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never-smoker NSCLC

Molecular Markers in Lung Cancer

It’s Possible to Live WITH Cancer

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This November, GRACE Honors the Empowered Patient.November is Lung Cancer Awareness Month. To mark it this year, GRACE is celebrating the empowered lung cancer patient. In this video, Linnea Duff, a 10-year stage IV ALK+ lung cancer patient, shares her journey from stunned patient to empowered patient.

Watch, read, and then share your own stories of empowerment in our online forum. Your story may inspire others.


The Inherited T790M EGFR Mutation and Risk of Familial Lung Cancer

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Here’s the pdf for this presentation: Inherited T790M EGFR Mutation


The Perils of Molecular Oncology: Mutations Aren’t Everything, or at Least They’re Not Infallible

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Every few months I see a patient who reminds me of the fallability of mutation testing.

One of the brightest rays of hope in the management of lung cancer and much of cancer care in the last decade has been the transition toward treatment guided by the presence or absence of particular molecular markers like EGFR mutations, ALK or ROS1 rearrangements, and potentially others being studied now.  However, I’d like to sound a note of caution about focusing too much on the results of a test. Specifically, I have seen a few patients, including one in the last couple of days, who highlight how tragic it would be for us to limit the use of the oral EGFR tyrosine kinase inhibitor (TKI)  Tarceva (erlotinib) to patients who are tested and have an EGFR mutation.

To backtrack, over the last few years it has become clear that most of the people who are major beneficiaries of an EGFR TKI are those with an activating EGFR mutation. We’ve also seen several studies that show that in the minority of advanced NSCLC patients whose tumors have an activating EGFR mutation, an EGFR TKI is extremely likely to be more effective than chemo as first line treatment.  Tarceva had already been approved by the FDA as a second or third line treatment for a broad range of molecularly unselected patients (no EGFR mutation requirement) based on a randomized trial that showed a 2 month survival benefit overall, so the question was whether when you take out the profound benefit seen in a minority, there’s still enough benefit in the “EGFR wild type” patients (no activating mutation) to have it be worth treating such patients with Tarceva.  

Though there are many who minimize the value of Tarceva in patients with EGFR wild type, the evidence indicates that such patients still receive an approximately 1.5-2 month improvement in median overall survival with it, so I routinely recommend Tarceva as a second or third line therapy after initial chemo in patients who test negative for an EGFR mutation. Most of the benefit is in the form of prolonged stable disease or at most a minor response, which can still translate to living a few months longer. In the back of my mind, as well, is the possibility that a small minority of such patients will respond extremely well, reminiscent of what we’d expect to see in someone with an EGFR mutation — because we know that the response rate to Tarceva in tested, EGFR wild type patients is low, but it’s not zero.  Continue reading


Dr. Alice Shaw on Clinical Factors Associated with Molecular Markers

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I’m happy to bring you now the second part of the Santa Monica webinar, developed with the LUNGevity Foundation, on “Molecular Markers in Advanced NSCLC: Who to Test and What to Test For?“, in which I was joined by Drs. Charles Rudin (Johns Hopkins University in Balimore, MD), Alice Shaw (Massachusetts General Hospital in Boston, MA), David Spigel (Sarah Cannon Cancer Center in Nashville, TN), and Glen Gloss (University of Ottawa in Ontario, Canada).  

In this short podcast, Dr. Alice Shaw reviewed the frequencies of different molecular markers in advanced NSCLC as a function of patient sex, smoking status, race, and tumor histology.  This work is very interesting, of course, because if we only do molecular marker studies of people with an adenocarcinoma or never-smokers, we not only won’t ever find potentially relevant mutations in people with other histologies and those with a smoking history, but we won’t have any good idea of the probabilities of finding them either.

Here is the podcast in audio and video formats, as well as the transcript and figures.

Molecular Markers SM Pt 2 Shaw on Markers by Clin Factors Audio Podcast

Molecular Markers SM Pt 2 Shaw on Markers by Clin Factors Transcript

Molecular Markers SM Pt 2 Shaw on Markers by Clin Factors Figs

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Who to Test for an EGFR Mutation or ALK Rearrangement: Filtering Based on TTF-1 Status

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Thyroid transcription factor-1 (TTF-1) is a protein seen on the surface of thyroid cells, but also on about 70-75% lung adenocarcinomas and only a small minority (~10%) of squamous cell NSCLC tumors. In fact, the presence of TTF-1 on a NSCLC tumor provides a good hint for the pathologist that this is an adenocarcinoma. It’s an immunohistochemical (IHC) test that is done on the vast majority of lung cancers, and there’s some new information that suggests it may also be useful for predicting which patients are especially unlikely to have an EGFR mutation or ALK rearrangement. This is especially important as we are now faced with a question of whose tissue to send for these particular tests, especially if this decision involves obtaining another biopsy.

A few months ago, a group from Seoul, Korea published their results on the correlation between ALK positivity in a series of 221 patients with lung adenocarcinoma and other clinical and pathologic features. In this somewhat selected group of Asian patients with an adenocarcinoma, 45 (20% had an ALK rearrangement, and this population skewed toward being younger than other patients (49 vs. 61), but didn’t differ in smoking status (about half were never-smokers in both groups for this population) or gender distribution, but they did have two striking features. ALK rearrangements were mutually exclusive with an EGFR mutation (they were never seen in the same patient), and there were no patients with an ALK rearrangement who tested negative for TTF-1 expression.

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