It is quite frustrating that I already wrote this entry and then it disappeared. Sometimes I really dislike blogger. Word to the wise. I am in the habit of highlighting all of the text that I would like spell-checked. However, if you do that in blogger, it will erase every word you have written. Forever. It drives me crazy. Beware of the evil spell checker.
Now, on with the story.
So, what I really was going to talk about was some of the work that I am doing for an upcoming art exhibition entitled "Life. Through the eyes of a child living with neuroblastoma." The show will last 3 months. Opening night is September 5, 2008 at the Fort Worth Community Arts Center. The exhibition will feature photography of neuroblastoma patients that were taken by Geno Loro (http://www.genoloro.com/). I can tell you that the photography is compelling and nothing short of incredible.
This whole journey began earlier this year. We were looking for a photographer to take some pictures of children with neuroblastoma. The original purpose of the photography was going to be for some CNCF marketing materials and for an upcoming neuroblastoma awareness campaign. We originally contacted Geno out of the blue but, through a strange twist of events, it turns out he had a very personal connection with the neuroblastoma world. It was believed at one time that his son had neuroblastoma. Thankfully it turned out to be a false diagnosis but the memory and the fear of what that meant never left Geno's mind. Much to our surprise he offered to donate his time to photograph these kiddos.
Taking the pictures was no easy task. This was not as simple as just snapping a few pictures. We were looking for much more. One of my greatest personal frustrations with photography of children with cancer was that it was scary. I have found that it was not only my feeling but that many turn their head when they see a child with cancer. This is true in magazines as much as it is walking through the grocery store. No one wants to believe that it could happen to their child, their grandchild, or one of their friends. Surely, there must have been something wrong with "those" kids. Somehow "they" are different. The problem with this sentiment is that the message never gets sent. People are to busy turning the page to ever get to the message. The easiest way to escape this imagery is to forget about it altogether. It is difficult to see a picture of anyone in true crisis, especially a child. It is my opinion that this has been one of the reasons we have so much difficulty garnering support for childhood cancer.
The challenge came in obtaining photography that was far less about cancer and far more about children. The photographs had to do, at a minimum, two things. First, you must have that feeling that the child in the picture could be your child. We wanted each picture to be a personal experience. It could not scare. It had to give that feeling that the child in the picture could be any child walking down the street. Secondly, the picture had to be compelling enough that you wanted to read the words. You wanted to receive the message. This is the difficult part. Capturing that look, that expression, where you want to read more.
Geno did that in ways that go beyond description. The photography is beyond compelling. I can tell you from those few that have actually seen the pictures that they are likely the best that have ever been seen. The have met all of our objectives and more. He has captured the true victims of neuroblastoma - average, normal, and otherwise happy children and families.
The problem now is that I have to describe them. I have to talk about their purpose. While I would much rather let the photography speak for its own (which I will) I have to communicate in the marketing and press materials what this is all really about.
It is no easy task. I know I can't do the photography justice.
I am hoping my pencil has purpose today. I have a deadline.
Thursday, July 31, 2008
Wednesday, July 30, 2008
Neuroblastoma in Overdrive
Wow, is this a busy time in the world of neuroblastoma! I don't know where to start or finish. I could sit here and do nothing but simply list the neuroblastoma-ish stuff going on and I am pretty sure it would be the longest entry I have ever written. No wonder I never get a chance to go into the level of detail that I would on any one subject. So, here is a two parter.
First part! These are my nerdy little twerps. For some reason the other day, they decided to dig out some old life jackets and put them on. The only difference was that they decided to wear them as diapers. They spent well over an hour floating around giggling in their make shift diapers. They giggled endlessly. They could not get over how funny they thought they were. I have to admit. I got a good chuckle myself. I hope you do to.
It has been awhile since we have had a good picture of the hairless Dudester. His hair has grown back in a bit more since this picture of him was taken a few weeks ago but I just could not resist. Here he is - the dapper dudely.
It has been awhile since we have had a good picture of the hairless Dudester. His hair has grown back in a bit more since this picture of him was taken a few weeks ago but I just could not resist. Here he is - the dapper dudely. So,what is going on in the neuroblastoma world. Well, for one, President Bush signed the Caroline Pryce Walker Conquer Childhood Cancer Act yesterday. This means it is official. The legislation authorizes $150 million over five years for pediatric cancer research and outreach, and reaffirms our nation's commitment to eradicating the number one cause of death by disease for children. You can read more about it here:
It is great news! However, the battle is not yet over. We still have to fight for the dollars to be appropriated. The next step is at the Defense Appropriations Subcommittee. Just because they passed the legislation does not mean we will get the dollars and, unfortunately, that is the tough part. Now the real work begins. You will be hearing more about these efforts in the days and weeks to come. We will need to write members of this subcommittee to urge them to prioritize childhood cancer funding or this will all be for not. I will provide more information in the coming days and weeks.
