Here’s a continuation of the webinar content by Dr. Lecia Sequist, who is an Assistant Professor of Medicine at Harvard Medical School and Massachusetts General Hospital (MGH).  At the time of her live presentation, she was unable to discuss some very new work that was about to be published on their experience at MGH in repeating biopsies on patients over the course of their ongoing treatment, and the interesting and sometimes treatment-changing results they found.

This second podcast includes her presentation on this very timely information that was, frankly, surprising to many in the lung cancer community, as well as to the investigators themselves.  The presentation is in video and audio podcast forms, along with the associated transcript and figures.

sequist-on-lessons-learned-from-serial-biopsies-audio-podcast

sequist-on-lessons-learned-from-serial-biopsies-transcript

sequist-on-lessons-learned-from-serial-biopsies-figures

Read the rest of this entry »

Podcast: Play in new window | Download

   In my last post I outlined the typical clinical scenario for pneumonic bronchioloalveolar carcinoma (BAC), which is typically the mucinous subtype of this unusual disease.  In fact, we are still actively learning a great deal about BAC, enough for the lung cancer experts to begin to develop a more sophisticated view that the mucinous and non-mucinous subtypes have different behaviors and respond differently to treatments.  Here is a case that illustrates a situation that I would consider to be typical for the mucinous, pneumonic form of BAC.

    Ella A. was 74 year-old woman with a very long smoking history of about 50 years, who quit last month in the face of worsening pulmonary and other symptoms.  Specifically, she experienced an initial dry cough that became productive of sputum over a six-month period, during which time she also developed increasing shortness of breath and a 20-pound weight loss for a woman who was pretty slender beforehand.  This led her to her primary care physician, which showed extensive “consolidation”, shadows in both lungs and particularly extensive on the left.  These findings were confirmed on a CT.

 (Click to enlarge)

As you might suspect, this led to a referral to a pulmonologist for a brochoscopic biopsy.  The pulmonolgist needed to start her on oxygen before he could do a thorough bronchoscopy.  The biopsy revealed well differentiated BAC, but the pathologist (an expert in lung pathology) didn’t have enough material to specify whether it was mucinous or non-mucinous.

   Frankly, at the time when I first met her, in December of 2006, there were only the early inklings that this could be relevant.  We don’t have much more information since then, except for the anecdotal experiences of myself and a few others who treatment many patients with BAC, which have corroborated the early impression that the well described effectiveness of oral EGFR inhibitors like iressa (gefitinib) and tarceva (erlotinib) in BAC appeared to be limited to the non-mucinous subtype.

Read the rest of this entry »

   One of the issues with BAC is that I’ve referred to it as potentially very indolent, but as we’ve learned more about BAC, it’s become clear that there is a great degree of heterogeneity in BAC cases.  We’re learning that the cases that are more often slowly progressing and sometimes exceptionally responsive to EGFR inhibitors like tarceva and iressa are far more likely to be non-mucinous BAC.  These typically have the appearance of innumerable small nodules throughout the lungs.  There is a form that is the opposite: with sweeping areas of consolidation (also known as opacity) throughout entire areas of lung, typically mucinous, and essentially never responsive to EGFR inhibitors based on what we know right now.  This form is called pneumonic BAC, and it is typically very aggressive and unfortunately seems to be resistant to most of our treatments. 

   It’s called pneumonic BAC because it looks for all the world like pneumonia on an x-ray or CT, and I suspect that just about every patient who is ultimately diagnosed with pneumonic BAC is treated for at least weeks and often months with antibiotics.  The classic example is that it involves much or sometimes all of a lobe of the lung:

Because it’s mucinous BAC, these patients often describe coughing up large amounts of frothy sputum.

   Read the rest of this entry »

An interesting trial presented at ASCO 2008 came out of Japan, asking the question of whether there is an advantage to continuing first line platinum-based doublet chemo for up to six cycles or whether it might be better to give just three cycles and then switch from chemo right to the EGFR inhibitor iressa in Japanese patients with advanced NSCLC (abstract here). I haven’t mentioned it before because the trial, although interesting and with some provocative findings, didn’t clearly provide conclusions that would lead to obvious management changes.

