical connoisseur. But I do consider communication should be judged on the quality of its content and only secondarily on the qualifications of its originator.
I recently posted (on the lung cancer threads) a list of all the labs that provide cell-growth and cell-death assays in the United States. I'll post it again here on the breast cancer threads.
I wish I did have a list of all the practicing oncologists that are knowledgable enough about cell-death assay technology and use it in the management of their cancer patients. I would think that each individual lab may have their own list of oncologists that utilize assay-directed therapy to complement their practices.
The choice of a lab may not be a geographical consideration, but a technical consideration. All of the labs are experienced and capable of providing very useful information.
However, the labs vary considerably with regard to technologies, approach to testing, what they try to achieve with the testing, and cost. Some labs have been offering these assays as a non-investigational, paid service to cancer patients, in a situation where up to 30 different drugs and combinations are tested, at two drug concentrations in three different assay systems.
The labs will provide you and your physician with in depth information and research on the testing they provide. Absent the assays, the oncologist will perform "trial-and-error" treatment until he/she finds the right chemotherapy regimen. You should have the right chemo in the first-line of treatment.
By investing a little time on the phone speaking with the lab directors, you should have enough knowledge to present the concept to your own physician. At that point, the best thing is to ask the physician, as a courtesy to the patient, to speak on the phone with the director of the laboratory in which you are interested, so that everyone (patient, physician, and laboratory director) understand what is being considered, what is the rationale, and what are the data which support what is being considered.
A listing for some of the reputable laboratories providing cell culture testing. These labs will provide you and your physician with in depth information and research on the testing they provide:
This laboratory provides a "cell growth" assay. The assay is excellent at identifying drugs most likely "not" to work (drug resistance). The assay is not as good at identifying drugs which are "more likely" to work (drug sensitivity) or to identify the disease-specific activity patterns of new targeted drugs. Used for drug de-selection and not for drug selection.
Exiqon (formally Oncotech, Inc.)
http://www.exiqon.com/dx
All the below laboratories provide a "cell death" assay. At one time, the goal of cancer treatment was to inhibit unregulated cell "growth." In the last twenty years, the goal is to induce cell "death" in order to successfully conquer concer. The much older "cell-growth" assays measure a drug's ability to inhibit cell "growth" and only succeeds in eliminating drugs that would "not" work for a patient (drug resistance). The more modern "cell-death" assays measure the ability of chemotherapy drugs to induce cell "death" (apoptosis) in a tumor biopsy from a patient (drug sensitivity). The assays are excellent at identifying drugs most likely "not" to work and identify drugs which are "more likely" to work.
Anticancer, Inc., San Diego, CA.
http://www.anticancer.com/
Cancer Therapeutics, Inc., Thomasville, GA.
http://www.cancer-therapeutics.com/
DiaTech Oncology, Brentwood, TN.
http://diatech-oncology.com/
Genomic Health, Inc. Redwood City, CA.
http://www.genomichealth.com/OncotypeDX/Index.aspx
Genoptix, Inc., San Diego, CA
http://www.genoptix.com/
Precision Therapeutics, Pittsburgh, PA.
http://www.precisiontherapeutics.com/
These laboratories, in addition to providing a "cell death" assay, provide a functional profiling assay which is the only testing that involves direct visualization of the cancer cells at endpoint. This allows for accurate assessment of drug activity, discriminates tumor from non-tumor cells, and provides a permanent archival record, which improves quality, serves as control, and assesses dose response in vitro (includes newly-emergent drug combinations). Only two assay labs, that have about the most extensive information about the technology with knowledge spanning decades, utilize functional tumor cell profiling. Besides identifying drugs most likely "not" to work (drug resistance) and identify drugs which are "more likely" to work (drug sensitivity), these assays can identify the disease-specific activity patterns of new targeted drugs.
Rational Therapeutics Institute, Long Beach, CA.
http://www.rational-t.com/patients/extra.aspx
Weisenthal Cancer Group, Huntington Beach, CA.
http://weisenthalcancer.com/
thanks for all the information. It's too bad that insurance companies will not pay for this testing.
It amazes me not only that some private insurance carriers don't like to pay for cell culture assay tests but that they don't emphatically mandate it as a requirement for obtaining chemotherapy reimbursement against ill-directed treatments.
A number of posters on the lung cancer and ovarian cancer threads have had their private insurance pay for the assays. Many of the country's private insurance carriers have been reimbursing patients on an individual "medically necessary" basis.
Medicare has determined that In Vitro Oncologic Chemoresponse Assays are part of the generally accepted medical practice and is a perfectly appropriate medical service worthy of coverage on a non-investigational basis. Medicare is billed directly.
I think that private insurance carriers and the FDA have a very real opportunity to make a substantial impact and contribution, an interest in saving the healthcare system perhaps billions of dollars a year (and thereby the healthcare system itself) by ensuring that expensive treatments are used appropriately.
