Prioritizing Neuroblastoma Research Part 2

On Wednesday I began talking about the issues with the slow pace of research. This seemingly slow pace is present through all of cancer research. To be honest, if you compare neuroblastoma to many other cancers you will find that neuroblastoma is moving forward much more quickly than most. In fact, for some it has been held up as a model of success. I know, as parents, it certainly does not seem that way but, in reality, it is the case. Still the problem remains, it isn't fast enough for our children and probably not for the ones that will be diagnosed tomorrow.

For neuroblastoma the problem is compounded by two factors - money and subjects (yes, our kids). There is only so much research that can be completed in any one year.

Our basic science research is limited by funding. There are only so many drugs we can test in petrie dishes and mice and there are only so many things we can do to understand neuroblastoma cells and how they work. That is a fact of life. We have plenty of researchers but only so much money to do the research. We have to be smart about which drugs we study and that we are only looking at the most promising basic science factors.

On the clinical trial side we have two factors that come into play. One is dollars. We could use more money for clinical trials. There are many promising trials that aren't available to our children because they are cost prohibitive. The other factor though is the one that probably slows us down the most. It is the fact that we have limited patient populations. In any given year there are only so many kids that we can put on trial. Period. That means that we can only have a limited amount of trials. If we have too many trials it takes years longer to complete any one clinical trial. This makes research take longer. Secondly, if we aren't providing the clinical trials with the absolute most promise then another clinical trial is holding up that promising research from moving forward and for those drugs to get into our kids.

It is for these reasons that we must prioritize research and clinical trials. We must ensure that only the most promising research is carried forward and only the best of those ideas make it to trial and our kids.

How do we do that? How do we prioritize research?

This is where researchers get a bad rap from us parents. Researchers keep doing all of this preclinical research. They keep testing and testing and testing. We just want to get it into our kids already?!?

You see, preclinical research is used as a predictive model for what will happen in our children. It is far less expensive to do preclinical research and the goal is for the researchers to to find out as much as they possibly can about a drug before they put it into our kids. This is part of the prioritization process. They want to insure that whatever idea is moved forward has the most robust data and holds the most promise. They want to make sure that it is better than all of the other options and they want to make sure that they are delivering the therapy optimally. This is one of the ways we speed up research. It makes sense.

Now, you may think that all of this talk is theoretical. It is not. I see examples of this everyday in the neuroblastoma world. Today, we have clinical trials that are open and accepting patients that are clearly not the best options out there. They never went through thorough preclinical research process. They were never prioritized. I can think of at least one trial right now that will cost us nearly $1,000,000.00 that is clearly not going to move research forward. Over the next 2 or 3 years it will absorb over 80 patients. That research is wasted - dollars, patients and years. Those resources could be used on something far more important- far more hopeful. Instead, for the next three years, we will be wasting valuable dollars and patients on research that is less promising than much of what is sitting in labs today.

That frustrates me. What a waste.

There are also very real examples of drugs and therapies that have been moved to patients well before we knew enough about how the drugs worked. I can think of one in particular that parents were clamoring for. It was a drug which had shown good preclinical activity but could not be replicated. Researchers were called every name in the book - publicly. The researchers would not open it up in trial and blocked most efforts to do so so that it could be studied further. They succeeded. After about six months they discovered that the drug needed to be administered at much lower doses to be effective. The drug is now in trial at those lower doses and is effective. However, had the researchers listened, not done more preclinical research, and just moved the drug to trial; it would have been administered at higher doses which would not have provided the activity level needed. It would not have worked. We would have wasted money, patients, and years.

I am not saying that prioritization is the only answer. There is more that has been done and it isn't a simple answer. It is a complicated question.

But we are out there fighting.

Everyday.

With purpose!

The best presents ever

Graham successfully survived his first day of being 5. He truly had a wonderful day. I might even venture to say that it was perfect through his eyes. Frankly, I don't know how it could have been any better. He woke up to find everyone clamoring about his birthday and it continued throughout the day. He even got to open one present before he left for school. This was a new pair of aviator skechers (tennis shoes for those us in the not so cool crowd). I know what you must be thinking. How exciting can that be? Well, to my boy, it was the one of two things that he had to get to have the perfect 5 year old birthday.

Do you want to know what the other thing he wanted was?

Well do you?

Underwear!

There I said it. My five year old son, my own flesh and blood, mini me, the minor Dudely, wanted new underwear for his birthday. Yes, you heard me. One of the two things he had to have was new underwear.

There you go. Graham wanted shoes and underwear for his birthday.

If we go back in time a few days ago when I was at Dilliards buying these two items, I kept feeling more and more sorry for him. I couldn't help myself. He had to have toys on his birthday. So, what did I do? You betcha, I went slightly psychotic and bought Walmart out of toys. I bought him cars and legos and action figures that shot plastic missiles. I fit as much little boy testosterone as I could fit into the cart.

So, what happened?

Well, he is proudly wearing his new underwear and shoes.
T
he other stuff is mostly still in the boxes.

See what I know.

Purpii are complicated - like women - but that is a story for another day.

Graham's 5th Birthday

No time to write today. It is Graham's 5th birthday. Tune in tomorrow for details.