For those of you that love country music a generous donor is offering an autographed guitar on eBay. The auction only has one day left. The sale will benefit the research initiatives of the Children's Neuroblastoma Cancer Foundation. More information can be found below. Please stop by and bid.
This weekend in Graham, Texas they will be have a rodeo and day of festivities to benefit the CNCF. You can bet that I will have my boots on. There are a ton of festivities planned. If you are looking for a good time it is the perfect way to entertain the family this weekend. I hope to see you there. More information can be found at:
You know what? I could go on. This is just two of the things that are going on at this minute. We also have an art auction in California. I am working on a really cool liposomal formulation of irinotecan. Yes, me! Isn't that totally cool? We are getting ready for scans next week. I am helping to put together a local neuroblastoma symposium. I am trying to find sponsors for the art gallery showing of "Life. Through the eyes of a child living with neuroblastoma."
The list goes on.
My purpose is full speed ahead.
Tuesday, July 29, 2008
CNCF Neuroblastoma Conference Part 2
Finally, I have a chance to get back to the conference before it all slips away. Thankfully, most of it will be available on video online. That is, of course, if I ever get the raw video. In the meantime, I can only offer whatever stuck to the sides of the tube that extends between my two ears. The last time I talked about the conference it was all about the transplant discussion. As I mentioned, there was not much that was comparable from one treatment to another. That was a little disappointing for us as parents of children with neuroblastoma but I think we have to realize also that it is not on purpose. The very nature of many of these studies make it impossible to compare. These differences come from the types of patients on trial (chemo sensitive vs. chemo-resistant, NMYC amplified vs. non-NMYC amplified, and responders vs. non-responders), the type of measure (overall survival, progression free survival, event free survival, or response), the amount of time (1 year, 3 years, 5 years), and the type of trial(phase I, phase II, or phase III). There simply is no direct comparison. This is why we have to be careful when making a decision. The key is not always the trial that has the highest percentage. It is critical to understand the differences. A trial with a seemingly low survival percentage (20%) may very well be better than one with a 100% survival rate. I know, I know, it sounds counter intuitive. It sounds wrong. But, it isn't! That statement is right on the money. If you want to compare one treatment to another you have to understand these seemingly subtle differences. It isn't just about the numbers - in fact, it is far from it. And, we have not even begun to weigh in on the toxicities.
Now, last week I kept telling you that even amongst this confounding statistical mess there were some rules that we could clearly discern. I would like to get to one that I felt was important. This one actually came from one of my questions and although my question was leading I was totally surprised to see agreement on the subject. Frankly, I had always felt it personally but I was bit shocked to see it addressed and agreed upon so openly amongst the experts. It is one of those things that I have seen happen all to often at many hospitals across the country. Essentially, my question was: If you have a child with resistant disease to induction should you be considering a single autologous transplant (or even a tandem - which I neglected to mention). There was a resounding "No, probably not." from the panel. Essentially, you should be considering other options at this point. This is not to say that a transplant may not be the answer. But you must be looking outside the box as well. I think this makes a lot of sense and I have always been surprised by those committed to sending kids into transplant with disease. While I have personally seen a few go into transplant with minimal disease and come out with a complete response, the vast majority have not or have relapsed so quickly they had little to fight with. This is just a Dad's view on five years of watching. I use no scientific measure. Although it is not always a perfect outcome I have seen many respond to other therapies and I thought this was a key point to make and question to ask.
When your child still has disease at the end of induction there are still viable options. Believe me, there is a surprisingly large number of patients that do not respond to induction. These kiddos have been successfully treated with other modalities. As a parent (or oncologist) you have to understand the type of disease (solid tumor, bone marrow, or bone disease) and what types of treatments that have historically worked well with that type(s) of disease. It is also very important to take into consideration the health of the child. This may also lead you to make a very different decision. Regardless, I think we clearly saw at the conference that kids with marrow disease clearly responded to antibody therapy and although it was not addressed directly I know of several examples of kids that have also had bone lesions respond. Another therapy that seems to work well in these cases is MIBG (+/-) transplant. I have seen many kids respond, some with solid mass, some with bone disease, and some with marrow. I just think this is important to realize and to soak in. One of my favorite comments that really drove the point home for me was: "If you have given your child chemo for all of these months and he(she) hasn't responded, why would you think that more chemo would cure them?" Although this is a very generalized statement I think it really drives the point home. What we are doing is not working. Let's try something else.
