The Predicament of Poorly Differentiated NSCLC/NSCLC NOS

A topic that came up in a recent expert round table case discussion was the issue of how to manage a patient with a lung cancer for which the pathology report says “NSCLC not otherwise specified (NOS)”, or “poorly differentiated NSCLC, NOS”.  What does this actually mean, and what does it mean in terms of treatment options?

Tumors of pretty much all types are categorized by their tumor grade, how “differentiated” they are, which basically means, “how much do the cancer cells look like the cells they started out as?”.  Different cells of the body start out as stem cells, which means that they’re not specialized to be any special kind of cell, like one that detects light in the back of the retina, lines the esophagus, or is optimized for lung function.   Most cells of the body are differentiated, so that the appearance under a microscope shows that it’s a liver cell, part of the kidney filtering mechanism, heart muscle, etc.

Cancer cells, however, have mutations in them that make them grow and divide faster than other cells (that’s why they make a tumor that pushes other tissues aside), and they usually have several.  As they grow and divide, they often make sloppy copies of their DNA that leads to more mutations.  Cancers therefore are made of cells that may look a lot like the normal cells they originated from (well-differentiated), or they have lots of mutations that make the cells look so chaotic that they don’t look at all like the cells they started out as (poorly differentiated).

Today, oncologists want to know whether a non-small cell lung cancer (NSCLC) is an adenocarcinoma, squamous cell carcinoma, large cell neuroendocrine carcinoma, etc.  But about 20% of the time on various studies, we get an answer back of “NSCLC not otherwise specified”.  As explained by Dr. Matt Horton, expert lung cancer pathologist, a lung tumor may be classified as NSCLC  NOS because of either of two reasons:

1) there isn’t enough tissue, because the biopsy material was very scant, or

2) the tumor is so poorly differentiated that even with all of the material in the world, a good pathologist couldn’t identify the underlying NSCLC histology

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Case Discussion with Experts, Drs. Julie Brahmer & Greg Riely, Part 1

Here’s a webinar case discussion I did with Drs. Julie Brahmer from Johns Hopkins in Baltime, and Greg Riely from Memorial Sloan Kettering Cancer Center in New York.  They’re great thoracic oncologists as wellas friends, and they were kind enough to join me for discussion of several complex cases that don’t have clear answers and illustrate the reality that even when we know the evidence, there’s plenty of room for judgment.

Our first case is about a 63 year-old woman who has a poorly differentiated NSCLC that is just outside of the range we’d feel feasible for radiating, and it brings up issues related to trying to integrate chemo and possible radiation, the debatable role of agents like Avastin (bevacizumab) and Alimta (pemetrexed) for cancers that are hard to classify, and then how we approach managing patients who have responded well — observation or maintenance?

Here is the audio and video versions of the podcast, along with the associated transcript and figures.

rt-brahmer-riely-webinar-case-1-audio-podcast

rt-brahmer-riely-webinar-case-1-transcript

rt-brahmer-riely-webinar-case-1-figures

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Podcast of Q&A Portion from Molecular Markers Webinar with Dr. Pennell

   Here’s the podcast of the Q&A portion of the excellent webinar with Dr. Pennell on Molecular Markers in Management of NSCLC. 

dr-pennell-molecular-markers-qa-audio-podcast

dr-pennell-molecular-markers-qa-transcript

dr-pennell-molecular-markers-qa-figures

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Round Table with Drs. Anne Tsao and Alex Farivar, Part 2: Mesothelioma

This is part 2 of my round table case discussion with Dr. Anne Tsao, a medical oncologist and thoracic oncology expert from MD Anderson Cancer Center in Houston, and Dr. Alex Farivar, a thoracic surgeon with expert training in mesothelioma at Swedish Cancer Institute in Seattle. This particular case covers a patient with a mesothelioma, cancer of the lining around the lung, which is also known as malignant pleural mesothelioma.

