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Bronchioloalveolar carcinoma, or BAC, is a unique subtype of non-small cell lung cancer (NSCLC) that has unique features in terms of the demographics of who gets it, how it appears on scans, how it often behaves, and potentially in how it responds to treatment. It is a subset of lung cancer for which most of what we know emerged in the last 10 years, with our understanding of this entity, and even the definition of BAC, still evolving.
What is BAC?
BAC was first identified and defined as a separate subtype of lung cancer by Dr. Averill Liebow in 1960. At that time, he highlighted it as a form of well differentiated adenocarcinoma of the lung that appeared to not be able to invade the surrounding lung scaffolding and spread within the lung(s), presumably aerogenously and/or through lymphatic channels.
Under the microscope, an image such as that on the left shows thickened walls of the gas-exchanging sacs in the lungs called alveoli. The classic description of this pattern is lepidic, meaning "scale-like." X-rays and other imaging shows a picture that looks remarkably like pneumonia, as shown on the right, and probably more than any other kind of lung cancer, patients with BAC are routinely diagnosed as having pneumonia for weeks or months before a diagnosis of cancer is actually established.
The diagnosis has undergone some revisions over the past 50 years, and the most widely used system is still the 1999 definition by the World Health Organization that defines "pure BAC" as a subtype of adenocarcinoma that has no invasive component. Under this strict definition, BAC accounts for only about 2-4% of NSCLC cases, but up to 15-20% of NSCLC tumors have a combination of invasive adenocarcinoma with some component of BAC.
There is actually a continuum from pure BAC to BAC with focal invasion, to adenocarcinoma with BAC features, and then invasive adenocarcinoma with no BAC component:
Although pathologists have sometimes been rigid in their use of the term "BAC" to describe the pure form, many clinicians have observed that the distinctive features of BAC in terms of natural history and behavior can be seen not only with pure BAC but in the more common situation of a combination of BAC with some component of invasive adenocarcinoma. Accordingly, clinicians have generally considered the eligibility for a clinical trial on BAC to depend on having an adenocarcinoma with at least BAC features, rather than restrict to a much msaller population of patients with pure BAC.
There are two main subtypes of BAC. The non-mucinous (NM-BAC) subtype is more common, comprising about 50-60% of cases, while the mucinous (M-BAC) subtype accounts for 30-40%, with the remainder designated as mixed subtype.
Although nearly all work in the field of BAC had not historically made a distinction made a distinction between the two main subtypes, early work is suggesting that the NM-BAC subtype is far more likely to have an EGFR mutation and respond well to oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) like Tarceva (erlotinib) and Iressa (gefitinib). In contrast, it appears that K-RAS mutations are more common in patients with M-BAC, in whom it appears that EGFR TKIs may be much less effective overall. However, this work remains very preliminary.
The BAC Population, and BAC symptoms
Although there is some controversy about this, BAC is generally felt to be rising in incidence, or at least being recognized and diagnosed more commonly. This is difficult to measure accurately, because much depends on how strictly or liberally BAC is defined (pure vs. any component of BAC). The demographics of BAC are also unique, in that about 1/3 of patients with BAC are never-smokers, far more than are seen for lung cancer in general, and more women are affected than men, which is a reversal of the trend for other forms of lung cancer.
A little more than half of patients with BAC present with no symptoms but are detected after an incidental finding is noted on chest imaging. The classic imaging finding on CT is a "ground-glass opacity", which is a non-solid lattice of increased density. In contrast, a semi-solid appearance has been associated with an invasive adenocarcinoma with BAC features, and specifically with the solid comp0nent of a lung lesion generally felt to represent the solid component on a CT scan. More advanced cases typically have multiple tiny lung nodules (sometimes descreibed as a "miliary pattern") or largerhazy lung infiltrates, which are sometimes diffuse and extensive throughout one or both lungs.
When people have symptoms, it is most commonly a cough, seen in about 30-40% of patients; this is sometimes productive of a frothy sputum, known as bronchorrhea, and this can be very copious, even a liter or more per day. This is generally felt to be a manifestation of the mucinous subtype. Shortness of breath is also a common symptom seen in about a third of patients.
Clinical progression of BAC, and Early BAC
Another important and distinct aspect of BAC is that the rate of progression can be extremely variable. More than any other type of lung cancer, BAC can be so slow that it doesn't clearly need any treatment for years, growing at a barely perceptible rate from one year to the next. Other BAC tumors can progress rapidly and lead to declines in a patient's lung capacity and activity level over a matter of just weeks.
The more favorable survival with BAC has been demonstrated for stage I BAC compared with other adenocarcinomas, as shown in a retrospective review out of Massachusetts General Hospital. In some recent series from Asia, the smaller, pure BAC tumors have been associated with a five-year survival actually approaching 100%. Because of this, several Asian studies have demonstrated that surgical outcomes can be excellent even doing a surgery less extensive than a lobectomy for BAC. In some parts of Asia, a wedge resection or segmentectomy are the standard surgical approach for small BAC lesions, and there is increasing interest in and acceptance of this approach in North America for the right case settings. This topic and other special considerations about surgery for BAC are covered in this post.
This has also led to a planned revision by the pathology community, and actually an elimination of the diagnosis of BAC in favor of it being considered "adenocarcinoma in situ" (in situ meaning that it doesn't invade into the tissues of the lung), technically a non-malignant condition. This reflects the fact that prognosis is extremely good for patients with small, non-invasive lung lesions. The proposal specifies that for people with a mixture of invasive and non-invasive adenocarcinoma, only the non-BAC component be included in the measurement of the tumor when determining stage and estimating prognosis accordingly. The non-invasive component is felt to contribute negligibly to risk of poor outcomes compared with the invasive adenocarcinoma component.
Advanced BAC
Other work from the same group out of Mass General has shown that the median overall survival of patients with advanced BAC is also significantly longer than that of patients with other subtypes of non-small cell lung cancer.
It generally hasn't been felt that this more prolonged survival has been due to greater responsiveness to chemotherapy. BAC historically hasn't been very well studied, given that it represents such a small proportion of non-small cell lung cancer cases. They have generally been pooled with other subtypes or sometimes excluded from trials, but in neither situation has it been possible to properly assess how BAC patients do with standard chemotherapy. Limited retrospective reviews have generated far-ranging conclusions.
As shown in the table on the bottom of this slide above, a careful look has shown that the benefit may be comparable between BAC and non-BAC lung cancer, but many oncologists have historically perceived that BAC is resistant to chemotherapy. This may be because the diffuse, poorly defined lung lesions that typify BAC aren't conducive to measuring tumor shrinkage in the same way as a more solid, circumscribed lung cancer.
But after years of being considered an unusual curiosity in the field of lung cancer, BAC became a source of much greater research focus when it was observed by lung cancer experts at Memorial Sloan Kettering and some other cancer centers that a minority of patients with advanced BAC can have a dramatic and rapid response to the emerging oral agents targeting the epidermal growth factor receptor (EGFR), such as gefitinib (also known as Iressa) and erlotinib (also known as Tarceva). Here you can see patient's chest x-rays taken just 5 days apart and demonstrating the remarkable response obtained with Iressa over that short time.
In addition, these responses could also be very long-lasting, as shown in this pair of CT scans taken two years apart in a patient with widespread BAC.
In fact, this particular patient had a mixture of adenocarcinoma and non-invasive BAC, so the impressive responses are not just limited just to patients with the pure form of BAC.
This work led to trials of the EGFR inhibitors in advanced BAC. I led one study through the Southwest Oncology Group (SWOG) that administered Iressa at 500 mg per day to patients with advanced BAC or a mixture of adenocarcinoma and BAC. A total of 135 patients with either chemo-naïve or previously treated disease were enrolled, and we saw a response rate of 16% and a median overall survival of 13 months. However, these rather unimpressive results don't really tell the whole story. Up to 30% of patients had prolonged stable disease even if they didn't show a response and significantly better overall survival results were seen in certain groups. Women, never-smokers, patients who developed a rash, and those with a better performance status did particularly well. But some patients did remarkably well, including six patients who continued on Iressa without progression for four years or longer. A look at the clinical and molecular characteristics of these patients showed that not all of these patients were women or never-smokers, nor did they necessarily carry an EGFR mutation or show EGFR gene amplification.
In fact, none of these six patients met the criteria for a formal response, but rather they all showed very prolonged non-progression for years, some still ongoing.
A study conducted through Memorial Sloan Kettering looked at a similar population of 101 patients with advanced BAC or adenocarcinoma with BAC features and gave the oral EGFR inhibitor erlotinib, also known as Tarceva, at the standard dose of 150 mg daily. The response rate and survival were a little better than SWOG saw with Iressa, but what the investigators focused on was the particularly favorable results among patients with an EGFR mutation, who showed a response rate of 83% and a median survival of approximately two years. As shown in the so-called "waterfall plot" that shows tumor shrinkage by a bar going downward from the higher horizontal line, most of the best responses, at the far right, are gray bars that note patients with an EGFR mutation.
However, many patients with no mutation, who are shown as orange bars, and even some with K-Ras mutations and shown with blue bars, had good tumor shrinkage or at least stable disease.
This study with Tarceva also showed that responses were more common in never-smokers than in former or current smokers, and in women more than men. In addition, responses were only seen in the patients who developed a rash. There was no evidence that the best results were only in treatment-naïve patients, nor was there any suggestion that results were better for patients with pure form of BAC. If anything, the response rate was better in patients with a mixture of BAC and invasive adenocarcinoma, as shown at the bottom of the table below.
In the last few years, those of us with a major focus on BAC have come to recognize that the two main subtypes of BAC, known as mucinous and non-mucinous, may well have many important and clinically relevant differences, as briefly noted above. Specifically, survival with EGFR inhibitors appears to be best for patients with the non-mucinous BAC or a mixture of adenocarcinoma and BAC, and it's rather poor with patients who have the mucinous subtype of BAC. This is illustrated in a set of survival curves from the SWOG 0126 trial of Iressa in BAC that I led, broken down by specific histology as interpreted by a central pathology lab:
As shown by the light blue bar, a few patients who were felt to have invasive adenocarcinoma and no BAC were actually enrolled by some institutions, highlighting the variability in interpretation of the BAC diagnosis from one center to another.
This same observation of far better results with Iressa with the non-mucinous subtype of BAC was also seen in a French study:
So while the work assessing differences between BAC subtypes is still preliminary, it appears that the favorable results with EGFR inhibitors are confined to patients with the non-mucinous subtype, and these are more likely to be never-smokers and carry an EGFR mutation. Greater responsiveness to standard chemotherapy agents may be seen in patients with the mucinous BAC subtype, although we have very little evidence to go by here.