I think another important point that was made during this particular discussion was related to toxicities. Dr. Yanik kept trying to give us some insight into the world of a transplanter. We, as parents, are always concerned about the toxicities that come from infection or organ failure. One of the organs that we rarely consider is the soil of our bone marrow. One of the toxicities that scare transplanters the most is damaging the soil that allows our stem cells to grow. Especially when we are considering multiple transplants or other highly toxic treatments. We run the risk of creating kids that are highly dependent on platelets for extended periods of time. We can do some serious damage. I think this is especially important to consider if you have a child that is unlikely to respond to these types of therapies. That is a significant risk of many of these transplant regimens and not something to take lightly. We must consider the relative risks and rewards for our child with every therapy. We have to be mindful of what has worked and what has not for children that are similar to our own.
Ask questions. Don't except the norm.
And, of course, I am just a Dad - NOT a medical professional. Ask your doctor. More importantly, ask an oncologist that specializes in neuroblastoma treatment.
You are your child's best advocate.
That is our purpose.
Now, last week I kept telling you that even amongst this confounding statistical mess there were some rules that we could clearly discern. I would like to get to one that I felt was important. This one actually came from one of my questions and although my question was leading I was totally surprised to see agreement on the subject. Frankly, I had always felt it personally but I was bit shocked to see it addressed and agreed upon so openly amongst the experts. It is one of those things that I have seen happen all to often at many hospitals across the country. Essentially, my question was: If you have a child with resistant disease to induction should you be considering a single autologous transplant (or even a tandem - which I neglected to mention). There was a resounding "No, probably not." from the panel. Essentially, you should be considering other options at this point. This is not to say that a transplant may not be the answer. But you must be looking outside the box as well. I think this makes a lot of sense and I have always been surprised by those committed to sending kids into transplant with disease. While I have personally seen a few go into transplant with minimal disease and come out with a complete response, the vast majority have not or have relapsed so quickly they had little to fight with. This is just a Dad's view on five years of watching. I use no scientific measure. Although it is not always a perfect outcome I have seen many respond to other therapies and I thought this was a key point to make and question to ask.
When your child still has disease at the end of induction there are still viable options. Believe me, there is a surprisingly large number of patients that do not respond to induction. These kiddos have been successfully treated with other modalities. As a parent (or oncologist) you have to understand the type of disease (solid tumor, bone marrow, or bone disease) and what types of treatments that have historically worked well with that type(s) of disease. It is also very important to take into consideration the health of the child. This may also lead you to make a very different decision. Regardless, I think we clearly saw at the conference that kids with marrow disease clearly responded to antibody therapy and although it was not addressed directly I know of several examples of kids that have also had bone lesions respond. Another therapy that seems to work well in these cases is MIBG (+/-) transplant. I have seen many kids respond, some with solid mass, some with bone disease, and some with marrow. I just think this is important to realize and to soak in. One of my favorite comments that really drove the point home for me was: "If you have given your child chemo for all of these months and he(she) hasn't responded, why would you think that more chemo would cure them?" Although this is a very generalized statement I think it really drives the point home. What we are doing is not working. Let's try something else.
I think another important point that was made during this particular discussion was related to toxicities. Dr. Yanik kept trying to give us some insight into the world of a transplanter. We, as parents, are always concerned about the toxicities that come from infection or organ failure. One of the organs that we rarely consider is the soil of our bone marrow. One of the toxicities that scare transplanters the most is damaging the soil that allows our stem cells to grow. Especially when we are considering multiple transplants or other highly toxic treatments. We run the risk of creating kids that are highly dependent on platelets for extended periods of time. We can do some serious damage. I think this is especially important to consider if you have a child that is unlikely to respond to these types of therapies. That is a significant risk of many of these transplant regimens and not something to take lightly. We must consider the relative risks and rewards for our child with every therapy. We have to be mindful of what has worked and what has not for children that are similar to our own.
Ask questions. Don't except the norm.
And, of course, I am just a Dad - NOT a medical professional. Ask your doctor. More importantly, ask an oncologist that specializes in neuroblastoma treatment.
