TOPICS
Before you have the biopsy to determine if you have a lymphoma or to evaluate tissue to see if you've had a relapse, contact your surgeon or oncologist and specify that you want a portion of the extra tissue snap frozen using CLIA standards.
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to determine if you are eligible for a clinical trial (now or in the future)
testing an agent that targets a pathway that might be present in the tumor)
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to produce a patient-specific cancer vaccine, should one of the three
vaccines coming up for approval within the year wins approval.
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to do advanced diagnostics, to determine if you have high or low risk lymphoma
(or as control tissue if negative for lymphoma!)
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to determine your eligibility to use approved targeted agents in future.
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NOTE: Keep in mind that having your tissue stored in this way is unlikely to provide clinical benefit. Clinical use of the tissue (such as to guide medical decisions) may depend on which studies utilize the tissue ... such as if the tissue is used to guide patient selection in a therapeutic trial or not. The general expectation is that the insights from the use of biospecimen in clinical trials will take many years to become useful in clinical practice.
That said, we do think this is wise practice, even if the potential for you to benefit clinically seems small at this time. Further, such centers will likely have higher levels of expertise in the diagnosis of lymphoma.
WHERE / HOW can I have this done?
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One way: Participate in the Genome Expression Study
(highly recommended when it's time for a biopsy)
Rationale: The observed variability in the clinical course of follicular lymphoma, along with
the diverse range of therapeutic options available, necessitates accurate prognostic
stratification of the individual patient.
Conditions: Lymphoma; Leukemia; Multiple Myeloma; Lymphoid Malignancies
Locations:
Nebraska Medical Center in Omaha,
Southwest Oncology Group centers- see for MANY centers in USA: swog.org
the British Columbia Cancer Agency in Vancouver, Canada;
the Norwegian Radium Hospital in Oslo, Norway;
the University of Würzburg in Würzburg, Germany;
the University of Barcelona in Barcelona, Spain; and
St. Bartholomew's Hospital in London, England.
Background: The Leukemia and Lymphoma Molecular Profiling Project (LLMPP),
a collaboration of researchers in the United States, Canada, and Europe NCI investigators
are working with researchers at the University of Nebraska Medical Center in Omaha
to define the gene expression profiles of all types of human lymphoid malignancies.
The project is supported by an international collaboration ... The LLMPP uses
"Lymphochip" cDNA (complementary DNA) microarrays, which are enriched in genes
that are expressed in and/or function in lymphocytes. Lymphochip microarrays allow
measurement of the RNA expression levels of the represented genes. Gene expression
profiles developed as a result of this project may someday be used for disease classification
(diagnosis), prognosis, and therapy selection. Already, results from the LLMPP indicate
that these profiles can improve diagnostic accuracy and provide prognostic information.
The LLMPP is initiating a multicenter clinical trial to evaluate a lymphoma diagnostic chip,
called LymphDX, which was designed by the company Affymetrix in collaboration with
NCI researchers using LLMPP data. The study will demonstrate the feasibility of
disseminating the LymphDX microarray technology to all of the participating sites and
will also evaluate the diagnostic utility of the LymphDX chip in a prospective study.
Source: cancer.gov
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IMPORTANT: Be sure to request a CLIA Certified Laboratory - "defined as clinical diagnostic laboratories certified by the DHHS Health Care Financing Administration ... as revised by the Clinical Laboratory Improvement Amendments (CLIA)". http://ohsr.od.nih.gov/info/sheet17.html
Also see Rationale, below.
Centers that are more likely to snap freeze tissue at biopsy:
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See NCI-designated cancer centers - Cancer.gov (in state order. Scroll down to list)
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SWOG centers in USA: swog.org
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Locate CLIA accredited laboratories by state: cms.hhs.gov pdf
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Locations participating in LLMPP:
Nebraska Medical Center in Omaha,
Southwest Oncology Group centers- see for MANY centers in USA: swog.org
the British Columbia Cancer Agency in Vancouver, Canada;
the Norwegian Radium Hospital in Oslo, Norway;
the University of Würzburg in Würzburg, Germany;
the University of Barcelona in Barcelona, Spain;
St. Bartholomew's Hospital in London, England.
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Objectives
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Advocate for the routine snap freezing of lymphoid tissue at each patient biopsy.
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Provide the rationale and notification of expectation to:
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treating physicians who refer patients for biopsies,
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clinical investigators and scientists who can advise us about where to put our efforts.
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cancer centers that must store the tissue, or package and ship the tissue elsewhere,
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surgeons who perform the procedures,
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pathologists who first receive the tissue,
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and the public who must inquire and know what to ask for when scheduled for lymphoid tissue biopsies.
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We will develop and distribute educational material so that the public and our representatives can understand the potential of this technology and the need to fund and support it.
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Identify research centers that will receive the tissue, or perform genetic testing on it.
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Identify methods to safeguard the privacy of patients who donate lymphoid tissue and provide clinical history.
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Identify and provide incentives for patients to donate lymphoid tissue and provide clinical history.
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Advocate for the creation of a centralized lymphoid tissue data bank at the NCI that will receive and evaluate tissue from outside sources.
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Advocate for open access to tissue and related data to help advance clinical progress. |
Rationale
The reasons to routinely snap freeze and store lymphoid tissue at biopsies so that the tissue can be profiled at a genetic level are numerous and compelling:
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Enables scientist to more rapidly identify the gene expressions that distinguish normal from malignant cells and assist in the "development of molecularly targeted therapies that have specificity and potency for defined cancer types." 4
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Enables scientists to link clinical behavior (how aggressive or indolent the cancer is likely to be ) to gene expression, and thus better advise patients about treatment selection and timing. Currently, the variable clinical course of patients given the same diagnosis stems, in part, from the underlying molecular diversity among their tumors. 4
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Enables identification of viral factors that may be present and may contribute to causing, promoting, or maintaining malignant behavior of lymphoma cells.