Finally, as noted above, there is a plan to have the World Health Organization change the classification of the previously noted spectrum of adenocarcinoma to non-invasive BAC. This is described in detail in a post dedicated to this subject. It remains to be seen whether this will be widely adopted and whether it will have an impact on clinical management.
To summarize, BAC is a unique subtype of lung cancer that accounts for about 2-4% of non-small cell lung cancer cases, but it's a component in about 15-20% of patients, in combination with invasive adenocarcinoma. Under the microscope, the pure form is noninvasive and spreads thinly over the walls of air sacs, interrupting gas exchange. On x-rays and CT scans, it typically appears as hazy infiltrates, often described as ground-glass opacities, or else as widespread small nodules within the lung only. The patient population typically includes a higher proportion of never-smokers and women than other lung cancer subtypes.
Among the most intriguing aspects in the study of BAC has been its response to treatment, which can include some of the most dramatic and long-lasting responses we ever see in lung cancer and it occurs consistently in a minority of patients who receive an oral EGFR inhibitor like Tarceva or Iressa. Responses may be more likely in certain patient subgroups and may be especially pronounced in patients with an EGFR mutation (this may be the main or only reason we have identified EGFR inhibitors as a preferred treatment for BAC). We are also gaining a new understanding that there may be clinically distinct subgroups even within the rather small population of patients with BAC. The non-mucinous subtype may be especially likely to respond to EGFR inhibitors, while pneumonic BAC, which is typically an aggressive mucinous BAC, has been especially difficult to treat effectively.
For additional information, including details on many aspects of what we've touched on here, please check the BAC folder within the subject archives.
Dr. West, I am curious about any data in regard to the number of ALK mutants with BAC. As you know, I am a veteran of the crizotinib trial (now more than 20 months on trial). I also have mucinous BAC. I am slowly becoming aware of how individual each of our cancers really are. If I were to draw a diagram of circles within circles representing the various subtypes in which my cancer is classified (never smoker, early onset, NSCLC BAC mucinous, ALK +, stage IV, > 5 year survival) it would seem to me that those circles would quickly become smaller and smaller. Correct? Thanks as always for the information. Linnea
Yes, yours is a unique case, but we've only had a very small proportion of people with BAC tested for an ALK rearrangement at this time. I do see some patients with mucinous BAC who have a relatively indolent disease and prolonged survival. We may see many more if we routinely do molecular testing and find that there are a significant proportion and many have an ALK rearrangement that can be treated for years with crizotinib. For the benefit of patients with BAC and as someone who has been following the field of BAC for a decade, I'd love to crack another piece of the puzzle by finding that mucinous BAC, which seems so unlikely to harbor an EGFR mutation, is often associated with an ALK rearrangement.
Thanks Dr. West. Should I hear any anecdotal reports from my peers, I will pass them along; as I'd surely like you to find that piece of the puzzle as well. As someone whose cancer seems to be relatively slow growing but also darned persistent, I am always looking around the corner for that next possibility. Until crizotinib, things were looking pretty grim. Although my cancer shows signs of developing resistance to this treatment, it (croizotinib) has bought me an incredible period of good health (in terms of not only extended longevity but quality of life). Everything I have learned about mucinous BAC has pointed to a hard to treat disease, so I am hopeful that several more effective treatments will be discovered. Linnea
Dr West,
Do you ever review a case? Just had a lung biopsy, no labs back but my lungs have 50% ground glass. I am 40 years old and never smoked.
Thank you
Christy Scott
I do second opinions, but at this point I'd need to meet with someone in person for that (trying to see about doing telemedicine consultations, but not quite able at this point).
If the actual diagnosis remains in question after a biopsy, it may be very easy to get a pathology second opinion from a center of excellence just by sending the biopsy material to a pathology department where they have a lot of expertise, but they wouldn't comment on how to intervene from there. Right now, I think you'd pretty much have to find your way to the particular doctor to get a full-fledged opinion.
Dr. West, my father has what I believe to be BAC in his left lung as well as a more aggressive lung cancer in his other lung. He is 82 years old and does not want chemo, but it would seem that either Tarceva or Iressa may be an optional oral medication that may not only provide an effective response to the BAC but also perhaps to the other cancer. I know it is NSC, but not sure if it is adenocarcinoma. Is Tarceva/Iressa effective against other types of lung cancer? I suspect he has had BAC for a number of years and it has barely changed, but of late it seems to be growing. Not rapidly…just changing more quickly than before. How many years do you think BAC could lie dormant (as it were) with barely noticeable changes? I have had small pleural and subpleural nodules without change for some time, but suddenly now it appears to have tripled over the past 18 months..or perhaps it is just a new nodule. But these nodules had no change in them for 7 years…is it possible for this to be BAC? Sorry for the wandering questions.
The EGFR inhibitors like Tarceva and Iressa have activity in a broader range of NSCLC than just BAC, so it would be very reasonable to try one (Tarceva is the only one currently FDA approved in the US). I can't give any exact number on how long a BAC could remain dormant, but I actually don't think it's really literally dormant as much as extremely slowly growing. However, if there is a combination of slowly-growing cancer and more aggressive cancer, the pace of the whole picture is likely to be dominated by the fraction that is growing at the greatest rate.
Dear Dr West: I recently had a PET Scan and have a lung nodule that grew from 7 mm in early 2009 to 11 mm May 2011; with 0.7 SUV which accounding to the PET Scan is suspicious for BAC. The rest of the PET Scan was negative.I do see a thorasic surgeon this month – but can you tell me do I need to be agressive at this point with treatment if the biopsy does show BAC? I am 58 years old; don't want too much down time from my job and am also thinking about CyberKnife to treat the 11 mm nodule if it does turn out to be malignant. What are your thoughts? Thank you so very much.
Dr West – I had given the wrong name of what they think the nodule might be suspicious of: My PET Scan says suspicious for: bronchoalveolar carcinoma since SUV was 0.7 on the 11 mm nodule.
Hi Julie,
That's pretty slow growth. You can read some comments br Dr. West in a similar situation here: http://cancergrace.org/forums/index.php/topic,9585.msg75904.html#msg75904
That's a very consistent picture of what I'd expect from a very indolent lesion like bronchioloalveolar carcinoma — the imaging shows a very slowly growing lesion (just a few mm over a couple of years), and a low but detectably increased SUV associated with very mildly increased metabolic activity.
When I see someone with this picture who is 79 and has other medical issues, it makes it a pretty easy decision to recommend against intervening, because the pace of the apparent cancer (which we would want to confirm with a biopsy before treating) is likely to be so slow that the time line to developing a problem from it is likely to be far longer than the time to develop other, more threatening medical problems. When I see this in a 58 year old without medical problems, it's still indicative of a very slow process with a prognosis that goes out years and years, but it is more likely to have a clinically meaningful impact if for no other reason than that there are no other apparent competing medical concerns on the horizon. Consequently, I think a much stronger argument can be made for treating an isolated and very indolent cancer in someone with a prognosis that may well go out decades otherwise.
With regard to the specific therapy, surgery would be the historical best textbook answer, but this is a situation in which I would be very receptive to the idea of focal radiation. It is likely to be effective (especially for a still very small lesion), have few adverse effects than surgery, and it is more likely to preserve surrounding lung tissue that often ends up being very needed if BAC recurs in a multifocal form in the future and thereby limits functional lung.
-Dr. West
Thank you so much. I was wondering why is there more adverse effects from cyberknife than surgery? I called a cyberknife facility & was told they would have to radiate 14 mm for the 11 mm nodule.
Very informative.
No, no. I would say that there should be fewer adverse effects from stereotactic radiosurgery, such as cyberknife, compared with surgery.
-Dr. West
Dear Dr West: I totally appreciate your very informative input to my concerns. After I go to the Thorasic Surgeon in 2 weeks I will post what he suggests; but I am really leaning towards havingt a procedure like cyberknife done instead of traditional removal of the lung. I have no other health issues at this time. Feel great – but this nodule has been watched by my primary doctor for the last 2 years. Thanks again. Julie.
I forgot to tell you that my insurance is not going to cover CyberKnife if I need it – I may have to wait until January 2012 to get a PPO so I can get it done. I had originally asked my doctor to get an authorization for me to see a CyberKnife doctor at their facility – they declined to authorize it. The CyberKnife doctor said they could do the biopsy and at the same time insert the markers just in case I will need CyberKnife treatment.
I need your help again. I just came back from seeing the thoracic surgeon and for my 11 mm nodule he wants to do a Video Assisted Thorocoscopic Surgery and while I am still under have the nodule biopsied and remove my lobe if it is suspicious for cancer. He also wants to check all my other 1-2 mm nodules at the same time and remove all my lymph nodes (whether I have cancer or not) because he said I do not need the lymph nodes? This seems very extreme. I just called my medical group and found out my primary doctor did not even try to get authorization for a consultation for cyberknife. What do you think? I need your help. Thank you, Julie
I think the surgeon is treating your case as a standard NSCLC tumor, which is understandable. The treatment recommendations made are what would be pretty clearly ideal for a faster-growing cancer with no suggestion of any other nodules. I suspect the surgeon is trying to offer the textbook correct answer for how to manage a lung cancer that may be early stage. While many people might tailor the reocmmendations based on the appearance of this being a slower-growing BAC, that's not a universal standard.
Yours is a situation in which a second opinion may be reassuring or may give you further reason to question the first recommendation. I think that these are really very individual situations in which a consultant needs to have more direct access to all of the information available before trying to make any specific recommendations.
-Dr. West
Yes your right – I need a second opinion. You are exactly right – he is treating me like a very aggressive cancer. I asked if I can wait until September – he said NO, I need to do this right away – get the VAC and get my lymph nodes removed whether I had cancer of not. I totally want to get another opinion and am disappointed that my primary doctor did not put thru an authorization for a cyberknife consultation. Thank you Dr – I did call my primary doctor today after I went to this doctor and was told "You don't need cyberknife" I told the doctor that I would not get cyberknife unless the biopsy showed cancer. My doctor was puzzled – asked me if the facility would actually do a biopsy???. Thanks again for your help. Julie
Dear Dr. West: My doctor is sending me to the "Orange County Radiation Oncology Center". I did call them and they told me they have treatments similiar to CyberKnife. I think my insurance at this time will not cover a CyberKnife facility unless I get a PPO. I was not aware you could get CyberKnife treatment outside of a CyberKnife facility. I have an appointment, but the problem is I still need to find a doctor to do a needle biopsy to confirm if I have a malignancy. The last doctor only specified VATS; and with VATS I do not have an opportunity to choose the treatment I want. I just get a lobe removed with all my lymph nodes in my lung if it turns out to be a malignancy. I also am concerned that they may not actually offer a treatment like CyberKnife; but I will wait for my appointment. Do you know if other facilities offer CyberKnife like treatment? I know you really are active in treatments for cancer and your opinion on this means so much to me. Thank you – Julie.