Prioritizing Neuroblastoma Research

The New Approaches to Neuroblastoma Therapy (NANT) meeting is right around the corner. In fact, late next week I will be basking sea side looking out the windows wishing the conference could be moved out doors. As part of this little yearly excursion, I have the deep honor and responsibility of presenting the parental perspective of the research process to all of the investigators in the room. Thankfully there is a pretty vocal group that I work with and everyone has been pretty forthcoming with ideas.

There are two points that come up every year. These subjects are the speed at which research moves and the need for more options for children. I am usually bombarded by email in the weeks preceding the meeting. Other parents want to ensure that we get these points across. The funny thing is that there is no doubt that the researchers and oncologists that attend these meetings feel the exact same way. For the most part, they are not just researchers, they are also oncologists. That means they are treating children with neuroblastoma everyday. Considering they are a collection of most of the best of the best they are also seeing the hardest and most dire cases. Trust me, they understand the need for drugs to help save these kids and they too are desperately searching to find answers quickly.

So, if we both believe the same thing, why is it still so slow and why don't our kids have more options?

See, to me, this is the really interesting question.

The biggest 2 problems that neuroblastoma faces in the research world is a lack of research funds and, oddly enough, a lack of patients. Believe it or not, it is the latter that causes more problems. We can only have so many trials open at any given time because we only have so many patients. For each trial we open up it slows down another trial because it is now taking patients from the other trial. So, although we may have more options, we may in fact be slowing down our quest for a cure. How do we make sure that we have the optimal number of trials open and how do we make sure that we are only having trails that include the most promising drugs and combinations?

Regardless of which side you are on, the answer is prioritization. The problem is how research is prioritized. This is where I see communication breaking down. Furthermore, I will argue that many times our two dreams, more options and hastened research, are often mutually exclusive. Often, what is best to speed the cure for neuroblastoma is not what is best for a patient with relapsed or refractory disease. It is a sad, but often true, reality.

We prioritize our children. When it comes to research, the medical community has to prioritize all children with neuroblastoma - not only those today but those that will be diagnosed tomorrow, next year, or in ten years. Their job as researchers is to save the lives of the most children with neuroblastoma. It is not our job which is, how do we save our child with neuroblastoma? As you can see, these are very different priorities and what is best for one may not be what is best for another.

Who is right?

I am not expecting an answer. I think we both are and I think a mix of the approaches is probably reasonable. Believe it or not, I also believe, to a certain extent, we are already achieving that.

The trick still remains in prioritization and this is where I think we are failing. On Thursday, I will dig deeper into this ever important issue.

Just because I have purpose doesn't make my purpose the only way.

Kind

On Saturday the Dudester, my only son, had his 5th birthday party. In the past, I have told you what a wonderful soul Graham was and this occasion was no different. I should probably give you a little background. When we first began to discuss birthday ideas with Graham he was very clear about what he wanted. He wanted a "sleep over" birthday party. At first, both Lynley and I were very supportive of the idea. CHEAP! It doesn't get much better than that. Rent a movie. Order some Pizza. Play some games. I could handle that. I was getting ready to save $250 without even batting an eye.

But, that soon changed. As Graham started to tell us what he had in mind we knew this was going to be an impossibility. The sleep over was fine. Unfortunately, the guests were not. You see, as he began to list off the names of the kiddos that he wanted at his sleepover birthday party, we realized that they were all the girls from his class. It was an interesting quandary for me, I don't know whether I was proud or worried. Regardless, we slowly had to break it to Graham that he could not have girls at his sleep over party.

Knowing Graham would want all of his friends at his party we had to consider other options. It was not long before everyone had decided on a pool party. It turns out that there is a women's fitness center with an indoor pool that rents out space for birthday parties. This was perfect for Graham because, given his February birthday, he was never given the option of a swimming party like his sisters. He was ecstatic.

Graham had a great time at his party. In all, there were 11 or 12 kiddos. I should also point out that only 4 of them were boys and 1 of which was Graham. Regardless, they had an absolute blast. I can not tell you how many of the parents took a moment to tell me what a great little boy Graham was. There were several parents who even described him as "kind" or "kindhearted." I don't think I have ever been prouder. He is such a good boy.

I often describe my father, with great admiration, as being unfailingly honest and kind. Until now I guess I never really understood the power of those words.

But right now, I could not be prouder - even if he wanted a sleep over party with girls.

My purpii bath me in pride.

A Fulcrum of Purpose

I have learned many things since we first began our journey through the neuroblastoma world. However, one of the biggest veils to be lifted from my eyes has been the politics behind so many decisions in the research world. This is not to point fingers. Much of it is due to what they call the "scientific process" I call it haggling. Regardless, there are so many different factors at play it is often difficult to put your finger on what is truly happening. Parents often blame researchers for being the reason that it takes so long to move new drugs and trails forward. After all, it is generally the researchers names who are on the protocols. Who else are you going to blame? What I have come to find out is that the answer is - not them but nearly everyone else. The researcher is hardly ever the problem. To this date, I am yet to see research slow due to the researcher. I have seen it due to pharmaceutical companies, the FDA, the NCI, an IRB or a myriad of other factors. With the limitations of resources and patient populations I have also seen things slow as researchers fight and jostle for position and priority amongst their competition. Everyone believes in their research and data. Even the most promising ideas hit roadblocks. Regardless, my point is that there is a lot that goes on behind every clinical trial and I am always amazed at the different factors that come to play.

