GRACE :: Lung Cancer

Bronchioloalveolar Carcinoma (BAC)

An Uplifting Case: Tarceva after Iressa Led to a Great Response

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I just wanted to tell people about a remarkable patient I just saw who is delighted to have had a remarkable response to Tarceva a few years after responding to Iressa. She made my day.

In truth, her case was remarkably long before this. She was diagnosed with bronchioloalveolar carcinoma (BAC) all the way back in 1995 (I was finishing med school, no kids — life was simpler then). She had undergone a left lower lobectomy for localized disease initially, but her cancer recurred in late 1998, confirmed on a bronchoscopy, and she began experiencing a cough then. She was initially treated with chemo and responded well for several years, with some changes in her chemo but generally doing well before being started on Iressa.

She recalls that within days of starting Iressa, her recurring cough improved dramatically, and she did well on it for over 5 years before her scans progressed and her cough worsened. She ultimately discontinued it back in May of this year, starting Alimta then. And though we might have hoped and expected that she’d show another great response, she actually continued to progress on that, with a worse scan and cough after two cycles. So this shows us that her cancer doesn’t quite respond to everything.

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BAC No More?

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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

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.

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New Podcast on the ABCs of BAC

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Here’s a video slide presentation that provides a basic introduction to bronchioloalveolar carcinoma (BAC), including the demographics, natural history, imaging appearance, and patterns of response that make it a unique subpopulation within lung cancer. The audio only version is below the video.

[display_podcast]

In addition, we’ve got the final slides in pdf form, so people can follow along with the audio or just study them at your own pace, along with the transcript from the presentation:

ABCs of BAC Slide Set

ABCs of BAC Transcript

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What I Really Do: BAC and Slowly Progressing Cancers

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In the last few years BAC has become increasingly studied and recognized as a distinct clinical subtype of lung cancer. The classic BAC syndrome is characterized by progression limited to the lungs, and its growth can be quite variable. The definition of BAC based on pathology has been applied pretty variably: although it should really be a non-invasive cancer that shouldn’t be able to spread outside of the lungs because it can’t invade into the bloodstream, most clinical trials now permit a combination of invasive adenocarcinoma with BAC features. Probably largely because of that, some of what is called BAC looks and acts and responds just like standard lung adenocarcinoma. At the same time, we are still learning a lot about even the pure form of BAC, such as the finding that the two major subtypes of BAC, mucinous and non-mucinous, may be fundamentally different.

BAC has historically been perceived as unresponsive to chemo, or less than other forms of lung cancer at least. That may be so, but in truth many experts believe that this really may be a misperception because the BAC syndrome includes a diffuse infiltrate of multiple lesions rather than a discrete mass that can be measured readily. At the same time, BAC is actually uncommon enough that that it hasn’t really been broken out from larger trials of NSCLC in general. The real interest in studying BAC has only developed in the last 5-10 years, and in that time BAC patients have been much more likely to have been studied in trials of EGFR inhibitors than chemo. In these trials, the EGFR TKIs have demonstrated response rates in the range of 15-25%, along a fairly encouraging survival. A minority of patients do remarkably well, with prolonged responses and survival (reviewed in prior post). And it looks like the impressive results with EGFR inhibitors are largely if not exclusively seen in patients with the non-mucinous BAC subtype (see prior post).

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Actions Speak Louder than Words: When Pathology and the Clinical Picture Don’t Fit

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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.

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