I'm sorry to say that these kinds of very practical and specific questions are not the one's we're really able to address here. In addition, I'm a medical oncologist nearly 1000 miles from there, so I don't address the details of exactly which type of radiation is available or preferred in this setting. A radiation oncologist would be better able to address this issue, but the general concept is of "stereotactic radiation", of which CyberKnife is just one but certainly not the only one.
-Dr. West
Thank you so much for your input. Yes your are right – I need to go to the facility and investigate what treatments are available., yes the doctor is a Radiation Oncologist and I will see him sometime this week. Thank you so very much for your very informative input. I will keep you updated …. Julie.
Just curious – have you heard that a biopsy can cause a cancer to spread. They want to do a needle biopsy on the nodule on my lower left lung. It is away from all blood vessels etc that can cause a problem during the biopsy (per the radiation oncologist). Then it is finding the right treatment. I sure hope my insurance will cover cyberknife in my case. The doctor said I was a lucky lady that the nodule is where it is and has an SUV of 0.7 and it was found so early. Have a great 4th !!!
Yes, that's vanishingly unlikely. It's very standard and overwhelmingly more likely to be helpful than harmful to biopsy a lung lesion that is suspicious for being a cancer.
-Dr. West
Hi Dr West – I had the needle biopsy yesterday morning – they took two samples – my lung collapsed and now I have a tube in my chest for a few day.
The pathology report states that I do not have lung cancer. I was in total shock when they told me.
Why the SUV was 0.7 is probably because I have some type of infection.
Thank you. Have a great weekend – Julie
Julie! No lung cancer? That's really great news. Sorry about the collapsed lung though. I hope you are able to celebrate soon.
I get the chest tube out Monday (tomorrow) morning after they do a chest X-Ray to make sure my lung is OK. I went to the swap meet today and kept busy. Did more than I should with a chest tube on.
And yes – I was so happy with the news. I have been having CTs for 2 years and 3 months now!
Didn't think about celebrating – good idea. I think I will ask my husband to take me out next weekend.
And thank you ts!
Hi – I went and got the chest tube out – X-ray showed that my lungs were ok. My nodule showed fibrosis with inflammation. They took two different biopsies of the 11 mm nodule. I have had slight shortness of breath for 30 years. Doctor said they have to keep doing CT Scans just in case it does turn into cancer. Now what does that mean? Fibrosis w/inflamation turns into cancer? This problem with my lung is never ending.
Thank you,
There is some question of whether cancers can arise from prior scars/inflammation. I would say the evidence is pretty sketchy, and that it's more likely that the question is really whether there is some cancer in the background that wasn't sampled. It would be most helpful to clarify with your doctor what the reasoning is that there is a remaining risk of cancer if the current diagnosis is felt to be clear from the biopsies.
-Dr. West
My primary doctor said I need follow-up. My doctor's specialty is Internal Medicine. I had the ultimate test done – needle biopsy and now am told further follow up is necessay. They checked two sections of the nodule; no cancer. I have multi-focal 1 – 2 mm nodules in my lungs.
I am feeling great now that my collapsed lung has healed.
Thank you Dr. West – your input means alot to me.
Sincerely, Julie
I'm glad you're feeling well. I hope your follow up scans remain very stable.
-Dr. West
Thank you Dr. West for everything. You have helped me so much in dealing with the nodules these past two years. Very sincerely, Julie
I have been researching this topic for the past few weeks since my mother was diagnosed with BAC through a needle biopsy. Yours is the clearest summary I have seen of the state of knowledge about BAC, so thank you, Dr. West. I have been unable to find any studies that look at outcomes with no surgery or other treatment. My mother is 81 years old and is being pushed toward wedge surgery by her doctors, but I'm wondering if it's advisable given her age and the fact that it's slow-growing and possibly nonmalignant as you say. The biopsy surgeon said it didn't look like cancer on the CT scan, more like an infection. Since it has only recently become apparent that it's a different animal from other adenocarcinomas, I'm just wondering if researchers have even considered whether no treatment for stage I might give just as good an outcome as surgery or radiation. My mother's tumor went from 1 cm to 1.2 from Dec 2009 to May 2011 and then jumped to 2.0 cm for a PET scan a month later. It was 2.2 cm during the biopsy in late Sept. Is it possible that the radiation from all the screening might be causing it to grow? She has had annual mammograms for 30 years now too (could that be why BAC is more common in women?). If so, wouldn't radiation therapy make it grow more? Also, with the wedge surgery, they will remove the lymph nodes–wouldn't that be removing her defense against it? I saw one study that suggested removing a single node might cause it to go multinodal.
I would say that with that kind of interval growth, it's not that indolent, so it's in the range of a clinically relevant cancer, not just one that can safely be ignored.
The amount of radiation in these diagnostic studies is completely irrelevant, and I would say that there isn't any remote basis for concern about radiation from diagnostic studies (whether CT scans or prior mammograms) facilitating or accelerating these cancers.
There are also many lymph nodes in the chest and in many areas throughout the body, so removing some is only associated with better outcomes, probably from being able to stage a person's cancer more accurately. There is no real evidence or even suspicion among leading people in the field that it either leaves someone significantly more at risk for infection or facilitates spread of the cancer.
-Dr. West
Thank you, Dr. West. Yes, I can see how the surgery may be advisable if only to get a better look at the extent of the problem. I forgot to mention that my mother has emphysema (she quit smoking 35 years ago), so cannot afford to lose much lung. Also, is there any evidence that removing a single BAC with wedge surgery could cause it to recur multifocally?
No, there is no evidence that a wedge resection would facilitate multifocal recurrence. That can certainly happen over a period of time, whether a person has surgery or doesn't.
-Dr. West
I got BAC and have had all the traditional treatments and a bunch of clinical trials. I had the right lung removed 18 months ago. BAC appeared in the left lung about a year ago. I've tried Cisplastin, Avastin, Tarceva amoung others and most recently MDX/PD-1. MDX was the only one that slowed the growth — for a while.
One of the options in front of me is a lung transplant. Do you have any survival rate statistics? Is a transplant common for BAC patients?
There aren't real stats. Transplants have been tried in small series of patients here and there, with short-term follow-up looking good in the year or two after surgery, but then no long term follow-up reported. My understanding is that there are typically recurrences long term, and it's not really clear that this is actually curative for people in very high risk (otherwise incurable) situations. Because BAC can often progress slowly, and this surgery is most likely to be offered to unusually fit patients, it's not clear at all that lung transplants as a treatment for BAC really add beyond what would happen with these people anyway (they are more likely to be the ones to do well for a few years). It's certainly not a common intervention and not one that is routinely recommended by lung cancer experts.
-Dr. West
I have been reading about BAC recently and am wondering if I might have some of it..I get scanned evry 2 months and I don't get copies of them any more because I will just obsess like crazy over them until I make myself totally crazy. But…the last one I had I noticed "ground glass" on it when the doc was holding it and telling me it is good..still stable . What I know is my last "main" nodule is cavitating and was the lowest SUV on my original PET way back when. But, I found out I have about 6 tiny (Under 6mm)nodules scattered in my right lung(everything that is left is in my right lung)that haven't changed all this time. I get my next scans 11/16..I am going to get a copy of this one. My Doc (who is awesome btw) has not mentioned BAC but I think he follows my lead in how much detail we go into. If I bring it up, I know he will discuss it with me and tell me if I have it. I have been stable since finishing chemo in Jan and am on maintenance avastin. I know it is possible to have BAC and Adeno right? My biopsy was done on my lymph node and was adeno.
My mother had wedge surgery on Nov. 2, but they ended up taking almost half a lobe because the tumor was deeper than anticipated. The surgery was very hard on her, but because my sister stayed with her constantly for a week and a half, she is recovering pretty well now. They determined the tumor is invasive poorly differentiated adenocarcinoma with focal bronchioloalveolar growth pattern, grade 3. There was no spread to lymph nodes, and the tumor was 2.2 cm, but the oncologist told me it was stage 1B. The two tests for targeted therapy were negative, so the oncologist recommended radiation therapy. My mother is already worn out from surgery, and I am worried radiation will be too much for her. What do you think?
It's absolutely possible and in fact very common to have a combination of BAC and invasive adenocarcinoma together.
The role for radiation after a wedge resection is debatable and not clearly indicated if the surgical margins are negative for tumor involvement. The most common approach would be to do a "completion lobectomy" if a person can tolerate it. A wedge resection is associated with a less favorable overall survival than a lobectomy for patients who are under around 71 — in older patients, there is evidence to suggest that survival can be as good with a surgery less than a lobectomy.
Overall, post-operative radiation is most commonly employed in the setting of positive surgical margins (tumor present at a margin) or with mediastinal (mid-chest) lymph nodes involved.
As an aside, I'd say that this kind of tumor (invasive adenocarcinoma with focal bronchioloalveolar growth pattern) is treated entirely as a standard NSCLC tumor — nothing about the BAC is directly relevant to its management, based on what you're telling me.
-Dr. West
Thank you, Dr. West. I don't know if you remember from my previous posts, but my mother is 81 years old. From the pathologist report, in the first section, the tumor was abutting against the margins, so the surgeon took a second section, in which the margins were clear. The oncologist said he took the second section because they found tumor at the margins, but the surgeon told us simply that the tumor was deeper than expected. So maybe it is just a matter of confusion on the oncologist's part. Do you know the average survival rate for a standard NSCLC tumor after surgery? I will try checking in that section on this website. Thanks again.
That's really so variable based on other factors that it's not a question that makes much sense when stated that broadly. It's like asking, "how much longer should an 81 year-old expect to live?".
It depends on the stage of the cancer, histology of the cancer, other competing medical problems a patient may have, etc. In truth, there is so little data on older patients with BAC that I don't think it's possible to glean any meaningful information from statistics. There aren't enough good quality data to address a very individual situation.
