Many patients with early stage NSCLC but marginal or just plain poor pulmonary function tests and/or significant comorbidities pursue non-surgical therapy options rather than resection of the cancer. This primarily entails definitive radiation therapy (RT), stereotactic body radiation therapy (SBRT), or radiofrequency ablation (RFA) of these lung tumors. There is far more experience with definitive RT than with the other options, but I’ve never covered it. I’ve really only covered the newcomer RFA (prior post here), which was recently the subject of an FDA announcement of a number of patient deaths following RFA to lung tumors (post here). So now I need to rectify that. The most common primary treatment modality for “medically unresectable” patients with early stage NSCLC has been definitive RT alone. There has been a wide range in the reasons for patients to be ineligible for surgery, and many of these patients have other serious medical problems. A meta-analysis of multiple trials that enrolled medically inoperable patients with stage I or II NSCLC who received definitive RT (abstract here) reviewed results of a total of approximately 2000 patients in 26 non-randomized trials. This analysis demonstrated that overall survival at two, three, and five years ranged from 22-72%, 17-55%, and 0-42%, respectively. Cancer-specific survival was 54-93%, 22-56%, and 13-39% for those time intervals, respectively. Notably, 11-43% of the patients enrolled died from non-cancer-related causes, highlighting the real competing risks of these patients. Results with surgically treated patients are clearly better, but it’s not possible to separate how much of this is from the benefit of surgery over RT vs. how much is due to the difference in general level of health in the surgical vs. non-surgical early stage NSCLC populations. Another central problem with interpreting non-surgical data is the fact that the latter are derived from clinical staging, which consistently understages patients compared with pathologic staging in surgical trials. Approximately 40% of patients with clinical stage I NSCLC are subsequently found to have higher stage disease on surgical staging (abstract here), so surgical series reflect a higher stage, while non-surgical studies report an inferior survival at a lower clinical stage.
In addition to RFA as an alternative local therapy, stereotactic body radiation therapy (SBRT) has emerged as a novel technique, and one that hasn’t been the subject of a recent FDA warning. I’ll cover that work soon.
posted by Dr. West @ 11:25 pm link to this post
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December 22nd, 2007 at 6:43 am
Dr. West,
I was disappointed to learn, in one of your recent posts, about the deaths attributed to RFA. I was hoping that this might emerge as yet another sorely needed treatment option for cancer patients.
Now your post above has made me think…aren’t there really inherent risks with all cancer treatments, and associated treatment deaths with almost all cancer treatment modalities as well? And aren’t the RFA studies targeting the poorest performance status or riskiest patients to begin with, so they have a built-in negative bias in their studies?
Shouldn’t RFA be looked at in a bit of a different light if the targeted populations are cancer patients that may not be suitable for any other types of cancer treatments (due to poor performance status, location or size of tumor, number of tumors, orgin of tumor, etc.)?
I guess that I am saying that maybe RFA should be given a little more “slack” for some treatments deaths because of the degree of illness of the patients targeted for the procedure, and the lack of alternative treatment options available?
Honestly I don’t know any of the statistics about RFA or the associated deaths, but I guess I’m just trying to open up our minds a bit even though RFA has had some recent setbacks.
And dare that anyone think that the large pharma companies, who’s profits may suffer if a new non-chemical treatment option emerges, might use their power and dollars to publicize and steer against such a new treatment option?
It seems like when a cancer patient dies from receiving Cisplatin in their treatment plan, it doesn’t make the news - and there must have been many deaths this year that were attributed to using Cisplatin as a part of their treatment plan. But again, there is an inherent risk with many drugs and treatment plans for cancer.
Jim
December 22nd, 2007 at 3:21 pm
Jim,
I don’t have access to the numbers of deaths, or any details, just the public announcement that the FDA had received a number of reports of deaths that they must have felt to be excessive.
You’re absolutely right that there are some risks associated with standard therapies. There’s an approximately 0.5 - 1% rate of death as a complication of standard chemo for advanced NSCLC, and more than that with ED-SCLC and treatment with chemo/avastin for advanced NSCLC. The treatment-related death rate is in the 5% range for the most aggressive treatment for stage III NSCLC. So sure, there’s risk. But when patients with squamous tumors were included in the early studies of avastin in metastatic NSCLC, the rate of serious, even fatal bleeding complications was more like 30%, and that was too much. It’s always a judgment, and it’s not always non-pharma products being viewed critically, and it’s not always the FDA.
Cisplatin has been proven in study after study after study to improve survival in lung cancer, even with its toxicities, which have been managed by oncologists since the beginning of medical oncology. RFA has never been shown to cure anybody, ever. It’s never been compared directly to radiation therapy. It’s done at a few places, and in some cases it’s been overhyped (in my opinion). Don’t you think it may be possible that RFA is actually NOT that great of a treatment and that the reports of deaths may be in such great number that the FDA could be doing the right thing rather than acting as the instrument of a threatened pharmaceutical industry? RFA makes essentially NO sense in patients with metastatic lung cancer, who represent a very large proportion of the lung cancer world, I’m afraid. I doubt that the pharmaceutical/biotech world was ever remotely worried about RFA being so effective it would impact the market for chemotherapy. RFA would have to have some data to show it’s effective at all in patients with lung cancer before it’s a real issue.
Most importantly, the FDA didn’t say that RFA shouldn’t be studied, but rather that further work on RFA for lung tumors should be part of a clinical trial. If RFA is really effective (such as in a comparison of RFA to RT for medically inoperable patients), then it will be worthy of a lot more discussion of its place.
-Dr. West
December 23rd, 2007 at 7:11 am
I do not know if it was something I did, or you did, but I greatly appreciate the larger print in the articles. It is difficult for me to read small print, so again I say thank you.
DrMom
December 23rd, 2007 at 1:42 pm
It’s actually a mistake I made with the formatting of this particular post, and it may be corrected, but the new website software will allow you to adjust the text size as small, medium, or large. I know that the standard font is very small and that we’ve needed a feature of font resizing. It wasn’t possible with the software we’ve had but should finally become routine soon.
-Dr. West
December 27th, 2007 at 4:29 am
My husband’s family seems to be predisposed for cancer; therefore, I’ve been viewing sites such as this one for informative purposes. This subject caught my interest. Re definitive radiation therapy - can death possibly occur from this treatment? I haven’t been able to find a site to research this - I’ve seen information regarding chemo risks, but never really see anything on radiation risks. In my mind, I imagine radiation “burning” tissue, blood vessels, etc. causing hemorraghing or other complications.
SherryB
December 27th, 2007 at 5:46 pm
Sherry,
Anything that can effectively fight cancer can have potentially severe and even fatal side effects, but radiation at standard doses is often very well tolerated and has a very minimal risk of life-threatening side effects. The doses that are routinely employed are limited by the point at which the normal structures would receive too much damage from the radiation. Because it’s a balance between attacking the cancer and protecting the normal tissues of the patient, we often push the envelope to go to higher doses while becoming more precise about where the radiation goes, but I’d estimate that the risk of death from definitive radiation without chemo is below 1%, likely comfortably below that. It’s only when concurrent chemo is given with aggressive chest radiation that the treatment-related death rate can get up in the 5-6% range.
-Dr. West