Genomic Analysis Brings Personalized Treatment to Lung Cancers

Gregory Riely

Medical oncologist Gregory Riely

Physicians have become increasingly aware that all lung cancers are not the same. Rather, different types contain specific genetic mutations that affect how they progress and respond to therapies.

At Memorial Sloan Kettering, lung cancer patients now routinely receive genomic testing of their tumors as a part of diagnosis and staging. For certain mutations, drugs already approved by the US Food and Drug Administration are available as treatments. For others, experimental treatments being tested in clinical trials may be the best option.

“We’ve made it a priority to do genomic tumor testing for every person with lung cancer treated here,” says MSK medical oncologist Gregory J. Riely. “We feel strongly that this type of information is essential for selecting the optimal treatment.”

MSK has led the way in this kind of tumor testing. Beginning in 2004, every MSK lung cancer patient’s tumor has been tested for a mutation in the EGFR gene, which is present in many patients with non-small cell lung cancer. Over the next decade, tests for additional mutations — found in KRAS, ALK, and other genes — have been added, as well as tests for additional mutations in squamous cell lung cancer. Patients with these specific mutations can be matched with available drugs to treat their cancer or research studies evaluating new drugs thought to target these mutations.

Research has shown that this approach is already transforming lung cancer care. A study published earlier this year, led partly by MSK medical oncologist Mark G. Kris, found that driver mutations — genetic changes that induce cells to become cancerous or spur their malignant behavior — can be found in about two-thirds of patients with advanced lung adenocarcinoma, a subtype of non-small cell lung cancer. Furthermore, survival was increased for patients given drugs matched to specific driver mutations.

Another Leap Forward

In 2014, MSK greatly enhanced its genomic analysis of lung tumors with the introduction of MSK-IMPACT, a test that examines 341 cancer genes that have been shown to play a role in the development or behavior of tumors. They represent all “actionable targets” — genes that can either be targeted with drugs or provide clinically relevant information about the disease if they are altered.

MSK-IMPACT is based on next-generation sequencing, cutting-edge technology that allows cancer genomes to be profiled very quickly and with great sensitivity. For example, the test can tell if a gene has been mutated or deleted, or if there are additional copies of it.

Dr. Riely explains that MSK-IMPACT allows clinicians to look for alterations that, while less common than EGFR, KRAS, and ALK mutations, still have important implications for choosing treatments.

“The IMPACT test includes the complete range of mutations that we can target in patients with lung cancer, and it does it all in one fell swoop rather than requiring multiple tests,” he says. “Its range is so broad that we might find some mutations that are each present in only 1 to 3 percent of patients — but when you add them all together, it probably represents another 10 to 15 percent of our patients who have an option for a new targeted therapy that would not have been possible before.”

For example, a phase II clinical trial led by MSK medical oncologist Alexander Drilon has been testing a targeted therapy, cabozantinib, in lung cancer patients whose tumors contain a mutation in a gene called RET. After MSK-IMPACT testing showed that a significant percentage of lung cancer patients had increased activity in a gene called MET — known to promote cancer cell growth through the same biological pathway as RET and thus likely to make tumors sensitive to the drug — the trial was expanded to include these patients.

“As the mutation testing continues to be applied to a growing number of patients, we will know more about the frequency of rare mutations and will be spurred to develop new clinical trials for patients with those mutations,” Dr. Riely says.

We've made remarkable progress over the last decade in lung tumor analysis, from testing just one gene to several hundred all at once.
Gregory Riely medical oncologist
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Continued Progress

Dr. Riely says MSK-IMPACT will be refined periodically as new actionable targets are discovered. Even those mutations that are not currently “targetable” with drugs nonetheless could soon provide important information — for example, how the cancer might behave, or which treatment, whether a targeted drug or a conventional treatment like chemotherapy or radiation, will be more effective.

In some cases, MSK-IMPACT could reveal targetable mutations that are rare in lung cancer but may occur in other cancer types. These patients may be eligible for treatment in a new type of clinical study called a basket trial, which focuses on specific gene changes and may enroll patients with many different types of cancer whose tumors carry similar mutations.

“We’ve made remarkable progress over the last decade in lung tumor analysis, from testing just one gene to several hundred all at once,” Dr. Riely says. “As more information is gathered, we expect a continued increase in the percentage of lung cancer patients who we can match with a clinical trial, and ultimately with approved new drugs.”

