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PET Scans for BAC
PET scans are an important way to discriminate between metabolically active nodules, suggestive of cancer but sometimes representing inflammation or infection, and non-PET-avid lesions that are felt much likely to represent cancer. They are also a cornerstone of “clinical” staging by imaging and patient exam (vs. “pathologic” staging by surgery to clarify where cancer is or isn’t). PET scans, however, require rapid metabolic activity to highlight a cancer, so there’s good reason to question whether PET scans can be used effectively for the BAC subset of lung cancers, which, as I’ve described in prior posts (here, for instance), can be remarkably indolent.
No specific prospective (planned ahead of time) studies of PET scanning in BAC have ever been done, but there are now enough BAC patients in other trials for us to look retrospectively at meaningful numbers, so we can now begin to assess the feasibility of PET scans for diagnosis and staging of BAC. Continue reading
Imaging Factors Predictive of Higher or Lower Risk for Recurrence of Early Stage NSCLC
Among the many variables that can potentially be helpful in predicting outcomes after surgery are some imaging results. One of these is cavitation, or hollowing out of the inside of some part of the tumor. Although most clinicians think of this as a feature of squamous cancers, it can also be seen with adenocarcinomas and other histologies less frequently. On a CT, this appears as a black area of air in the middle of a nodule or mass, and this generally occurs from a cancer growing to outstrip its blood supply, so that the inside of a tumor no longer gets nutrients and dies, from the inside out. In fact, a study from MD Anderson of stage I cancers with or without cavitation (abstract here) indicated that those with cavitation are associated with a significantly worse survival:
(Click to enlarge image)
Although this is a small trial, with just 72 patients included, it does suggest that tumor cavitation may be a helpful tiebreaker in cases where people are on the fence about pursuing post-operative therapy.
Another potentially relevant issue is the standard uptake value (SUV), a measure of the metabolic activity of a tumor on a PET scan, which just about everyone now gets before surgery to clarify staging. SUV is a measure of labeled glucose (sugar) uptake by a tumor, which is increased by higher metabolic activity like rapidly dividing cells, which leads to faster tumor growth. At the World Conference on Lung Cancer in Korea, Dr. Goodgame and colleagues evaluated variables that predicted recurrence among 136 patients with stage I NSCLC tumors resected at Washington University in St. Louis (abstract here): Continue reading
PET Scans For Restaging After Induction Treatment for Stage IIIA NSCLC
Purists have considered mediastinoscopy, which is invasive staging of the mediastinum through a small incision just at the base of the neck to get down behind the sternum, or breastbone, to be the “gold standard” for determining whether lymph nodes in the mediastinum, or middle of the chest, is involved with a cancer. The procedure is as shown:
(Click on image to enlarge)
As noted in an earlier post, these lymph nodes are very important in initial staging and also repeat staging after induction therapy; specifically, results after surgery appear to be far superior for patients who have no evidence of residual tumor in the mediastinal nodes after induction therapy, whether chemo or chemo and radiation together. Some thoracic surgeons have a patient undergo mediastinoscopy for initial staging followed by a repeat mediastinoscopy after induction therapy in order to assess response. In fact, that is probably the most definitive way to clarify staging before and after induction treatment. However, mediastinoscopies are not only an invasive procedure but are more complicated when done a second time, and they are also potentially more complicated after treatment, especially if radiation is included. One other potential option for reassessing the mediastinum after surgery is to use imaging, with particular attention to the value of PET scans for determining whether there was a response of the mediastinal lymph nodes. Continue reading
Lung Cancer Screening, Part III: Present and Future
Well, as I suspected, the topic of lung cancer cancer screening has been a bit of a minefield, but I’m going to end now by trying to pull together where we are here and now, at least in the US. The article about the very impressive results of the I-ELCAP trial that was published in the New England Journal of Medicine (NEJM) (abstract here) concludes that 80% of deaths from lung cancer could be prevented by CT screening and that such a screening program has a cost-effectiveness comparable to that of mammography for breast cancer. This conclusion has met with a range of views. The Lung Cancer Alliance, a national non-profit organization dedicated to patient support and advocacy for lung cancer, now recommends that higher-risk patients “should have a detailed discussion with a doctor knowledgeable about lung cancer screening on the potential risk and benefits of undergoing a baseline CT scan”. Those higher risk patients are defined as any smoker or former smoker over age 50 with a greater than 10 pack year history of smoking, or any adult with a significant exposure to cigarettes and a first-degree relative diagnosed with lung cancer before age 50, and there are some other groups, noted here, who they recommend should consider a screening discussion.