In this sense, I am always interested in what is happening behind the scenes. We often hear that a trial was opened or that something got funded. We rarely get insight to all of the work and effort that it took to get there. That is my favorite part. That is how you speed things up. That is how you make things happen.

You may not be aware but the National Institutes of Health (NIH, the parent company, if you will, of the National Cancer Institute, NCI) quietly received an increase in their budget of 34% due to the stimulus package. I would love to take credit for that idea when I suggested it a month ago but I don't think they read my diary. While the dollars have not been carved up yet I fully expect to see a substantial increase in the NCI's budget as well. While I hope and pray that the trickle down effect works for pediatric cancer, I can already tell you that many of neuroblastoma's researchers are working to get those dollars.

What do these two stories have to do with each other?

Well, like I said, I am always amazed at what happens in the background to make things like this happen. In this case, much of the story was captured in the New York Times. To my surprise, a very savvy Arlen Spector, got the job done. It is worth a read. You can read the article here:

http://www.nytimes.com/2009/02/14/health/policy/14specter.html?ref=science

Pretty incredible, huh? It is amazing to me how solutions often come down to the quiet actions of those with purpose, drive, and focused energy.

This is an incredible example of purpose at work. It just makes me want to try harder.

Double Digit

Well, I had originally intended to begin addressing by 2nd Unwritten Rule of Neuroblastoma Treatment today but I had a few important neuroblastoma family treatment emails to address this morning and time slipped away. That is really okay because, to be honest, there was another funny story that I wanted to write down so that I could remember it for eternity.

The other day Graham was at school. His class is working on addition. He is in Pre-K so they are learning things like "1 + 7", "2 + 3", and the like. They are working on single digit addition.

Now, before I tell you this story, I should tell you that Graham is a clever kid. He just scored in the 98th percentile in a national achievement test. There is no doubt that he is smart. I tell you this because, by the end of this story, you may wonder.

Regardless, from what Graham has told me, the teacher was having the kids work on math problems on the board. For some reason, she challenged Graham with a math problem which had a two digit answer. In other words, it was something similar to "9 + 2". Graham had never done math at this level and became confused. The teacher explained that the answer was a "double digit." She used this as an opportunity to teach the class about this next level of math. Well, throughout the rest of the day many of the boys started calling him "Double Digit." By now, you know how sensitive he is. Due to the fact that he had missed the question at the board and it embarrassed him, Double Digit now became a bad name. He was quite upset.

Fast forward to yesterday. It is now common place in Graham's class that, whenever someone is doing something nerdy or silly, the kids in the class will call them a Double Digit. Believe it or not, it has become a bad word.

Ironically, yesterday Graham got mad at another kid yesterday and starting calling him a "Double Digit." This disrupted the class. In the end, Graham was asked to change his green sticker to yellow and he was sent home with a note about being disrespectful to his friends.

While I completely understand the teachers point of view I could not help but laugh to myself. That is so typical of Graham. He is such an incredibly good boy. Like any child, he gets frustrated and mad on occasion. But, I am always amazed by the way he chooses to express himself. The meanest thing he can ever think to call someone is a "not nice head" or a "meany." As mad as he gets, the meanest thing he will do is threaten not to snuggle with you at bed time or not invite you to his birthday party. Those are the worst things he can possibly think of and a sign of how incredibly gentle his heart is.

I hate to brake it to him but he is a double digit.

God, I love him.

Furthermore, given my purpose that probably makes me a quadruple digit, making him only 1 or 2 digits off the old block.

Obsessive behaviour understood

Good morning! After the last few entries it should probably not surprise you that Ainsley is currently at my feet putting together a puzzle of Winnie the Pooh. Although I am amazed at her continued tenacity I must say that it is bordering on obsession. Yesterday she was home from school due to her strep throat. In the three hours that I watched her she must have put together about 15 puzzles. She did nothing else. I must admit though, based on the sense of pride that I can see in her eyes, I am almost as addicted to her success as she is.

On the business front I can tell you that things have continued to move forward even with the sickos at home. I guess that is the award one gets from waking up at 2:00 AM. There really is quite a bit going on right now. It seems like every time I turn my head there is yet another research issue to address. There are three that I am looking at right now. First, there is the ongoing saga of ABT-751 and Fenretinide. You may remember that this is the phase 1 trial that we have been trying to get going for almost 3 years. In fact, the NANT has had the protocol ready to go for over a year. The problem has been trying to get Abbot, the manufacturer of the drug, to provide the ABT-751. There have been many issues surrounding this ongoing drug saga and, unfortunately, it isn't like we can run down to the pharmacy to get the drug. There has been significant finger pointing over the years and now we have come full circle. I can list a litany of different problems that I have heard over the years but I must admit that the latest nonsense just irritates me more than ever. I am beginning to fear that this is one promising combination that will never make it into patients. It is disappointing. None the less, I will be making one last attempt to hopefully get the politics of this one straightened out - or at least understood. The problem remains that everyone is pointing a finger at someone else. No one will stand up and say that they are the reason that this trial is not moving forward. Chicken! So, it becomes very difficult to identify the source of the hold up and address it. It just boils my blood that this is not in kiddos right now.