You are your child's best advocate.
That is our purpose.
Monday, July 28, 2008
Twerp Reunion
Wow, I am still recovering from the family reunion. We had an incredible time. The kiddos are still reeling as well. In fact, they are flat out in shock. They had no idea they had such a big family. The first night we stopped by the hotel where all of the family was staying to say hello, I clearly remember getting back in the car and hearing things like "Wow, are they all our family?", "Are they all our brothers and sisters?", and "Wow, do they all live there?"
On Saturday afternoon the festivities were at our house. For one of our family reunions the numbers were somewhat small. There were only about 30 or 40 of us. It was sad that so many could not make it. On the other hand, they were all probably smart enough to know how hot it was going to be. Yes, there is apparently a smarter bloodline that is coursing through their veins. Regardless, we all had a great time. The youngest generation of kiddos had a fabulous time. They spent time playing in the playroom, swimming in the pool, jumping on the trampoline, swinging on the swing set, sucking down Popsicles, and there were even a few that followed me around as we performed magic tricks. It was a blast.
No Dungan reunion would be complete with out 12 decks of cards. That has indeed the case with this group. There were hours of gin, cribbage, and backgammon. Then, of course, each night ended with high stakes gambling crowded around the biggest table we could find for hours of black jack. Yep, Dungans, at least it kept us off of the streets.
I was really proud of Sydney, Graham, and Ainsley. I was very impressed with their manners and good spirits. Maybe it was that I wasn't playing as close attention because I raced to spend as much time as I could with everyone who attended. But, I never really noticed them being anything but perfect little twerps. That was a big challenge because twerptations were in abundance and there were many opportunities for drama. Nope, my kiddos just kept hanging on to their sanity. Most importantly they also had one heck of a time and were truly saddened to see everyone go. They are already making plans to see a few of them in the weeks to come.
Well, I had best be off. A mountain of email awaits.
And, I have purpii to attend to.
On Saturday afternoon the festivities were at our house. For one of our family reunions the numbers were somewhat small. There were only about 30 or 40 of us. It was sad that so many could not make it. On the other hand, they were all probably smart enough to know how hot it was going to be. Yes, there is apparently a smarter bloodline that is coursing through their veins. Regardless, we all had a great time. The youngest generation of kiddos had a fabulous time. They spent time playing in the playroom, swimming in the pool, jumping on the trampoline, swinging on the swing set, sucking down Popsicles, and there were even a few that followed me around as we performed magic tricks. It was a blast.
No Dungan reunion would be complete with out 12 decks of cards. That has indeed the case with this group. There were hours of gin, cribbage, and backgammon. Then, of course, each night ended with high stakes gambling crowded around the biggest table we could find for hours of black jack. Yep, Dungans, at least it kept us off of the streets.
I was really proud of Sydney, Graham, and Ainsley. I was very impressed with their manners and good spirits. Maybe it was that I wasn't playing as close attention because I raced to spend as much time as I could with everyone who attended. But, I never really noticed them being anything but perfect little twerps. That was a big challenge because twerptations were in abundance and there were many opportunities for drama. Nope, my kiddos just kept hanging on to their sanity. Most importantly they also had one heck of a time and were truly saddened to see everyone go. They are already making plans to see a few of them in the weeks to come.
Well, I had best be off. A mountain of email awaits.
And, I have purpii to attend to.
Friday, July 25, 2008
Neuroblastoma Handbook Help!
Three solid days of superior twerptitude. While it is not quite a habit yet we very definitely have a trend. I am happy to report that Sydney mastered the skill of sweet human being yesterday. I am quite proud of the change. I am hopeful that we have hit onto something here. We will see what today brings. It is high pressure time for her, this is the official start of the Dungan family reunion (at our house - isn't Lynley happy with me). The kiddos will not be the center of our attention and will have ample opportunity to sneak off to reek havoc. There will be many temptations. It is a great test for the twerp leader. I have no doubt that she will do a wonderful job.
Now, on the front of important neuroblastoma stuff. Now that the Neuroblastoma Handbook has been launched it now becomes the tough job of making everyone aware that is available. When most children are diagnosed one of the first places their families look for answers is on the Internet. We need your help to ensure that they can find the neuroblastoma handbook. We need to get it out there. We need to blog about it, post it, and put it everywhere we can possibly think of. In this way, it will be sure to be found. I am calling for a bum rush on all social media to get the word out. I have written an article that has a step by step list of everything we need to do to get it out there and into their hands. I am asking for your help. I have written step by step directions on exactly what we need to do. If you have a moment please click on the link below. It has simple instructions for what we can do to help get the word out.
http://www.nbhope.org/blogs/news/archive/2008/07/25/put-a-nb-handbook-badge-on-your-site.aspx
Hopefully, in no time at all, we can get it on the first page of Google.
