In the Clinic

On Cancer: Lung Cancer Patients Will Benefit from New Molecular Testing Guideline

By Jim Stallard, MA, Writer/Editor  |  Wednesday, April 3, 2013
Pictured: Marc Ladanyi & Gregory Riely Molecular pathologist Marc Ladanyi (left) and medical oncologist Gregory Riely

In recent years, rapid advances in clarifying the molecular underpinnings of lung cancer have led to more-personalized medical treatments for people with the disease, the leading cause of death from cancer in the United States. Today, doctors can analyze a patient’s tumor for specific genetic abnormalities to determine which targeted therapies are likely to be beneficial. 

Despite the availability of these tests and treatments, a significant portion of lung cancer patients around the country do not have their tumors analyzed upon diagnosis, due partly to confusion among many doctors over which patients would benefit.

Now three leading health organizations have jointly issued a guideline establishing clear standards regarding tests for two common genetic abnormalities linked to lung adenocarcinoma, the most common type of lung cancer. The guideline recommends that all patients with advanced lung adenocarcinoma should be tested for abnormalities in two specific genes, EGFR and ALK, regardless of clinical variables such as sex, race, or smoking history.

“This guideline establishes what we consider to be the minimum level of genetic testing for any patient diagnosed with lung adenocarcinoma,” says Memorial Sloan Kettering molecular pathologist Marc Ladanyi, one of three co-chairs of the international expert panel that developed the guideline. “We hope this guideline will be used by doctors nationally and globally, making it standard practice for lung cancer patients to receive the most-essential molecular testing of their tumors.”

Significant Patient Population

Approximately 20 to 25 percent of patients with lung adenocarcinoma are thought to have one of these two genetic abnormalities in their tumor, and targeted therapies already exist for both types. The abnormalities are both more commonly found in lung cancers from people who never smoked but also arise in smokers.

Using molecular testing, we’re able to guide treatment for a significant proportion of patients in a way we never could before.

-Gregory Riely, medical oncologist

Patients with an EGFR abnormality in their lung cancer can be treated with the drug erlotinib (Tarceva®), while people whose lung tumors contain an ALK abnormality can receive crizotinib (Xalkori®). In addition, new drugs targeting these disease pathways are being tested in clinical trials.

As co-chair, Dr. Ladanyi represented the International Association for the Study of Lung Cancer (IASLC), which drew up the recommendations in collaboration with the College of American Pathologists and the Association for Molecular Pathology. Dr. Ladanyi was asked to serve as the IASLC’s co-chair because of Memorial Sloan Kettering’s widely recognized expertise in molecular testing of lung cancer.

The guidelines are published this week in three journals — Archives of Pathology & Laboratory Medicine, the Journal of Thoracic Oncology, and the Journal of Molecular Diagnostics.

The Rapid Rise of Molecular Testing

The new guideline reflects the growing importance of genetic biomarkers in the diagnosis and treatment of cancer.   

“Even today, some oncologists might say, ‘This person is a smoker. It’s not worth testing for EGFR and ALK mutations,’— which is not correct,” Dr. Ladanyi explains. “We want to make clear that just using clinical parameters to select patients for genetic testing is no longer medically acceptable.”

In addition to advocating testing for EGFR and ALK mutations, the guideline sets standards for the methods by which tumor samples are tested and how quickly results should be made available by the laboratory so the oncologist can make treatment decisions.

Impact on Treatment

Memorial Sloan Kettering has tested for the EGFR mutations since 2004 and for the ALK abnormality since 2009 and continues testing all lung cancer patients for these and other mutations as part of the initial workup of patients with lung cancer.

“Using molecular testing, we’re able to guide treatment for a significant proportion of patients in a way we never could before,” says Memorial Sloan Kettering medical oncologist Gregory J. Riely. “This testing lets us select drugs that are going to work better and longer than standard chemotherapy, often with less toxic side effects.”

Dr. Riely believes the guideline will help ensure that routine testing is adopted by oncologists everywhere.

“I think the release of the guideline is a major step forward for advancing personalized medicine throughout the world,” he says. “It sets a minimal bar, explains the standard of care for patients with lung cancer, and helps to identify the key factors that help us pick drugs for patients today.”

Dr. Ladanyi says that continued research identifying new molecular biomarkers will require that the guideline be regularly revisited and revised, possibly as often as once a year, because the pace of discovery is so swift. The guideline was developed based on studies that were already published, so many ongoing studies and clinical trials could not be included but will soon produce new information that needs to be incorporated.

For now at least, the guideline establishes an unequivocal standard that doctors diagnosing and treating lung cancer will be expected to follow. “Ultimately, doctors who are not testing all lung adenocarcinoma tumors will have to justify why they are deviating from the guideline,” Dr. Ladanyi says.

Comments

Since these are genetic abnormalities, is there a specific genetic marker to test for in a healthy person who has a family history of lung cancer ( my mother, non-smoker). I've always wondered if it was genetics that caused her lung cancer (non small cell adenocarcinoma) or an environmental cause.