This link should take you to physicians who use the rational therapeutic labs. The Weisenthal group no longer accepts Medicare.
http://www.rational-t.com/patients/content2.aspx?rid=16
This does not mean that the Weisenthal group does not perform testing for Medicare beneficiaries.
http://weisenthalcancer.com/Patient%20Pages/BillangandInsurance.htm
Only physicians and suppliers can decide not to accept assignment. If your physician or supplier does not accept assignment for covered services, your physician or supplier may require that you pay most or all of the bill at the time you receive services or supplies. However, the physician or supplier is still required to file a Medicare claim on your behalf. Medicare then pays its share of the bill directly to you.
As for private insurers, having the additional support of drug patient-specific activity as determined by extensive laboratory tests could very well bolster your argument to the insurance company in seeking payment for the test and treatments.
Thank you for posting this information. I have thought a great deal about this testing since making the choice to go forward with chemo for a stge IV diagnoses in July 2009. I had a single met develop in my left ovary invasive to the fallopian tube and some invasion to adipose around tube. All was removed and put into frozen section after election of complete hysterectomy. Hyst. was my choice as the ultrasound called this a cyst. but I was cocerned at speed of growth. Confirmation of a breast met was made by 3 pathologists including the great path team at Vanderbilt.
No other mets showed up by CT-PET. I would have sent it for sensitivity testing if another was seen, and I kick myself for not thinking of this prior to surgery.
I made the choice to go with avastin-abraxane (after consulting with 5 oncs) for this Er/PR pos/HER-2 negative tumor because it was aggressive and I watched it grow rapidly by sonogram measurements while I was on femara. There are only a handful of studies on how to treat oligometastatic disease, but all suggested chemo can be of benefit, I didn't want to take the chance of just endocrine therapy as I had taken femara for the last 5 years, tamo for about 2, and aromasin for about 2 switched back to tamo after side effects. I took a lot of chemo, CAF/ followed by high dose chemo (STAMP V) stem cell trasplant in 1998-1999 for 11 pos nodes, which is a poor prognostic for oligometastatic progression. I never had a taxane so I went with that, (so I guessed) I assessed that my tumor fit in to the luminal b category because of a high proliferation index, and I saw that the "cyst" had a nice blood supply (I made them measure it by doppler) so elected Avastin. My onc agreed to go off label with metformin and I take some supplements that supposedly make taxol work better, like DIM and curcumin.
My question to you is, have any studies confirmed that breast cancer patients do better when having these tests performed on the tumor? I can clearly see the benefit for early stage, when there is nothing to measure, but what about stage iv that is measureable?
I ask this because many studies have shown that the microenvironment of the tumor and where it is situated can sometimes effect how chemo behaves. So I have been wondering if these test perhaps are better at predicting what won't work rather that predicting what will work?
Thanks for your thoughts, I truly appreciate the work and effort that you put into this and will copy and paste this into my own files.
Natada. In regards to your frozen tumor specimen.
Paraffin embedded, fixed, minced, or frozen tissue can change over time. One gets more accurate information when using intact RNA isolated from "fresh" tissue than from using degraded RNA, which is present in paraffin-fixed tissue (preserved in paraffin wax).
Established cell line is not reflective of the behavior of "fresh" tumor cells in primary culture in the lab, much less in the patient. You get different results when you test passaged cells compared to primary, fresh tumors.
Established cell lines have been conclusively proven to have no predictive value at all with respect to the clinical activity spectrum.
Molecular testing methods detect the presence or absence of selected gene mutations which theoretically correlate with single agent drug activity. Tests are performed using material from dead, fixed or frozen cancer cells, and are never exposed to anti-cancer agents.
Cell culture methods assess the net effect of all inter-cellular and intra-cellular processes occurring in real-time when cells are exposed to anti-cancer agents. Tests are performed using intact, living cancer cells plated in microclusters.
Cell culture methods allow for testing of different drugs within the same class and drug combinations to detect drug synergy and drug antagonism.
Some patients' tumors respond to chemotherapy and some do not. A pathway/mechanism - cancer stem cells - may be the cause. To prevent cancer's return may require one therapy to shrink a tumor and another therapy to kill the abnormal seeds that sprouted it. Conventional cancer therapies have been good at shrinking tumors, but the ability to shrink tumors has little or no correlation to survival times. Newer treatments need to decrease the number of cancer stem cells.
There is a communication between stem cells and a tumor. It sends out a signal that make the different cells of the tumor and the cancer cells then (send chemical messages) that cycle back to the cancer stem cell. Every tissue and organ in the body is made of cells. In order for cells to grow, divide, or die, they send and receive chemical messages. These messages are transmitted along specific pathways that involve various genes and proteins in a cell.
Finding the protein that prevents cancer from metastasizing, isolating factors within the stem cell microenvironment, can influence tumor cell fate and reverse the cancerous properties of metastatic tumor cells. However, it is not the only tumor suppressive factor within the stem cell microenvironment. Not all genes and proteins have a critical role in the survival and growth of cancer cells.
In some cases, targeted drugs may kill tumor cells without killing microvascular cells in the same time frame. In other cases, they may kill microvascular cells without killing tumor cells. Yet in other cases, they could kill both types of cells or neither type of cells. The ability to these targeted agents to kill tumor and/or microvascular cells in the same tumor is highly variable among the different agents.