This purpose is not only extremely meaningful but also fun.
Now, on the front of important neuroblastoma stuff. Now that the Neuroblastoma Handbook has been launched it now becomes the tough job of making everyone aware that is available. When most children are diagnosed one of the first places their families look for answers is on the Internet. We need your help to ensure that they can find the neuroblastoma handbook. We need to get it out there. We need to blog about it, post it, and put it everywhere we can possibly think of. In this way, it will be sure to be found. I am calling for a bum rush on all social media to get the word out. I have written an article that has a step by step list of everything we need to do to get it out there and into their hands. I am asking for your help. I have written step by step directions on exactly what we need to do. If you have a moment please click on the link below. It has simple instructions for what we can do to help get the word out.
http://www.nbhope.org/blogs/news/archive/2008/07/25/put-a-nb-handbook-badge-on-your-site.aspx
Hopefully, in no time at all, we can get it on the first page of Google.
This purpose is not only extremely meaningful but also fun.
Thursday, July 24, 2008
The CNCF Neuroblastoma Conference - a review
Good morning! Well I am happy to report that we have officially turned the corner on Sydney's behaviour. It seems like we have officially established some boundaries and she understands what they are. Now, I can't guarantee that she will never act out again but I can tell you that she is aware of her behaviour. She knows what is unacceptable even when she is angry. Yesterday, aside from a few pouts that some things did not go her way, she was utterly perfect. 2 days down and only 19 more to go until we have established an official habit. We will watch closely. I am not saying that she is no longer a twerp, just a more balanced one.
Well, before it escapes my mind I really want to talk about the conference. I know there are parents out there that are really curious as to what was said. I think one of the most interesting discussions concerned transplant options. We had a panel consisting of Dr. Bolotin, Dr. Yanik, Dr. Yamashiro, and Dr. Cheung. Each were responsible for representing a certain opinion on transplant. We discussed the new Topotecan containing single autologous transplant regimen from City of Hope, MIBG/transplant Combinations, tandem transplants, allogenic transplants and Sloan's option of no transplant at all.
Over all ,I though the discussion was very good. As one should expect it became very clear that there is no answer right now. There just isn't. I am not being sneaky, biased, or opinionated. There is simply no clear answer.
There are some general rules, however.
Tomorrow, I will hit upon some of the general rules that I think we established. Today I will hit upon why there is no clear answer between one decision and another. People will always continue to compare statistics from one institution to another. This is only relevant if the statistics that you are comparing are actually the same. I can tell you from the basis of our discussions at the conference none were using the same measure. I will explain.
Dr. Bolotin showed a survival curve for their Topotecan containing transplant. Ironically, you could not see a curve because it was a straight line at 100% survival. That seems the obvious choice doesn't it? Hold on? Her curve only included 8 patients and it was only for a period of 333 days. That is not long. That means the eight patients they studied were all transplanted sometime in the last 333 days and they were all surviving so far. I don't mean to shock anyone but that isn't surprising. First off, this transplant regimen only includes responders to upfront therapy. I would fully expect the vast majority of them to be responding at this point regardless of the treatment. It shows that City of Hope is a good transplant center but beyond that it really does not answer many questions. We need to wait another 5 years to look back on the data and see what an actual curve looks like then. In this case we are looking for lower toxicities and hopefully no reduction in survival. It is interesting to note that Topotecan could actually increase the survival in this regimen due to a mechanism of action that was totally not expected or anticipated. You will need to watch the video to find out more.
Dr. Yanik showed several curves but I will start with MIBG. I don't remember the exact survival percentage but it was in the neighborhood of 25 to 35% over 3 years. Would you believe that this could possibly be the best option? You see his data was event free survival. Not overall survival. So, many kids may be surviving that are not in this curve because they are taken off the curve for many different reasons. They are taken off for "events," like severe toxicities, relapse, etc. The good news is that we know that the "survivors" are doing fairly well. The other incredibly important thing to note is that these statistics also include the hardest patients to cure. You see, when this data was collected you could not be on an MIBG/transplant trial without having failed induction chemotherapy. These kids are the worst of the bunch and the hardest to cure. The fact that so many of them survived so far out is incredible. This study was also hard to get a handle on as many patients were treated at different dosing levels. Although the number of patients was good (nearly 80 or 90 if I remember correctly) it clearly was not comparable to some of the other options.