Learn more about the MSK-IMPACT test and how our scientists developed it.

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To all the Doctors, nurses, researchers, scientists and countless others who invisibly comprise support staff and personnel enabling all of the dedicated men and women of the MSK family, to do what they do, you are all the true miracle workers of our generation and generations past, and the real pioneers of the 21st century. Ceaselessly scouring each and every one-way street, dead-end and unpaved dirt road of our genetic universe, that is the human body, please know that I am only here to leave this message, at age 59, because of discoveries and advances made solely by your efforts and countless others like you. At age 49 I was made aware of a tumor that just 5 years earlier, more than likely would have ended my life within a year. But thanks to all of you and the genius that is Dr. Bruce D. Minsky, and countless others at MSK who have dedicated their life's work to finding a cure, I have been cancer free since completing my treatment at MSK. And if that was not enough, when my sister was diagnosed with stage IV lung cancer less than a year ago at age 56, only a few months after she finally retired from a 30 year career, I urged her to abandon her local physicians and community hospital after a few weeks of torturous indecision and go to MSK to obtain the best possible care, not 6 months later, a literal "magic pill" taken twice a day has completely stopped her cancer in its tracks, those tracks having already traversed her brain, her lungs, her liver, her abdomen and countless other parts of her body. The magic pill, a new "genetic mutation based treatment", developed and perfected by you, the miracle workers at MSK, without any chemo, radiation and only the most minor surgery, has completely reversed her undetected, symptom-less spiral toward the premature ending of her life. How can we ever express our gratitude properly? Her local doctors, of course dedicated and sympathetic could not even identify the type of cancer she had from her biopsy slides. Knowing that time is always of the essence, I went and got those slides and in the same afternoon took them from Long Island to MSK via a short LIRR ride, the NYC subway for 10 minutes and finally the MSK shuttle (What a blessing that shuttle has been!!) and within 36 hours, only because she was now being seen by MSK, not only did she know the kind of cancer, but the original biopsy slide had enough genetic material still usable by your staff to identify a known and treatable mutation. Within days her "magic pills" were being delivered to her by UPS and all evidence of her stage IV cancer, everywhere, continues to shrink, as confirmed by her repeated scans and follow up appointments; all in not much more than 6 months from the day I carried her slides into your good hands.
From the bottom of my own heart, having been saved by you 10 years ago, and now my only sibling, my sister, likewise being saved by you, I wish to thank you all for truly these gifts of life. In my family, lightning did strike twice, but each time your dedication and devotion to science and finding the cure has won out. I know too many lives have been lost, for many, many generations because the progress was just not there. But I and my sister are here to say, Your amazing, hard work and dedication to finding a cure IS paying off and we are both living testaments to that truth. Thank you to the men and women pioneers and miracle workers of MEMORIAL SLOAN KETTERING. (Albert J. Rodrigues)

How long will it take for the results of a lung tissue sample submission for the MSK-IMPACT test to be completed?

Jane, thank you for your comment. Once the tumor and blood samples are received in the lab, it usually takes 2 to 3 weeks for the MSK-IMPACT test to be complete.

How is msk-impact gene study different from Foundation one gene study?

Edward, thanks for writing. We reached out to genomics researcher Michael Berger who co-invented the MSK-IMPACT test. He says MSK-IMPACT is very similar to the Foundation One test, both in concept and approach. The number of genes analyzed by MSK-IMPACT is slightly larger. Also, MSK-IMPACT utilizes DNA from both the tumor and blood, which makes it possible to identify with high level of certainty all “somatic” mutations that are specific to a patient’s tumor and not present in his or her normal cells. In contrast, Foundation One utilizes only tumor-derived DNA.

I have been a cancer survivor for over 23 years thanks to sloan Kettering and dr bajorin. I have emphasema and would like to know if there are ny new treatments
Thank you

Dear Josephine, we are a cancer hospital and do not treat emphysema. If you are having problems, we suggest your reach out to your primary care doctor. Thanks so much for your comment.

I am a patient at MSK. I have not seen my medical oncologist in three years because there has been no disease progression. My MSK medical oncologist has worked with me and my local oncologist since my initial diagnosis in 2006. Currently, my local oncologist monitors my disease and administers maintenance chemotherapy per MSK instructions. MSK did some tumor testing in 2009. Should I ask my MSK physician to test my tumor again using MSK-IMPACT so that we have up to date information readily available should I need a change in treatment?