-Dr. West
Dr. West
My father had a biopsey done and the pathologist said he has BAC, nothing showed up on the PET, which I have read is normal. With BAC being a not as common form of lung cancer I haven't found to many user friendly websites. I will be going with him to the onconolgist next Tuesday and need some help.
1. What kinds of questions should I ask to make sure I understand my fathers situation and options fully?
2. NM-BAC and M-BAC, what are the different risk and concerns between the two. Also, if he has been coughing up white mucus does it mean he has M-BAC?
3. What are ALK arrangements and how do they effect BAC?
4. Could you let me know what different types of treatment are avaiable?
Thanks for any type of help you can give.
I answered as many of these questions as I could feasibly do on the discussion forum, where you had these same questions posted. Actually, I'm not sure I got to the ALK question, but it's really too early to say much. BAC is a subtype of adenocarcinoma, and ALK rearrangements are definitely seen in adenocarcinomas, but there hasn't been enough research to say anything definitive about the prevalence of ALK rearrangements in either BAC subtype: I'm just definitely inclined to test for ALK in patients with BAC, but I don't think we can say much about what to expect.
I hope that between the posts here and my responses, we can provide guidance that is helpful.
-Dr. West
Dr. West,
I am desperate for some guidance.
My husband was diagnosed with stage four adenocarcinoma with BAC in August last year. As you may, or may not, recall from my previous post.
We started chemo in December and did a full round ending two weeks ago.
Treatment was Avastin, Taxol and carboplatin.
We did treatments every week for the full round of three treatments. he tolerated them better than most, but has of resent lost his appetite and has slept much of the three months away.
We just got the results of the CT scan to see if there was a response or not and unfortunately we were told today there was no response…. as you can imagine we are devastated.
We were offered Alimta to in their words "maybe help prolong his life a little more."
We were told we most likely do not have years, but months.
Here is where I need your help; I need to make sure I have given this 100% for my own piece of mind and as the pressure from his family to do more mounts.
Should we see another doctor?
Is there more out there in terms of treatment that the regional cancer treatment center is maybe unaware of?
They (family) keep saying go to a very well advertised place who speaks of some miracle they performed on a woman who was also told she was going to die <~~~ do they know something the rest of the treatment centers don't?
Do you have a suggestion on an alternative treatment?
Thanks for anything you can help me with.
Hi Linny_B. I'm so sorry to hear about your husband. There are no miracle cures in lung cancer, but there are some good drugs that can prolong life. Alimta has helped a number of people here. Have your husband's doctors considered Tarceva? As to second opinions, I'm linking to a post by Dr Weiss about how to approach a second opinion and what to ask:
Very best.
I'm very sorry to hear about your story. Please understand that we cannot give you direct medical advice, but rather are limited to discussing general principles of treatment.
You say there was not a response, but was there worsening (progression) of the cancer? Stable disease is still a favorable outcome and does not mean the treatment is not working, so wanted to make sure.
For patients who progress on platinum doublet chemotherapy, second line options like pemetrexed or Tarceva are reasonable options but the assessment of "months not years" is accurate for most patients in this situation. Another common alternative is a clinical trial, which is an experimental treatment and the exact details of trials would vary by institution. Please understand that a trial does not guarantee a better outcome, just the options of something different and may add to our knowledge of disease that may help others down the road.
As for the "well advertised" cancer center, I am sure I know who you are referring to and in my opinion they do not offer ANYTHING you cannot get at a reputable regional medical center except for hype and expense. This is only my personal opinion.
However, a second opinion somewhere does make sense if you are confused or worried that you may not be hearing all the options. Just for your own peace of mind I am a big fan of second opinions.
I agree with Dr. Pennell's comments and would just add that if someone hasn't had a particularly good response to first line chemotherapy-based treatment, this makes me more inclined to favor Tarceva (erlotinib) as a non-chemotherapy "wild card"; people rarely do better with later lines of chemotherapy than they did in the first line setting.
I also definitely agree that the centers offering a very different level of hope are almost certainly peddling false hope, which is a very profitable ruse for people desperate for new answers to difficult questions. The old dictum that "if something seems too good to be true, it almost certainly is" still rings true.
-Dr. West
Linny_B, I'm sorry you are having to deal with all this, and family pressure makes it that much harder. We had the same situation with our children until we got a second opinion from a well respected teaching hospital that agreed with the diagnosis and treatment offered by our local oncologist. Now we rely mainly with the local oncologist, seeing the other for another second opinion as the situation changes. At this point it is working well for us.
Thank you all so much for your responses.
– Dr. Pennell, by "no response" I meant worsening, not getting better.. I should have clarified.
I appreciate everyone's response and I feel as though I have the information I need to make a better decision.
I feel helpless and my nature is to fix everything and I am beside myself with this.
We will be seeing the oncologist next week, so I am going armed with a little more information and that's the best I can hope for.
You have no idea how much i appreciate all of the responses.
I feel so much support and caring here on this site
Hello, Linny, and I am so sorry you are going through all this. My father, mother and father-in-law all have/have had very serious and in 2 out of 3 cases inoperable cancer. My dad's is Stage IV/metastatic but he is now going on his 6th year since diagnosis. From all this my husband and I have become firm believers in second opinions from top-notch specialists like those here on cancergrace (and Dr. Weiss has a great article explaining why this can be so helpful). Depending on where you are, your oncologist may be very good but just have to be a jack-of-all-trades and not be aware of other possibilities your husband might benefit from. You didn't mention at all whether you had had molecular testing done, but in certain cases knowing that information can make an enormous difference in effectively treating a particular type of cancer. From our experience, if you are able to do so, I would get a second opinion from a major research center. You can look at where the docs are geographically on this site, and of course there the places like MD Anderson, Mayo Clinic, Sloan Kettering, Johns Hopkins, most of which are set up in a such a way that they have inns/hotels/shuttles connecting directly to the hospitals. It may seem like a big deal to get there, but once you are there you will likely find everything is managed well for you, and all in one place, with top-notch doctors. In our case, getting to Mayo Clinic in Rochester for surgery made all the difference for my dad. If resources are an issue, you might have to do some digging on the internet, but there are some companies that offer help (Corporate Angels Network, flying patients to treatment, or places that offer free lodging while you receive radiation, that sort of thing). Whether or not you can get to a major center, I would encourage you to ask your doctor about the molecular testing; there is a lot about that on this website. all the best to you.
Regarding Linney_B's husband:
Hasn't mutation testing been suggested before? At the very least for EGFR and ALK. Smokers are more likely to have the not-so-good KRAS mutation driving their cancer instead, but even never-smokers have a higher chance of KRAS than rarer ones like the Xalkori-druggable (via drug trial) ROS1, so one would be triple-negative for EGFR, ALK, and KRAS before testing for ROS1 might be worthwhile. Did I miss something about his history like he was already tested? If EGFR (and not one of the resistant variants like T790M on exon 20), then Tarceva is likely to help for a number of months; if ALK or ROS1, Xalkori is likely to help for a number of months.
I have mucinous BAC/adenocarcinoma that was assumed to be unlikely to respond to conventional chemo. Testing by Dr. Shaw at the Harvard-affiliated MGH in Boston uncovered I have the rare ROS1 mutation that her team was leading research on, enabling me to join the Xalkori-for-ROS1 trial. My symptoms vanished (mostly) within a day or so, the cancer shrank and remains stable over 5 months later. If I had not pushed for mutation testing until I had the name of my enemy (ROS1), my right lung would be half way to total crap by now. This disease will eventually kill me, but not yet. Not everyone is lucky enough to have a drug-targetable mutation, but more than half of never-smoker adenocarcinomas are lucky (and some smokers and some other NSCLC's too).
BTW, where are you located, Linny_B?
Best hopes,
Dr West it is me again. Can you tell me if you recieved my second posting to you, gosh I am sorry I seem to be having probs navigating the site I think. Will endevour to keep trying as I would truly appreciate your thoughts,
I'm not sure I did. Please go to "ASK A QUESTION ABOUT ____", then click on lung cancer in the pull-down menu, and you can start a discussion thread.
I'd be happy to provide some general thoughts and information, but please don't provide a huge amount of detail and request a recommendation for treatment. That's not a service we're legally permitted to pursue.
-Dr. West
maybe should try being brief here and you may see and reply? Here goes. I am female 53 ex smoker. Gave up 7 yrs ago, smoked approx 10 a day for 20yrs. Developed nasty cough 2000. Not what most would call a normal cough, the cough I had/still have can truly be awful. Mostly productive, mostly white, very white actually and frothy. When infection poresent, which is more often nowadays, then sputum can be green. Diagnosed with Vin 111 2005, surgical removal of clitoral area and surrounding , clear margins achieved. My cough cough cough has much attention from both my family Dr ( GP) & specialist alike. Initial diagnosis, Asthma, then COPD, then COPD with elements of Asthma, bronchitis. Treatments have been spriva,seritide, uniphyllin, daily for pass 10 yrs peak flows 250/280 always. . Bronchcospy x 2 showed diffusely inflammed bilateral airways. Steriods 15mg introduced to try to get inflammation under control. Also NERD suggested and Zoton fast tabs 2 x daily. CT scan 2010 showed bilateral multiply lung nodules. Follow up for year one, no changes, follow up 18moth slight change one single lower left lung nodule, 2yrs scan indicated growth and again slight change in appearance. CT/PET scan arranged . Results inconclusive. uptake from the nodule of concern mild ( 1.7). Ruled out primary lung cancer & metasticies. Differentials….. adenoma, hamartoma, chondroma.. Then states " there is small possibilty of a small BAC or Carcinoid. Even with such small change can not be confident nodule benign. Wonder if nexgt best step for lady ( if suitable) resection for diagnosis and cure.
My consultant and multi team discussed and informed me needle biospy. I am unhappy, unsure, confused.
Question. If benign why would they want to biopsy. If as pet scan report suggest maybe small BAC will needle biopsy confirm, my research on BAC makes me feel not, that the only unequivacal way to confirm BAC surgical removal. Can carcinoid be confirmed by needle biopsy. I really just want them to remove it if at all possibvle. Am I being to drastic. Any thoughts you can share would be so appreciated. Many thanks. Peg99
They aren't saying it's definitely benign: that's what the biopsy would hope to confirm. It's true that a needle biopsy doesn't provide a diagnosis of BAC, but you can get a good sense from a core biopsy of the likely scenario, compared with a fine needle aspirate (FNA), which provides considerably less information. A carcinoid could also be diagnosed by the same procedure.