Dr. Yamashiro presented some data on allogenic transplants. It was this section that I probably learned the most about from the entire conference. Essentially the idea from an allogenic transplant is to create a graft versus tumor (GVT) effect. In this case you not only receive the benefits from a typical transplant but many also benefit from the GVT effect. In this scenario the donor cells not only reseed the marrow but the also attack tumor. It is very interesting. The problem with allogenic transplants is that the are extremely dangerous and come at a cost. His review showed a morbidity rate of a little over 30%. This means over 30% did not survive the allogenic transplant. The survival rates were not bad but we have to be concerned about at what cost. In an effort to reduce the morbidity Dr. Yamashiro started doing autologous transplants followed by a mini allogenic transplant. It is the science and technique of how this is done that was such a learning experience for me. Regardless, the hope was that this method would reduce the toxicities associated with a complete allogenic transplant while still benefiting the patient with GVT. Based on the data it certainly looks like he is able to meet both of these objectives. It was hard to compare his survival statistics as well. The numbers weren't bad but his patient numbers were small. Also, I happen to know from reviewing this study at the ANR in 2006 that his patients were ultra high risk. It included many n-myc amplified kids. To me it looked like the group was one of the hardest to cure when looking at them at diagnosis. The point is that this group, too, was not really comparable to the other two.
Both Dr. Yamashiro and Dr. Yanik also gave a review of the rationale behind single and tandem transplants. A couple of things were clear from these presentations. In the COG hands, a transplant was clearly better than no transplant (although they never used antibody for consolidation). Another thing that occurred to me that there is hope that a tandem transplant will be better than a single. From what was presented, early clinical data seems to lean that way. Also it was interesting to note that the toxicities did not seem to be any worse. Strangely enough, in some studies they were even better. Regardless, this data was presented at 3 year Event Free Survival and since it is not comparable to the others I don't really see the pointed in repeating them here. They are well published in prominent journals.
Finally was MSKCC's option of using antibodies for consolidation instead of transplant. Dr. Cheung used an entirely different measure in an entirely different patient population than the other groups. At first his 3 year survival curve of approximately 77% looked great until you started to pick apart exactly what was being measured. This isn't to say the Dr. Cheung was intentionally deceiving anyone. He is not sneaky as far as I am concerned. In fact, he sought me out and we discussed statistics at length (about 30 minutes). He genuinely believes his measure is the most important measuring stick of success. I understand that. I don't necessarily agree but I genuinely see his point that "event free" survival curves are nebulous at best. Regardless, as much as I fought for a comparable answer we did not have one. The MSKCC survival statistic was only based on survival. It did not include "events" or "relapses". It was survival - period. The population included the best subset of stage 4 and nmyc amplified kids over the age of 18 months. These patients were also only ones that responded to upfront therapy. In essence they were the best patients that had a history of clearly responding. It simply isn't comparable to anything else that we have seen. I like Sloan. I like the people. But, this statistics gave us absolutely no indication of whether their therapy is better or worse than any other.
Put in it's simplest terms. After they finished their presentation I asked the question of which treatment strategy was best. I think it was clear to everyone that there is absolutely no answer. There just isn't.
Finally, not one of these studies was shown at 5 years (mainly because the data was not available because the studies are not old enough.) That is a far better time period for us as parents to make a decision. I think everyone agrees upon that. A lot more shakes out over that time period.
The trick becomes, how do we use this information. Well, the good news is that even though all of this is extremely tricky and murky we were able to get to the bottom of a few rules that were agreed upon by everyone. There are answers amongst all of this mess.
Everyone seemed to have purpose. They just couldn't agree on how that purpose should be measured.
Well, before it escapes my mind I really want to talk about the conference. I know there are parents out there that are really curious as to what was said. I think one of the most interesting discussions concerned transplant options. We had a panel consisting of Dr. Bolotin, Dr. Yanik, Dr. Yamashiro, and Dr. Cheung. Each were responsible for representing a certain opinion on transplant. We discussed the new Topotecan containing single autologous transplant regimen from City of Hope, MIBG/transplant Combinations, tandem transplants, allogenic transplants and Sloan's option of no transplant at all.
