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ASCO Updates Policy Statement on Genetic and Genomic Testing

DiGiulio, Sarah

doi: 10.1097/01.COT.0000472794.49863.e2
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The American Society of Clinical Oncology has updated its policy statement on genetic and genomic testing for cancer susceptibility. A key reason for the update was to address the opportunities and challenges of new next-generation sequencing as it applies to cancer screening and cancer treatment decisions, according to the authors. The statement is published online ahead of print in the Journal of Clinical Oncology (DOI: 10.1200/JCO.2015.63.0996).

“The availability of broad based next-generation sequencing at affordable prices creates the opportunity to identify a greater proportion of those with increased genetic risk for cancers—and thereby offer them maximal surveillance and prevention options,” explained Noralane M. Lindor, MD, an oncologist and medical geneticist at Mayo Clinic who is a member of ASCO's Prevention Committee that co-developed and co-wrote the updated policy statement with ASCO's Ethics Committee.

“But with this new technology, there is definitely greater complexity in having conversations with patients about their goals and expectations, and in preparing them for the numerous possibilities—helpful results, surprising results, ambiguous results, disappointing results, or no result—which increases the responsibility of the ordering clinician proportionately,” she said via email.

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New Next-Gen TechnologyChanges the Game

She noted that the previous ASCO policy statement on genomic and genetic testing for cancer susceptibility was published in 2010 when direct-to-consumer genetic testing had just emerged and next-generation sequencing-based tests—which the new policy statement focuses on—were not yet available. “The clinical introduction of next-generation sequencing technology was much more rapid than generally was anticipated.”

Next-generation sequencing now permits broad, inexpensive testing for both germ-line and tumor DNA changes, which means clinicians can test broad panels of genes or entire exomes for tumor DNA changes. But the new possibilities that arise from having these tests require a new standard for pre-test counseling to ensure that patients are ready for the results—“and a recommitment to ongoing education for oncologists so they are prepared to provide the care indicated,” Lindor said.

Patients may not find out just what they intended to find out from a genetic test—such as a target for therapy or an explanation for a striking familial predisposition to a cancer, but also need to be prepared for the possibilities of finding variants in genes seemingly not related to the patient's family history, gene variants for which there is not much literature (such as MRE11), variants of uncertain clinical significance (whether in well-characterized or poorly characterized disorders), and variants known to cause severe autosomal recessive disorders, such as Ataxia Telangiectasia due to ATM mutations (in which case the heterozygote carriers will need to be educated about the potential risks associated with such mutations), she said.

The new statement reiterates the traditional counseling points from the previous ASCO recommendations, and also lists new points for multigene panel testing for germ-line variants, as well as for somatic testing. “All of the principles of genetic counseling for a single gene test still apply, but the amount of information provided for each gene on a panel will of necessity need to be grouped or abbreviated in some manner.”

The updated policy statement reviewed evidence in and made recommendations for five key areas, which are summarized here (see box).

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Call for Better Regulation

Another focus in the updated policy statement is support for regulation of laboratory-developed and commercial tests to maintain high-quality standards for such tests, but in a way that does not limit patient access or compromise innovation.

“A new paradigm is needed to attain a healthy balance of protecting the public from bad science yet not stifling innovation and not denying the public access to what information they could have, which one may argue may be better than nothing at all,” Lindor said.

“Most regulations were written with individual gene testing in mind with a focus on analytic validity and clinical validity. This approach will not scale to account for the fluid nature of ever-changing multigene panels and rapid growth of the knowledge base in genetics.”

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Ongoing Challenges

Among the ongoing challenges, Lindor said, will be to figure out how to provide high-quality ongoing education for oncologists in practice about the new technologies so that their patients can benefit from the advances being made. “The time pressures and reimbursement challenges of today's practices are not conducive to the careful discussions needed with patients; and there is a shortage of genetic providers in some health plans and in some geographic areas. So, the workforce needed to maximize use of genetics for patient care is not fully in place.

Another big challenge, she said, is the dearth of evidence and literature on various technology and outcomes as advances are made.

Lindor noted that the closing paragraph of an editorial accompanying the statement—co-written by ASCO President Julie M. Vose, MD, MBA, FASCO; Past-President Peter Yu, MD, FACP, FASCO (first author); and President-Elect Daniel F. Hayes, MD, FASCO (JCO DOI: 10.1200/JCO.2015.63.3628)—sums up the current dilemma: “Increasingly we will be the recipients of data that we did not anticipate, or perhaps, even seek to know. Accordingly we will be in the uncomfortable position of reacting to that data on the basis of an immature and incomplete understanding of what that data mean.”

In the editorial, Yu, Vose, and Hayes highlight the importance of the updated policy statement and conclude: “Robust discussions among a diverse set of stakeholders will be needed to ensure that all perspectives are listened to and that genetic cancer susceptibility services are comprehensive and patient-centric.”

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Enough Emphasis on Education and Pre-Test Counseling?

The statement and recommendations from ASCO on genetic and genomic testing for cancer susceptibility should be commended, said Joy Larsen Haidle, MS, CGC, President of the National Society of Genetic Counselors (NSGC), who was asked for her perspective for this article.

