The tissue bank is a powerful con­cept

[Guest guest]

Greetings,

Here's an excellent article on the purpose of standardized tissue banking.

Importantly, this project seeks to involve community oncologists and is

focused on translational research.

~ Karl

PS Thank you, Donna, for bringing this very clearly written information to

our attention.

=

© 2006 Elsevier Inc. All rights reserved.

" There are great opportunities for community oncologists to do an even

higher level of clinical research.'

==

Atul Dhir is a man of di­verse accomplishments. Having been trained as a

physician, he also holds a Doctor of Phi­losophy degree from Oxford

University, where he was a scholar. In his doctoral research, he

sought to un­cover the molecular basis for infectious meningitis. ...

In his professional life, he has been a McKinsey healthcare con­sultant, a

vice president at Monsanto, and an entrepreneur, having founded and served

as president of a company that provided consulting services to hospitals and

physicians.

Seven years ago, Dr. Dhir joined US Oncology and now serves as pres­ident of

its Cancer Information and Research Group, which oversees the company's

clinical research and bone marrow transplant services. About half of the

almost 1,000 physicians in US Oncology's nationwide network of

community-based oncologists take part in the clinical research portion of

the network that Dr. Dhir oversees.

The group's clinical research net­work is the central component in a major

new initiative the company has launched with the Molecular Profil­ing

Institute of Phoenix, Arizona: creating a repository for the storage and

genomic analysis of cancer tis­sue specimens.

.... Called TBAC (Tissue Banking Analysis Center), the facility utilizes many

of the same technolo­gies employed by the Biospecimen Core Resource

facility, recently estab­lished by the National Cancer Insti­tute (NCI) and

the National Human Genome Research Institute, which are now compiling a

comprehensive genomic atlas of human cancers.

US Oncology brings its network of clinicians and their patients to the

pri­vate TBAC partnership; Florida-based Ameripath, Inc., brings a large

network of pathologists; and the Molecular Profiling Institute provides a

state-of­the-art facility and technologies for tissue storage and analysis.

A recently concluded pilot program resulted in the successful " banking " of

2,000 speci­mens.

More than 100 of US Oncology's clinician-researchers are now collecting

samples from patients enrolled in five clinical trials. As they are trained

in collection procedures, over time, physi­cians throughout the group's

research network will be able to participate.

The tissue bank is a powerful con­cept, both in terms of its potential

impact on patient care and the op­portunity it provides Ifor community­based

oncologists with an interest in research, as Dr. Dhir explained in a recent

interview.

=Community Oncology: How did US Oncology's tissue bank project come about?

For a number of years, we've been looking into the question of how the 500

physicians in our research net­work can participate in more innova­tive

clinical trials. This is where drug development in oncology is

headed ­trials in which you can ask thought­ful scientific questions based

on the target a candidate drug is designed to address or the genomic profile

of the patient's tumor. But the single biggest barrier to doing this has

been a lack of tissue samples.

=So having a patient's sample and subjecting if fa various genomic

technologies and diagnostics will enable the physician to select a targeted

therapy?

That's the ultimate objective. But specifically, in the case of our tissue

bank, having the sample will help our clinicians-researchers determine, in a

clinical trial setting, why drug X worked or did not work in a particular

patient. In many types of cancer, more than 50% of the patients fail to

respond to the first line of treatment. ...

Why did it fail? Should they even have gotten the therapy they were given?

....

The therapy failed them be­cause we really didn't understand the tumor, and

if we knew the tumor in a more precise fashion, maybe these patients would

have received different therapies. To this end, we will be ap­plying several

techniques to analyze the samples-immunohistochemis­try, DNA micro arrays,

and proteomic analysis, although they will vary ac­cording to trial type.

=You said that not having tissue samples has been 'a barrier.' Please

explain.

When I say " samples, " I mean high-quality tissue, collected in an ethically

appropriate fashion and correlated with the patient's clinical information.

This is the critical ele­ment. If, in the context of analyzing clinical

trial results, we have a tissue sample and see a certain genomic profile of

interest, but we don't know if the patient responded to treatment or not, we

don't know what to make of that information.

=You're saying that such samples are not readily available.

Science in this instance is far ahead of the logistics. The problem is that

the patient and the patient's tissue sample are often in completely

different institutions. For example, the patient goes to a surgeon in a

hospital, and a tissue biopsy is taken to help make the diag­nosis. That

tissue stays in the hospital, in the pathology department. ...

Howev­er, after diagnosis the patient goes to an oncologist-more often than

not a community-based oncologist-who takes over the patient's care. But the

tissue sample remains under the juris­diction of the pathology department.

The community oncologist's practice has limited ability to obtain that

tissue from the pathology department at the hospital, and the pathology

depart­ment doesn't have any access, at that point, to the patient or the

clinical in­formation regarding that patient.