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Enables scientists to discover how genes function in immune cells and apply to the treatment of numerous diseases.
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Enables retrospective testing to correlate genetic expression with individual responses to treatments. The potential benefits will enable doctors or researchers to:
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Multiple samples from the same patient,
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enable the identification of changes to gene expression and other tumor characteristics in response to treatments and over time. |
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enable the identification of changes to gene expression and other tumor characteristics that correlate to refractory disease, or transformation to aggressive disease, or the lack thereof.
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Enable identification of tumor-associated antigens that can form the basis for therapeutic cancer vaccines.
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Enable discovery of cells in the lymphoid microenvironment that may be promoting or inhibiting lymphomas.
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Enable production of patient-specific therapeutics, such as cancer vaccines or therapeutic antibodies. |
“The inadequacy of the current diagnostic methods is evident in the heterogeneous treatment responses of cancer patients within a diagnostic category. The importance of establishing a new molecular diagnosis of cancer is two fold. First, the assignment of cancer patients to molecularly diagnostic categories will often provide prognostic information that can guide patients to the most appropriate treatments. Second, a molecular diagnosis of cancer provides a detailed blue print of the abnormal molecular circuitry of the cancer cell, which will lead to the development of molecularly targeted therapies that have specificity and potency for defined cancer types.” – Louis M. Staudt, Annu.Rev.Med.2002.53:303–18
Snap-freezing of lymphoid tissue at biopsies
At the time of biopsy a portion of the tumor removed by surgery – not used for histology testing – can be snap frozen in liquid nitrogen and stored at -80 C degrees for later processing (DNA or RNA extraction). Storing the material is very simple. It only takes a few seconds or minutes. In short, it is required to have liquid nitrogen at the local were the biopsy is being done. All hospitals have liquid nitrogen, which is not expensive.
Immediately after removing the tissue, it has to be introduced into a tube and then into liquid nitrogen. After that the tubes can be securely transported to an -80 C degrees freezer. We estimate that the cost of the initial storing of the material in the freezer will be modest.
IMPORTANT: Be sure to request a “CLIA Certified Laboratories” - "defined as clinical diagnostic laboratories certified by the DHHS Health Care Financing Administration ... as revised by the Clinical Laboratory Improvement Amendments (CLIA)". http://ohsr.od.nih.gov/info/sheet17.html
Notification of Expectation
For Patients: How to inquire and what to ask for when scheduled for lymphoid tissue biopsies.
How will extra tissue be stored at this center?
Will it be snap frozen?
Will it be accessible for research, including clinical research I may participate in later?
May I review your consent document on the use and storage of extra biospecimen?
"If so, I would like to have the lymphoid tissue taken at my biopsy snap frozen so that DNA analysis can be done, and so that I have the option to use a portion of it for therapeutic purposes in future, such as identifying molecular targets that may be targeted by recently approved or investigational therapies, or for making a tumor-specific cancer vaccine.
For Treating Physicians, Surgeons, and Hospital Centers
We believe that the benefits of participating in this program will far exceed the costs, which we estimate to be approximately $?? per patient. Costs are probably modest and relate to storage and supervision of tissue.
History tells us that difficult problems can only be solved only by taking proactive steps, and by coordinating our efforts.
The potential benefits of this program are twofold: It can potentially help patients living with the disease today, and it will help future patients by assisting in advancing the science.
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References:
[2] Specific Gene Patterns Linked to Treatment with EGFR Drugs, Cedars-Sinai Medical Center 3-Jun-03 - Abstract 763, ASCO
[3] Clinical translation of gene expression profiling in lymphomas and leukemias. Semin Oncol. 2002 Jun;29(3):258-63. Review. PMID: 12063678 - PubMed
[4] Staudt, Gene Expression Profiling of Lymphoid Malignancies - Annu.Rev.Med.2002.53:303–18 - PubMed
Resources:
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Molecular Targeting in the Treatment of Cancer: An Interview With Brian Druker, MD - Medscape (free login req.)
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Molecular Diagnosis of the Hematologic Cancers, Staudt - NEJM May 1, 2003
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Hematological Tumor Profiling, Kris Novak, PhD Clinical Editor: Sara M Mariani, MD, PhD - Medscape
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Clinical pharmacology - mja.com.au
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DNA arrays diagnose, predict survival for Sezary syndrome cancer patients -
New technology validated, dozens of potential drug targets identified - Eurekalert.org Jun_03
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Bioinformatics and microarray gene expression profiles - PDF
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The LymphoChip - Staudt Lab
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Application of tissue microarray technology to the study of non-Hodgkin's and Hodgkin's lymphoma. Hum Pathol. 2002 Oct;33(10):968-974. PMID: 12395368 - PubMed
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Drug response linked to genes in lymphoma patients - GNN 2_21_03
"The researchers identified about 150 genes in lymph tumors that could help predict the drug response. The activity of these genes differed significantly between patients who responded to treatment and those who did not. "
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Gene profiles predict survival - NCS Infoservices, 04_02
The activity of as few as 17 genes can be used to predict lymphoma patients' response to treatment, scientists reported at the 18th UICC International Cancer Congress in Oslo this week.
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Recommendations for the Reporting of Lymphoid Neoplasms - Medscape (free login req.)
A checklist for pathologists and surgeons on how to evaluate and store lymphoid tissue at biopsy.
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