“I largely agree with all of the points they highlighted,” she said in a phone interview. “But from a genetic counselor's perspective, where education is needed and why collaboration with people who have expertise in genetics, needs to be emphasized.

“Right now the whole notion of looking at a genome of a tumor is pretty new; it's really exciting, and it can help to drive oncology care. But, there is a huge need for education amongst providers and amongst patients to understand the kind of information that might be gleaned from this type of testing—and to ensure that the conversations in that pretest counseling happen in a specific way to maintain patients' autonomy over their choice in the kinds of test they have.”

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Somatic Mutation Profiling

The recommendation on somatic mutation profiling is one such area, she said. The goal is to find a genetic weakness that could indicate a particular treatment might be effective. But there will be times where germline mutations are identified, she said. “The education piece is critical. The recommendation will only work as long as the pretest counseling is done and contains the critical components to make sure that patients understand and have the ability to select what information they want to receive as far as germline mutations or secondary findings before the test is run.

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“What I am personally concerned about is that it will ultimately be considered a routine pathology type of test versus remembering that the test can reveal more than that,” she added.

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Pre-test Counseling Content

Another important point is the content of the pre-test counseling, she said. Someone needs to draw out the very specific components of the tests and possible results as part of that counseling so the patient can fully be a part of the decision process.

“Without a purposeful conversation to learn preferences, the information and its implications for [the patients] themselves and family members are learned after the fact,” Larsen Haidle said. “Right now that happens on a much-too frequent basis. Unless providers make a more concerted effort to ensure secondary findings are purposefully discussed in the pretest counseling, the opportunity to consider patient preferences is missed.

“The results from these tests have implications for future cancer risks, including for a second cancer or cancer risk for other members of the family,” she said.

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Need for Collaboration

Genetic counselors can be a valuable part of the health care team and a valuable resource to help patients and providers understand the mutations that are identified outside of a physician's subspecialty (in addition to the mutations the patient and provider are looking for), Larsen Haidle continued.

Not all tests are created equal—while the same genes may be listed on the test, the techniques used to evaluate each gene can vary markedly between laboratories, making it difficult for the average provider to determine how well a given gene was analyzed and if additional testing is needed, she said “We need to help providers select the best tests for the purpose at hand.

“Education and collaboration with people who have expertise in genetics is very valuable to both the providers and the patients,” she said. If a physician or practice does not have access to a genetic counselor to consult with in that practice or hospital, Larsen Haidle recommended the “Find a Genetic Counselor” tool on the NSGC website, which was created for providers and patients to identify genetic counselors in a specific area (you can search by state and city or zip code) or those who offer telephone consultation services (nsgc.org).

—Sarah DiGiulio

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Recommendations

The updated policy statement reviews evidence in the following five areas and makes these recommendations:

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1 Germ-line Implications of Somatic Mutation Profiling

  • ASCO calls for further research to develop best practices for the delivery of incidental and secondary germ-line findings;
  • ASCO encourages research aimed at improving understanding of patient preferences, optimal pre-test education and informed consent, and multi-level outcomes (such as patient, provider, health care system delivery, and cost) in this area;
  • ASCO recommends that laboratories choosing to conduct secondary analyses should develop mechanisms to report only somatic results for patients who decline to receive germ-line findings; and
  • ASCO recommends that patients be educated before testing about the possibility that germ-line variants might be identified and that providers communicate the limitations and risks of receiving germ-line findings.
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2 Multi-gene Panel Testing for Cancer Susceptibility

  • ASCO asserts that providers with particular expertise in cancer risk assessment should be involved in ordering and interpreting multi-gene panels that include genes of uncertain clinical utility and genes not suggested by the patient's personal and/or family history; and
  • ASCO encourages research to delineate the optimal use of panel-based testing, development of evidence-based practice guidelines as data emerges, and education of providers on the challenges of using these tests.
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3 Quality Assurance in Genetic Testing

  • ASCO recommends appropriate regulation of tests that detect inherited genetic variants and supports a risk-based approach to FDA regulation for laboratory-developed tests and commercial tests—in a manner that does not compromise innovation or limit patient access to testing;
  • High quality standards should be adopted that allow providers and patients to understand the accuracy, benefits, and limitations of genetic tests conducted by individual laboratories; and
  • ASCO supports efforts to catalog and annotate all genomic variants and to create rigorously curated, open access libraries of the variants for use by all laboratories.
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4 Education for Oncology Professionals

  • ASCO recommends continued education of oncologists and other health care professionals in cancer risk assessment and the management of individuals with inherited predisposition to cancer; and
  • ASCO recommends that oncology training programs develop a set of core skills for new trainees and ensure adequate time for achieving these skills.
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5 Access to Cancer Genetics Services

  • ASCO calls for coverage policies that support access to cancer risk assessment and prevention services for individuals who are suspected to be at increased genetic risk;
  • ASCO opposes any payment policies that have the potential to negatively impact the care of patients with cancer by serving as a barrier to the appropriate use of genetic testing services; and
  • ASCO continues to support pre- and post-testing counseling when a patient is considered to be at risk for a hereditary susceptibility for cancer by a qualified health professional so that patients have the benefit of informed decision-making regarding genetic testing.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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