=The two are disconnected.

That is one aspect of the problem. In part because of this disconnect,

there are important unresolved ethical issues surrounding the process of

tissue collection. How do we do it in a scien­tifically disciplined, IRB

[institutional Review Board]-reviewed, and patient­consented fashion? The

fact is, even if you have a tissue bank, samples will not be usable unless

they are collected and " banked " in a manner that is stan­dardized and

ethically appropriate.

= What are some of the ethical issues involved in tissue collection? What

kind of consent is called for and who owns the tissue once it has been

collected?

In complete candor, these are issues that are still being worked through.

Collectively, we will have to wrestle with issues of ownership and the like.

But we are clear about the process: to be able to create a tissue bank that

can provide answers to some of our questions means that collection has to be

done in a clinical trial setting. ...

You're getting tissue from the patient that may not be of immediate medical

benefit, but may help provide benefit in the future. We cannot promise the

patient that the tissue they're giving, versus tissue given for normal

diagno­sis of the tumor, is going to directly affect their treatment

decision-mak­ing or outcome. That's why it has to be handled with the same

ethical sensitivity as when you are testing an investigational drug.

=How does a tissue bank such as the one you have established differ from the

biorepository just organized by the government in connection with the NCI's

Cancer Genome Atlas project?

The government has just created a core repository for cancer tissue in

connection with its intention to cre­ate a database for understanding the

genetic sequences of different tumor types at different stages of tumor

de­velopment. It is hoped that genetic changes characteristic of different

cancers can be catalogued, codified, and published for research purposes.

....

Our tissue bank has a specific purpose. It's a translational effort focused

on collecting tissue for clinical trials funded by pharmaceutical and

bio­tech companies. The goal is to speed clinical development of targeted

treatments.

Although ours is a private tis­sue bank, we are leveraging similar

technologies and the same location as the Biospecimen Core Resource

facility, which is the repository for the government's Cancer Genome Atlas

project. In fact, our pilot project predated the government effort and

involved non-profit partners- TGen [Translational Genomics Research

Institute] and IGC [international Genomics Consortium] who have since been

chosen to manage the government repository. ...

And while our private tissue bank benefits the pharmaceutical and biotech

compa­nies that are interested in making tri­als more efficient and

effective, to the extent we are successful, we are also benefiting cancer

patients.

=You've noted that good tissue samples are essential for sophisticated

analysis of patients and tumors. Can You say a bit more about how this will

work in practice?

Tissue samples will help in trials that involve targeted therapy. We're

already designing trials that require the presence of a certain genomic

profile in selecting patients who will be candidates for the therapy being

tested. Ideally, you want to be able to give targeted therapy only to those

pa­tients who are most likely to respond. ...

By trying to ask the most precise sci­ence questions, you will need fewer

patients in a trial than you would if you were randomly testing unprofiled,

untargeted patients.

= So by selecting only those patients who ore good candidates for forgeted

therapies, you are more likely to shorten the time it takes to get the

therapy through the approval process.

That's one aspect. The second per­tains to trials in which the therapy is

not targeted. In analyzing trial results in those cases, we don't know why

some patients responded and others did not. To be able to refine the

questions for subsequent trials-again, to acceler­ate the pace of drug

development, so you're not asking the same question over and over and making

the same mistakes-you can refer to tissue that has been collected from

patients who were enrolled in the initial trial and is already in the tissue

bank. You can go back and see, retrospectively, if there are any correlative

genomic data that help you get a deeper understanding of why a given

patient's tumor responded or did not respond. ....

This step enables you to refine the question and identify more precisely the

future population for trials, limiting it to patients who are likely to

respond.

=What, then, is the bottom line for community oncologists about tissue

banking? Is there an opportunity for them?

There are three great opportuni­ties. First, because community oncolo­gists

see 85% of cancer patients, they are uniquely positioned to make a huge

contribution to future progress. They'll be the ones who have the greatest

abil­ity to access the tissue and the clinical information that is vitally

needed. ...

Second, they can offer to their pa­tients the trials and therapies that will

help target the tumor in a more precise fashion than has been possible

previ­ously. So they are helping accelerate the development of those

therapies and bringing those choices to their patients sooner. ...

Third, because of this program, community oncologists who have an interest

and capability will have the chance to do an even higher lev­el of clinical

research than they have been able to do historically. Until now, questions

that require collec­tion of tissue specimens could only be answered in an

academic setting. ...

Because of the disconnect between tissue samples and clinical infor­mation

about patient care, for the most part, patients were excluded from the

trials that asked the most advanced questions. Our program provides a great

opportunity for community oncologists to design and participate in the

leading edge of clinical trials.