"In one PowerPoint presentation from 2000, a Bristol-Myers Squibb executive told employees that oncologists’ biggest concern was “Reimbursement Today, Reimbursement Tomorrow, Reimbursement!”
"Dr. Robert Geller, an oncologist who worked in private practice from 1996 to 2005 before leaving to join a biotechnology company, said that cancer doctors knew the profits they could make and in some cases would change treatment regimens or offer unnecessary care to make extra money.
“It’s clear that physicians stopped making decisions based on what made scientific or clinical sense in lieu of what made better business sense,” Dr. Geller said."
http://www.kaisernetwork.org/daily_reports/rep_index.cfm?DR_ID=45527
At the page below, click on FUTURE EFFECTIVE policies.
http://www.medicarenhic.com/cal_prov/policies.shtml
As
part of this favorable coverage decision, the contractor (National
Heritage Insurance Company) carefully documented the historical
progression of Medicare policy dating from the "colony assays" of the
70's to the (noncoverage) National Coverage Decision regarding "stem
cell" assays (1980), to the 1999 National Medicare Coverage Advisory
Committee
review
(discussed and documented below on this website), to the initial
coverage by National Heritage in late 2000 (in the absence of a formal
LCD), to the present comprehensive review, culminating in this
favorable Local Coverage Decision.
As discussed in the editorial
referenced
below, the clinical trial of Cree, Kurbacher and associates achieved
exceptional
chemotherapy response rates in platinum-resistant ovarian cancer, but
with
no clear improvements in overall patient survival. This study, in
the context of the existing clinical trials literature, points to the
need
for changes in our approach to the chemotherapy of the most common
forms
of adult cancers (continued,
click here).
In the pre-chemotherapy era of the 1960s, the median survival of patients with metastatic breast cancer was a little less than two years. Since then, the greatest cancer centers in the world have performed hundreds of prospective, randomized clinical trials, involving tens of thousands of patients, in an attempt to identify the best treatment to give to the average patient, to improve treatment outcome. The results of these trials have been summarized by Dr. Lawrence Shulman, of Harvard's Dana Farber Cancer Center (click here , reference given here). In short, there has been not a hint of progress, with median survivals remaining exactly the same, just under two years... (continued: click here).
The American Society of Clinical Oncology (ASCO) is a trade organization, representing the interests of its membership, who are largely medical oncologists in both academic and private practice. ASCO has recently drawn scrutiny and criticism (described below) for its attempts to maintain a reimbursement system in which oncologists derive most of their income not from being doctors but from running a retail pharmacy concession, which encourages the maximal use of chemotherapy (as opposed to other treatment modalities), which encourages infusion chemotherapy over oral dose chemotherapy, which encourages certain (more financially lucrative) forms of chemotherapy over other (less financially lucrative) forms of chemotherapy, and which discourages the individualization of drug selection through the use of cell culture drug resistance testing (CCDRT). ASCO has never supported either the study or use of CCDRT, because of short-sightedness and unwarranted dedication to a failed clinical research paradigm (the identification of the "best" treatment to give to the average cancer patient, through endless generations of prospective, randomized clinical trials pitting one form of empiric therapy against another form of empiric therapy). The failings of this paradigm were recently exposed, in an investigative report (PDF file) in the March 22, 2004 issue of Fortune Magazine, written by the Executive Editor of Fortune, himself a cancer survivor.
In the September 1, 2004 issue of the Journal of Clinical Oncology (the official organ of ASCO), there were two (hopelessly inept and misleading) "technology reviews" published on CCDRT (referred to in the articles as "chemosensitivity and resistance assays" or CSRAs). Appearing below on this website are various discussions and writings relating to ASCO's position on CCDRT/CSRAs, based on the controversial September 1, 2004 Journal of Clinical Oncology papers.
Starting with the section below (dated November 9, 2004), it is easy to see that the concepts of information control and censorship are much in evidence at the Journal of Clinical Oncology, official organ of the American Society of Clinical Oncology (ASCO).
November 9, 2004 Weisenthal's
correspondence to the Journal of Clinical Oncology concerning the
September
1, 2004 JCO reviews relating to "chemotherapy sensitivity and
resistance
assays" (also known as Cell Culture Drug Resistance Testing, or
CCDRT).
