Introduction

When I wrote my first review article on the treatment of the elderly, I entitled it, “NSCLC in the elderly—the legacy of therapeutic neglect.” Dr. Corey Langer and I chose the title to directly criticize the major mistake that we perceive in the treatment of the fit elderly—a therapeutic nihilism that leads oncologists to not give sufficiently aggressive treatment to the fit elderly. Lung cancer is a terrible cancer and failure to suppress it with sufficiently active therapy leads to great suffering. This is as true in the older patient as in the younger patient. However, there is great misunderstanding about the efficacy of therapy in the fit elderly patient, the subject of this post. I will seek to summarize coverage of this topic on GRACE previously, highlighting the now published French data on 1^st line treatment of the elderly. You may have noted the repeated use of the word, “fit.” Not all elderly patients are as fit as younger patients—aging brings with it more medical problems and more pills; not all elderly patients are as fit as younger patients with lung cancer. I will address this topic in a follow up post dedicated to this important topic.

Read the rest of this entry »

The third and last podcast from our discussions with Dr. Lecia Sequist, of Massachusetts General Hospital and Harvard Medical School, covers the question & answer session that followed her excellent webinar on acquired resistance to EGFR tyrosine kinase inhibitors, as well as the update I did with her on the latest information from their experience of re-biopsying lung tumors over the course of treatment.

Here are the audio and video versions of the podcast, as well as the transcript.

sequist-qa-session-audio-podcast

sequist-qa-session-transcript

Read the rest of this entry »

Podcast: Play in new window | Download

The Importance of Identifying Molecular Markers in Non-Small Cell Lung Cancer

To understand the importance of molecular markers in the current and future treatment of lung cancer, one should first understand how lung cancer was classified up until the beginning of this decade. Pathologists would look at a sample of a patient’s lung tumor under a microscope, and then make a judgment of whether the cells represented small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC). Although that is an oversimplification, for all practical purposes, that is what oncologists cared about when it came to choosing treatment. If the diagnosis was NSCLC, then oncologists treated the patient with platinum doublet chemotherapy using one of many standard regimens that were felt to be equally effective. Unfortunately we knew that these regimens only worked in a certain proportion of patients, but we had no way to predict ahead of time who would benefit and who would not.

At the same time pathologists and molecular biologists have know for some time that NSCLC is not really just one disease, but rather a constellation of many diseases that all share the distinction of starting in the lung. For example, major subtypes such as adenocarcinoma, squamous cell carcinoma, and large cell carcinoma were often reported in pathology reports but did not influence treatment choice. Since 2004 we have taken this one step farther, asking pathologists to tell us not just that the lung cancer is non-small cell but also that it is non-squamous cell, for purposes of safety with Avastin (bevacizumab) and efficacy with Alimta (pemetrexed), but that is the topic for another chapter.

As our understanding of the molecular basis of cancer has grown, we have developed a number of new molecularly-targeted agents with promise in the treatment of lung cancer. However, targeted drugs tend to have limited or no effect on cancers that lack the “target” of the drug, creating a need for markers to guide us.

Read the rest of this entry »

Several weeks ago I had the opportunity to discuss a series of cases of locally advanced NSCLC with a couple of expert colleagues: Dr. George Blumenschein, medical oncologist in the Division of Thoracic & Head/Neck Oncology at MD Anderson Cancer Center in Houston, TX; and Dr. Walter Curran, radiation oncologist who heads the Division of Radiation Oncology at the Winship Cancer Center at Emory University in Atlanta, GA.  Dr. Curran is also the head of the Radiation Therapy Oncology Group, the US-based cooperative oncology group leading important questions about radiation oncology in various cancer types.

The first of the cases we covered is a patient of mine with stage IIIA N2 NSCLC, the most controversial setting in lung cancer management, where many options are all considered as reasonable alternatives throughout the oncology field.

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

stage-iiia-n2-nsclc-case-drs-blumenschein-and-curran-audio-podcast

stage-iiia-n2-nsclc-case-drs-blumenschein-and-curran-transcript

stage-iiia-n2-nsclc-case-drs-blumenschein-and-curran-figs

Read the rest of this entry »

Podcast: Play in new window | Download

   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

Read the rest of this entry »

Podcast: Play in new window | Download

Dr. Alan Sandler is an international leader in the lung cancer world, also identified as among the most down to earth and funniest people in the field (and though that might not sound like much, he travels with an audio clip of a rim shot to play after his jokes).  His talks are light-hearted, but he’s so highly regarded because he has also been deeply involved in several of the pivotal research activities that have helped shape our current treatments.  He led the original study that led to the approval of gemcitabine in lung cancer, and more recently he led the ECOG 4599 trial that was published in the New England Journal of Medicine and established the benefit of Avastin with carbo/taxol for advanced lung cancer.

Dr. Sandler recently moved from Vanderbilt to my corner of the world (more or less), where he leads the Division of Hematology and Oncology at Oregon Health  & Science University in Portland.  He was kind enough to participate in our NSCLC Patient Education Forum, where he provided a general introduction to the biggest questions of managing advanced NSCLC: does treatment really help, and how much?  He also provided an overall review of the landscape in how we approach first line therapy for metastatic NSCLC, from someone who has been a big part of developing those standards.

