1. Oncologists prescribe patients one standard empiric chemotherapy regimen after another, until they find one that works. This often can expose patients to the side effects of chemotherapy, without showing any cancer-killing results. Guesswork can be done in a laboratory instead.

The tactic of using biopsied cells to predict which cancer treatments will work best for the patient, by taking pieces of "fresh" tumor tissue, apply different chemotherapy treatments to it and examine the results to see which drug or combination of drugs do the best job killing the tumor cells.

An example of this testing, researchers have tested how well women with relapsed ovarian cancer would respond to a combination of a pancreatic cancer drug and an ovarian cancer drug. They found the combination worked on a number of women, and testing cells in petri dishes predicted which women would respond to this combination and which wouldn't.

Or a metastatic pancreatic cancer patient can be treated successfully with a combination of drugs commonly used to fight lung, pancreatic, breast and colorectal cancers.

There are pre-tests that can report to a physician specifically which chemotherapy agent would benefit a 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.

Posted at 7:57AM on Apr 13th 2007 by Gregory D. Pawelski

2. There's no evidence that pre-testing on pancreatic and ovarian cells has any benefit.

None.

Perhaps, in the future, but not now.

Posted at 9:28AM on Apr 13th 2007 by hchcec

3. Apparently Medicare contractor, National Heritage Insurance Company, which spent six months reviewing everything about pre-testing assays, thinks there is benefit of these tests. 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.

Posted at 11:43AM on Apr 13th 2007 by Gregory D. Pawelski

4. I wouldn't say that a decision by a local Medicare contractor means that the chemotherapy assays have benefit. It's certainly not a National Medicare decision.

I mean, Medicare covers many "therapies" (some obesity treatments, tobacco dependence treatment, some mental health therapies, heart and lung rehab, i.e. expensive exercise) that have been proven to be of little or no benefit. Even,you, yourself, claim that many chemotherapeutic agents have no benefit yet Medicare covers them.

So, you couldn't possibly be indicating that a Medicare position on chemosensitivity has any validity, could you?

Unfortunately, at this time, there is no evidence at all of benefit to chemoresistance testing. A March 2007 update is located here:

http://www.regence.com/trgmedpol/lab/lab06.html

Posted at 11:36PM on Apr 13th 2007 by hchcec

5. ASCO and BC/BS's 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. In fact, when most academic oncologists refer to "chemosensitivity testing," they are virtually always referring to and thinking about "the human tumor stem cell assay" or " the clonogenic assay," yet this technology hasn't been used by any private sector laboratory for more than 15 years.

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. Excluded from consideration in their tech assessments of Cell Culture Assays were studies which relate to the performance characteristics (predictive accuracy, sensitivity and specificity).

National Heritage Insurance Company (NHIC) found this omission so significant that they 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 their present comprehensive review.

Medicare coverage has always been available for drug resistance testing since 2000 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.

It was unfortunate that ASCO and BC/BS 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.

Posted at 8:45AM on Apr 14th 2007 by Gregory D. Pawelski

6. "not a single diagnostic test in history has been shown to improve outcomes."

huh? OK, everybody. No more colonoscopies for you!

"Everyone is scared to death at what is going to happen to the healthcare economic system with the introduction of increasingly expensive new drugs.."

Really? Who?
For twelve years after its discovery, not enough penicillin existed to save even one person, yet over twelve billion units of penicillin can be made each year now, and at a cost of ONLY 3% of what it had cost during the war.

We've heard this all before.

"It should serve their interest not only in discovering new cancer treatments, but also using currently-available cell culture technologies to improve the effectiveness of existing drugs.."

There's no evidence at this time that these offer any benefit. None. So why should I, as a taxpayer, pay for a completely unproven test?

Let's let the studies begin and complete before I pay big bucks for an unproven test or unproven "therapy" like Essiac tea or a psychic healer, etc.

Posted at 11:42AM on Apr 14th 2007 by hchcec

7. Aetna's recent reimbursement policy regarding medical tests require "demonstrated improvement in clinical outcomes." However, not a single diagnostic test in history has been shown to improve outcomes. The smoking gun of hypocracy is in their guidelines for molecular tests. With the new gene-based tests, the language was altered to read "anticipated" or "expected" improvements in treatment outcomes. While the language for cellular-based tests still reads "proven" improvements in treatment outcomes.