Hi, Jennifer, we spoke to cancer geneticist Kenneth Offit, who said that if there is only one case of lung cancer in your family this is not likely a hereditary situation. If there is more than one case of lung cancer among nonsmokers, it is possible there may be a hereditary cause, although those are rare. If you would like to learn more about our Clinical Genetics Service, you can go to http://www.mskcc.org/cancer-care/hereditary-genetics. Thanks for your comment.

My father was a pioneer at Memorial Hospital and now I was diagnosed with stage 4 nonsmall cell lung cancer two years ago I have chosen to not treat it and in two years it has not changed. My oncologist is amazed.

My mother received tarceva for her lung cancer and lived Two years and ten months having stage four adenocarcinoma. I was so grateful for that medicine. Dr. Nair of Allentown , Pa was wonderful in his care and explaining this med to all of us.

Please contact me my great grandmother died of lung cancer and my grandmother and my mother... all non-smokers and I have 2 lung nodules. On Pet Scan looks benign , I live in SF what can I do? I have a daughter ,two sisters and nieces. Also, I have second cousins with lung caner death all women and non-smokers!

Thank you for your comment. To consult with one of our genetic counselors, please call 646-888-4050. To make an appointment with a doctor at Memorial Sloan-Kettering, please call 800-525-2225. You can also find a list of National Cancer Institute-Designated Cancer Centers around the country here: http://www.cancer.gov/researchandfunding/extramural/cancercenters/find-a-cancer-center.

what drugs do you recommend if those oral drugs are not an option

Thank you for your comment. You can learn more about how we diagnose and treat lung cancer here: http://www.mskcc.org/cancer-care/adult/lung. If you would like to make an appointment with a Memorial Sloan-Kettering physician, please call 800-525-2225.

My mother did a chest x-ray and CT scan and they discovered multiple nodules in her lungs with a biggest nodule being 2.3 cm. The suspicion is for metastasis in her lungs. She also had some nodules in her thyroid, with biggest nodule 2.4 cm. The thyroid biopsy came back negative for cancer. What would be your recommendation for the next step? Which doctor should she see in your hospital: pulmonologist, oncologist, or endocrinologist? can we just contact that department and send her tests for a review?
Thanks, Glen.

Hi, Glen. Please call our Physician Referral Service at 800-525-2225. They will be able to help you figure out which type of doctor your mother should see and schedule an appointment. Thanks for your comment.

My Mother is 74 years old and was recently diagnosed with Lung Cancer, adenocarcinoma in the Left lung. Part of the lung has collapsed due to the tumor and it is also affecting the larengial nerve making it difficult for her to speak.The scans indicated the medial stymen is involved and the oncologist we saw last night told us it was in stage 3 and felt that it was inoperable. He is sending the speicimen to the pathologist to have it scanned for abnormalities before starting target treatment. He does want to start Chemotherapy in the next week or so. Does this sound like the best plan of action? I want to do what is best for my mother and get her the best treatment avaliable. Any advise you might be able to give me would be very helpful.
Thank you

Thank you for your comment. Unfortunately, we cannot comment on specific medical situations on our blog. To make an appointment to receive a consultation at Memorial Sloan-Kettering, please call 800-525-2225.

I am a 54 yr female smoker (38yrs) and was recommended by family dr to particapate in CT scan study due to fact I was coughng more then normal, no other systoms. Well they found bilaterlal nodules ground glass looking the biggest being 7mm. Follow up ct scan in 6months. I am very concerned. Based on studies what percent are cancerous and growth rate?

Cindy, we are unable to answer personal medical questions on our blog. If you'd like to make an appointment with a Memorial Sloan-Kettering physician, please call 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment. Thank you for your comment.

I am having a cat scan tomorrow to define a 2 cm mass in my chest. It was first noticed in December 2012, before a lumpectomy for stage 1 breast cancer. There has been no node involvement when my axillary nodes were tested in January 2013. I have been coughing for a few weeks and have larengytis. We thought it was allergies. Maybe it is and all this is unrelated.
What is the connection between breast cancer and lung cancer?

Meryl, unfortunately we are not able to answer personal medical questions on our blog. We recommend you speak with your doctor about this. If you would like to make an appointment to speak with a Memorial Sloan-Kettering doctor, please call 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment. Thank you for your comment.

If you are having anxiety about tomorrow's scan, you may also find it useful to read our recent blog post about "scanxiety." You can find it here: http://www.mskcc.org/blog/coping-scanxiety-during-and-after-treatment

What is a ground glass nodule? I have attempted to research this but am unable to find a definitive answer. Thank you.

Sheri, thank you for your comment. For this specific question, we suggest you call the National Cancer Institute’s Cancer Information Service at 800-4CANCER (800-422-6237) or visit

http://www.cancer.gov/aboutnci/cis/page1

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