Some other things I am the midst of discussions about right now are a new oncolytic virus study and the new 3F8 antibody study which will be offered through United Pharmaceuticals. The good news about this latter study is that 3F8 will now be available to some (refractory) patients outside of Sloan Kettering. The bad news is that I am not so sure about the quality of the study from a patient perspective. I have heard many different claims from many different parties and I am anxious to sit down and read the protocol and requirements myself. Regardless, I am happy that patients will have an option outside of travelling to New York or St. Judes for antibody therapy. Right now, they don't even have the option to have the ch14.18 study that Sydney underwent as the study has been halted, hopefully temporarily.

Well, as you can see there are several research irons in the fire and it does not even begin to get into the work I have in the NANT or elsewhere. It will be a busy, busy month on the research front.

Wow, it just occurred to me that this whole neuroblastoma research thing is just one giant puzzle. I am beginning to better understand my daughters obsession.

My purpose is part obsession, you know.

One precious twerp at a time

Yesterday was genuinely wonderful. I guess I should also say that a little surprisingly. I always enjoy spending time with the kiddos but yesterday was more than that. I must admit that yesterday I had a little bias. I spent a significant amount of my day alone with Ainsley. I rarely get to spend one on one time with her so this was particularly special. In the usual storm of kiddo-dom it seems I rarely get the opportunity to appreciate my twerps individually and I really had a nice opportunity to yesterday.

While all of the children were home from school, both Graham and Sydney remained pretty occupied. Graham spent most of the morning over at DeeDee's house and Sydney spent the morning in the play room working on the computer. That left Ainsley with me - craving entertainment. She started at my feet putting together puzzles as I typed away on the computer. It was not long, though, before she had me down on the ground with her.

You may not know this about Ainsley but she is a puzzle savant. I don't know any other way to say it. She is certainly the only 3 year old I know that can keep herself occupied for hours putting together puzzles. One after the other, over and over again, she just keeps plugging along. When it comes to puzzles she has more patience than I and more perseverance than her mother. She is simply, utterly amazing.

It turns out that Ainsley also had a doctor's appointment in the morning. I dropped Sydney off with DeeDee and we were off for hours of waiting. The bad news is that she Ainsley was diagnosed with strep. The good news was that I had a few more hours to watch her put together puzzle after puzzle. In all, we completed 23 puzzles yesterday. I am not talking about 4 or 5 piece puzzles either. I am talking about puzzles with 24, 48 or more pieces. I helped occasionally but I must admit I spent the bulk of my time cheering her on in amazement. I was incredibly proud. I felt like I won the price cabbage at the fair - my twerp puzzle savant - call the Guinness book of world records. Later that afternoon I would take Sydney to the H/O clinic for a checkup. She and I had the pleasure of passing time by practicing her Korean.

As a side note, I discussed leg pain along with a myriad of other things with Dr. Granger. As I suspected, we will watch and wait. However, that is not the point.

After several hours we were on our way to Tae Kwon Do. Lynley and I performed a kiddo switch and the next thing I knew I was on my way back home with Ainsley. We then played 19 rounds of neighborhood sound bingo. I have to tell you. I really enjoyed it. It was so nice focus on one child and to appreciate her for what she was.

I realize now that I could not see the forest for the trees. Heck, I could not see the tree for the forest.

I have to remember to take one twerp at a time.

That is what purpose is all about.

Real success is not immediate

Today is a holiday. You may not know that but the kiddos are fully aware that this is a day home from school. It is also my turn to stay home with the gaggle of twerps while Lynley works. For some reason, us grown up twerps don't get the same holidays that the kiddos get in school. It doesn't make sense. I don't know whether I am arguing for a day off from work or a day back at school but it just doesn't seem right. The holidays should be the same. Now, Lynley feels guilty for not being home. I feel guilty for not being at work. Thankfully, I suppose, the kids don't care about how either of us feel.

I do have some exciting news. It seems as though Tae Kwon Do is really paying off. Sydney can ride a bike without training wheels. Do you see the connection? No. Well, the whole reason that we started Sydney with Tae Kwon Do was to get over her embarrassment of not being a professional at anything the first time she tried it. Instead, Sydney became a professional quitter. If she could not do it perfectly she refused to do it ever again. She was missing a very, very valuable lesson in life. She had no concept that if she tried really hard she would eventually learn. In her eyes, she had no successes. We were hopeful that the discipline of Tae Kwon Do would get her through this.

Well, over the last week or so we have been watching Sydney sneak out to the back yard to ride her bike. She would mount it at the top of the hill by the swimming pool and ride it down to the swing set - with no training wheels and no help. At first she failed - a lot. She fell over nearly every time. But after a few days of practice she was successfully riding down the hill. This was a huge milestone. Previous to this, with the exception of one time over at a friends house, she had refused to ride her bike in over a year.

Well, yesterday she finally decided it was time to take the bike out onto the pavement and give the sidewalk a shot. Within minutes she was safely riding up and down the block.

She did it! All by herself.

At dinner she said. "Wow, I never knew that if I tried real hard I could do it. I never did that before. I am so proud of myself. "

That is one of the great successes in life. I could not be prouder either.

It seems Sydney is learning purpose as well.