It isn't feasible to remove it all if you're saying that there are many nodules in the lungs…and I don't think that would be a remotely desirable thing to do if there are many and they aren't growing over a course of years of follow up (with just a single nodule changing minimally).
It sounds like this may well be multifocal BAC, but one that is growing so incredibly slowly that there is arguably a greater risk from overtreatment than from undertreatment. Specifically, it's hard to understand the value of doing any intervention in this situation.
Good luck.
-Dr. West
Dr West first may I thank you so very much for replying, it is very appreciated. I do have multiply lung nodules, 7/8 right lung 6/7 left. Have been monitored over past 2 yrs, and prior to CT/PET which was done 4/3/2012 Dr said he was satisified no need to be concerned about any of the nodules other than the one in lower left lung that showed minimal growth twice over a one year period and was conspicious? My understanding of BAC is that mostly it is a very slow growing type of cancer. May I ask you if I have interepreted your last remarks correctly. You feel it is hard to understand the value of doing any intervention in this situation ? Just leave it, do nothing ?? May I also just ask this, is it possible that the chronic, not very responsive to meds, cough cough cough I have could be connected. Also it is true that they are not saying it is benign, however my worry is if they were to biopsy and result was benign, how would that rule out BAC if BAC can not be confirmed ? Does that make sense ? Thank you, truly for your time and thoughts, both are very appreciated.
I couldn't say whether the cough is likely connected without seeing the films directly. If these nodules were involving a significant fraction of your lungs, then yes, a cough could well be related to these nodules. But it sounds like these are very small, so a little peppering of small nodules in a sea of good lung tissue probably wouldn't cause any symptoms.
I understand that you can't be completely reassured a lesion is benign even if it doesn't show a cancer on the biopsy. I think the question of whether to do a biopsy depends on what you'd do with the information. If you found that it's cancer, would you want to take out one lesion and leave >10 others behind? The only argument you could make for that is that this would make sense if the others aren't growing at any perceptible rate AND the one that is growing is progressing at a pace that would be anticipated to be clinically relevant. In other words, if it's growing by a millimeter every year, it's hard to feel that there is a clear urgency to intervening against that one spot, especially if others could eventually show progression over years and years. On the other hand, if it looks like one lesion is clearly outpacing everything else and likely to cause problems long before anything else would, that's a situation in which going after the one growing lesion (I think of it as "getting the lead runner", to use a baseball analogy) does make sense, I'd say.
-Dr. West
Again thank you very kindly. I will think very long and hard about questions to put to the specialist looking after me. Will pop back to see you too and let u know where I am at from time to time.
Enjoy your evening
Dear Dr. West: So the 2 biopsies i got don't confirm that I do not have lung cancer? The doctor kept taking samples until he felt that he could get a clear picture of what what happing with my nodule. Confirmed by biopsy that I have fibrosis………should I be worried? I don't feel any different than I felt three years ago when this nightmare with a CT for something else found nodules …….. now I feel like I am going crazy……. many CT scans – PET scan; biopsies……….when will this ever end? Why did I get the biopsies if the doctors are still going to say I may/or may not have lung cancer? Would I not have signs of lung cancer…cough, weight loss, etc. etc…I have none of these sign…been gaining weight……I weight 115 and used to weigh 105….when I got pregnant 30 years ago I weighed 88 pounds…..I think the doctors were too agressive when I was diagnosed with nodules….have 5 CT scans within 2 years…..plus a PET Scan….when are we going to get better diagnosis so that others don't have to go through what I went through. Negative is positive in their eyes…..I get negative results and they want to keep testing me……..thanks for listening. Julie
Your situation illustrates one of the dangers of screening. Sometimes finding nodules can lead people onto a roller coaster of study after study, with ongoing anxiety. And we may find things that are ultimately proven to not be cancer, or sometimes might be technically called a cancer but may not lead to any clinical problems for years and years, if ever.
I'm sorry for all you've been going through.
-Dr. West
Thanks again Dr West. My multi-focal nodules were found by mistake while they were looking for something else, so I totally agree with you. In my case it would of been much better off if I had never had the bleeding uterine fibroid and the CT done to rule out pulmonary embolism since I was anemic from the bleeding fibroid which has since been removed without removal of my uterus. Thank you for caring Dr West, this negative adventure with my nodules has sure done a number on me for over three + years and there is no end in sight. I am always anxious now and have never had this problem until they diagnosed these nodules and no matter how negative my tests are I can't relax because they keep telling me I am not out of the woods. I am still debating weather to have the next CT Scan. Will keep you updated.
After reading the above comments by Julie 2009, leaves me with a question regarding blood work and pulmonary embolism. I have learned that blood clots can be more common when someone has cancer and that when someone gets real short of breath that could be a sign of a blood clot,, but what if someone's blood work comes back showing anemia does that mean they have a higher chance of throwing a blood clot or does the two not go together?
Yes, people with cancer, and particularly an adenocarcinoma, are more likely to develop a blood clot than people who don't have cancer, but anemia isn't particularly associated with this.
-Dr. West
Hi Dr. West!
My sister has been follow GGO in her lung that was incidentally discovered 2 years ago during an exam for a separate issue. In an exam last year, 1 year after being discovered, it appeared that the GGO had not changed. In an exam this afternoon, March 19, 2013 (1 year later), it appeared that the GGO has changed, in that it was a little larger and was more "dense", but not "solid".
My sister's physician would like to complete a bronchoscopy to take a biopsy for BAC or another form of carcinoma. He has noted that the lesion is in a difficult place to reach in the upper lobe close to the esophagus, and if in fact the lesion is malignant, that he would likely have to take the top quarter of her lung to resect the growth.
I'm sure he was just trying to cover all of his bases in terms of what info he provided to my sister so as not to surprise her with anything, but without the results of a biopsy, I thought his comments were a bit premature, especially considering the characteristics of the lesion. However, my question doesn't have to do with his be-side manner. I'd like to know if you can tell me if there is a preferred method of resection for these types of lesions? Lobal resection? Wedge? I ask because it seems to me that a complete resection of a lobe would seem radical if the same could be accomplished with a wedge, or perhaps cyberknife.
I'm getting a little ahead of myself, but I want to make sure my sister and I are prepared in the event of bad news, and I would prefer that she not have to make a snap decision on the spot to have a lung lobe removed that doesn't need to be.
Any insight you can give us on this would be greatly appreciated!
Thank you,
Jim Tancredi
It's an undefined question. The textbook answer for resecting an established lung cancer is a lobectomy, but especially if it's under 1 cm and known to be growing very slowly, a wedge resection or segmentectomy would be a completely appropriate recommendation (and probably my preference). For an established cancer larger than a centimeter (or especially larger than 2 cm), a lobectomy would be favored by the vast majority of US-based thoracic surgeons, and I too would be far less enthusiastic about a wedge resection in someone fit enough to tolerate a lobectomy for a first lung cancer and surgery.
Stereotactic body radiation therapy is very reasonable, but it's definitely not as established an approach as a lobectomy or sublobar resection. Would it be a reasonable idea in an informed patient? Absolutely yes, and it could arguably be the best choice, but it is the least established option and will leave an area of obscure haze around the treated lesion that will likely remain an ambiguous question of "is it growing cancer or just post-treatment effect?" for years and years of follow-up scans.
-Dr. West
Dr. West,
Thank you very much for this info! We ask questions on our side, but never seem to get the kind of answer(s) that you just provided. This kind of elaboration just helps the patient make a much more informed decision when the time comes to make that decision.
I'm sure I will have additional questions down the road especially if my sister's test result in a malignant diagnosis, but in the meantime, we both thank you for your time in providing us with this information.
Jim Tancredi
Hi Dr. West,
I have another quick question. My sister's physician had noted to her that her GGO was more dense than before, but not solid. What does that mean, and what is the significance of it?
Thank you!
Jim Tancredi
Based on how my scans progressed before treatment, that is how my mucinous BAC progressed. It starts spreading to a near area as GGO haze, gets increasingly dense in small patches, and eventually appears to consolidate into a solid mass. My lower-right lobe was looking very ugly, mostly filled but with varying densities. I might describe it as looking like a random-pattern stained-glass window of different densities ranging from light (not much of that left there) to solid.
So my guess is that the increased density simply means the cancer in that specific location was growing, but not expanding out. And I might make an amateur speculation that being contained in a location (instead of spreading diffusely) might suggest it showed a limited tendency to spread and invade for the moment.
That's a fellow mBAC's patient's guess.
Best hopes,
The transition from ground glass to semi-solid or solid is typically correlated with a greater probability that the lesion is cancer, and that it has an invasive component under the microscope represented by the solid component seen on the CT. BAC is classically defined by its non-invasiveness, but as I noted in the post above, there are often invasive and non-invasive components intermingled.
Good luck.
-Dr. West
Dear Dr. West,
I have a question regarding mucinous BAC. My grandfather, 79 years old was diagnosed with mucinous BAC (5cm node at left lower lobe). Left lobe resection would be done, but at the beginning of surgery, surgeon noticed modified tissue spread over all left lobe (it was not possible to saw on CT), stopped intervention and just collected tissue sample for pathology. Surgeon told us that it was not possible to perform resection, because cancer is too much spread and it is stage IV. But after pathology results surgeon completely changed his mind, he told us that modified tissue was scars not a cancer like he thought, and that he suggest new surgery now.My grandfather after first surgery suffered postoperative delirium, and he is exhausted now. Other option is chemotherapy. Please, let me know your opinion, what would be better for man of his age, new surgeon or chemotherapy?
Thanks in advance.
Best regards,
I don't have enough information to make a recommendation. An online forum isn't the right place to give medical advice. I would say that if there is recurrent cancer within a year or two after surgery for a mucinous BAC, it is extremely unlikely that it will be cured with more surgery. It is right to be skeptical about the benefit vs. risk of more surgery.
Good luck.
-Dr. West
Dear Dr. West,
My grandfather passed away two weeks ago.He could not recover from postoperative delirium of BAC mucinosum.
He also had knee pain with swelling few months before surgery but doctors gave diagnosis of rheumatoid arthritis based just on X-ray, without further analysis. I have found manuscript about knee synovial metastasis from primary large-cell lung carcinoma as dreadful prognosis. Average survival after discovery is 5 months. Please, let me know your comment about synovial metastasis from lung cancer and survival prognosis?
