FAQ: Large scale genomic tumor testing

Frequently asked questions about large scale genomic tumor testing

Q: What is large scale genomic tumor testing?

A: Large scale genomic tumor testing aims to detect DNA changes, or variants, in tumor cells to aid in diagnosis, prognosis and identification of targeted treatments. Large scale refers to the dozens or even hundreds of genetic variants that are analyzed, with implications for many different cancer types. These variants are in genes with associated FDA-approved treatments, or in genes where off-label treatments are available or in context of clinical trials. While large scale genomic tumor testing is relatively new and changing quickly, oncologists have used more targeted genomic testing to guide therapeutic decisions for some time now, testing for single, specific genomic variants in solid tumors, such as EGFR variants in lung cancer. As our understanding of genomic drivers of carcinogenesis has grown, so has the library of useful tumor biomarkers. At the same time, the power and efficiency of genomic testing has increased. Together, this has enabled the use of large scale genomic tumor testing, where a patient’s cancer is interrogated for hundreds or even thousands of variants.

Q: For which patients is large scale genomic tumor testing appropriate?

A: Currently, there are some clinical guidelines for using specific genetic variants to guide treatment, but none that guide decision-making about when large scale genomic tumor testing may be appropriate. Providers may choose to use it for patients with advanced cancers whose disease has progressed during standard treatments, or for those with particularly aggressive or metastatic disease, while others may use it with newly diagnosed patients to assess all treatment options.

Q: What are the benefits?

A: Large scale genomic tumor testing may identify opportunities to treat the patient with therapies targeted to specific genetic variants driving cancer growth. These targeted therapies may be FDA approved for the cancer type, approved for other cancer types, or are available through clinical trials. It may also provide diagnostic or prognostic information which could be used to inform treatment decisions.

Q: What are limitations?

A: Not all patients whose tumors are tested will have a variant that changes treatment. Studies have shown that 8-38% of patients will have a change in cancer management based on tumor results, such as receiving a different therapy or enrolling in a clinical trial. One challenge of large scale genomic tumor testing is that some variants lack evidence for a change in treatment. Some therapeutics in certain cancer types may lack evidence of efficacy, variants of uncertain clinical significance may be identified, or variants occurring in only a few cells in the tumor sample may not be detected.

Results may not show the complete molecular picture of the cancer and some treatment options may be missed. This is because tumors are often heterogeneous, and a biopsy sample only represents a subset of the cancer. Also, the genetic makeup of a tumor changes over time as the cancer cells divide. Variants detected in the original tumor biopsy often differ from those found in metastasized sites, and it may not be possible to obtain biopsies from all sites.

Additionally, some patients may have limited access to treatment options identified by testing, whether due to a lack of an appropriate trial nearby or lack of insurance coverage.

Q: How is the testing done?

A: Most commonly, CLIA-certified labs extract DNA from a tumor biopsy for large scale genomic tumor testing. Using next-generation sequencing (NGS), the lab identifies variants in the genes on the panel. Labs differ in which genes they include in their tests, but most include those involved in pathways that affect the development or growth of cancer.

Q: What can results tell you?

A: Large scale genomic tumor testing is typically done to assess a patient’s likelihood to respond to targeted therapies. Testing can help determine if the patient’s tumor or tested metastases carry any of these targetable genomic variants. In some cases, results may also inform prognosis or origin of the cancer if it has been difficult to determine otherwise.

Q: Can large scale genomic tumor testing identify individuals with hereditary cancer syndromes?

A: Yes. You may already be familiar with genetic testing for hereditary cancer syndromes (e.g., Lynch syndrome, hereditary breast and ovarian cancer syndrome). This testing typically involves a blood or oral sample to identify germline pathogenic variants (mutations) that are passed from parent to child. Variants in these cancer susceptibility genes increase a person’s chance of developing certain cancers in their lifetime.

Large scale genomic tumor testing examines variants within the tumor itself and is not seeking to determine if the cancer diagnosis was due to a hereditary predisposition. In a small number of cases, however, a variant detected through somatic testing may indicate an individual has an increased risk for a hereditary syndrome. In these cases, referral to a genetic specialist is indicated for follow up on the result.

Not all variants associated with hereditary cancer syndromes may be included on large scale genomic tumor tests. Even when the variants are included on the panel, they may not be reported or may be undetectable. It is always important to assess the patient’s personal and family history of cancer to determine whether further evaluation by a genetic expert is warranted, regardless of the results from testing.

Q: What have patient experiences been with large scale genomic tumor testing so far?

A: Cancer patients consistently report a high willingness and interest, but may not understand much about genomics or the implications for their care. Managing patient expectations should be part of the conversation when considering large scale genomic tumor testing. See Facilitating shared decision making about somatic tumor testing for more information on discussing options with patients.

Learn more

Precision Medicine for Your Practice: Exploring Somatic Cancer Panel Testing (CME / CNE). Learn how to determine for which patients large panel genomic tumor testing is appropriate and benefits and limitations to large versus small panels, as well as much more in this free, interactive module from JAX.