GRACE :: Lung Cancer

early stage NSCLC

Do You Seek and Do You Use Molecular Marker Information in Patients with Early Stage NSCLC?


Dr. Karen Kelly of University of California, Davis, presents her current view on using molecular markers in early stage non-small cell lung cancer and explains the RADIANT study that she leads.

Dr. Heather Wakelee: How Should We Use Molecular Marker Information for Management of Earlier Stage Non-Small Cell Lung Cancer?


Dr. Heather Wakelee from Stanford University discusses the open question of whether patients with resectable or locally advanced NSCLC should have testing for molecular markers, as well as how we might use this information in clinical practice.

Case in Point: Recommending Post-Operative Chemo for a Patient with a Smaller NSCLC Tumor but High-Risk Features


This is the first in a series of “uncut” videos that I’m starting that will focus on illustrative cases from my clinic that highlight some broader teaching points.  This particular video is on the decision-making process that led me to recommend adjuvant chemotherapy for a patient who underwent surgery for a 3.5 cm lung adenocarcinoma without lymph node involvement. Though this size is under the threshold we often use for recommending post-operative chemo, which is 4 cm, her particular cancer had some other features that made me concerned it may represent a high enough risk to favor additional treatment, in combination with her overall good health and desire to pursue a more aggressive approach if there is a good rationale for it.

As always, I’d welcome your thoughts, questions, objections, etc., as well as any feedback you want to offer about the format of using clinical cases to review broader concepts.  And any ideas for topics are also welcome.

Webinar on Refining Prognosis of Early Stage Lung Cancer by Molecular Features, with Dr. Johannes Kratz


The next live webinar to be done through the partnership of GRACE and LUNGevity Foundation will be on the timely subject of using molecular features of a resected non-small cell lung cancer in order to better understand the probability of the cancer recurring. This will be on November 14th, 7 PM Eastern/4 PM Pacific, and will hope to answer the question, “Could these molecular features improve upon current staging efforts to help us refine our recommendations of which patients should receive post-operative chemotherapy in order to reduce the chance of recurrence?”

To help us answer that question, we’ll be joined by Dr. Johannes Kratz, surgeon at Massachusetts General Hospital in Boston, who participated in important research while previously at the University of California in San Francisco on a molecular profile that can be performed on archived tissue (stored in wax after completion of the surgery) and has demonstrated an ability to discriminate between patients with a better or worse prognosis after surgery. This research was published in the prestigious journal The Lancet (with Dr. Kratz as lead author), was highlighted in one of my posts at the beginning of this year as an exciting new development, and this testing platform has recently become commercially available.

Dr. Kratz will review various efforts pursued to use tumor biology to refine treatment recommendations in patients with early stage NSCLC, including the benefits and limitations of different strategies. He will discuss ongoing research and current standards of care in this clinical setting.

Continue reading

The ChEST Trial: Pre-Operative Chemotherapy Looks Great, But That Ship May Have Already Sailed


We’ve covered the potential value of systemic therapy for early stage NSCLC in a wide range of posts and podcasts, and to summarize what we’ve learned in a sentence, it’s basically that chemotherapy can significantly increase progression-free survival (PFS) and overall survival (OS) in patients who have undergone curative surgery for stage I-III NSCLC, but the benefit is far more convincing in patients with a high enough risk to justify the potential adverse effects of chemotherapy.  In fact, in patients with node-negative cancers that are smaller than about 4 cm, the evidence isn’t very good that chemotherapy improves outcomes, and there is a strong suggestion from the limited available evidence that it may be net harmful.  This makes sense to me: chemotherapy represents a fixed negative effect (both quality of life and risk of adverse effects) whether a patient has a high risk of recurrence or a low risk of recurrence and can reduce the chance of the cancer recurring by a certain proportion. If the risk of recurrence is high (such as in someone with stage II or III resected NSCLC), chemo can reduce that risk quite a bit, so the net effect is very positive: big anticipated benefit exceeds small risk.  However, in patients with smaller node-negative cancers, the magnitude of benefit is going to be very low because the risk of recurrence is too low for the chemo to have much absolute effect: small risk exceeds even smaller anticipated benefit.

In recent years, we have generally focused on post-operative, or adjuvant chemotherapy, because the majority of positive trials for early stage patients have used an adjuvant strategy.  However, going back in time ten years, both pre-operative (neoadjuvant) and post-operative chemotherapy were investigational approaches, and they each have their advantages and disadvantages.  Post-operative chemotherapy has the benefit of being able to make treatment recommendations based on the most accurate staging information (from surgery) and provides the opportunity to do the most pivotal treatment immediately, but many patients are simply not able to consider chemotherapy within the first couple of months after surgery, and/or they need to abort treatment before the intended therapy has been delivered.  Pre-operative chemotherapy provides the earliest opportunity to treat potential micrometastic disease, should improve the probability that treatment will be delivered as planned (because few people will decide to abandon surgery), and it gives the chance to get feedback on how effectively the systemic therapy shrunk the cancer.  However, it also entails a small but real chance that the person’s cancer will grow and even potentially no longer be able to be resected, and possibly that chemo could increase the risk of surgical and post-surgical complications.   Pre-operative therapy may also have an advantage of allowing a patient to receive a less extensive surgery after a good response to initial systemic treatment.

So it’s fair to say that there is a good rationale to test both of these strategies, and studies have been pursued with surgery followed by randomization to chemo or observation, immediate randomization to chemotherapy followed by surgery or immediate surgery alone, and even one trial that randomized patients to pre-operative chemotherapy followed by surgery, surgery followed by chemotherapy, or neither pre-operative nor post-operative therapy and just surgery alone.   By 2003 and 2004, several trials of post-operative chemotherapy were reported as positive, and this led to early closure of several of the important pre-operative chemotherapy trials, since the emerging picture was that chemotherapy provided a benefit that made randomization of patients to a surgery alone arm unethical.

It is in this context that we can now review the significance of the newly published Chemotherapy in Early Stages Trial (ChEST), which was conducted at 45 centers in 15 countries in Europe and attempted to assess the benefit of three cycles of cisplatin/gemcitabine before surgery, compared with surgery alone.  The trial was designed with an intent to enroll 712 patients with stage IB to stage IIIA NSCLC (stage IIIA only if they had no mediastinal nodal involvement, so T3N1) and was looking to detect a 20% improvement in PFS as the primary endpoint, but from 2000 to 2004 only 270 patients were enrolled (129 randomized to pre-op chemotherapy, and 141 randomized to surgery alone).  It closed early in light of the mounting evidence supporting a role for chemotherapy. Continue reading

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