Best regards,
I'm very sorry about your grandfather's recent death, and it makes sense to seek answers. That said, your grandfather had BAC, which shouldn't leave the lungs and has never, in the history of medicine, metastasized to the knee. It is not the same as a primary large cell carcinoma, and really the paper bears no relevance at all to your grandfather's case — it's as if you found a paper about knee metastases in a patient with pancreatic cancer. It's a completely different, completely irrelevant situation, and I would say that the odds that your grandfather had cancer spread as the cause of his knee pain and swelling is about 1 in 5 million.
-Dr. West
Dear Dr West,
Thank you for quick reply. Please, see mentioned manuscript, Synovial metastasis from lung cancer at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3523761/, they wrote "Adenocarcinoma has been the most common type of synovial metastasis encountered." If there are different sub types of adenocarcinoma of the lung and BAC is one of these sub types, I thought that it is true. I am very sad about his dead, because I have insist on surgery, as well as his doctor, rather than chemotherapy, but he suffered postoperative delirium and could not recover, he passed away less than two months after surgery.
Best regards,
It's true that BAC is a subtype of adenocarcinoma, but there are MILLIONS of patients with adenocarcinomas, and less than 0.001% of them will have a metastasis to the knee. Moreover, BAC rarely spreads outside of the lungs and has never, ever been reported to spread to the knee. I can essentially guarantee that there is no association between his lung cancer and his knee pain.
-Dr. West
Hello Dr. West,
I can't thank you enough for the excellent service you are giving people with this website. Knowledge is power. Most of us in the non-oncology medical world are not informed on many of the latest oncology treatments and more rare cancers (such as BAC), so having access to a content expert like you is very reassuring.
I'd like to ask for your advice on a few topics regarding my mother.
My mother is a 72 yo previously healthy, non-smoker woman that has had a non-productive cough for 3 months. CXR showed a LLL opacity and CT Chest showed 'diffuse ground class opacity with consolidation and air bronchograms filling nearly the entire Left lower lobe and minimal similar changes in the lingula, and a trace left pleural effusion'. She was initially diagnosed with pneumonia and treated with antibiotics, but her cough remained (despite 2 rounds of antibiotics). She then had a bronchoscopy done last week, and the bronchial lavage cytology showed 'many clusters of high grade malignant cells, consistent with non-small cell carcinoma positive for non-small cell adenocarcinoma'. She was told she had Bronchioalveolar Carcinoma. It sounds like she has the 'Pneumonic' pattern, and that she likely has mucinous lung adenocarcinoma.
The CT Scan did not show any enlarged lymph nodes and the PET scan was negative for any lymph node involvement (so an EBUS could not be done). I assume this is good news, but I'm not sure how helpful the PET scan is for helping with the prognosis for this diagnosis and also this 'pneumonic' pattern of BAC.
Initially reading about the better prognosis for BAC and reading about the improved survival for patients with erlotinib was encouraging, but then reading about the poor prognosis with the Pneumonic pattern of BAC and that the EGFR mutations are mostly in non-mucinous lung adenocarcinoma has been discouraging. What a roller-coaster of a week.
I have some questions that I could use your expert advice on prior to my mom's evaluation next week with a renowned thoracic surgery at Sloan Kettering
1. How would you stage this type of cancer? stage X?
2. Is the Lingula considered a 'lobe' of the lung? The CT Scan showed findings in her Left Lower Lobe and some findings in the lingula, and I know surgery is not recommended if it is involved in more then 1 'lobe'. I didn't know if the lingula is considered a 'lobe'.
3. Do you have any data on the median survival for Pneumonic pattern of Bronchioalveolar carcinoma with normal PET scan and no enlarged lymph nodes on CT? With this Pneumonic pattern, how often does the cancer recur if it is resected, and when does it most likely recur? A lot of papers refer to the 2000 study done by Sloan Kettering of the 100 BAC pts regarding prognosis for Pneumonic pattern, but that study only included 7 Pneumonic Pattern patients (and because they were labelled stage X, I don't know if they had any lymph node involvement)
4. It sounds like the Pneumonic pattern of BAC does not usually have the EGFR mutation, so it sounds like erlotinib will not be an option my mom. What other non-surgical treatment options does my mother have if the surgeon does not recommend surgery?
5. It sounds like the ALK rearrangement is pretty rare, but if my mom has this, then she could be treated with crizotinib, correct?
6. It sounds like she may have the KRAS mutation, because she likely has a mucinous adenocarcinoma, correct? If so, then do you have any experience with the investigational MEK inhibitor selumetinib with docetaxel?
7. Any recommendations for chemo options or new medication trials?
8. Any questions I should be asking the surgeon next week?
Thank you again for any help you can give in this difficult time. I've tried to read as much about BAC as I could in the past week, but I have no experience with this disease, so an expert opinion such as yourself could really be helpful
I can't feasibly reply to a long list of questions for everyone, which is why I put out so much general information that provide the key principles that people can apply to their own situation.
It does sound like stage X disease. The lingula is technically part of the left upper lobe, basically a large segment of it. I think it is a matter of judgment more than rules as to whether she has resectable disease. The surgeon might not recommend surgery, which may be a wise judgment, but if he/she does, she might have just the left lower lobe and the lingula resected, leaving the remaining port of the left upper lobe. However, what we know about pneumonic BAC is that it very, very often recurs within a short time after surgery, so she and you and her surgeon would need to decide whether it's worth the risk of surgery for a rather remote possibility of cure. If the surgeon is overly optimistic, they either don't understand enough about this disease or they're just pushing a surgery for the sake of business.
In terms of molecular markers, it makes sense to check the markers before making conclusions. What we know is still based on limited numbers here and there — nothing definitive. The basic suggestion I'd offer is that non-surgical BAC, whether mucinous or non-mucinous, should be treated just like any other lung adenocarcinoma: it depends on the presence or absence of molecular markers. If you have an EGFR mutation, treat with an EGFR inhibitor. If you have an ALK or ROS1 rearrangement, treat with crizotinib. If you have a KRAS mutation, there are some trials here and there, but no specific standard treatment recommendations other than chemotherapy-based treatment. And in terms of chemotherapy, a platinum and Alimta (pemetrexed) combination has tended to be a strong choice for many adenocarcinomas and perhaps especially for BAC — good results can be seen with mucinous as well as non-mucinous disease.
Because we've really come to learn that BAC should be managed essentially the same way as other lung adenocarcinomas, there aren't specific trials for BAC anymore — they have been supplanted by molecularly-defined subgroup trials in lung cancer.
Good luck.
-Dr. West
Thank you Very much, Dr West! Sad news, but very honest and helpful. I appreciate it
Sorry, but one more question, if surgery is not an option and if the molecular markers turn out not to be a option, so then cure is not an option, then would you even recommend chemo? Would the possible extra 2 month survival be worth the decreased quality of life and side effects from the chemo?
Thank you
First, I am not directly involved in her care and am not able to say whether cure is not possible.
With regard to your second question, there is a huge amount of variability in how well or poorly people do with treatment. It is absolutely incorrect to just presume that everyone gets a couple of months longer survival from treatment. Some get two months, some get 4, some get 6 or 12, some get years, and others get none or may even be harmed by treatment. The averages tell how a population of 100 or 1000 people do, but they absolutely don't tell how an individual patient will do.
Also, even if it is a matter of 2-4 months improved survival for many patients, if chemo is very well tolerated, many people would prefer to live longer than a shorter period. If I see a $10 bill on the ground, I'm happy to bend over to pick it up even if it doesn't profoundly change my life. It's a modest gain but not much effort. I wouldn't feel that way if I had to scale 50 flights of stairs to get it, but if the cost is minor, even relatively modest gains are worth seeking.
If you or your mother feel that the likelihood of a benefit in the range of a few months is not meaningful, that's perfectly fair, but a lot of people are eager to do a lot to pursue even a hope of a potential benefit, even one likely to be very marginal, well beyond what I could clearly recommend.
-Dr. West
Dr. West,
Thank you! That makes complete sense. I'll leave the decision up to my mother. Because of my lack of experience in this area of medicine (and most physicians lack of experience with the Pneumonic BAC pattern), I'm trying to gather as much information as possible from the experts in this field (clearly you are a world expert!), so that I can get my mother the best treatment, or if we can't find a curative treatment for her, then I want to make her remaining months (hopefully years!) as comfortable as possible.
Again, I can't thank you enough for providing your expert advice is this arena. I'm very appreciate of all of your comments, and I will certainly be contributing to this site.
A world class oncologist providing free and immediate up-to-date information and recommendations to frightened patients and families that are suddenly thrust in to overwhelming and intimidating world of oncology and then expected to make inexperienced decisions that will decide a loved one's… what you provide is a beautiful, beautiful thing.
Thank you
Eric (apple81),
I have mucinous BAC (or at least it's been behaving like it) and I've known a couple other mBAC patients via online forums (and then via that in real life).
It sounds to me like you're jumping to assumptions before all the test results are in, based on some sense of aggregate statistics which may or may not be valid today, and may or may not be applicable to your mother's individual case (the odds of something for an individual are either 0% or 100% and you won't know which until the results are seen). I'd recommend (1) reconfirming the staging as best you can and if actually an early stage or stage 4 then (2) rush to getting the cancer's genes tested and you'll see if new options emerge. That's what happened in my case and I've been living with stage 4 mBAC for 4 years . . . and still counting (though I some progression is starting). FWIW, there's a brief profile of me at http://cancer.org (I kid you not — for this month you can click on the article "Lung Cancer Survivor Finds Help Through Clinical Trial").
Some of my remaining comments will be redundant of what Dr. West has already said, so I'd defer to him of course, but it might help hearing a fellow patient's view.
As I understand it, it isn't uncommon for mBAC to not show up on PET scan if it follows the most common behavior of relatively slow growth (e.g., mine was growing about half-normal speed). If the cancer is growing slowly, i.e., slow metabolism, and if it has been only forming a layer of surfaces rather than consolidating into a solid mass, it would be understandable if a PET scan (test of metabolic activity) doesn't distinguish the cancer very well vs. normal lung tissue. (My original PET scan only showed the consolidated mass that had accumulated.) I don't see that as a reason EBUS can't be used — EBUS is endotracheal ultrasound, a method of "echo" guided bronchoscopy. I had both regular and EBUS bronchoscopies, and in my case the EBUS did a far better job of snagging better samples and more of them.