You still need to measure the net result of all cellular processes, including interactions, occurring in real time when cancer cells actually are exposed to specific cancer drugs, not just the individual molecular targets. Improving cancer patient diagnosis and treatment through cellular-based enpoints will offer predictive insight into the nature of an individual's particular cancer and enable oncologists to prescribe treatment more in keeping with the heterogeneity of the disease.
The presence of a mutated gene in a biopsy sample is associated with primary resistance to drugs. The whole concept of genetic markers is not to put patients in the position of having to receive toxic cancer drugs if they're not going to do any good (what won't work).
However, the cell is a system, an integrated, interacting network of genes, proteins and other cellular constituents that produce functions (processes). It would be a benefit to analyze the systems’ response to drug treatments, not just one target or pathway.
Gene and protein testing involves the use of non-viable, formalin-fixed cells that are never exposed to chemotherapy drugs. Gene and protein tests cannot elucidate issues relating to drug uptake or show if the drug will be excluded from the cell before it can act or what changes will take place within the cell if the drug successfully gains entry.
No genetic profile test can discriminate differing levels of anti-tumor or anti-microvascular activity occurring among different targeted therapy drugs. Nor can it identify situations in which it is advantageous to combine a targeted drug with other types of conventional cancer drugs.
A couple of private cell-based assay labs, using a functional profiling methodology, have been clinically evaluating anti-tumor and anti-microvascular activity on individual (not population trends) patients live (fresh) cancer cells, based on using real-time, real patient data, under real-world conditions, to guide medical evidence and treatment.
Targeted drugs are poorly-predicted by measuring the ostansible target, but can be well-predicted by measuring the effect of the drug on the function of live cells. You still need to measure the net effect of all processes, not just the individual molecular targets.
These two labs have the capabilities to measure the net effect of all processes. Both of them utilize what is called functional profiling. Functional tumor cell profiling is a combination of a morphologic endpoint (DISC) and one or more metabolic endpoints (MTT, resazurin, ATP). It measures morphologic (structural) effects and metabolic (cell metabolism) effects, measuring the "profile" of the whole cell (it's entire genome). It is analogous to measuring thousands of genes before and after drug exposure.
The key to understanding the genome is understanding how cells work. The ultimate driver is a functional assay (is the cell being killed regardless of the pathway/mechanism) as opposed to a target assay (does the cell express a particular target the drug is supposed to be attacking). While a target assays tells you whether or not to give one drug, a functional assay can find other compounds (up to 30 of them) and combinations and can recommend them from the one assay.
The core of the functional assay is the cell, composed of hundreds of complex molecules that regulate the pathways necessary for vital cellular functions. If a "targeted" drug could perturb any one of these pathways, it is important to examine the effects of the drug within the context of the cell. Both genomics and proteomics can identify potential new therapeutic targets, but these targets require the determination of cellular endpoints.
Cell-based functional assays are being used for screening compounds for efficacy and biosafety. The ability to track the behavior of cancer cells permits data gathering on functional behavior not available in any other kind of assay.
By investing a little time on the phone speaking with the lab directors, you should have enough knowledge to present the concept to your own physician. At that point, the best thing is to ask the physician, as a courtesy to the patient, to speak on the phone with the director of the laboratory in which you are interested, so that everyone (patient, physician, and laboratory director) understand what is being considered, what is the rationale, and what are the data which support what is being considered.
Sources:
Cell Function Analysis
European Science Foundation
BMJ 2007; 334(suppl_1):s18 (6 January)
American Association for Cancer Research
Literature Citation:
Functional profiling with cell culture-based assays for kinase and anti-angiogenic agents Eur J Clin Invest 37 (suppl. 1):60, 2007
Functional Profiling of Human Tumors in Primary Culture: A Platform for Drug Discovery and Therapy Selection (AACR: Apr 2008-AB-1546)
another testing company I found on the web is CCC Diagnostics (www.cccdiag.com) in Baltimore. Apparently they test for certain proteins that indicate which drugs might work best. They do direct cell visualization on samples cut from parriffin blocks. Thier website says that the procedure is covered by many insurance companies and Medicare
The endpoints of molecular profiling are gene/protein expression. The endpoints of tumor cell functional profiling are expression of cell death (both tumor cell death and tumor associated endothelial [capillary] cell death).
Genomics is far too limited in scope to encompass the vagaries and complexities of human cancer biology when it comes to "drug selection." Efforts to administer targeted therapies in randomly selected patients often result in low response rates at significant toxicity and cost.
While researchers continue to develop molecular probes to select candidates, the cell culture analysis platform serves as a functional profile capable of examining the nuances of cellular response to drugs. To exploit the full potential of targeted anticancer therapies, physicians will need laboratory tests that match patients to specific drugs.
Cell culture assays are able to accurately predict how an individual patient's cancer cells will respond to an array of drug combinations. It is able to quantify synergistic drug combinations and individually tailor treatment.
http://theoncologist.alphamedpress.org/cgi/content/full/12/3/301
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