Everyone is scared to death at what is going to happen to the healthcare economic system with the introduction of increasingly expensive new drugs that benefit only a small percentage of patients who receive them, hence the headlong rush to develop tests to identify molecular predisposing mechanisms whose presence still does not guarantee that a drug will be effective for an individual patient. Nor can they, for any patient or even large groups of patients, discriminate the potential for clinical activity among different agents of the same class.

However, profit is a powerful motivating force. Among the payors, the profit motive is entirely consistent with the goal of the test, which is to identify efficacious therapies irrespective of drug mark-up rates.

The FDA finds themselves under increasing pressure to allow new drugs into the marketplace while at the same time protecting the safety of potential recipients of those drugs and also the financial interests of those who will have to pay for them.

It explains the new paradigm of requiring a companion diagnostic as a condition for approval of new targeted therapies. The pressure is so great that the companion diagnostics they've approved often have been mostly or totally ineffective at identifying clinical responders (durable and otherwise) to the various therapies.

It should be in the FDA's 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. It should serve their interest not only in discovering new cancer treatments, but also using currently-available cell culture technologies to improve the effectiveness of existing drugs and save lives today by administering the right drug to the right patient at the right time.

Posted at 11:42AM on Apr 14th 2007 by Gregory D. Pawelski

8. "In many cases, these same tests have induced highly durable remissions in patients whom current medical literature have deemed otherwise hopeless."

There is not a lick of evidence at this time that this is in any way true. Notice that no data accompanies the above post (because there is none). This is why scientists, researchers, and physicians await the data before making statements like the above and before there is widespread approval for these expensive tests.

Until then, be careful what you read. It's not that one should understand that this blog is, as indicated above, for "informational purposes only," but one should also understand that this information can be misleading.

We should call the posters on this.

Let's hope for ever greater cancer breakthroughs. However, we need to be smart about it.

Posted at 11:43AM on Apr 14th 2007 by hchcec

9. The methods of cancer medicine during the last thirty some years are coming to haunt the "one-size-fits-all" establishment. Technologies, developed over the last twenty years by private researchers, hold the key to solving some of the problems confronting a healthcare system that is seeking ways to best allocate available resources while accomplishing the critical task of matching individual patients with the treatments most likely to benefit them.

Posted at 12:46PM on Apr 14th 2007 by Gregory D. Pawelski

10. The effects of drugs targeting EGF (Iressa, Tarceva, Erbitux) are poorly predicted by measuring the ostensible target (EGFR), but can be predicted more accurately by measuring the effect of the drugs on the function of live cells. 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.

Cell Function Analysis tells us that Whole Cell Profiling measures the response of the tumor cells to drug exposure. Following this exposure, they measure both cell metabolism and cell morphology. 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. No matter which genes are being affected, Whole Cell Profiling is measuring them through the surrogate of measuring if the cell is alive or dead.

For example, the epidermal growth factor receptor (EGFR) is a protein on the surface of a cell. EGFR inhibiting drugs certainly do target specific genes, but even knowing what genes the drugs target doesn't tell you the whole story. Both Iressa and Tarceva target EGFR protein-tyrosine kinases. But all the EGFR mutation or amplificaton studies can tell us is whether or not the cells are potentially susceptible to this mechanism of attack.

It doesn't tell you if Iressa is better or worse than Tarceva or other drugs which may target this. There are differences. The drugs have to get inside the cells in order to target anything. So, in different tumors, either Iressa or Tarceva might get in better or worse than the other. And the drugs may also be inactivated at different rates, also contributing to sensitivity versus resistance.

There are many pathways to altered cellular (forest) function (hence all the different "trees" which correlate in different situations). It serves to validate Whole Cell Profiling. The forest is looked at, and not the trees. Whole Cell Profiling measures what happens at the end (the effects on the forest), rather than the status of the individual trees.

Cancer is a complex disease and needs to be attacked on many fronts. The best thing to do is to combine these different tests in ways which make the most sense. The future of cancer therapy will be personalized treatments for individual patients, and will require a combination of novel diagnostics and therapeutics.

Improving cancer patient diagnosis and treatment through a combination of cellular and gene-based testing 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 biologies are very different and the response to given drugs is very different.

Posted at 8:02PM on Apr 15th 2007 by Gregory D. Pawelski