As a mBAC patient you might assume my cancer was EGFR driven since that's more common (if I recall correctly), but no, mine is driven by a ROS1 fusion. My role model "Linnea" has had mBAC for 10 years (she wasn't stage 4 at the start) and hers is driven by an ALK fusion. ALK is rare and ROS1 even rarer, but they do occur in some patents, more commonly in never-smokers, and odds of "what's left" go up as more common ones like KRAS and EGFR get ruled out. And I bet there are some pneumonic BAC patients with EGFR-driven cancer; conversely though KRAS is rarer in never-smokers, some have that. So you can see what I mean when I say it's best to avoid assumptions even if the odds might be low. I can say, though, that for me it was well worth getting tested to find out the name of my enemy (if that was possible) so I could at least follow the research for it, though in my case I got lucky early.
I am under the impression that "pleural effusion" usually means stage 4, i.e., local treatment is no longer going to be an effective option; systemic treatment is what would be needed. If fluid is building in the pleura that can be sampled and tested for the presence of any cancer cells, that can confirm whether there's plural effusion or not. If not, then it might be an earlier stage, but if it's already spreading from one lobe to the next I'd wonder if it might also have started to spread undetectably further away (or almost undetectably) like in my own case.
Glad to hear you're getting a consultation with a MSK doc, but you might want to check with an oncologist, too, not just a surgeon like I did. Actually my "2nd opinion" was with a U. Penn "top doc" lung cancer surgeon and even he said "I don't think this is what you think it is" although he didn't get as specific as his lung cancer oncologist colleague (he got me an appointment the next day since I was booked for surgery after that weekend) who was able to show me how it was stage 4.
FWIW, anecdotally I've heard from other patients/caregivers that it isn't uncommon to go into surgery thinking it is early-stage mBAC only to find 2-6 months later that is had already spread elsewhere. I'm sure there are cases where it works out magically, but based on the anecdotes I tend to assume (as a fellow patient, not a medical professional of any type) that if there's any evidence of cancer to another area there might be more seeding started. That doesn't mean surgery couldn't set back the frontrunner problem if it's the best option, and there are some cases who do better that way (look up oligometastatic lung cancer) but as that surgeon I saw said, in the overall averages the odds of 5 years survival are lower if starting with surgery (rather than starting with a systemic treatment) if it really is stage 3 or 4.
Yes, if ALK+ then crizotinib would be the 1st line drug of choice with high odds of benefit (although not 100% odds). If it is really mBAC and behaving like it doesn't spread outside the lung, then the risk of brain mets is low, making crizotinib a fine choice. (Crizotinib doesn't protect the brain very well.) Besides, some early data suggested that sequencing 1st gen (crizotinib) – then – 2nd gen provides longer total duration of benefit collectively than jumping to a more potent (and brain-penetrating) 2nd gen ALK inhibitor . . . assuming brain mets aren't an issue.
You left out ROS1 fusion. If ROS1+ then also crizotinib. It works even better for ROS1 than for ALK (possibly esp. so for mBAC like mine).
KRAS driven lung cancer hasn't found a high-odds inhibitor drug yet because KRAS+ cancer tends to have other bypass mechanisms around a direct KRAS inhibitor and there are other bypass mechanisms besides just MEK (though that's a key one). Research continues and I hope that someday they'll find the secret sauce to blocking the necessary doors and windows without insufferable side effects.
FWIW, KRAS patients often have a smoking history and that improves the odds of an immunotherapy option like an anti-PD1 or anti-PDL1 drug. (I don't know whether KRAS+ trumps smoking history or not, but about 10% of never-smokers still get a response, vs. about 30% for the smokers.)
If stage 4, then if EGFR+ or ALK+ or ROS1+, I would think the research has been finding a targeted inhibitor would be preferable to chemo due to high odds of benefit. There might be research on applying the inhibitors to earlier stages, but I've lost track of the research lately and might have missed that; in the past inhibitors where only offered to stage 4 patients since early stages had at least hope of cure vs. inhibitors don't cure and don't inhibit forever.
FWIW, there's been a little research suggesting that never-smokers may fare better than smokers when given a chemo combo that includes both Alimta (pemetrexed) and a platinum-based chemo (cisplatin or carboplatin). See the Alice Shaw paper on that (which was pursued in order to determine if ALK+ patients do especially well with Alimta, though it turned out to be more of a never-smoker issue in their patient sample).
FWIW, in general I've been told my by local oncologist (and it seems consistent with some results of some trials that had a control group) that a good chemo triplet tends to have about 50% or better odds of benefit for some period of time. My non-scientific impression is that the odds go down in later combinations or drugs, e.g., only 10% per drug so there might be a time when a person choose to not find out if they might be one of the lucky ones, but I sure wouldn't want to give up a 50% chance of living longer unless after trying it and seeing how well I tolerate it (and then how well the cancer tolerates it).
Best hopes,
"Craig in PA"
Hi Craig,
Thank you very much for all of the above information, and congratulations on your success. My concern/pessimism stems solely from the words 'poor prognosis' in literally every article I've read about the 'Pneumonic Pattern' of BAC. Unfortunately, you can't really stage this 'pneumonic' BAC, so it's called Stage X… but I refer to it as Stage 'V', because patients with Pneumonic BAC (even without lymph node involvement at time of diagnosis) actually do worse then even Stage IV multifocal BAC patients.
If you or anyone on this forum know of anyone with Pneumonic BAC that is doing well 1 year after diagnosis, then please let me know! That would be so inspiring for me to hear good news is possible with this horrible pattern of BAC.
Thank you again, and I wish you continued good health.
Yes, Eric, my stage 4 mBAC also had a poor prognosis — at the time of my staging I expected to be dead in about 2 years if nothing worked, and the odds didn't seem good that anything would work. Of course that completely changed when a useful driving mutation was found. Yes, not everyone has one, but never-smoker adenocarcinomas actually have pretty fair odds, and downright good odds of at least experimental trials that might be worth trying at some point if you test for all the mutational possibilities (e.g., Foundation Medicine's Foundation One test) so you know what's there. So my point is just that the emergence of target therapies (either useful driving mutations or newly emerging immunotherapies) in the last few years can improve the prognosis for many patients. My memory of the statistics is a little fuzzy, but it changed my stage 4 prognosis from a 1%-2% chance of surviving 5 years to having a very useful driving mutation (EGFR or ALK or ROS1) where patients have a 30% chance of surviving 5 years. Yes, it's good to be objective and be prepared for the worst, but do the testing and hope for the best because sometimes it does happen.
Best hopes,
Craig in PA
Hello again Craig,
Thank you again for ALL of the information you gave me. I've now finally had the time and chance to digest all of your email, and you gave me some Great information! What an inspiration you are, and I really appreciate you trying to help me and my family!
Yes, we're just waiting for the molecular markers to come back. Despite how pessimistic my last question to Dr. West sounded (sorry about that), I'm actually trying to stay positive, but I'm also trying to be prepared for any and all situations that we may face (and the no surgery and negative molecular markers is a situation that would be tough to face).
Congratulations again on your success, and just hearing about your success inspires our whole family.
All the best,
Hello again Dr. West,
I have recently given a fairly generous donation to this website, and I'm
still very appreciative (and a bit shocked and inspired) that expert advice
like yours is so readily available to anyone!
In brief, my mother is a 71 yo previously healthy non-smoker woman with 4 mos of non-productive cough, initially dx with L LE pneumonia (dx by CXR and CT; L LE infiltrate seen; no lymphadenopathy seen), and didn't improve with antbiotics. BAL then showed NSCLC, and biopsy showed non-mucinous NSCLC. PET scan showed no lymph node involvement, no mets, no malginant cells in the trace pleural effusion previously seen on CT, but it showed some increased uptake in the Left Upper Lobe (although her oncologist actually does not think the L Upper lobe involvement is cancer). MRI Brain was nml
In preparation for our meeting with the MSK surgeon and oncologist tomorrow, I'd like to ask your advice
on a few more topics, if I may:
1. We're waiting for the molecular markers to come back, but interestingly the lab only tests for EGFR, ALK, and KRAS. Do you think ROS1 (and BRAF) should also be tested for? Any others?
2. If surgery is not recommended, even if the EGFR mutation is negative in the lab test, should she still be treated with erlotinib now, because: she's a non-smoking woman that is chemo-naive and has a non-mucinous pneumonic-type adenocarcinoma (P-ADC) so she may be more sensitive to EGFR-TKI therapy, there is a high incidence of EGFR mutation in P-ADC (and maybe there is a false-negative in the lab?), EGFR-TKIs have been shown in some studies to be used as 1st line for non-resectable P-ADC, and because the less-then great results with chemo for this diagnosis?
3. Her pulmonologist said she had BAC, but then there was no mention of BAC on pathology reports, and her oncologist does not use the term BAC, but rather just non-mucinous adenocarcionma. I'm confused with the exact diagnosis that my mom has, and from the information I've shared, would you be able to help with the name of her diagnosis? Her presentation does appear to fit for the previously used 'Pneumonic BAC' term. Does she have: Pneumonic BAC vs Pneumonic-type Adenocarcioma (P-ADC) vs Adenocarcinma with mixed invasive and BAC predominant subytpe (ADC-BAC)? Is there a P-ADC-BAC? What's the most appropriate term, which can help me with looking up treatments and prognosis?
I understand your concerns about recurrence after sugery, but we're still hoping the surgeon will feel she is a surgical candidate for a lobectomy.
Thank you!
1) I would be inclined to do molecular marker testing if surgery is not pursued, since these systemic treatment approaches are only tested and have a role in patients with advanced disease. If surgery is done for potentially curable disease, then there is no standard role for any molecularly directed therapy. But if molecular marker testing is done, I would include ROS1.
2) No. The best evidence we have is that the reason many patients with non-mucinous BAC have done well with an EGFR inhibitor is because many have an EGFR mutation. However, if a patient doesn't have an EGFR mutation, chemotherapy is clearly the far superior approach. While a false negative result is always possible, a true negative result is still more likely, and an EGFR TKI is an inferior choice as first line therapy. I'd offer it at some point, as second or third line therapy, which should cover the possibility that it will be profoundly beneficial.
3) I would strongly suggest not getting too caught up in the names, which transition over time and are NOT etched in stone. The term BAC is no longer favored according to some leaders, while many people who work in the trenches continue to believe there's some use in that descriptor. But you are really becoming tied up in semantics. "Pneumonic" was just a term that was proposed in one key paper that isn't an official one — it simply tends to be associated with a high risk of recurrence if surgery is undertaken.
I'm afraid that I honestly don't think you will find more information than I've provided about BAC here. Nobody anywhere writes more about it. At the risk of sounding pompous, there simply isn't any better information about the subject available anywhere. There is still room for judgment, so my perspective is not the absolute word from God, but you just cannot and will not ever find a best answer. You will be hard pressed to find much more information.