Here is the audio and video versions of the podcast, along with the transcript and figures.

round-table-with-drs-tsao-and-farivar-part-2-meso-case-audio-podcast

round-table-with-drs-tsao-and-farivar-part-2-meso-case-transcript

round-table-with-drs-tsao-and-farivar-part-2-meso-case-figures

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Watching Small Lung Lesions Do Nothing: “Ground Glass Opacities” Don’t Progress Over Years If They’re Watched, Not Resected

In one of my earliest posts about bronchioloalveolar carcinoma (BAC) (in the dark ages, pre-Twitter), I wrote on the subject of managing small BAC-type lesions, which tend to appear as small hazy areas called “ground glass opacities” (GGOs) and suggested that some of these cancers may be so indolent that they don’t need to be treated, even if they have the word “carcinoma” in the diagnosis.

(a representative GGO identified by arrow)

Now there is a proposal to change BAC to “adenocarcinoma in situ“, a pre-cancerous condition, reflecting the idea that these lesions have such a favorable prognosis that they shouldn’t necessarily be put in the same category as invasive lung cancers (pure BAC is a non-invasive lesion that shouldn’t be able to get into the bloodstream and spread outside of the lungs).  And now, there’s a new article out of Japan that describes the experience of patients with BAC and multiple GGOs, some of which were resected and some not very accessible and some just watched.  It turned out that just watching seemed to be a pretty good strategy.

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Podcast by Dr. Camidge on ALK Rearrangements and a New Era of Molecular Oncology

   Last week, Dr. Ross Camidge from the University of Colorado joined me on a webinar entitled “One Size Does Not Fit All” in which he discussed the early work on ALK rearrangements and the novel agent PF-02341066 (now known as crizotinib) in particular, and the new era of molecularly defined practice of oncology in particular.   This story has been widely considered to be among the most important in the field of lung cancer over the last few years, and Dr. Camidge did not disappoint.

   Not only did many of the participants in the live program write comments here expressing their positive feedback on the great energy and overall quality of the program, but both our transcriber and the editor of our podcasts independently commented to me that they thought it was a terrific podcast and that they learned a lot (and they don’t have a special, vested interest in lung cancer issues).

   Here’s the audio and video podcast links, as well as the transcript and the figures from the webinar:

dr-camidge-on-alk-inhibitors-and-molecular-oncology-audio-podcast

dr-camidge-on-alk-inhibitors-and-molecular-oncology-transcript

dr-camidge-on-alk-inhibitors-and-molecular-oncology-figures

   Finally, I’d like to personalize this a bit, because one of the people who was mentioned in the podcast, Andy Hill, has also been featured in the local news in both Seattle (link to news report here) and Denver (link here) as a remarkable example of the promise of molecular oncology.   He’s also been a dedicated and extremely helpful supporter of GRACE in terms of both financial support and participating in our recent programs and some meetings as we work on the future directions for our organization.  So I’d like to dedicate the program to Andy and hope he continues to redefine the great success of this work in how well he does.

   Speaking of which, we could really benefit from your support for these programs.  This webinar wasn’t from a grant but rather from your contributions.  I hope you find these activities helpful and will support them.  I’d also encourage people to tell others, provide the link, if you know of anyone else who might benefit from learning the material in our educational programs.  We’d hate to think of the Andy Hills out there who may miss a chance for a very helpful treatment because they simply didn’t know such a possibility might exist.  And unfortunately, many oncologists are still not aware of these developments: the field is simply moving too quickly.

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A New Series of March Webinars

That short month of  February makes it so that March really sneaks up on you! We’re just a few days from March and our first of several upcoming webinars I need to tell people about.

The first will actually be on Monday, March 1st (just 4 days from now), with Dr. Jared Weiss from University of Pennsylvania joining me at 8 PM EST/5PM PST for a discussion of two very different but timely topics.  First, Dr. Weiss will cover the controversial and completely open question of what role EGFR inhibitors might play in early stage NSCLC, or whether we should even be talking about and checking for EGFR mutations in patients who don’t have advanced non-small cell lung cancer (NSCLC) (where most of the research and discussion has been concentrated).  Next, I’ll turn to a debate that has been ongoing for decades in lung cancer: should the minority of patients with very localized small cell lung cancer (SCLC) undergo surgery?  A very recent review of results from a large database put this topic back in the lung cancer news.  So should SCLC ever be managed surgically?  I’ll try to highlight the pros and cons.