Over all ,I though the discussion was very good. As one should expect it became very clear that there is no answer right now. There just isn't. I am not being sneaky, biased, or opinionated. There is simply no clear answer.
There are some general rules, however.
Tomorrow, I will hit upon some of the general rules that I think we established. Today I will hit upon why there is no clear answer between one decision and another. People will always continue to compare statistics from one institution to another. This is only relevant if the statistics that you are comparing are actually the same. I can tell you from the basis of our discussions at the conference none were using the same measure. I will explain.
Dr. Bolotin showed a survival curve for their Topotecan containing transplant. Ironically, you could not see a curve because it was a straight line at 100% survival. That seems the obvious choice doesn't it? Hold on? Her curve only included 8 patients and it was only for a period of 333 days. That is not long. That means the eight patients they studied were all transplanted sometime in the last 333 days and they were all surviving so far. I don't mean to shock anyone but that isn't surprising. First off, this transplant regimen only includes responders to upfront therapy. I would fully expect the vast majority of them to be responding at this point regardless of the treatment. It shows that City of Hope is a good transplant center but beyond that it really does not answer many questions. We need to wait another 5 years to look back on the data and see what an actual curve looks like then. In this case we are looking for lower toxicities and hopefully no reduction in survival. It is interesting to note that Topotecan could actually increase the survival in this regimen due to a mechanism of action that was totally not expected or anticipated. You will need to watch the video to find out more.
Dr. Yanik showed several curves but I will start with MIBG. I don't remember the exact survival percentage but it was in the neighborhood of 25 to 35% over 3 years. Would you believe that this could possibly be the best option? You see his data was event free survival. Not overall survival. So, many kids may be surviving that are not in this curve because they are taken off the curve for many different reasons. They are taken off for "events," like severe toxicities, relapse, etc. The good news is that we know that the "survivors" are doing fairly well. The other incredibly important thing to note is that these statistics also include the hardest patients to cure. You see, when this data was collected you could not be on an MIBG/transplant trial without having failed induction chemotherapy. These kids are the worst of the bunch and the hardest to cure. The fact that so many of them survived so far out is incredible. This study was also hard to get a handle on as many patients were treated at different dosing levels. Although the number of patients was good (nearly 80 or 90 if I remember correctly) it clearly was not comparable to some of the other options.
Dr. Yamashiro presented some data on allogenic transplants. It was this section that I probably learned the most about from the entire conference. Essentially the idea from an allogenic transplant is to create a graft versus tumor (GVT) effect. In this case you not only receive the benefits from a typical transplant but many also benefit from the GVT effect. In this scenario the donor cells not only reseed the marrow but the also attack tumor. It is very interesting. The problem with allogenic transplants is that the are extremely dangerous and come at a cost. His review showed a morbidity rate of a little over 30%. This means over 30% did not survive the allogenic transplant. The survival rates were not bad but we have to be concerned about at what cost. In an effort to reduce the morbidity Dr. Yamashiro started doing autologous transplants followed by a mini allogenic transplant. It is the science and technique of how this is done that was such a learning experience for me. Regardless, the hope was that this method would reduce the toxicities associated with a complete allogenic transplant while still benefiting the patient with GVT. Based on the data it certainly looks like he is able to meet both of these objectives. It was hard to compare his survival statistics as well. The numbers weren't bad but his patient numbers were small. Also, I happen to know from reviewing this study at the ANR in 2006 that his patients were ultra high risk. It included many n-myc amplified kids. To me it looked like the group was one of the hardest to cure when looking at them at diagnosis. The point is that this group, too, was not really comparable to the other two.
Both Dr. Yamashiro and Dr. Yanik also gave a review of the rationale behind single and tandem transplants. A couple of things were clear from these presentations. In the COG hands, a transplant was clearly better than no transplant (although they never used antibody for consolidation). Another thing that occurred to me that there is hope that a tandem transplant will be better than a single. From what was presented, early clinical data seems to lean that way. Also it was interesting to note that the toxicities did not seem to be any worse. Strangely enough, in some studies they were even better. Regardless, this data was presented at 3 year Event Free Survival and since it is not comparable to the others I don't really see the pointed in repeating them here. They are well published in prominent journals.
