Here’s another case in the recording I did with Drs. Jyoti Patel from Northwestern and Bob Doebele from University of Colorado, discussing a series of perplexing cases in lung cancer management, then combining their comments with the responses from several other terrific experts (Drs. Suresh Ramalingam, Jonathan Goldman, Julie Brahmer, Heather Wakelee, and Karen Reckamp) about the same case.  From each one, you can get a sense of the variability in how different lung cancer experts share the same set of data but have their own interpretation and style for cases where there are significant gaps in what the data tell us.

This particular case is one we struggle with all the time, and one for which many people have asked questions here.  Once someone with unresectable stage III NSCLC has completed initial chemo/radiation, typically over an approximately seven week period, should we recommend any additional treatment after that.  We are generally tempted to do so, in hopes of providing better results than what we might expect without it, but we don’t have evidence that it helps.  I think you’ll get a clear sense of the uncertainty (at least mine), but several of the speakers also note their different mindset for those patients treated with weekly carbo/Taxol (paclitaxel) (which we believe doesn’t give meaningful systemic dosing to eradicate micrometastatic disease, but it can help make the radiation given concurrently more effective) versus “full dose” cisplatin/etoposide (which we feel does treat possible distant disease in addition to helping make the radiation more effective where it is directed).

So here’s the audio and video versions of the podcast, along with the transcript and figures from the presentation.

grace-cases-stage-iiib-nsclc-chemort-and-consolidation-q-audio-podcast

grace-cases-stage-iiib-nsclc-chemort-and-consolidation-q-transcript

grace-cases-stage-iiib-nsclc-chemort-and-consolidation-q-figures

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Our multidisciplinary thoracic oncology tumor board is dynamic and a highlight of the week, facilitated in equal parts by the fact that our group genuinely enjoys each other’s company and that it is the source of some engaging debate about the potential best way to manage several complex scenarios in lung cancer. There are a few that have become recurring debates, among them the question of whether to pursue surgery for a patient with a locally advanced NSCLC, perhaps felt to be unresectable or on the outer limits of resectability, who has undergone chemotherapy and concurrent radiation to a potentially curative dose, has encouraging but ambiguous imaging findings, and is now being considered for surgery. Essentially, this is a troubling struggle of trying to balance our concern for over-treating vs. potentially under-treating this patient.

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We’ve recently received a series of questions on the question of whether it makes sense to give an oral EGFR inhibitor like Tarceva (erlotinib) or Iressa (gefitinib) concurrently with radiation.  This is really a poorly studied question, but a paper just published in the Journal of Thoracic Oncology describes a clinical trial that helps to address this question.  Unfortunately, for reasons that aren’t very clear, the results didn’t look very favorable overall.  But let’s explore this in more detail.

The Cancer And Leukemia Group B (CALGB), one of the three main cancer cooperative groups in the US, noted that EGFR inhibitors were apparently active for at least some patients with NSCLC and with often modest side effects, most typically rash and a tendency toward diarrhea.  The investigators from CALGB started trial 30106 to ask a slightly different question in two different clinical populations:

1) For patients with a good performance status (PS) and unresectable stage III NSCLC, does adding daily Iressa to initial chemo followed by concurrent chemo/radiation lead to more favorable results than would be expected from this approach without Iressa?

2) For patients with a marginal PS and unresectable stage III NSCLC, does adding daily Iressa to initial chemo, giving Iressa with radiation instead of chemo/radiation lead to favorable results?

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Here is the second case in my expert round table discussion on locally advanced NSCLC with medical oncologist Dr. George Blumenschein froMD Anderson Cancer Center and radiation oncologist Dr. Walter Curran from Emory University.

We focus in this case on the decision of which patients with a Pancoast tumor should undergo surgery or a nonsurgical approach of chemo/radiation, the challenge of trying to define the right time to repeat scans after chemo/radiation in locally advanced NSCLC, and we also debate the merits of close observation vs. further interventions in the face of worrisome but still ambiguous imaging findings.

I’ll add that I do find it instructive how varied the advocated treatment approaches are among the various experts when discussing not only this case but so many others I present.  These are admittedly challenging cases that don’t fit into any “classic” treatment approach, but these discussions of the range of alternatives offered by experts from so many places speaks to the fact that there is rarely one best strategy.