Click for (1) Weisenthal's
cover letter, which accompanied manuscript submission, (2) manuscript
submitted to the Journal of Clinical Oncology, and (3) decision
of Dr. Daniel Haller, Editor in Chief, regarding publication of the
submitted manuscript.
October
4, 2004 Public
Interest Watch Calls for Government Investigation of American
Society
of Clinical Oncologists (ASCO)
As described elsewhere
on this website, ASCO has worked shamelessly to preserve a system
which
presents an impossible conflict of interest for both cancer centers and
treating oncologists. This is a system in which there is a
financial
incentive to choose certain forms of chemotherapy over certain others
and
to administer infusion chemotherapy as opposed to providing other forms
of patient care (click
here for full report).
Wall Street Journal health columnist Tara Parker-Pope answers a reader's question: "I was very interested in your article about chemosensitivity and resistance assays, and would appreciate [knowing more] about having the test done." Ms. Pope provided detailed and helpful information in two paragraphs and then concluded as follows: "To get started, patients should discuss [cell culture] testing with their doctors. Several patients wrote to say their doctors initially resisted the idea, but the patient insisted or found a different doctor." The columnist went on to quote me: "The most important thing is to have both surgeon and pathologist on board in advance." She concluded by noting that "a list of labs that do the tests can be found on weisenthal.org under frequently asked questions."
September 14, 2004 Wall
Street Journal article (full article
available/clickable
only to WSJ subscribers after Sept. 21) on
cell
culture drug resistance testing .
*************************************
From the Wall Street Journal
Health Journal September
14, 2004; Page D1
"A lab test that may help predict which chemotherapy drugs will work best in a patient has sparked controversy after a leading cancer panel ruled the tests aren't ready for routine use.
"The tests, known as chemo sensitivity and resistance assays, or CSRAs, have the potential to revolutionize cancer treatment by testing different chemotherapy drugs directly against a sample of the tumor to identify which is the most effective.
"Right now, chemo drugs are prescribed
based
on their overall performance in past clinical trials. But even the best
drugs may fail to help between 30% and 60% of patients, depending on
the
disease. It's impossible to predict the outcome of a particular cancer
treatment for any individual because every cancer is different." (For
article summary and discussion, click here)
September 4, 2004 Streaming Video
(finally
works!):
27 minute explanation
of technology and data behind cell culture drug resistance testing ("chemosensitivity
testing"). Streaming
video
in WMV (Windows Media Viewer) format. Note: works well in Explorer 6
browser.
Viewer may not initialize properly in Mozilla or Netscape. Presentation
by Larry Weisenthal.
(for the remainder of the Press Release, click here)
August 20, 2004 Bad
link repaired. It was just brought to my attention that one of the
links
on this website wasn't working. This is the link summarizing results
of assay-directed chemotherapy in ovarian cancer. This link has now
been repaired.
The September 1, 2004 edition of the Journal of Clinical Oncology
will contain two reviews relating to cell culture drug resistance
testing
(CCDRT). Electronic versions of these reviews are available (to JCO
subscribers)
on the website for the Journal of Clinical Oncology. Links to the
abstracts
are provided. I have read the full text versions of each, but copyright
restrictions prevent me from posting the full text versions of the two
papers. However, these papers are potentially important, and I would
like
to discuss them (click
here for this discussion and for links to the abstracts).
August 16, 2004 Cell Culture Drug Resistance Testing (CCDRT) is the "Rosetta Stone" for relating microarray gene expression patterns to clinical drug resistance
The August 5, 2004 edition of the New England Journal of Medicine
contains a
truly seminal article (New Engl J Med 351:533-542, 2004), relating
microarray gene expression patterns to clinical drug resistance.
The investigators used a 96 hour suspension culture drug resistance
assay
with a cell death (MTT) endpoint to define cut-offs for
"sensitivity"
and "resistance." They then used these data to define gene
expression
patterns associated with sensitivity and resistance to each of 4 drugs
commonly used in the treatment of childhood leukemia. They were
then
able to show that these gene expression definitions of sensitivity and
resistance were significantly and independently associated with
treatment
outcome on multivariate analysis.