For trial 0203, the West Japan Thoracic Oncology Group (WJTOG) enrolled 600 patients with previously untreated advanced NSCLC, with asymptomatic brain metastases permitted. Unlike North American NSCLC patients, among whom 10-15% are never-smokers, 31% of the patients in this Japanese trial were never-smokers; about 78% had adenocarcinomas (a higher proportion than in North America or Europe). They were randomized to receive chemo for six cycles vs. three followed by Iressa. The chemo could be carbo/taxol or cisplatin with gemcitabine, taxotere, navelbine, or irinotecan, all comparable in activity.

Read the rest of this entry »

   I’ve been involved in a wide range of discussions, both here and in my own clinical, about the fairly common situation of how to approach a situation in which the story on paper and what you see actually happening are incompatible.  For instance, last week I and several of my colleagues participated in a journal club (a group discussion of a new and/or controversial journal article or two), in which the topic was the potential utility of doing surgery for unusually early small cell lung cancer tumors.  We’ve also had several recent questions about patients in whom the diagnosis of bronchioloalveolar carcinoma (BAC) is being considered, and it’s not clear whether to treat this sometimes very indolent cancer as a full-fledged NSCLC, a non-entity that might sometimes be ignored, or as a separate category worthy of being managed differently from the standard approaches for other NSCLC subtypes.

It’s important to highlight that the discrepancy between the expected outcome based on a pathology report and the clinical picture in front of you can cut both ways.  In some cases, you may have a biopsy of a lung nodule that shows no cancer, but if it’s growing and continues to grow, that’s not very reassuring, and you’d suspect that the biopsy missed the diagnostic part of the tumor that would confirm viable cancer.  In other settings, a biopsy of a lung nodule might diagnose cancer, leading down a path toward the typical management with surgery, etc., but if you happened to have old films that showed that the nodule was actually minimally changed over 3 years or more, it might be reason to take a step back and wonder whether you haven’t already been furnished with some valuable information that might lead you to individualize and change your treatment plan.

Read the rest of this entry »

   One of the abstracts in lung cancer that I noted as being particularly noteworthy before ASCO 2008, but which I haven’t managed to mention since, is a trial of a monoclonal antibody known as CP-751,871 that targets and inhibits insulin-like growth factor receptor-1(IGF-1R), a molecule that appears to be involved with cell growth, balance of programmed cell death, and likelihood of metastatic spread (abstract here):

This was a rather complex study, presented by Dr. Dan Karp from MD Anderson in preliminary form last year (abstract here), in which patients with previously untreated advanced NSCLC were randomized two to one to receive either carbo/taxol alone or the same chemo combination with this IGF-1R antibody at either of two doses, IV every three weeks.  After randomizing 150 patients and seeing especially encouraging results in patients with squamous cancers, they then enrolled a few additional patients with squamous cancers to all receive chemo with the higher dose of the IGF-1R antibody.

Read the rest of this entry »

   In the past couple of posts we’ve seen that based on evidence from Japan and Rome, number of lymph nodes resected and also the absolute number of positive nodes and/or proportion of positive nodes may be important prognostic variable.  A third abstract I reviewed on the same subject came from Peoria, IL, and illustrated a key reason why using these variables may not be as consistently useful as we’d like, at least in many parts of the world.  In the study from Japan I discussed in a recent prior post, the investigators evaluated records from 574 patients and excluded the 27 (5%) of cases in which fewer than 10 nodes were removed at surgery, because they considered this to be a suboptimal resection.  Meanwhile, the study from Italy that I reviewed in my last post wasn’t as stringent but also identified 10 lymph notes as an important separation point for better vs. worse survival. 

    So how do we do in the US? Peoria is a town in Illinois that is considered to be so representative of Anytown, USA (at least any small to medium-sized town) that the phrase, “But how does it play in Peoria?” is a common way of asking whether something is representative of a broader American experience.  As it happens, the last presentation I reviewed tells us something about these surgical questions in Peoria, because it reviewed the experience of 98 patients who underwent surgery for stage IA NSCLC at a hospital in Peoria, IL over a 7-year period (abstract here).  Stage I NSCLC is defined by an absence of any lymph node involvement, so the investigators excluded the patients who didn’t have even a single lymph node removed at surgery (not exactly a high bar compared with the experience in Japan, where they excluded the 5% of cases where fewer than 10 nodes were removed! (And we don’t even know how many cases in Peoria missed that rather non-ambitious cutoff…)  They found that, as in the Italian study, prognosis was better in the patients in whom more lymph nodes were removed, as shown here:

Read the rest of this entry »

   In the last post I discussed some interesting work from a group in Japan that suggested that the number of lymph nodes that are removed and positive for NSCLC may be a very important prognostic variable, potentially an even more important factor than location of the nodes, which is the basis for how we stage nodal involvement in NSCLC now.   Following along the same theme was another interesting presentation I reviewed at the recent ASCO meeting that came from Rome, where investigators at the Regina Elena National Cancer Institute reviewed the detailed results of 415 consecutive patients who underwent surgery there for stage I to stage IIIA NSCLC (abstract here).   They attempted to assess the prognostic value of many variables reported to be useful in prior work, such as age, patient sex, tumor size, tumor grade, and also focused on the variables of the total lymph nodes removed at the time of surgery (regardless of whether they were involved with cancer or not), and the proportion of positive nodes compared with the total number removed (related to the concept in the previously described Japanese abstract about the number of positive nodes as a number alone).  From there, they also developed a new system of weighted variables that could assign patients as low, intermediate, or high risk of recurrence and death from lung cancer after surgery. 

Read the rest of this entry »

   At this year’s ASCO meeting, I had the opportunity to review and provide commentary on several presentations from other researchers, all on the topic of how to refine our ability to predict how patients will do after surgery for stage I - IIIA NSCLC, with an idea that this information can help guide decisions about who should receive chemo and who shouldn’t.

   One of the interesting abstracts came out of Japan, where a group of investigators led by Dr. Matsuguma looked details about the surgical results and long-term outcomes of 574 patients who all underwent surgery at a single center, asking the question of whether the number of lymph nodes involved with cancer is important for prognosis, and specifically whether this variable might be more important than the location of the lymph nodes in its correlation with prognosis (abstract here).  Our current system of assigning node stage is based not on number of lymph nodes but rather where any nodes with cancer happen to be.  Lymph nodes in the same lung as the cancer are called N1, while nodes outside of the lung and in the middle of the chest are designated as N2 on the same side of the chest as the main cancer, or N3 on the opposite side.  Lymph nodes above the clavicle are also considered N3.  This staging from N1 to N2 to N3 is somewhat associated with worse prognosis, primarily because involved nodes further from the cancer are associated with a greater risk of spread of the cancer to distant parts of the body.  A lung cancer generally needs to have some ability to spread to get out to N2 or N3 nodes, and that’s associated with a higher likelihood of recurrence outside of the local area of the chest. 

   The group recognized that at the time of surgery it can be hard to know which nodes came from what exact area, and also that sometimes we see “skip nodal metastases” in which N2 or N3 nodes are involved without any N1 nodes involved, which you wouldn’t expect to happen with a stepwise escalation of aggressiveness.   They also thought it might matter whether one lymph node is involved or multiple nodes is involved in a given location.   So they looked at the question of whether you could do a better job with the current system that uses nodal location by also adding information about how many nodes were involved.   And they found that compared with the current system (left side of the figure below, with little separation of the N1 vs. N2 groups, so not great at offering prognostic information), adding information about the number of either N1 nodes involved (4 or fewer vs. more than 4; upper curve on right) or N2 nodes involved (6 or fewer vs. more than 6; lower curve on right) could help stratify the prognosis for both groups, providing a clear separation of a better and a worse subgroup):

Read the rest of this entry »

   I think one of the most important lead stories from ASCO 2008 got buried.  Nobody’s really talking about it yet, but they should. 

   Amidst the results that led to an arguable role for erbitux and more compelling evidence to move second line chemo to bridge first and second line chemo together, we also received what I would consider to be very convincing clinical evidence that we can identify populations of lung cancer patients who are far more or less likely to benefit from alimta (pemetrexed), one of our most commonly used drugs in advanced NSCLC.   Although alimta is considered a conventional chemo and not a targeted therapy, we’re getting increasing evidence of how to target our convention chemo (such as by using ERCC1 levels to predict sensitivity to cisplatin, as discussed in a prior post).  The new data from the JMEN trial of maintnenance alimta vs. placebo provides what I’d consider to be downright convincing evidence that alimta is a quite effective treatment for patients with non-squamous NSCLC and also appears to be far less effective or even simply not effective for patients with squamous cell NSCLC.  

Read the rest of this entry »