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Endoscopic Staging Studies for the Mediastinum
I’ve described mediastinoscopy as a “gold standard” preoperative procedure in patients who are candidates for surgery. Although it’s controversial whether patients with a very low likelihood or a very high likelihood of cancer in the mediastinal nodes (mid-chest, between the lungs) need to have this confirmed by obtaining tissue to review under a microscope, we strongly prefer to get tissue for patients in whom this is a reasonably open question. For patients who are good surgery candidates and in whom there is no evidence of cancer in the lymph nodes of the mediastinum, surgery is the preferred next step. For patients who are good surgery candidates but have lymph node involvement confirmed on the same side as the main cancer (N2 nodal involvement), we most commonly recommend chemo and sometimes radiation before pursuing surgery, or recommend chemo and radiation without surgery. And for patients who have cancer in the mediastinal lymph nodes on the side opposite the main tumor (N3 nodal disease), we generally recommend chemo and radiation rather than a surgical approach. Why the difference in management? Because as nodal stage increases, the risk of cancer recurrence outside of the chest becomes greater, meaning that we need to think about distant disease (and chemo to cover it) more and more, because even excellent local treatments like surgery or radiation, or both, just can’t address micrometastatic disease outside of the treatment area.
While the gold standard has been mediastinoscopy, it’s invasive and requires general anesthesia. Serious complications are rare, but it’s not a trivial procedure either. And it’s very difficult to do a repeat mediastinoscopy to assess response to induction (pre-operative) chemo or chemo/radiation if a prior mediastinoscopy was done for initial staging. So having another option for getting tissue from mediastinal lymph nodes, especially if it is minimally invasive, would be very welcome.
One of these options that is gaining traction uses endoscopy, a tiny camera on the end of a tube, which can be used to look down the esophagus at the stomach (“upper endoscopy” or EGD, for esophagogastroduodenography), or the bronchial tree of the lungs (bronchoscopy). These procedures usually just require sedation, don’t require any incisions, and don’t leave visible scars. An endoscope can have an ultrasound probe attached to it so that a trained physician can get an idea of the shape and size of things behind visible barriers, allowing them to find enlarged lymph nodes that may be behind the walls of the esophagus or bronchi. The endoscope also includes a needle that can be injected into a suspicious node or tumor within the bronchus.
(Click on figure to enlarge) Continue reading
Comments Back Up, including the recent posts
We’re back up, so people can leave comments after these posts, register, etc.
The plan is to move over the all of the post content to the GRACE website, and then start a new forum section there, freezing the OncTalk forums so that they can be read and searched, but not added to. Instead, a very similar forum structure has been started in the GRACE website, separated by “verticals”, so that questions about drug side effects can be attended to not only by me and Dr. Laskin but also Dr. McCune, a Pharm D, radiation oncology questions can be fielded by expert radiation oncologist Dr. Vivek Mehta, and other questions can be covered by the most qualified expert(s). The division by subject will also exist with the articles/blog content the faculty provide, so people can find multiple posts about radiation oncology or social work/coping with cancer all together.
I expert that there will be some tweaking to do once we move, so please provide your suggestions. We can always continue to improve it.
But expect that sometime in the next week or so you’ll be directed over to the posts at GRACE instead of OncTalk, and from the OncTalk discussion forum to the forum at GRACE to add new entries. Please jump in when the time comes. We will likely auto-redirect the web browsers at some point in the future, once the kinks are ironed out (most, at least).
Ugly Turn in Lung Cancer Screening Controversy
Thanks to member Carlos for bringing to our attention a high profile article in the New York Times today about some controversy now surrounding the Early Lung Cancer Action Project (ELCAP) trial, probably the most influential study of CT screening that has been done. Let me disclose immediately that my own institution, Swedish Hospital in Seattle, is a participating site in ongoing CT screening work led by Dr. Claudia Henschke and the group at Cornell Weill Medical School in New York.
It’s hard not to discuss the idea of CT screening for lung cancer without mentioning Dr. Henschke, who I would say has been the leading and most visible proponent of lung cancer screening in the entire medical community. She has led work in this field for many years, and her paper published in late 2006 (abstract here) reported an 88% 10-year survival, remarkably different from the typical overall survival for lung cancer without screening, which is closer to 15%. And while many experts noted major flaws in extrapolating that one could expect anything close to that in the real world, the trial represents one of the strongest points in favor of CT screening for lung cancer.
