I always try to be fair when debating different perspectives on neuroblastoma treatment. In fact, I feel very comfortable arguing either side of just about any issue. Generally, I always choose to argue the side that I feel is being misrepresented. Regardless, the problem always seems to arise that you make someone mad on the other side of the argument. I mention this because I am guessing that this will be a very sensitive subject and one that will draw fire.
After all of my discussions on the Sloan vs. COG or 'no transplant' vs. 'transplant' discussion, I received a significant amount of email. That was not surprising really. I actually expected more. As a result of that discussion though, it apparently got some people thinking, as I received support for an argument that I had not seen before in print. In fact, I had never even heard it discussed outside of a small group of people. Regardless, since I gave this person ample opportunity to post the information and they have not (Yes, I am calling this very intelligent person a chicken.), I will post it here.
For years, there have been many arguments that Sloan had higher survival rates than the rest of the COG. I think this argument came from some survival curves that were published on Sloan's website about 5 years ago which appeared to show an increase in survival of almost 15% for patients at Sloan Kettering. The problem with these statistics was that they fell victim to the same problems that I have been talking about for years. The statistics were not comparable. The survival statistics were over different time periods, included different patients, and fell victim to the differences between Event Free Survival and Progression Free Survival. None the less, many did not understand these differences and took them at face value. It became a mantra for many.
Today, there are finally some comparable survival curves and, oddly enough, they show the complete opposite of what was believed by many.
Until recently, the PFS survival curves from Sloan Kettering were always higher than the published EFS curves from the COG. It was still difficult to sort out the true differences though because of the differences in the types of curves that each used. Sloan uses progression free survival (PFS) which only shows the patients that did not progress with disease. The curve still includes all of the patients that had a secondary cancer or some other event - such as significant toxicities. The COG uses event free survival (EFS) curves which show survival after secondary cancers and other events. For this reason, even with the same exact group of patients, in the case of high risk neuroblastoma, an EFS curve would most likely be substantially lower than a PFS. How much is the question? After all, at one point, Sloan had a secondary cancer rate of roughly 8% (as compared to the COG's of less than 1%), Unfortunately, even today, we really do not know how many patients in Sloan's PFS curve have secondary cancers or other events. In this way, it continues to be difficult to compare.
The issue that we have before us today is that the 2 year EFS curve (2 years from randomization) from the COG as reported at ASCO this year in Dr. Yu's presentation is 66%. If you go back to the 2007 ASCO annual meeting in Dr. Cheung's presentation of "
Reducing therapy for low-risk and advancing immunotherapy for high-risk neuroblastoma" you will see that Sloan published a curve which showed that their 2 year PFS curve was only about 60%.
This would seem to indicate that the COG survival curve is significantly higher than the Sloan survival curve. According to this data, following the COG standard of care would increase your odds of survival by at least 6%. I say 'at least' because we still do not know how many events and secondary cancers are included in the Sloan PFS curve. Sloan's comparable EFS could be significantly lower. I do know that recently they have reported that they have greatly reduced their secondary leukemia rate which would keep the curves closer together but, still, certainly no less than 6%. Additionally, Sloan's curve does not show patients in partial response. The COG's curves do. One would assume that this would also lower your survival curve and we do not know what impact this would have or how far it would reduce Sloan's survival curve.
Now, is this definitive? Well, at 2 years it is pretty clear. However, what we don't know is what will happen to these curves in another year or two. Additionally, we don't know how how much power the Sloan curve has. They make no mention of patient numbers. Finally, these curves are only talking about patients that had a CR, VGPR, or PR to induction. It does not discuss those patients with refractory or progressive disease. That could be a different story. Will the superior survival associated with the COG curve continue to hold?
Time will tell.
None the less, this is a very interesting perspective that I have not seen published anywhere. I think it is worth discussion.
That is what purpose is all about.
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