Note that this work could not have been done without the prior work in more than a thousand CCDRT assays from children with leukemia to define sensitivity and resistance cuf-offs for each of the four drugs. The cell culture assays, therefore, are the "Rosetta Stone" which allows for identification of clinically relevant gene expression patterns which correlate with clinical drug resistance for different drugs in specific diseases. This further shows how short-sighted it has been for the academic and clinical oncology community not to support the development and clinical application of CCDRT ( click here for additional details ).
June 14, 2003-Synergy
analysis of "classic" and newer drug combinations. Click
here.
Introduction
30 years' worth of prospective, randomized clinical trials based on attempting to identify "best" one-size-fits-all treatment regimens have produced no important progress in the chemotherapy of advanced (Stage III, IV, and recurrent/refractory) ovarian cancer. (For continuation of this introduction, click here.)
Summary of data indicating that CCDRT improves clinical outcomes in ovarian cancer
In the case of ovarian cancer, there have been over 600 published correlations between assay results and clinical response. Overall, patients treated with drugs having good activity in the assays had a 77% response rate, while those treated with drugs having poor activity in the assays had a response rate of 11%, in a population of patients who overall had a 51% response rate. Also reported were highly positive associations between assay results and patient survival (click here for summarized data correlating CCDRT results with patient survival in ovarian cancer ).
Three different groups have
reported
clinical outcomes of ovarian cancer patients treated on the basis of
the
results of cell culture drug resistance testing (CCDRT or
"chemosensitivity
testing").Click
here for summarized data reporting clinical outcomes of patients
treated
with the knowledge of results from CCDRT.
March 25, 2003-Cell
culture drug resistance testing predicts for patient survival in
ovarian
cancer. There
have now been 5 different studies of the relationship between the
results
of cell culture drug resistance testing (CCDRT) and patient
survival
in ovarian cancer, and all 5 studies show significant correlations
between
CCDRT and patient survival. To
review summaries of these studies, click here.
This journal was created as a forum for sharing information
relating
to Human Tumor Assays. It is a site for presenting research results,
publishing
editorials and reviews, and providing links to sites which pertain to
the
testing of fresh human tumor specimens to determine the probability
that
different forms of cancer treatment will be effective in individual
patients
and in different classes of neoplasms.
"We relentlessly combined chemotherapy agents in various regimens, with ever-increasing dose intensity...as seen in this compilation of data, the survival for patients participating in these studies is exactly the same, less than 2 years. These four studies are a snapshot of hundreds of studies done throughout the world, spanning 30 years, utilizing innumerable combinations of standard dose chemotherapy without a hint of significantly improved survival."
-- Lawrence N. Shulman, M.D., Vice Chair for Clinical Services/Adult Oncology, Dana-Farber Cancer Institute (Harvard Medical School), Boston.
His commentary (click
here)
is remarkable in that it pulls no punches in describing the lack of any
progress whatsoever in the chemotherapeutic treatment of metastatic
breast
cancer since 1970. He also raises the question of whether "standard"
(i.e.
empiric) chemotherapy of metastatic breast cancer is, in fact, a zero
sum
game.
Invited review prepared for publication in the journal ONCOLOGY 7/19/2002
Current
Status of Cell Culture Drug Resistance Testing (CCDRT)Click
here for optimally-readable text
Click
here for printer-friendly PDF file
History behind the above paper: Editorial Review vs. Censorship?
The Human Tumor Assay Journal
is soliciting contributions of original research, reviews, and
editorials.
The Editor will provide a private review and suggestions within one
week
of submission, but the final decision on whether to publish and what to
publish will rest with the submitting author. All scholarly papers
submitted
will be published within 10 days of submission. Readers are invited to
submit uncensored reviews and these will be published as received,
linked
to the original paper.