Something to be Enthusiastic About

I have always said that I hated the fact that my daughter had cancer. I despise the fear. I loathe the fact that chemotherapy put her in hearing aids, thinned her hair, and leaves us waiting for which long term effect will come next. I detest what she has had to endure. But, in the same breath I have always also known that it had brought something beautiful to our family. We developed an appreciation for life that could not be understood without the experience and we have a bond that transcends anything I have ever known. But, there is still something more that it gave us and I have always had trouble putting a finger on it. Yesterday, I heard a quote on the radio which gave me some clarity.

We act as though comfort and luxury were the chief requirements of life, when all that we need to make us really happy is something to be enthusiastic about.

-Charles Kingsley

Perhaps that is what this whole purpose thing is about.

The Mental Side of an Email

Good morning! Okay, so I am a little mental. Everyone knows that. To date, I have mentioned three times in my diary that I would be writing Dr. Eames about Sydney's leg pain. And, yes, I am still yet to pull the trigger. In fact, I have a fourth draft of an email sitting on my laptop in front of me. Originally, when I began writing the email last week it just sounded ridiculous to me. After writing down the sequence of events and looking at the symptoms it just did not look like anything other than normalcy. Yes. there was some pain but it was sporadic and went away. Before pushing the send button, I elected to wait it out just a little bit longer.

I have now done that four times.

In fact,I was so close the last time I forwarded the email to Lynley for review before I sent it off.

She thought it was too long.

Come on! You ask me, me of all people, to write an email to the oncologist and you expect it to be short. It just isn't going to happen. I don't have that in me. I carefully craft words. I think about angles. I carefully navigate bias. I address arguments from both sides.

Then, I have to make it funny.

The only thing I apparently don't care about is whether it is punctuated correctly or whether I used the right "there" of "their", "weather" or "whether", and "its" or "it's".

It's true. I am above that.

Regardless, what you are not going to get out of me is a nice short email.

Lynley took two days to edit it. She made it devoid of funny or interest. It is clinical and cold - probably perfectly appropriate.

Sydney now hasn't had any pain in two days and the last pain she experienced was due to injury. In fact, I have trouble remembering the last time she had any truly unexplained pain.

So, here I sit in front of an email that I am pretty sure that I won't send today.

Boy am I mental. I guess I can't say that purpose keeps you sane.

GCSF

Last year while I was in Japan at the Advances in Neuroblastoma Research Meeting there was an article published in the Journal Of Pediatric Surgery. The subject of this study was GCSF, or Granulocyte Colony Stimulating Factor. AS you may or may not know, GCSF is used regularly in neuroblastma treatment to help patients recover their neutrophil counts more quickly. By using this drug we are able to give significantly more chemotherapy and we are able to give it more often. Surprisingly the researchers of this article found that, like certain blood cells, neuroblastoma cells also had a GCSF receptor. More interestingly, they had found that GCSF actually increased neuroblastoma cell proliferation and invasiveness.

Yes, I said it made neuroblastoma grow.

As one might expect, this article created quite an uproar amongst the parent community. Many went rushing back to their doctors refusing to allow them to use GCSF on their children. Many others were wondering what to do. It just so happens that when I received the news about the article and saw the emails flying back and forth between the parents I also happened to be sitting next to one of the articles authors.

Handy!

The short and the long of the story was that although this was very interesting research it was probably too early to throw the baby out with the bath water. While GCSF might promote growth of neuroblastoma, at this point its benefits severely outweighed the disadvantages. Future research was now aimed not at getting rid of GCSF but on learning how to use it more effectively. The trick for me became damage control. How do we get the word out that GCSF is still an important and integral part of neuroblastoma therapy. Thankfully, the authors drafted a letter to the families explaining the study and its implications. Additionally, Dr. Heidi Russell even offered to speak on the subject at the CNCF's Neuroblastoma Conference for Parents and Caregivers. I posted this video on the CNCF site. it can be found here:
http://www.nbhope.org/blogs/neuroblastoma_conference_videos_2007/archive/2009/02/11/cncf-2008-gcsf.aspx

I wonder if purpose has a GCSF receptor

Leg Pain Revisited

Okay, so I had a talk with Sydney. She is a confusing little twerp. It is clear that I do not understand big girls or little girls. Regardless, I went through the whole rigmarole. I explained all of the different reasons that she could have pain in her legs. At the very last moment, of course, I had to sneak in "and, also, it could be cancer coming back." If you can imagine me saying that very quickly at the end of a sentence, then you have a pretty good picture of what happened. Sydney knew that fact but I think she needed to hear me say it. I know that sounds strange but otherwise it was just a big elephant in the room. She knew it. We knew it. We simply had to state it as a fact so that we could move on. My ulterior motive was to get her to help give me a clearer picture of what was going on. She had a genuine interest in trying to help me get to the bottom of the pain. However, in the end, I was no closer to an answer.

She was honest with me. Furthermore, as of yesterday morning, she had not had pain in a couple of days. I was feeling more comfortable with our situation. I was prepared to wait it out. I felt confident we were moving out of the leg pain worries.

Then, I picked her up from school.

She came to me almost in tears. I don't know whether she was more upset that she received an 89 on her spelling test or the fact that her leg was hurting. She was very dramatic. I was immediately scared. My dreams of no leg pain were coming to an end.

