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Dr. Jack West is a medical oncologist and thoracic oncology specialist who is the Founder and previously served as President & CEO, currently a member of the Board of Directors of the Global Resource for Advancing Cancer Education (GRACE)


What I Really Do: BAC and Slowly Progressing Cancers
Wed, 08/27/2008 - 17:03
Howard (Jack) West, MD

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).

Putting this together, when I see a patient with BAC, I try to determine whether this patient really has a disease acting like BAC or whether it’s really standard invasive adenocarcinoma, and then if it is behaving like BAC, whether it’s a mucinous or non-mucinous BAC. I’m more inclined to recommend early EGFR TKI therapy, potentially as first line therapy, for patients with non-mucinous BAC, although I think even very few lung cancer specialists make any distinction among BAC patients in how they manage the two major subtypes. This is because it appears overall that at least some patients may do remarkably well with EGFR TKIs, and for a long time, and we really don’t tend to see striking responses with clearance of BAC infiltrates from standard chemo.

However, it’s fair to say that just as is the case for never-smoking patients with lung cancer, we don’t have any good evidence that treating BAC patients the same way as other patients is wrong, and I think it’s perfectly reasonable to follow the same algorithm as for the broader NSCLC population. For most of the last nearly 50 years since BAC was first described, it was put in the same clinical trials as other forms of NSCLC. But in a patient who needs to start treatment (more on this point below), I offer and may well suggest an EGFR TKI, although I’m most happy to do this as part of a nationwide clinical trial I lead with SWOG that tests the combination of avastin and tarceva in patients with BAC or adeno/BAC. Another clinical trial that SWOG is running gives single agent alimta, which may be particularly active in BAC, and that’s also a nice option. I would consider these two trials to represent two leading choices for first and second therapies, with the patient deciding which approach they’d prefer as initial treatment.

The bigger question, I think, is the rate of progression, and this is a question that isn’t really specific to BAC, although many of the slowest growing cancers are BAC. While most lung cancers progress fairly rapidly, over a course of weeks to months, a minority of lung cancers progress very minimally over many months or even years. For instance, sometimes a patient is referred who had a surgery for an adenocarcinoma with BAC features 4 years ago, and last year a new nodule measuring 4 mm was noted. It then grows by 1 mm 3 months later, and after maybe 12-18 months it’s grown to 7-8 mm and a few 2-3 mm tiny lung nodules are appearing in the background. This prompts a biopsy of the largest lesion, which confirms BAC. Now you’ve got biopsy-confirmed multifocal/recurrent BAC. Not surprisingly, this person doesn’t feel these tiny lesions and is completely asymptomatic.

Now you can treat this reflexively, with chemo and perhaps avastin, but that’s going to incur some real risk of potentially serious side effects and, at the very least, a decrease in a person’s quality of life, since you can only go downhill from asymptomatic. And even though I’ve seen some very impressive results with the EGFR TKIs and sometimes with chemo for BAC, these treatments don’t work indefinitely. So I look at the trajectory of the cancer, based on how healthy the patient is and how much or little the scans have changed over time, and I’m quite comfortable recommending a vigilant watchful waiting approach for the folks who have a cancer that looks like it won’t affect their survival for the next few years. My sense is that it burns no bridges for later and that you don’t need to accept any risk of adverse effects from treatment. Moreover, you don’t burn up a potentially helpful treatment long before you need to. If tarceva may produce a stunning response, why use it to melt away a few tiny specks on the CT of an asymptomatic patients rather than save it for a time when the patient might actually feel a difference?

I’ll emphasize that although this issue comes up most often with BAC, there are sometimes patients with other NSCLC tumors for whom you can see that the cancer has progressed far more slowly than usual, and the patient hasn’t experienced a clinical decline despite not being on treatment. In these patients, who seem more commonly to be older and therefore also sometimes less inclined to pursue aggressive treatment. But my point is that there are some patients who may be well served by leaving treatment options in their back pocket, if both the patient and the doctor can overcome the reflexive sense that if you find something called cancer it needs to be treated aggressively and immediately. As we move toward a more individualized approach to lung cancer, we may find that the standard approach actually overtreats a minority of patients with an unusually indolent cancer, and BAC sometimes follows that pattern.

This is all under the heading of “what I really do”, so it’s my approach and not the only way to manage these cases, but there you have it.

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