Legal Case Against Wellpoint Blue Cross of California for Non-Payment of Services Related to Cell Culture Drug Resistance Testing 6/18/2002
Introduction: Blue Cross of California was previously a non-profit corporation and approved payment for Cell Culture Drug Resistance Testing (CCDRT) as stipulated in an "internal directive" dated December, 1993. However, this company later became a wholly-owed, for-profit subsidiary of Wellpoint, Inc., and then denied coverage for CCDRT, on the grounds that the service did not meet Wellpoint's medical necessity guidelines. Greater than 10 court cases were brought against Wellpoint Blue Cross in California by patients seeking payment for CCDRT by Wellpoint Blue Cross. In each and every case, Wellpoint Blue Cross was found by the court to be in the wrong, and was ordered to provide full payment of services as originally billed, plus court costs. In a small claims court case argued and adjudicated in January, 2002, Wellpoint Blue Cross appealed the judgment to the Superior Court of California, County of San Diego. Oral arguments were heard April 12, 2002, with follow-up written arguments filed on behalf of both plaintiff (April 25, 2002) and defendant (May 9, 2002). The State of California Superior Court Judgment was rendered June 3, 2002.
Presented on this website are:
Effective immediately,
Medicare
will provide payment for "cell culture tumor resistance" assays, while
continuing to withhold payment for "human tumor cell sensitivity"
assays.
Click here for
details.
History of Randomized
Clinical
Trials in Ovarian Cancer: Pre-Taxol Era
For many years (from the early 60s to late 70s), the
"standard" ovarian cancer chemotherapy was single agent melphalan....
Taxol Bursts Upon the
Ovarian
Cancer Scene
Midway into the above 2,500 patient study, the
glamour
drug of the 1990s, paclitaxel (Taxol), came along. A prospective,
randomized
trial ....
News and official
government
transcripts pertaining to national Medicare coverage for Human Tumor
Assays
Selected
quotationsfrom each of the
Medicare
Coverage Advisory Committee members, capturing the "take home message"
conclusions of each of the committee members, after hearing
detailed
pro and con presentations from both proponents and critics of Medicare
coverage for Human Tumor Assays. January
19, 2000
Medicare Coverage Advisory Committee Meeting on Human Tumor Assays - Baltimore, MD. November 15/16, 1999
Announcement: At the just concluded 2 day national Medicare Coverage Advisory Committee meeting in Baltimore to consider human tumor assay systems (following in depth pro and con presentations by me and by other proponents, by the NCI, FDA, HCFA, ASCO, and by outside consultants), the eleven voting members of the expert panel clearly expressed support of cell culture drug resistance testing as a covered service for Medicare beneficiaries. [November 17, 1999]
News Story : Medicare Advisory Panel Concludes Chemo Lab Tests Offer "Clinical Utility" Meeting of MCAC panel highlights new era, process for seeking Medicare coverage. HCFA's new FDA-like "applications process" for national Medicare coverage decisions got a full workout on medical device issues November 15-16. After listening to detailed clinical evidence, a subcommittee of HCFA's Medicare Coverage Advisory Committee (MCAC) concluded that a group of lab tests known as human tumor assay systems (HTAS) can aid physicians in deciding which chemotherapies work best in battling an individual patient's form of cancer. HCFA will now take the panel's recommendations into account in developing national coverage policies for the tests, which are currently not covered by Medicare. [ November 22, 1999]
Verbatim Transcript of Medicare Coverage Advisory Committee (MCAC) Meeting November 15,16, 1999 at which time pro and con testimony relevant to Human Tumor Assays (HTAs) was considered and voted upon.
Reviews, Editorials, News Stories on Human Tumor Assays
January 29, 2003Reuters
news story on cell culture drug resistance testing (http://www.cancersourcern.com/tools/print/print.cfm?ContentID=26539)
News Flash! DNA Microarray most powerful prognostic marker for breast cancer survival yet reported. December 17, 2002
In the December 19, 2002
issue of
the New England Journal of Medicine1, there appears perhaps
the most remarkable clinical oncology paper I have ever read. A team of
scientists from the Netherlands Cancer Institute reported absolutely
astonishing
correlations between long term survival of early breast cancer patients
(Stages I and II, small tumors, age less than 55 years) and the results
of a DNA microarray test which measured the patterns of expression of a
set of 70 different genes. The correlations reported were vastly
superior
to those obtained with standard prognostic marker studies. These
results
have enormous implications for the short-term future of cancer research
in general, and, if confirmed, will be one of the truly great cancer
breakthroughs
of our time. This DNA microarray work will, I predict, prove to be
highly
complementary to what I anticipate will shortly be parallel
breakthrough
efforts in targeted therapy through cell culture drug resistance
testing
(CCDRT). Stay tuned.