I got the gaggle loaded into the car. Then, carefully and calmly, I began to dissect her leg pain story. Where did it hurt? How did it hurt? How long? How intense? Sharp or dull? Based on the answers I wasn't too pleased with what I was hearing. Finally, I asked, "Did something happen to your leg to make it hurt?"

"Oh, yes, I bumped it on the table in Spanish."

My heart started beating again. I could not believe that I did not ask that question sooner. We then went through some more discussion. She was a bit worried about it because she feared that the pain was coming from another spot about an inch from where she "thought" she hit it on the table. Maybe I should have been concerned but at that point I was still reliving the high of relief.

Later that evening it was clearly tender at Tae Kwon Do. However, when we were not paying attention to her it miraculously got better.

She spent the evening chasing her brother and sister around the house.

No owies.

So, it was a day of ups and downs. Sydney still seems to be milking this situation. Lynley and I have agreed to not mention anything about pain or her legs for the next few days and we will see what happens. In the meantime, I have agreed to write Dr. Eames an overview of what we are dealing with to see if she wants to do anything about it. I imagine she will be content to wait it out but we shall see.

Other than the chaos (or with it) it was just a normal day of purpose around the Dungan household.

To scan or not to scan. That is the question.

Good Morning! Well, the response to "The First Unwritten Rule of Neuroblastoma" was very good. Secretly, I was hoping for someone to stand up and argue another side. I was really, really prepared for it. I still haven't given up but, being honest, I knew it was a pretty easy argument. That is the reason I started with that subject. Some of the other rules I plan to write about will be more open to dissenting opinion. I must admit arguing for a second surgical opinion for one of the most difficult tumors in the world to remove is not really a stretch.

Yes, I played it safe.

So, I also received several email and messages asking about the status of Sydney's leg(s?). I would love to tell you that it had gone away but I can't. I can tell you that it has moved, changed legs, and come and gone. But, unfortunately that does not make us feel any better. If anything, it makes us feel a bit worse.

We are still trying to decide what to do.

There are two issues. First, there are 1 million and 1 reasons she could have pain in her legs that have nothing to do with neuroblastoma. Some of our top suspicions include injury, the fact that she has recently begun Tae Kwon Do, she has been playing a game which specifically tires her leg muscles, or the fact that she is growing. We have some very solid leads. We also can't rule out long term effects. She has very definitely injured one of her thighs. There is a bruise and we can tie that to a specific injury. And, yes, at one point or another she has said that the spot hurt. The problem is that she has also identified other areas and every time we talk to her we seem to get a different answer. The left leg has hurt and the right leg has hurt. It has hurt near the top, near the middle and on the side.

So, in short, we have a bunch of good possibilities of why her legs could hurt and where they hurt. It is just that nothing is clear to us.

The second issue is the scanning. It isn't like a quicky x-ray will provide us any value. Think about it. If it is neuroblastoma, it isn't likely that we would see it on an x-ray unless it was pretty advanced. And, even at that, we would have to follow it with other scans. What if it did not show us anything? Would it give us any confidence that it wasn't neuroblastoma? No. We just might feel better that it hadn't eaten through the bone. So that leaves us with a bone scan, MIBG, and marrows. Bone scan would be non specific. She may no longer be MIBG positive. Finally, the bone marrows may not show anything in the hips when the issue is in the thigh. So, you see, there is no simple test. If we commit to doing this we have to go all the way. We are talking about a week of scans for Sydney. How worried are we? Is it worth the increased risk from radiation exposure and contrast?

I don't know yet. I think Sydney and I will have to have a big heart to heart this morning.

Purpose does not mean easy answers.

The First Unwritten Rule of Neuroblastoma - Surgery

First, a disclaimer, I am a dad. I am not a medical professional. Verify everything I say with a medical professional who is an expert in neuroblastoma. Second, if your oncologist tells you I am wrong, ask another one - ask a neuroblastoma expert.

The First Unwritten Rule of Neuroblastoma is regarding complete surgical resection. This is a tough subject. The leaders of the neuroblastoma community are split on this topic. Although there is a sizable body of research on this topic there is no definitive answer in literature. Furthermore, if you chose to read the literature on this topic, be skeptical. Just when you think you understand it, you will realize that the opposite is also true. Both sides of this issue are right. Finally, I am not advocating radical surgeries that put children's lives in more risk.

I have a safer plan.

First, there are two really incredibly well-respected big neuroblastoma brains that are at odds on this topic. I deeply respect both of them and I honestly believe they are both right. These are Dr. Sue Cohn and Dr. Mike LaQuaglia. For the sake of argument, I believe that Dr. Sue Cohn would probably disagree with some of what I have to say. I have incredibly deep respect and admiration for her.

Technically, she is smarter than me and, frankly, she is much better dressed as well.

Let's begin.

My rule is: If your surgeon does not have a strong level of confidence at being able to completely remove your child's tumor, do not walk, run to get a second opinion from a surgeon that is respected as the best in the field of neuroblastoma.

Wow, I could just feel about 20 of my favorite oncologists cringe at that statement. In fact, before I even began to state why I believed this to be true I could already feel my inbox starting to fill up with nastygrams. Just wait, let me finish.

Well meaning physicians do not like statements like this for many reasons. First, they fear that parents will be taking more risks than necessary. They fear that statements like this will raise the incidence of radical procedures that put kids lives in jeopardy. They also fear for those that can not afford to get a second opinion or go to another institution. What affect do my words have on them?