Dear Julie, thanks for your question. It’s best to get in touch with your doctor’s office directly to find out if MSK-IMPACT is something that could benefit you. Thanks again for reaching out.

My mom is recently dx'd with cancer with suspected primary site from the lung. We are awaiting pathology results and her PCP referred us to an oncologist who gave us an appointment on 1/9. Although I am sure they are great, I want my mother to have an evaluation at MSK. What does she need to bring for a consultation? Will she have to have all the tests done again ie. PET scan and biopsy?

Lana, thank you for reaching out. If you contact our Physician Referral Service at 800-525-2225 they will be able to answer your questions about a consultation and what would be needed for an evaluation at Memorial Sloan Kettering.


Dominick, we are not able to answer personal medical questions on our blog, but there are some types of lung tumors, or nodules, that are not cancerous. If you’d like more information, we recommend that you call the National Cancer Institute’s Cancer Information Service at 800-4CANCER for more information. Thank you for your comment.

Is nausea a common problem when taking Tarceva orally?
Thank you

Dear MSK,
My mom most likely has small cell lung cancer but in very early stages. We are waiting on path results that should come in today. Are there any oncologists that specialize in JUST lung cancer or SCLC?

Kelly, thank you for reaching out. Yes, MSK definitely has experts who specialize in specific types of lung cancer, including small cell lung cancer. If your mother would like to make an appointment with a Memorial Sloan Kettering physician, please call our Physician Referral Service at 800-525-2225 or go to Thanks for your comment.

My best friend in Melbourne Australia has been diagnosed with monophasic synovial sarcoma left lower lobe . How many of these cases have been handled at Sloan - surgery (if operable) chemo and radiation
I have read some from articles from Google

Cecily, thank you for reaching out. Even though sarcomas are rare, MSK physicians specialize in treating them and see a large number of cases, including synovial sarcoma.

If your friend is interested in a consultation, he or she can contact our international center by calling 1-212-639-4900 or going to to learn more. The email address is [email protected].

In addition, you can learn about treatment of sarcoma at MSK here:…

how does the MSK test differ from the foundation one test for lung cancers? what genetic variants does the MSK test detect beside the usual (egfr, kras, alk) that are actionable?

Is MSK-Impact used for determining INTRK Fusion, & does Medicare cover the cost of this test?

Frances, thank you for reaching out. We consulted with MSK physicians and this is the response:

“I assume they are referring to NTRK fusions. Current version of MSK-IMPACT covers ETV6-NTRK3 fusions and most NTRK1 fusions. Additional NTRK3 and NTRK1 fusions are detected by a targeted RNA-Seq assay. NTRK2 fusions are extremely rare.

The Medicare program does not currently have a national coverage determination for genomic sequencing procedures. At this time, each claim is evaluated individually for coverage decisions. MSK’s local Medicare contractor, National Government Services, recently released a draft coverage policy for non-small cell lung cancer and we hope that other diseases will be included in future policies.”

If you would like to make an appointment with a Memorial Sloan Kettering physician, please call our Physician Referral Service at
800-525-2225 or go

Thanks for your comment.

Hello. Can chemotherapy or radiation treatment for NSCLC alter the genome mutation analysis findings produced by either MSK IMPACT analysis or the results produced by Foundation One. Thank you.

Hi Larry, we sent you question to Mike Berger, one of the researchers who helped develop MSK-IMPACT, who said, “Yes, both chemotherapy and radiation treatment can damage DNA and produce additional mutations that can be detected by MSK-IMPACT or Foundation One. Chemotherapy can also lead to the outgrowth of tumor cells harboring additional ’drug resistance’ mutations that were undetectable in the
original tumor. While most of the mutations that arise during treatment are not biologically or clinically significant, occasionally new mutations do influence the way a patient responds to therapy and can lead to changes in treatment.” Thank you for your comment.

I'm curious about the number of cases of malignant pheochromocytoma with mets to the lungs MSK has treated. Also, for the MSK-IMPACT testing, would this require a new biopsy if a patient has already had several cycles of chemotherapy or would the original tissue sample be sufficient? Thank you.

Dear Amy, if you would like to learn more about MSK’s expertise in treating this disease as well as what is required for MSK-IMPACT, we recommend that you make an appointment with one of our experts to discuss this. Currently MSK-IMPACT is available to MSK patients only. To make an appointment you can call 800-525-2225 or go to for more information on making an appointment. Thank you for your comment, and best wishes to you.