The fact that the I-ELCAP manuscript was published in NEJM certainly suggests that it is an important result that might potentially alter general practice. NEJM is arguably the most visible and influential medical journal in the world, and papers published there often change medical practice overnight. The editorial that accompanied the I-ELCAP paper noted that the survival in the large I-ELCAP trial of 88% was certainly superior to the general survival rate of 70% for stage I NSCLC at 5 years but also noted that this was an observational rather than a randomized trial, and that lead time and overdiagnosis bias could have been introduced in the survival analysis. Rather than saying that the study makes CT screening for high risk patients an appropriate new standard, or saying that these results are not adequate to change screening recommendations (which have been that there is not evidence sufficient to recommend screening), author Michael Unger called the I-ELCAP results “provocative” and left the rest of the world to fight about what this all means. No real help there. Continue reading
Lung Cancer Screening, Part II: The Downside
The topic of lung cancer screening is a very charged one, with most people, patients and physicians alike, having a strong opinion, either for or against. This is also an area in which there can be suspicion that any argument against screening is due to a financial calculation in which saving people from lung cancer isn’t worth the cost of imaging. Any screening discussion also entails a consideration of cost, financial and other, vs. benefit, but here I’ll focus on the issues related to the possible shortcomings of lung cancer screening in terms other than cost. Continue reading
Lung Cancer Screening, Part I: The Arguments FOR CT Screening
The issue of CT screening for lung cancer is a big one, and to handle it properly I’m going to write about it in a few installments. It’s also quite controversial, so today I’ll start with the reasons in favor of CT screening. Just by means of background, I’ll start by saying that chest x-rays have been studied for screening, but they don’t provide enough detail, requiring tumors to be larger before they are reliably detectable, and location of the tumor can be a problem. For instance, you can see here a chest x-ray (CXR) and a CT scan from the same patient, in whom there is really no way to find anything wrong with the CXR on the left, but the CT shows a small, well-hidden nodule (circled in red) behind the mediastinal blood vessels and other structures:
(click to enlarge)
Other relevant background information is that only approximately 25% of lung cancers are detected as stage I or II NSCLC (or about 30-35% as LD-SCLC), so most patients present with at least locally advanced NSCLC, and at least 40-50% of patients with lung cancer first have it diagnosed as advanced disease, when it cannot be cured. There is no government or medical authority that recommends routine screening for lung cancer at this time, so the current policy is essentially that you don’t start a work-up unless or until someone develops symptoms, at which time, they often have very advanced disease that has little or no chance of being cured. Here’s an unfortunate CXR appearance we see far too often at the start of a work-up:
It’s a system that leaves a lot of room for improvement. Continue reading
Early Disease Control: More Predictive of Clinical Benefit than Response
In my last post, I described our evolving recognition in the lung cancer field that significant response as the threshold for clinical benefit is too high and that stable disease is likely a relative benefit as well. An important trial presented by Dr. Lara at UC Davis at ASCO (our biggest cancer meeting) in June, 2006 (abstract here) highlighted not only that or disease control rate (DCR), or “non-progression” is more predictive of improved survival outcomes than response rate (RR), and that the prediction can be made reliably in the second month after starting treatment, usually after two cycles of chemo (I recently wrote about early follow-up PET scans to predict outcome in advanced NSCLC, but a CT scan after two cycles of chemo is much more commonly practiced).
Obviously, disease stage is the most important factor in predicting survival in cancer patients. Staging is designed to separate anticipated survival into various groups. But when I meet new patients just starting on therapy, I tell them that the second key piece of information that we don’t have yet is how responsive their cancer is. Dr. Lara’s study demonstrates that we can get a good idea of longer term outcomes within the first couple of months, and that the survival of patients with stable disease is closer to that of responders than that of progressors. Continue reading
EGFR Mutations and Acquired Resistance After Responding
Thus far, the vast majority of patients who have an initial response to EGFR tyrosine kinase inhibitors like Iressa and Tarceva will eventually become resistant to them. At this year’s ASCO, our huge annual US-based oncology conference, a report was made by the group at Memorial Sloan Kettering Cancer Center (Riely abstract here) on a small series of patients who had progressed after a prolonged period of responding to Iressa or Tarceva. They found that patients who had slow progression, generally without symptoms, and then came off of their EGFR TKI therapy would often experience a rapid worsening of symptoms.
Continue reading
Staging BAC: Not the Ideal System Yet
Right now we use the same conventional staging system for BAC as with other lung cancers. I don’t have a great alternative just yet. I can tell you that as the lead investigator on several BAC trials, there are huge differences in the natural history of their cancer, regardless of what our treatment does. For instance, the trials for BAC are generally for metastatic/recurrent disease, which can mean anything from a single 1 cm spot coming up 4 years after a lobectomy for lung cancer (expect years and years of doing well, whether on treatment or not), to both lungs filled with BAC lesions (still can be variable, but often a lot less favorable). That’s all still in the same patient group, making it pretty hard to figure out what the treatment is really doing. A trial will look great even if you give sugar cubes if it’s filled with people who have a small amount of
slow-moving BAC.
Using “response rates”, or the frequency of the measured tumors shrinking by 50% or more is a challenge because BAC can appear more like wispy clouds that don’t have clear edges than discrete masses you can draw circles around. So the wisps or cloudy infiltrates in the lungs can become less dense from a useful treatment, and you might breathe easier, but it may not be a response because the edges don’t change.
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