They are right. I have the same fears.

Let's be straight! I am not advocating radical nephrectomies or anything of the like. I am advocating that, if you find yourself in this position, you talk to the best of the best. Period.

You may think that I am saying all of these things because I believe that a complete resection has a higher degree of survival than an incomplete resection. That is not my point. Actually, it is not even my reasoning. Let me explain.

If you look at the research over the years there is actually conflicting data on this subject. Some studies show that complete resections have impact in certain subsets (different stages) of patients and others do not. Personally, I believe that less disease is better than more. I believe that a complete resection has a better survival than an incomplete resection. I can say that the majority of the research bears this fruit out. In fact, Sue Cohn's article in the January, 2006 edition of "The Journal Of Pediatric Surgery" even supports this theory. However, the article's rationale behind the claim that children with complete resections have better survival than those with incomplete resections is smack on. In simple terms the argument is this: the kids that had complete resections had better survival because their disease was less aggressive. They could be completely resected because the disease was not as bad. They proved (small numbers, nothing is truly proven) that the kids that had complete resections had fewer local recurrences. The real determining factor in survival, though, was metastatic relapse (relapse in other parts of the body) not local relapse. However, one could also argue that the presence of local tumor would probably increase the risk of metastatic relapse. Regardless, I think we can see that there are many sides to the issue.

See, it is murky. Yes, it is true. Kids with complete resections tend to do better. However, were they destined to do better in the first place because their disease was less metastatic in nature? Quite possibly! I don't know the answer and this is the reason that my argument for getting a second opinion is not based on this survival statistic.

My argument is based on reality. It is based less on the resection itself and more on what follows. You see, resection is a key decision point in treatment. In many ways it dictates destiny, not necessarily survival destiny although that is a factor. You see, when you don't have a complete resection it complicates everything that follows and more often than not will lead to more toxic therapy that is probably less likely to produce the desired result - a happy, well- balanced and ALIVE 40 year old.

Think about it. Once you have an incomplete resection everything changes. Will a transplant do any good with bulk tumor present? Will it be as effective? Will the radiation be enough to get deep enough to reach far enough to kill every cell. Is every cell in the tumor susceptible to radiation and chemotherapy? What happens when you finish transplant and you still have disease present? You probably will. Is Accutane enough? Do you need MIBG therapy? Post transplant surgery? What consolidates you then?

You see, there are mountains of questions and complications.

Surgery is one decision point you want to get right.

So, yes, I know I have simplified it and generalized some things. Who would want to have an incomplete resection when you could have a complete one.

"I mean, come on, Mark. Just because we want one doesn't mean we get one. We don't get one because we don't have the option."

Wrong! The one thing we have is options. We may not like the options but we do have them. Furthermore, we can all agree that some surgeons are definitely better than others. Some have different styles, some are more aggressive, some are less, and some are simply gifted.

I am a good golfer. I really am. I am impressive. I even played professionally. Now, if we you were going to play in a tournament for $1 million who would you want on your team. Me or Tiger Woods? Tiger Woods, of course! Would it matter if you needed one of us to make a 1 inch put. Probably, not! Either of us could do it with equal prowess. He may be more stylish? He might be more funny? He might even be better to look at. I would probably try harder? But, we would both get the job done. But, if we were on the 18th fairway and all of the money was on the line, there was a gusty breeze and the green was sloping treacherously down towards the water; who would you want on your team?

You had better say "Tiger Woods" or I can't help you.

When the game is on the line, when there is question (any question) get Tiger Woods on your team.

Now, let's talk about what I have seen. I have seen hundreds of kids have incomplete resections that could have had a complete resection had they been in the hands of the right surgeon. I know that sounds arguable but I can't tell you how many second surgeries I have seen (performed by a second surgeon) that produced a complete resection and it had nothing to do with the fact that the tumor "become" easier to resect. I have seen many kids with incomplete resections have local relapses that later had to be removed (and this time by a surgeon that was capable of getting the job done.) I have seen them endure multiple surgeries, mountains of chemo, radiation, and a slew of medications and treatments that put their lives in jeopardy. Where, had they looked elsewhere - had they gotten that second opinion - they probably would have had to only accept a small amount of risk to avoid a relapse and a mountain of toxicity. To be fair, I have also seen the other side. I have seen radical surgeries that have left kids in pretty bad shape for weeks and sometimes months. But, when the experts have been in the room I can honestly say that regardless the cost, most parents still came out with a sigh of relief.

Ask the question! Don't believe any one surgeon. It is too important of a decision. It changes the game. It impacts every decision made from that point on. If you don't do this you will always doubt your decision. You will always wonder. This is the number one regret I hear from other parents.

I offer no guarantee that the best surgeon in the world will be able to resect your child's tumor. I offer no guarantee that the risk of surgical complication will be worth the increased risk of relapse. I have no idea whether the risk of a more radical surgery is as bad as the toxicities from further treatments.

I don't know.

That is your decision.

But, you don't know either. You don't know, until you go ask.

It isn't just the surgery. It impacts everything.

Go do it. Go advocate for your child. Go get the second surgical opinion.