Good luck.
Hello Dr. West,
I could use your advice… again.
My mother is a 72 yo previously very healthy woman non-smoker with normal PFTs diagnosed with non-mucinous pneumonic BAC non-small cell lung cancer in Dec '15 after presenting with a non-productive cough for 3 months. PET scan didn't reveal any metastasis or lymph node involvement and it showed involvement mostly in the Left lower lobe but possibly also in the Lingula and Left upper lobe, and CT Scan showed involvement of nearly the entire Left lower lobe and possibly the Lingula (also possible faint involvement on the CT in the Left Upper Lobe and maybe even also in the Right Upper lobe; although different radiologists and different oncologists had different opinions). Difficult to stage her due to the pneumonic pattern. Sloan Kettering Thoracic Surgery did not recommend surgery.
My mother's lung cancer turned out to be positive for the EGFR mutation (we felt like we won the lottery!), and she has been on Tarceva since Dec '15. She's been doing fantastic ever since taking the Tarceva (except for some expected side effects), and a repeat CT Scan last week showed that the only remnant of the lung cancer was a spiculated nodule in the peripheral left lower lobe measuring 10 x 10 x 9 mm.
My mom feels great, and the CT Scan looks phenomenally improved, but one question now is what do we do, if anything, with this remaining LLL nodule?
Her Oncologist at Mass General offered us a few options for this remaining nodule:
1. Do nothing for that remaining nodule and just stay on the Tarceva 150 mg (although maybe a lower dose; by the way, when do you typically decrease down to a lower dose of 100mg or 75mg)?
2. Try to get involved in a new Stereotactic Body Radiation Treatment (SBRT) trial they are doing for lung cancer at Mass General
3. Follow up with a thoracic surgeon to discuss removal of the nodule (?lobectomy)
What would you recommend?
Also, my main concern is what to do if my mother's lung cancer develops resistance to the Tarceva, and, in that case, what would be your recommendation for the next step? Tagrisso?
Thank you again!
First, I need to state that GRACE can provide general information but is not able to tell people what they should do — we can't and don't make medical recommendations for people who are not our patients. That's illegal.
Speaking in general terms, there is truly no benefit in doing a local therapy such as surgery or radiation if the cancer was ever more advanced. If there was disease outside of the left lower lobe, then the disease is still advanced but just not visible. It's great to have a very dramatic response, but the cancer doesn't become lower stage than it was to begin with. Just like rocks under water are still there when covered and below the water line, the cancer will still appear elsewhere when acquired resistance develops if it was advanced disease previously. There is no evidence that doing radiation or surgery will do no more than using Adobe Photoshop to remove the nodule from the scan. It might make you and the doctors feel better to see that, but it almost certainly doesn't change the underlying biology at all, and the cancer outcome will still be determined entirely by what happens everywhere else in the body outside of that nodule.
It's not that this isn't a tempting idea, but it doesn't work. In fact, just today I saw a patient who had what I strongly suspected was stage IV pneumonic BAC with some other small lung nodules on the other side, but they were (mistakenly) called pneumonia or some other hand-waving BS diagnosis. I started him on Tarceva for stage IV NSCLC, at a time when he was very sick, and he became much better. The main cancer shrunk to just a tiny residual bit, and the other nodules all went away. He campaigned for surgery, and he got it. Because he had already been on Tarceva for several months, I suggested that we watch him off of Tarceva after his surgery to see if he could be cured, because being on Tarceva indefinitely after surgery was really not giving any indication of how helpful surgery was going to be. Not surprisingly, his cancer was back in many places by the first post-operative scan, and I put him back on Tarceva. He responded and continues to do well on Tarceva to this day (literally, because the scan was today, and it still looks great 2 years later).
So what did surgery do? It removed 1/2 of one lung (his was also left lower lobe). What did Tarceva do? It is the driving force behind his excellent response. And if he comes off of it, his cancer will return within 6 weeks.
For advanced lung cancer, local therapies just treat the scan. The systemic therapy treats the underlying disease.
If the cancer was limited entirely to one lobe, I do think that surgery or radiation is very reasonable and could potentially be curative. There is no way to say which is better here. Surgery is the more aggressive approach, which is good and bad. It's a bigger hit against the cancer but removes a lot more lung and is much more for a person to go through, especially if the role for either local therapy is very dubious.
Good luck,.
-Dr. West
P.S., I have no specific facts nor references to offer and I might be confusing something I misread, but I'm under the impression that some oncologists are experimenting with removing or destroying sites of residual disease seen on CT scans (e.g., usually the site of origin) after responding well to targeted inhibitor. I assumed they don't think that would eliminate the cancer (note: they don't discontinue the inhibitor drug), but are just hoping to delay how quickly drug resistance emerges — on the assumption (perhaps false) that although resistance can emerge anywhere the cancer had been before maybe they imagine it might arise sooner where there was the most cancer before. It sort of reverses the sequence of awaiting for initial resistance to occur and then zapping spots when they emerge in order to extend the usefulness of the drug, but speculates on where that resistance might occur. I don't think there's any reported evidence supporting that thought yet, but if there are formal trials of that then eventually research results will probably be presented or reported.
Craig's comment is very fair — there certainly are oncologists who are recommending radiation to residual spots after initial treatment, and most lung cancer specialists (myself included) are favoring a local treatment if there is a new single site of new or progressing disease after a good response, a setting we're increasingly thinking of as "oligo-progression" (oligo meaning few, and the idea being that this single area is behaving differently from the rest of the cancer in the body and may therefore be treated differently).
As I typed my long answer, I thought about the untested possibility that surgery or radiation to remove or ablate a solitary area of visible, viable cancer might postpone resistance. It's definitely clearer that this isn't curative, but could this practice postpone resistance? It might, but there is only conjecture at this point, without any evidence at all to support this — we need trials, which may or may not ever be done, to properly test this idea.
I do make a distinction between radiation or resecting oligoprogression and radiating residual disease in someone still responding well, and in this particular case, we're talking about the latter. In radiating or resecting oligoprogression, we're definitely extending the time someone can stay on a treatment that is highly but not completely effective. In the case of giving local treatment for residual disease, I feel that this is done more because people just want to do it and then can backfill a plausible justification for why it might be a good idea — but there isn't a scrap of evidence to say it's a good idea, and it could be harmful in the end to remove or radiate good lung tissue around the residual disease.
Hello Dr. West,
Thank you, as always, for your straight-forward, insightful, and expert opinions. I can't thank you enough for your help, and all of the information you are able to give me (and my family).
I have now contacted the Radiation Oncologist at Mass General that is doing this SBRT trial, and interestingly he is doing a study looking at giving SBRT with proton or photon radiation for residual nodules in patients taking a TKI. The Radiation Oncologist stated, "We have a clinical trial where we treat before progression occurs. The rationale is that sites of residual disease may harbor the greatest tumor burden and the highest likelihood of containing tumor cells that will acquire drug resistance. Our own practice data indicate that there is a high (>80%) chance that the first recurrence is in primary tumors that were at least 3 cm in size at time of diagnosis. So your mother's tumor would qualify for this protocol."
The trial is Phase II, and here is a very recent study that he shared with me which appears to support doing this trial:
Al-Halabi, H, et al. Pattern of Failure Analysis in Metastatic EGFR-Mutant Lung Cancer Treated with Tyrosine Kinase Inhibitors to Identify Candidates for Consolidation Stereotactic Body Radiation Therapy. Journal of Thoracic Oncology, Volume 10, Number 11, November 2015
Does this Al-Halabi study change your opinion of whether someone should enter in this trial? Also, what do you think about my mother flying out to Seattle to be seen by you in your practice?
Thank you again!
If I understand correctly, the trial is randomizing between proton and conventional (photon) radiation, but everyone gets radiation. My impression is that there is no arm of the study that treats according to the current standard of care, which is no radiation. Therefore, it doesn't even pretend to be able to clarify whether it is truly helpful to deliver radiation, but rather assumes radiation is automatically beneficial. That is a bad assumption unless you are paid to deliver radiation therapy.
The article you share shows that many patients progress in areas of initial disease. This is not specific to patients with an EGFR mutation, and it does not imply that patients will live longer by doing it. My perspective is that this is a trial that basically just tries to justify giving radiation without having a compelling reason to do so, nor does it even offer a pretense of contributing to our knowledge base in a way that will properly test whether it truly helps or not. If you obliterate the existing lesion, of course the cancer can't progress there. But that doesn't mean anything if patient survival is limited not by that but by when their cancer progresses in various other parts of the body.
Your mother is very welcome to come visit my clinic for a full discussion.
-Dr. West
Dr West, Any thoughts? Ive already had upper right lobe removed….Met with surgeon today, good news is he can do VATS & a wedge resection on upper left lung, unless when he gets in there possible he might need to take the whole lobe and (possibility of having trouble finding it because it is only 0.9 cm).
Then he says well were not even sure if it is cancer & he thinks its a BAC tumor?! Pet Scan wasnt positive, but I guess these BAC tumors dont always show positive, But Tumor has grown in size and density over the last 3 years……And I could just watch it and get another CT Scan in 3 to 6 mons. Or I could opt to do nothing at all. He wouldn't give me any indication of what I should do or what he would do. He is sending it before a second tumor board for more opinions. I have asked for referral to Oncologist now. And have asked for copies of CT Scans to get second opinion at a non Kaiser hospital. Have any of you heard of this BAC Lung Tumors… What can you tell me, Looking forward to your comments and opinions…
thanks Sandi
I'm kinda thinking of having the surgery and be done with it, so I wouldn't be worried & wondering all the time…
This is a very complex situation that requires an individualized approach. I really can't make a recommendation on a complex case of a patient I've never met, based on scans I've never seen. Legally, I and GRACE can offer information that includes useful principles for other people, but I/we can't give advice for individual people who aren't our patients.
The fact that a lesion doesn't light up on PET suggests that it is likely to be a VERY indolent process, so there is a real risk of over-treatment. The treatment may well be worse than the disease, especially if the surgery could be a big one, like removing an entire lobe, and other lesions could emerge in the next few years. Patients often regret having undergone a major surgery and losing a lot of their lung tissue for a surgery that turned out to not be curative and ended up removing a lot of good lung in the process.
This is a summary of the key ways that I approach recurrent or multifocal indolent cancers like BAC:
Good luck.
-Dr. West
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