GRACE :: Lung Cancer

Repeat Biopsies

GRACE Video

How a Diagnosis of Lung Cancer is Made: The Biopsy

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Dr. Gerard Silvestri, Medical University of South Carolina, describes several procedures used to obtain biopsy tissue in order to diagnose lung cancer.

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When I meet with patients who have a new spot on their lung, I tell them I want to do three things and I do it in lay terms and then describe what that means in medical terms. So I ask the question, what is it — that’s the diagnosis, where is it — that’s the stage, and then what can we do about it — those are the treatment options.

As far as diagnosis is concerned, that means getting a tissue biopsy, and there are a number of ways that we can get tissue from patients’ lungs. One is by numbing up the skin on the chest and doing a needle biopsy through the chest wall and into the spot itself. Another is by a procedure called bronchoscopy. That’s where we take a look down into the lungs, the patient is given sedation medicine, and then we take a biopsy from the inside out. There are a number of other ways, including a surgical biopsy where a patient is asleep in the operating room, and the patient gets a small surgical biopsy of their lesion.

Now sometimes we direct our biopsy outside the chest so that we can make a diagnosis and a stage at the same time. For example, if a patient has a liver lesion on a CT scan, we may choose to numb the skin in the abdomen and do a needle biopsy that way, and that gives us both a diagnosis and a stage at the same time.

It’s critically important to make sure that we get those three things right before we embark on treatment: what is it — diagnosis, where is it — stage, what can we do about it — treatment options.


GRACE Video

Repeat Biopsies and Emerging Technologies for Plasma Sampling of Mutations Seen with Acquired Resistance

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Dr. Leora Horn of Vanderbilt University reviews the rapidly evolving issue and growing value of repeat biopsies, including plasma sampling as a “liquid biopsy” option, in the setting of acquired resistance to a driver mutation in advanced NSCLC.

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GRACE Video

What is the Current Role of Serum Based Biomarker Testing?

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Drs. Ben Solomon, Leora Horn, & Jack West assess the utility and limitations of “liquid biopsies”, serum-based testing for molecular marker testing in lung cancer.

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Dr. West:  At the World Lung meeting, we saw more new data and materials being promoted about serum-based testing of biomarkers — certainly more than I’ve seen at a prior meeting, and it seems like the technology is approaching a cusp of true clinical utility. What are your thoughts — how are you using serum-based testing, or even urine-based testing, I’ve seen little bit of work one, is that something that you’re using at all now, is it something that you think is fast-approaching, or still kind of in the distant future and inferior to tissue-based testing? Ben, I’ll start with you.

Dr. Solomon: Yes, so, I think a challenge with lung cancer patients is getting serial biopsies, and now we’re in a situation where getting a repeat biopsy can actually change treatment, and the example of that is a patient with en EGFR mutation who’s progressing on what we now call first-generation EGFR inhibitors. If these patients have another biopsy of their disease that has progressed, that shows a T790m mutation, then they’re likely to benefit from a third generation inhibitor. But, for a lot of patients, these biopsies are difficult to get, and I think that’s the real place that plasma DNA testing is likely to first make a clinical impact, and things like T790m change over time. Technology like blood-based testing allows us to follow that in a patient in a very non-invasive manner, so I think that’s probably the first place that…

Dr. West:  And these drugs are really coming out, hopefully in the next few months, where there’s going to be a much greater demand for repeat biopsies of some type, whether it is tissue biopsies, or a so-called liquid biopsy — a blood serum test. Leora, what are your thoughts here?

Dr. Horn: So, Lecia Sequist had really nice data at ASCO, showing that there was good sensitivity with a blood-based testing for T790m. So, I think that it is something that’s going to be more readily used. It’s easier for patients, especially in smaller community settings where there may not be an interventional radiologist or an interventional pulmonologist who can readily go get tissue, and patients, if they know their disease is progressing, will want to switch. I think where it will get a little bit difficult is if we start using them routinely, and you see a patient on an EGFR inhibitor has now developed T790m in their blood, but their CT scan looks good, you know, are we going to be using this for monitoring, and what do you do in that situation?

Dr. West:  Yeah, I think that’s a different question of using it sequentially to monitor impending progression, or, you know, serum-based progression versus clinical progression. I personally feel like that would be a real mistake. We don’t have enough good therapies that we should discard any effective therapy too early based on a number that doesn’t have any good clinical correlate. To me, it’s like looking at a telescope and seeing a meteor coming in, you know, thirty years and freaking out about it now. Already, you could do things like PET scanning all the time, or use something as old as CEA levels — and sometimes we see people get taken off of chemotherapy, or a targeted therapy, that they’re tolerating well and their scans don’t change, but their CEA went from 33 to 40, and that triggered what I would say is an ill advised change, and I’d be afraid of someone seeing T790m on a blood test and making a change too early.

Dr. Solomon:  I agree, there is no current data that supports changing from a first generation EGFR inhibitor to a third generation, just based on the presence of a T790m mutation in blood, in the absence of disease progression, on the basis of the current data.

Dr. Horn:  I agree with you, but you’re going to see it, and that’s what I worry about.

Dr. West:  No doubt, we already see people getting taken off of treatments based on CEA levels or a PET scan — to me it seems like you’re just changing lanes in traffic, it’s not getting you anywhere faster, it’s just — don’t just stand there, do something, as if that’s a reason to make a change.


GRACE Video

The Potential Value of Repeat Biopsies in Acquired Resistance

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GCVL_LU_Potential_Value_Repeat_Biopsies_Acquired_Resistance

 

MSKCC medical oncologist Dr. Greg Riely explains the growing value of a repeat biopsy after the development of acquired resistance in patients with an EGFR mutation.

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So, after initial therapy with EGFR tyrosine-kinase inhibitors, patients often develop — always, really, develop progressive disease, known as resistance, where the tumor has become resistant to therapy. How we manage patients and how we treat their disease, after development of resistance, is a complicated area. One way we can learn a little bit more about a patient’s tumor, and help to refine our decision making, is to do a biopsy of a site of progressive disease.

What we learn from a biopsy really is two-fold. The first, and easiest part, is the pathologist looks at it under the microscope and says, “is this still non-small cell lung cancer, or is this changed?” A relatively rare phenomenon is transformation of non-small cell lung cancer into small cell lung cancer — it happens maybe one to three percent of the time, but it’s a relevant thing to find, and we would adjust chemotherapy as a consequence of this.

Another thing to look for when we biopsy a site of resistance is acquisition of new mutations. One of the most common new mutations identified, it happens in about two-thirds of patients, is a secondary mutation called T790M. The important thing about identifying T790M is that we can now, in clinical trials, and hopefully in the future, with FDA approved drugs, target that T790M mutation with a new drug; we have two new drugs that are being developed now, one is called rociletinib and one is called mereletinib — these are specifically designed to target T790M. Now, importantly, any given biopsy has a chance of finding a mutation that’s present, and it also has a chance of missing it — whether that’s because we biopsied a site that didn’t have that mutation or, for whatever reason, our testing didn’t identify the T790M mutation. I think it’s important to know that as a caveat before going in to re-biopsy, but I do think that biopsying tumors at the time of resistance to EGFR tyrosine-kinase inhibitors does help devise the next best therapy for a patient.


GRACE Video

Questions & Answers with Drs. Riely, Weiss and Sequist; Moderated by Dr. West

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Acquired Resistance Forum Video #4: The first three speakers at the Acquired Resistance in Lung Cancer Patient Forum sat for a moderated Q&A with Dr. Jack West. 


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