A Different Take on Induction

Yesterday there was a discussion on one of the list services in which I participate in which I found myself at odds with one of the common opinions held by other parents and I thought worthwhile to explore it here. After all, I have never seen my opinion expressed by others and, yet, I truly believe that it is a worthwhile strategy. The topic came from a father of a child that was recently diagnosed. His question was age old but one that seems to have gotten more play as of late. Essentially it comes down to this:

Is my child's oncologist leading us down the right path? He said survival was X% but I heard it was higher at Sloan Kettering. Should we go to Sloan Kettering?

There are a bunch of arguments that people use to argue that Sloan Kettering is a better than anywhere else in the world. Unfortunately, most of these arguments do not hold water and, in actuality, just show a complete misunderstanding of statistics rather than any clear benefit. Now, I say this as someone who had a child that had part of their treatment at Sloan Kettering. I say this as a father who believes that Sloan Kettering is one of the reasons that my daughter is still here. And, I say this as someone who has tremendous respect for the team at Sloan Kettering. My goal here is not to bash Sloan Kettering but rather to shed light on some of the reality.

Over the years, I have written volumes on the statistical differences between how COG trials and Sloan Kettering trials are reported. For that reason, I will not repeat it again here. The fact remains that they use different measuring sticks. It is not right or wrong. They are just different and can't be compared. Until Sloan Kettering has a randomized phase 3 trial that uses event free survival as a measuring stick it will never be comparable. This difference in statistics is not to be taken lightly. Today, even a difference by as much as 20% (made up number) or more in survival between Sloan and the COG is meaningless. It is apples and oranges. That is, of course, assuming that the survival statistic at Sloan is higher which, frankly, I do not know to be true any longer. Furthermore, the opposite does not hold true. Regardless, at this point in time, making a decision based on these numbers is just as likely to lead you to make a bad decision as a good one.

That is of course, unless you understand them and understand exactly what they are saying and what they are not.

Bottom-line, there is no right answer. There is no definitive proof that treatment at Sloan Kettering is any better than any standard COG protocol that grants you access to antibody therapy (or vice versa). Do not feel guilty because you do not want to separate your family by traveling back and forth across the country. Do not feel guilty that you can not afford to travel for treatment. Sloan Kettering is a tremendous neuroblastoma center but it is not the answer for everyone. There is no magic elixir.

With all of that being said, there are some interesting facts that are worth investigating. Now, before we begin, throw the survival statistics in the trash. Let's talk response statistics. This is that same mantra that I have been chanting for years. Until you have definitive comparable proof you must make educated decisions based on what you do have. Response statistics we do have.

One of the incredibly interesting statistics that comes out of Sloan is their response rate to induction (all of the treatment prior to transplant). It is significantly higher than the response rates that we have seen in the COG. In other words, more kids that are treated at Sloan Kettering achieve a complete response (CR) or very good partial response (VGPR) than they do elsewhere. With that being said I would not be performing my due diligence if I did not also point out that there may be patient selection bias at play in their response statistics or a myriad of other factors that can cause results from a single instution to be skewed. However, for the sake of this argument, let's just assume it is a reality.

Why would the response to induction be higher at Sloan Kettering?

For years it has been assumed that it was the dose intensive induction chemotherapy that made the difference. After all, much of the induction regimen that the world follows (except for Europe) is based off of the successes that were seen at Sloan Kettering. However, after the thorough beating of this pony from all over the world, nobody has been able to recreate their success. In fact, even Sloan Kettering has backed off of the amount of chemotherapy that they administer. Yet, it is interesting to note, it does not appear that their response rates have necessarily changed for the worse. Given that, it probably isn't the dose intensity.

Is the difference because of the way they administer the chemo? After all, Dr. Kushner is a brilliant chemotherapeutist (is that a word?) He is aggressive. He insures the chemo gets in and does its job. Is that the answer? Maybe, partially. But, if I am being honest, that is not the major difference I see.

Is the difference in the dosage or amount? While this could be true, it is doubtful. They are very similar and no one has even come close to reproducing the results. There must be another factor.

My belief is that the higher response rates lie in the hands of the surgeon. Hence, the reason, I wrote the First Unwritten Rule to Neuroblastoma Treatment. If you follow the literature, Sloan Kettering has a significantly higher complete resection rate. And, if you are completely removing more tumors you are going to have more complete responses and very good partial responses. There are other theoretical arguments as well. For example, they also resect the tumors much earlier. Perhaps this also adds a slight advantage. Does it? Well, clearly this effects response rates but, keep in mind, we still don't know it's impact on survival. The answer isn't out there - yet.

It looks like I have spent quite a bit of time tearing down Sloan Kettering only to make an argument that everyone should go there for induction. Don't make your travel plans just yet. Even given all of this interesting response evidence, that still is not the decision I, personally, would make and this comes to the real reason that I wrote this article in the first place.

I have a difference of opinion.

But unfortunately, no more room to discuss it today. So, with that, I will begin tomorrow where I tried to begin today.

Trust me, these ramblings do have purpose.