1ref: van de Vuver,
MJ, et al. A gene expression signature as a predictor of survival in
breast
cancer. N Engl J Med 347:1999-2009, 2002
Cell Culture Drug Resistance Testing (CCDRT) Cell Death Assays: Misconceptions Versus Objective DataCell culture drug resistance testing (CCDRT) refers to obtaining fresh biopsy specimens of human neoplasms, isolating tumor cells from these specimens, exposing the tumor cells to drugs during short-term (3 - 7 days) culture, and assessing drug effects by measuring either cell proliferation or cell death.[August 31, 1999]
Milestone Publications Relating to DISC and MTT Cell Death (Apoptotic) Assays
Cell Culture Drug Resistance Testing (CCDRT) refers to testing a patient's own cancer cells in the laboratory to drugs that may be used to treat the patient's cancer. The idea is to identify which drugs are more likely to work and which drugs are less likely to work. By avoiding the latter and choosing from among the former, the patient's probability of benefiting from the chemotherapy may be improved. [ September 15, 1996]
Physician's Weekly : Should chemotherapy protocols be individualized by drug-resistance testing? Point/Counterpoint - Two sides of the issue discussed by Larry Weisenthal, M.D. Hematologist, Oncologist, Medical Director, The Weisenthal Cancer Group; Associate Clinical Professor of Medicine, UC Irvine and William P. McGuire III, M.D. Section Chief, Chemotherapeutics and Research, Gynecologic Oncology Center, Mercy Medical Center, Baltimore [September 23, 1999]
Response to Issues Raised in Physicians Weekly Debate on Human Tumor Assays. [September 23, 1999 ]
Scientific
American Article: Pretesting Tumors - Long derided, test-tube
screening
for cancer-drug sensitivity slowly gains acceptance . (Scientific
American, February 1999 )
Featured Studies:
August 14, 2002 Bosanquet and colleagues report that (1) fludarabine resistance in the DiSC assay correlates with patient survival in CLL; (2) apoptosis-related Bax and Bcl-2 expression do not correlate with patient survival; (3) reduced Bax expression correlates with resistance to alkylators, doxorubicin, and vincristine, but not with resistance to fludarabine or glucocorticoids; (4) Bcl-2 expression does not correlate with resistance to any drug. They conclude that apoptosis-activation pathways are different in the case of fludarabine and glucocorticoids than in the cases alkylators, doxorubicin, and vincristine. The abstract and literature reference for the study may be found here .
March 8, 2000
Dr. Peter Staib and colleagues from the Universities of Cologne and
Munich
reported at the American Society of Hematology annual meetings on Dec.
4, 1999 in New Orleans that DISC assay results (in 122 patients)
provided
the strongest independent prognostic factor for survival in adult acute
non-lymphocytic leukemia. The abstract describing the study may be
found hereor
at the ASH
Annual
meeting web site.
A listing of Websites for some of the laboratories providing cell culture drug resistance testing follows.
Rational
Therapeutics,
Inc.
Oncotech, Inc.
Bath Cancer Research
(Bath,
England)
Anticancer Inc
Human
Tumor Cloning Laboratory, U of Arizona Note:
web check 8/4/2002 shows site no longer active
Diatech
Oncology
(Montreal, Canada)
L.A.N.C.E.
(Bonn, Germany)
Precision
Therapeutics, Inc.
Genoptix, Inc.
Oncovation, Inc.
Genomic
Health ("Oncotype DX" gene expression prognostic assay)
Cancer
Therapeutics, Inc. (A tumor cryobanking service)
Weisenthal Cancer Group
Feedback (
3/24/2004) - A compilation of messages, case
summaries,
reviews, and critiques submitted by readers (professionals, patients,
family
members, or other interested readers)
| Contact us at the Human Tumor Assay Journal . Email your comments |
Latest update: March 13, 2009