Finally was MSKCC's option of using antibodies for consolidation instead of transplant. Dr. Cheung used an entirely different measure in an entirely different patient population than the other groups. At first his 3 year survival curve of approximately 77% looked great until you started to pick apart exactly what was being measured. This isn't to say the Dr. Cheung was intentionally deceiving anyone. He is not sneaky as far as I am concerned. In fact, he sought me out and we discussed statistics at length (about 30 minutes). He genuinely believes his measure is the most important measuring stick of success. I understand that. I don't necessarily agree but I genuinely see his point that "event free" survival curves are nebulous at best. Regardless, as much as I fought for a comparable answer we did not have one. The MSKCC survival statistic was only based on survival. It did not include "events" or "relapses". It was survival - period. The population included the best subset of stage 4 and nmyc amplified kids over the age of 18 months. These patients were also only ones that responded to upfront therapy. In essence they were the best patients that had a history of clearly responding. It simply isn't comparable to anything else that we have seen. I like Sloan. I like the people. But, this statistics gave us absolutely no indication of whether their therapy is better or worse than any other.
Put in it's simplest terms. After they finished their presentation I asked the question of which treatment strategy was best. I think it was clear to everyone that there is absolutely no answer. There just isn't.
Finally, not one of these studies was shown at 5 years (mainly because the data was not available because the studies are not old enough.) That is a far better time period for us as parents to make a decision. I think everyone agrees upon that. A lot more shakes out over that time period.
The trick becomes, how do we use this information. Well, the good news is that even though all of this is extremely tricky and murky we were able to get to the bottom of a few rules that were agreed upon by everyone. There are answers amongst all of this mess.
Everyone seemed to have purpose. They just couldn't agree on how that purpose should be measured.
Wednesday, July 23, 2008
The purpose hunter
Today I am feeling much better about the state of the world. It is amazing what kind of an effect good kiddo behavior can have on you. Yesterday Graham and Ainsley went to the water park. This had been prearranged. Sydney, however, did not get to go. Her behavior had been so poor the day before that we elected not to let her. This was just one of many punishments on the list. She had been punished severely for her transgressions. She also lost many of her favorite toys. She spent the majority of the day in her room and was left out of just about everything she likes to do. Of course, these days of punishment (technically only about 28 hours) were also chock full of talking.
I still don't know what Sydney's issues are. I can tell you that she was the perfect picture of politeness and niceness yesterday. She clearly knows how to be good. Yet, I just don't understand how these episodes escalate into these screaming violent fits of rage. We need to learn how to recognize and how to turn it off before she boils over. Only then will we be able to teach her to do the same. To me it seems like it is relatively simple. We just have to learn when to grab the reigns and get her to snap back to reality. We have to catch it before the adrenalin really starts pumping all of this "illogic" through her brain.
So what is making her mad? Well, I don't know specifically. There is a pattern of her exhibiting this behaviour when she doesn't get what she wants. That is definitely part of the puzzle. There is another ingredient, however. Because, I can tell you for sure, she is usually not this way. She understands sharing. I am constantly amazed by her ability to share with her brother and sister. Furthermore, I can also ask her not to do something or tell her she can' do something and she is quite pleasant about it. There is some other trigger. Either these episodes are occurring because of a state of mind that she is already in or there is something that is adding fuel to the fire. I just don't know what it is.
I am happy to say, however, that yesterday was wonderful. She was a perfect princess. I will keep a close eye on her again today and look for clues. We will get to the bottom of this.
I am the purpose hunter.
I still don't know what Sydney's issues are. I can tell you that she was the perfect picture of politeness and niceness yesterday. She clearly knows how to be good. Yet, I just don't understand how these episodes escalate into these screaming violent fits of rage. We need to learn how to recognize and how to turn it off before she boils over. Only then will we be able to teach her to do the same. To me it seems like it is relatively simple. We just have to learn when to grab the reigns and get her to snap back to reality. We have to catch it before the adrenalin really starts pumping all of this "illogic" through her brain.
So what is making her mad? Well, I don't know specifically. There is a pattern of her exhibiting this behaviour when she doesn't get what she wants. That is definitely part of the puzzle. There is another ingredient, however. Because, I can tell you for sure, she is usually not this way. She understands sharing. I am constantly amazed by her ability to share with her brother and sister. Furthermore, I can also ask her not to do something or tell her she can' do something and she is quite pleasant about it. There is some other trigger. Either these episodes are occurring because of a state of mind that she is already in or there is something that is adding fuel to the fire. I just don't know what it is.
I am happy to say, however, that yesterday was wonderful. She was a perfect princess. I will keep a close eye on her again today and look for clues. We will get to the bottom of this.
I am the purpose hunter.
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