As always, here is the podcast in both audio and video formats, along with the transcript and figures.

imaging-issues-after-chemoradiation-case-blumenschein-curran-audio-podcast

imaging-issues-after-chemoradiation-case-blumenschein-curran-transcript

imaging-issues-after-chemoradiation-case-blumenschein-curran-figures

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Our next podcast slide presentation comes from Dr. Shirish Gadgeel, medical oncologist at Wayne State University in Detroit.  He came out to Seattle for a physician education program I run and was kind enough to stay for our NSCLC Patient Education Forum, where he spoke on our Current Standards of Care for Locally Advanced (Stage III) NSCLC.

Here’s his presentation in audio and video formats, along with the transcript and copies of the slides.

gadgeel-management-of-locally-advanced-nsclc-transcript

gadgeel-management-of-locally-advanced-nsclc-figures

gadgeel-management-of-locally-advanced-nsclc-audio-podcast

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Perhaps the most unexpected clinical trial result in lung cancer over the past 5 years was the finding in the large Southwest Oncology Group (SWOG) 0023 trial that randomized several hundred patients to maintenance therapy with either the oral EGFR inhibitor  Iressa (gefitinib) or a placebo after chemo/radiation concurrently and then consolidation taxotere (docetaxel).  While just about everyone in the lung cancer community expected to see either a significant benefit or, at worst, no real effect from maintenance Iressa, the actual trial was stopped early and demonstrated a statistically and I would say clinically significant decrease in overall survival with maintenance Iressa.  The median overall survival (OS) in the final publication was a full 12 months lower in patients who received Iressa compared with those who received the placebo .

To me, not only did this study demonstrate that giving consolidation EGFR inhibitor therapy was probably a bad idea, at least outside of a clinical trial, it also suggested that we don’t necessarily know as much as we presume we do about how trials will turn out, so it makes sense to do the studies rather than just start a new strategy without the evidence to back it up.

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“Locally-advanced NSCLC” is a term generally applied to lung cancers with tumors that have either grown into major structures (such as vertebrae or spine bones, the central airways, or involve the main blood vessels supplying the lung or central chest) or those cancers that have spread to lymph nodes in the central chest (the mediastinum).   In the case of many of these cancers, removing them with surgery is not possible, but treatment with the combination of chemotherapy and radiation given at the same time may be used with the goal of curing the cancer.

While administering chemotherapy and radiation at the same time (termed “concurrent therapy”) is more effective at killing cancer cells than when the treatments are given separately, this approach also causes increased side effects for the patient.   Side effects may include nausea, vomiting, neutropenia (decreased levels of white blood cells which can lead to increased risk of infection) with or without infections, anemia, fatigue, and pain with swallowing (from radiation “sunburn” to the esophagus).   In order for a patient to tolerate this rather stout combination, they need to be fairly healthy and active, and to have a strong physical reserve (measured with a term “performance status”).

Most studies of the combination of chemotherapy and radiation, although not excluding older patients, have enrolled younger patients.   Typically, the average age of patients enrolled on trials like these is 64 or 65.   This allows for decent conclusions to be drawn for patients of this age group and younger, but how do these studies apply to the elderly; patients 75, 80, older?

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   Dr. Suresh Ramalingam is a longtime friend of mine and a national leader in the field of lung cancer.  He is the Director of the Lung Cancer Program at the Winship Cancer Institute at Emory University in Atlanta, and he was kind enough to sit down with me to talk about his perspective on the current optimal treatment for patients with stage III, or locally advanced, NSCLC.  We also spoke about managing metastatic disease, which will be covered in a separate podcast.  It’s an audio interview, but if people watch the video version, there are some figures synchronized with the discussion.

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   Ask and ye shall receive!  The leading requiest for a video podcast presentation was for a summary of the subject of locally advanced, unresectable stage III NSCLC.  Here you go:

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Sorry it’s a little rushed, but it’s a struggle to do a topic justice with a 10 minute limit (the most YouTube accepts).  In the future, we’ll try to divide bigger topics into two podcasts if it’s going to require cramming into a 10 minute interval.   It may help for you to have the images and transcript available, so here they are:

Locally Advanced NSCLC vodcast images

Optimal Mgmt of Loc Adv NSCLC transcript

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   As we move forward in our audio/visual odyssey, we’re going to add audio interviews with experts in various aspects of cancer care.  The first of these is from our own Vivek Mehta, who sat down with me to go over current radiation approaches for patients with early stage NSCLC, as well as management locally advanced NSCLC.

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And along with that is the transcript for this interview, here.  Dr. Vivek Mehta Interview I Transcript

We’re still trying to get the optimal setup, which this isn’t.  There’s some background noise, but it’s all audible.  And things will only get better.  There are a few more in the works.

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