The brouhaha stems from the new discovery that much of this work, particularly early on, back in 2000 or so, was actually being funded by the tobacco industry, and there’s some suspicion that the leaders at Cornell may have been less than forthright about the source of funding, since the tobacco money was used to start a new foundation that was not appreciated to have been tied to the tobacco industry.
And why would the tobacco industry have a stake in this? Presumably, if people felt reassured that we can detect lung cancer early enough to cure it most of the time, people would feel less of a compulsion to stop smoking, or maybe even pick it up as a habit. Yikes. Continue reading
“Occult” or “Surprise” N2 NSCLC
I was reminded of the important topic of occult N2 NSCLC by a comprehensive review that just came out in the Journal of Thoracic Oncology (abstract here) by a friend, thoracic surgeon Frank Detterbeck, who leads the thoracic oncology program at Yale. To review the basics of lymph nodes for lung cancer, N0 means no lymph nodes are involved; N1 means that lymph nodes are involved on the same side as the primary cancer and inside the confines of the lung; N2 nodes are in the middle of the chest, in the mediastinum, which is between the lungs, and on the same side as the main cancer; N3 nodes are involved and on the other side of the mediastinum or above the clavicles. Lymph nodes beyond those points are M1, or metastatic sites, and would be treated as advanced lung cancer. Occult N2 disease is also sometimes called unsuspected or surprise N2 disease as well, and it refers to a surprise upstaging of patients who were thought to have stage I or II NSCLC before surgery, but after the operation, there’s evidence that one or more mediastinal nodes are involved.
For NSCLC, one of the important aspects of staging in patients who don’t have obvious stage IV disease is staging, which is done largely based on scans, but getting tissue from mediastinal lymph nodes is a controversial central feature. However, I think the controversial nature is whether it’s definitely needed or recommended for patients who have what appears to be a stage I lung cancer (in whom the likelihood is so low it’s not definitely needed), or who have imaging that is very, very consistent with cancer in the mediastinum (in whom the likelihood is so high it’s not definitely needed). In between are many potential surgical candidates with larger stage I, or stage II, or not entirely clear but likely stage III NSCLC. In such patients, most well trained thoracic surgeons will try to get tissue with a mediastinoscopy (or other approach, like a transbronchial ultrasound or transesophageal ultrasound, both of which can sample mediastinal nodes) before surgery, because we know that outcomes are not good with surgery alone for such patients, and our standard is to give chemo or chemo/radiation before possibly proceeding with surgery. However, some surgeons don’t do mediastinoscopies, even in cases with enlarged mediastinal nodes or other features that should suggest a high index of concern (you can’t find a fever if you don’t take a temperature). You’ll never lose surgery business if you are willing to do surgery indiscriminately, on people who shouldn’t as well as should have surgery. They may feel that surgery is the most important factor, so it’s worth just pressing forward and dealing with the outcomes later. That’s below the standard of care, but that’s exactly what happens all too often, particularly when surgeons who aren’t specially trained in thoracic surgery do lung cancer resections. What is worse, sometimes during the surgery, they don’t bother going into the mediastinum to look for nodes (this can be done as a mediastinal dissection during the larger operation, if not as a separate mediastinoscopy procedure from the lower neck, going below the sternum (breastbone).
I’ll just emphasize that selection of a well trained and careful thoracic surgeon is extremely important in managing stage I – IIIA NSCLC. A poorly trained or just not motivated surgeon can do a remarkable disservice to a patient and sabotage their best opportunities for good results, and a well trained and thoughtful thoracic surgeon can maximize that. I say that as a non-surgeon. There should be a book on “When Bad Surgery Happens to Good People”. However, even if patients are treated exactly by the book by a great surgeon or oncology team, sometimes you find unsuspected mediastinal disease at the time of the full surgery, even in patients whomay have had a negative mediastinoscopy (which is a sampling, not an exhaustive search for nodes) before surgery. Continue reading
Bevacizumab (Avastin) Dose: An Open Question
Several members have asked about the appropriate dose of avastin (bevacizumab), which is really still a controversial subject. It’s worth exploring how we got here and where we are now.