Here is the audio and video versions of his presentation, along with the accompanying figures and transcript.

sandler intro to first line treatment of advanced nsclc audio podcast

sandler-intro-to-first-line-treatment-of-advanced-nsclc-figures

sandler-first-line-treatment-of-advanced-nsclc-transcript

I’m trying to leverage my proximity to Dr. Sandler, as well as my longtime friendship with him, to get him to involved with more of our GRACE activities.  Fortunately, he’s been very gracious and generous with his time, so get more of his perspective , and maybe even some good jokes, from him in the future as well.

Podcast: Play in new window | Download

This is the first of the presentations by guest speakers at our NSCLC Patient Education Forum back in September.   Dr. Gerard Silvestri is a pulmonologist, a lung disease specialist (not only cancer), and he is also one of the most important leaders in lung cancer within the field of pulmonology, as both a writer of some very important work and as a great speaker.

His talk was a general introduction to the process of the workup and approach to staging a lung cancer.  Below you’ll find the links to audio and video versions of his presentation, the figures, and the transcript for his talk.

Silvestri Lung Cancer Workup and Staging Audio

silvestri-lung-cancer-workup-and-staging-figures

silvestri-lung-cancer-workup-and-staging-transcript

Read the rest of this entry »

Podcast: Play in new window | Download

The most expert lung cancer pathologists in the world are planning a revision of the classification of lung adenocarcinomas that is expected to be approved and implemented next year, and it’s going to make some big changes.  Specifically, it’s planning to eliminate the diagnosis of bronchioloalveolar carcinoma (BAC), reflecting our evolving understanding of this disease.

BAC with lesions less than 2 cm is now being designated as a pre-cancerous adenocarcinoma in situ (AIS), which essentially means it’s a pre-invasive condition with a favorable prognosis.  In fact, the available literature, largely from Japan but also including evidence from other parts of the world, shows a 100% 5-year survival for a <2 cm AIS, which is far more commonly the non-mucinous BAC sybtype.  The size limit is significant, however, because larger lesions are felt far more likely to have at least some area of invasive disease.

The invasive portion of what is now in the spectrum of BAC with focal invasion to adenocarcinoma with BAC features has a major impact on prognosis.  In fact, the size of that invasive component is what drives prognosis, not the invasive part:

The Invasive Component in AdenoBAC Drives Prognosis

So a largely pre-invasive (adenocarcinoma in situ) lesion with a small area of invasiveness will now be designated as minimally invasive adenocarcinoma, and it also has a 100% cancer-specific survival at 5 years.

Read the rest of this entry »

In the last post that presented the highlights of the FLEX trial that tested the benefit of adding Ebritux (cetuximab) to standard chemo.  The trial was technically positive, statistically significant, but the results in the overall population of the trial were so marginally superior with Erbitux that a very logical follow-up question is whether we might identify certain subgroups of patients who benefit more, enough to definitely add Erbitux, while not pursuing it for other subgroups that appear to benefit much less.

It’s important to add a word of caution about interpreting information gleaned from patient subsets.  Clinical trials are generally designed to have enough patients to show differences in the entire trial with everyone. Nevertheless, when you dissect it ten different ways, the smaller subgroups don’t have adequate numbers to show significant differences, even when they may really exist.  At the same time, doing multiple different comparisons escalates the chance that you’ll randomly find differences that aren’t real, and that occur just as a product of random chance.  In fact, trials are generally powered to consider a difference as significant only if the probability of the difference happening by chance is less than 5%, but if you slice and dice the results to do ten different subgroup tests, the likelihood of at least one coming up positive just by chance is now 22%.

So these comparisons aren’t really conclusive and are better suited for shaping our ideas for future research than for guiding our treatment decisions. In reality, people (present company included) tend to pick and choose which subgroups they focus on to support their inclinations, while discarding other comparisons.

To provide the general picture, there’s a figure called a forest plot that shows the performance of multiple subgroups simutaneously.  Here, the size of the different subgroups is represented by the size of the black ovals, and the position of the oval to the relative to the vertical line shows whether the Ebritux group did better (if the oval is to the left of the vertical line, sometimes referred to as “unity”) or the chemo alone arm did better (if the oval falls to the right).

FLEX Trial Forest Plot

(Click on image to enlarge)

Read the rest of this entry »

   The ASCO meeting I’m at right now is so busy that there really isn’t time to write a new post (though I’m still “tweeting from the meeting”).  Though the talk show hows just air re-runs of old shows when they’re on vacation, I’m trying to continue to add new content to the website during this time (and it’s about as far from a vacation as anyone has in Orlando).  

   Here’s an interview I did with Dr. Suresh Ramalingam, medical oncologist and Director of the Thoracic Oncology Program at Winship Cancer Institute at Emory University.  It covers the current status of initial treatment for advanced NSCLC, including controversies and shifting standards for first line and then the transition into maintenance therapy.   There’s also an associated slide set (as a pdf file), a transcript, and a link to the audio (mp3) version.

ramalingam-podcast-figures-on-first-line-rx-and-maint2

ramalingam-first-line-and-maintenance-rx-transcript

Ramalingam First Line and Maintenance Rx for Adv NSCLC Audio Podcast

Podcast: Play in new window | Download