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Round Table Discussion with Experts: Indolent BAC in an Elderly Man

This is the first part of a case presentation I did with two great colleagues: Dr. Anne Tsao, who is a medical oncologist and lung cancer expert at MD Anderson Cancer Center in Houston, and Dr. Alex Farivar, who is a terrific thoracic surgeon at my own institution, Swedish Cancer Institute in Seattle.

This case is an elderly gentleman who has a very indolent but growing lung lesion.  His story brings up questions of how concerned to be in following a nodule in a patient of advanced age and with competing medical issues, whether surgery that is less than a lobectomy might be considered, as well as the systemic therapy options for bronchioloalveolar carcinoma.

Here are the audio and video versions of the podcast, along with the transcript and figures.

expert-round-table-tsao-and-farivar-pt-1-bac-audio-podcast

expert-round-table-tsao-and-farivar-pt-1-bac-figures

expert-round-table-tsao-and-farivar-pt-1-bac-transcript

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Loading the Dice: Comparative Trials of EGFR Inhibitors in Patients with EGFR Mutations (or, When Bad Trials Happen to Good People)

The IPASS trial that randomized Asian never-smoking or light previously smoking patients with previously untreated advanced NSCLC to either standard chemo or the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI)  inhibitor Iressa (gefitinib) is widely considered among the most important and standard-changing trials of the last few years in the field of lung cancer.   Nevertheless, it’s important to bear in mind that patients were identified for enrollment on that trial based on clinical factors, with about a third of the 1217 enrolled patients having their tumors analyzed for EGFR mutation status.   The post-hoc results for that molecularly defined subset was the most interesting component of the trial, demonstrating that the patients with an EGFR mutation had a very significantly longer progression-free survival (PFS) with Iressa than with the standard chemo combination of carbo/taxol (paclitaxel).  In contrast, the exact opposite was true for patients who were Asian never-smokers with an adenocarcinoma but didn’t have an EGFR mutation.

That comparison of chemo vs. an EGFR inhibitor in a clinically selected population was a perfectly appropriate question when the study was designed and enrolled, since we didn’t have evidence that one approach was superior to another in clinically or molecularly selected populations.   This line of inquiry has been taken one step further by work from the North East Japan Gefitinib Study Group from Kobayashi and colleagues that tested Iressa against chemo in 200 previously untreated patients with advanced NSCLC who were prospectively selected for having an EGFR mutation.  It was designed to enroll 160 patients per arm, but an interim analysis showed that the results were so overwhelmingly more favorable for recipients of Iressa that the trial was closed early because it was felt to be unethical to continue to randomize patients if the answer to the question was already clear.  Although overall survival was not mature and wasn’t shown, preliminary results of this trial presented at ASCO 2009 revealed that the patients on the Iressa arm had a far superior response rate (74.5% vs 29%, p < 0.001) as well as PFS (10.4 vs. 5.4 months, p < 0.001).  The curves for the latter are shown below.

(click on image to enlarge)

Along with this trial, a remarkably similar European trial is being completed that randomizes a population of previously untreated patients with an EGFR mutation to either erlotinib or cisplatin/docetaxel.

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Webinar with Dr. Ross Camidge: Learn about his Experience Treating Patients with EML4-ALK Translocation

I just wanted to offer a reminder that Dr. Ross Camidge, medical oncologist and lung cancer expert from the University of Colorado in Denver, is going to be speaking with me during a webinar this Wednesday, 2/17, at 8 PM EST/5 PM PST.  Among the topics we’ll cover is the EML4-ALK translocation, which is widely considered to be among the most exciting developments in the lung cancer field over the last several years.

Dr. Camidge was kind enough to agree to give a primer on the new and emerging story of EML4-ALK and the investigational drug PF-02341066, which Dr. Camidge was one of the first people to use in lung cancer patients.  He’s currently treating some patients having sensational responses, so he can tell us more from the perspective of someone who has been directly involved with the research program.

We’re also going to cover a bit on the question of the role of surgery in more locally advanced NSCLC that is treated initially with chemo and radiation.  I’ll present some background on this, including a new article that is coming out describing this experience.  I’ll also invite Dr. Camidge to give some of his thoughts on this work as well.

Otherwise, we’re going to try to leave some time for questions on these subjects from people participating in the webinar.  If you’re interested in being one of those people, please register for the Feb 17th webinar; registration is free but limited.

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