While other doses of avastin have been used with other tumor types, the first study in lung cancer that used avastin tested two different doses, 7.5 mg/kg or 15 mg/kg combined with carboplatin and taxol (paclitaxel). This work was done at Vanderbilt Univ. Cancer Center by Dr. David Johnson and colleagues, and Dr. Laskin worked with them for a couple of years. This study had the following design:
(Click on image to enlarge) Continue reading
Tarceva vs. Standard Chemo Compared for Marginal Performance Status Patients, by Dr Laskin
One of the issues we struggle the most with, as oncologists, patients, and families, is how to choose a therapy that won’t make someone feel worse. There are so many things to factor into these decisions: what is the baseline function of the person, what comorbidities (other chronic illnesses) might interact or interfere, what side effects are acceptable or worth the risk, to what degree is the cancer interfering with their functioning and can this be reversed with chemo, and of course what does any individual patient want and expect from chemo? Not to mention the choices between a few different agents or combinations of agents!
The issue of “performance status” (PS) is fundamentally important in lung cancer, especially in non-small cell lung cancer (NSCLC). There are different scales we use to measure this, which have been posted and discussed previously. Most publications use the Eastern Cooperative Oncology Group (ECOG) scale – partly because it’s rated 0 – 4 which is easy to remember. Zero is normal, and 4 is very debilitated, essentially bed-bound. Perhaps it is somewhat surprising that despite all of the fancy molecular markers and blood tests we have, a person’s functional impairment of PS is one of the most important predictors of how “bad” a cancer is. The other two factors are stage (how much cancer is there?) and degree of weight loss. It is well described, and there are other posts on the site elaborating on this, that if someone is very sick either from the cancer or from other concurrent illnesses, standard chemotherapy will only make things worse. But there’s an “in between” group, with a performance status of 2, who may not be as well served by the more aggressive standard approaches but still may benefit from cancer treatment.
The great hope of the next generation of “targeted” therapy is that oncologists will be able to more accurately predict who will benefit from which drug and that the newer drugs will be less toxic and thus perhaps even better for people who are too sick to tolerate our current forms of chemotherapy. Continue reading
Information and a Resource for Managing EGFR-Based Rash
There’s a really helpful resource for patients, developed by several leading experts in EGFR-based therapy and specifically the very common skin toxicity associated with EGFR inhibitors like iressa, tarceva, erbitux, and some others. I’ve already described some early ideas about rash management (prior post) and a more recent medical education program video on the same subject (prior post here). This is a summary article (here) published in the free oncology journal The Oncologist, but I think that more important than the brief review article are the summary poster and brochure for patients. Rather than recapitulate the content myself, I’ll just reproduce them for you to view here (click on any of these images to enlarge).
Here’s the poster (also available as a pdf here):
Oral Topotecan in Previously Treated Advanced NSCLC
During the entire time I’ve been commenting on the most evidence-based and commonly used agents for previously treated patients, I’ve focused on taxotere, alimta, and tarceva (example in prior post here). In fact, that overlooks an agent that has actually been tested in a large study and been found to have similar activity to taxotere, but it remains pretty much an afterthought. The drug is topotecan, tested in an oral form that is just becoming commercially available; here I’ll summarize the trial that illustrates that topotecan is a reasonable option but also suggests why it remains relegated to a lower priority than the other three options we tend to think of more readily.
At the ASCO meeting in 2005, Dr. Rodryg Ramlau from Poland presented the results of a large phase III international trial (ASCO abstract here) that directly compared oral topotecan to the standard of IV taxotere as a second line therapy for advanced NSCLC (subsequent publication abstract here). This study randomzed 829 previously treated patients enrolled from both Western and Eastern Europe to receive either taxotere at the typical dose of 75 mg/m2 IV one day every three weeks, or the altenative of topotecan by mouth at 2.3 mg/m2 for each of the first 5 days of a three week cycle. Treatment continued until there was evidence of progression or excessive side effects:
(Click on image to enlarge) Continue reading
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