For those interested in finding the very best neuroblastoma surgeons in the world you can find them all over the Internet - one in particular. You can also write me and I will give you a list. However, I will not state them here because I don't want this to turn into advertising for a particular surgeon or group of surgeons. That is not the point.

If your child has a tumor that is not believed to be completely resectable go to the best. Get a second opinion.

There you go, purpose - without any medical advice. How did I do? Let's hear your thoughts!

The Unwritten Rules Rebuttal

First off, I received great advice from 'Anonymous' yesterday. Yes, I should not go over to the dark side. I whole-heartedly agree. I am serious. Absolutely.

I should not give medical "advice." Period.

In fact, to this day I never do. My answer is always "Go talk to this expert and ask them about this.", "Ask them these questions.", "Grill them about this."

Often I am asked what I would do. I answer. But, I never, ever, ever tell someone what they should do for their child. Every decision is risk and reward and I always present both sides.

For example, we chose for Sydney to have antibody therapy. Would I do it again?

You betcha!

Is that the right answer? I don't know. I put her in regularly scheduled doses of weeks of pain for 2 and half years for a treatment that has absolutely no proof of increasing survival. In fact, if I had to speculate based on the results of the COG phase 3 trial (given what is published) one would have to assume that, if it has impact, it is minimal. Then again, if you look at the published long term German study, it does "look" like their could be some long term benefit. Maybe this is a bad example. Regardless, forget that.

Would I do it again?

I have seen antibodies kill neuroblastoma in kids - 100s of them. That is published. It does it. It kills neuroblastoma. I know you have seen it in my diary 100 times.

1. I have seen kids with neuroblastoma.
2. I have seen kids take antibodies.
3. I have seen their neuroblastoma go away.

So, should I be telling everyone to give their child antibodies?

No! Resoundingly, No!

Does it work for every child?

Clearly not!

Heck, I still don't know what the unknown risks are. 15 years out Sydney may sprout mouse whiskers and develop a worse craving for cheese. On a more serious side, she could be at more risk of a late brain relapse for all I know.

But, none the less, I believe it is my responsibility to help families learn all of the facts and to make their own decisions.

To me this is not a life or death decision but rather an example of information that should be passed onto parents that regularly is not.

In this sense, I am pretty sure I am every pediatric oncologist's worst nightmare. But, I want other parents to see all sides of an issue. I want them to be prepared to ask the really difficult questions that most don't know that they should be asking - and, in some cases, that researchers don't want them to. However, they are key points and, win or lose, they are considerations that every family should be aware of. There are no guarantees, no answers, just calculated risks.

However, unlike this topic. There are life and death decisions that are equally as murky. There are things that almost no one will say in public. But, they need to be said. Ironically, many of them have been said but only by the experts themselves - the absolute best of the best. But somehow, those decisions never make it down to everyone else. It is those things I want to bring to light. I can't guarantee the golden ticket. I know that. But I can help others increase their chances. The fact is there are oncologists treating kids with neuroblastoma (that are not experts) that are making bad decisions for kids. Period. They aren't following the direction of the experts. The problem is that these rules aren't always documented. They aren't always proven. But, there are some decisions that should always be made. I want those facts to come out.

I don't want to see another child die that doesn't have to. Families have a tough enough life without their child's treatment being unwittingly sabotaged by a lack of information.

What about those that can not afford to make a decision or can not get to an expert? Those are the hardest for me. But, again, there are no guarantees. However, you have to know the options. You have to know the cost. Only then can you make a decision you can live with.

Now, Anonymous has me up against a wall but I think we are saying the same thing. So, I intend to prove it. I will let he or she decide if what I have to say is important or out of hand. Again, the purpose is to help other parents.

So tomorrow, I will write about the first unwritten law of neuroblastoma. If you think it is inappropriate, I challenge you to leave a message in my blog. I won't delete them. In fact, I will publish them for all to see. If someone makes a case that what I am doing is, in fact, hurting families I will agree (beforehand) to delete my entry. If you have a different opinion, state it. Let's get it out there. However, before you pass judgement on what I say, let me say it first.

Purpose is a powerful thing.

P.S. Anonymous, thank you.

The Unwritten Rules

For the record, we are still watching Sydney's leg. She did not say anything about the pain yesterday. That is a good thing. Unfortunaely, Lynley was being sneaky and under the guise of massaging Sydney's leg, she caused Sydney to flinch when she touched the area of concern. I don't have an answer. We will see what happens today.

On another note, I really do need to finish a conversation that I began with myself yesterday but which never made its way to paper. I think as I grow older I am becoming less and less able to be completely unbiased. However, as I continue to watch children in the neuroblastoma world, I become more and more frustrated. I am less able to be completely unbiased when I am continually confronted by contradictory data and reality.

On the other hand, I don't want to ever provide information to other parents which is not fact. I have always provided them with all of the information surrounding and issue and allowed them to make their own decisions without my bias. Honestly, I am often left frustrated because many make decisions based on the factual data which I still truly believe is the wrong decision. I know, how full of myself am I? What right do I have? Who says that I know what I am talking about? None the less, I continue to see the same patterns. Can I guarantee that, if they went the direction I believed in, the outcome would be different? No. But, I can tell you that more do well. I have seen it too much to keep my mouth shut anymore.

There are certain unwritten and unproven rules about neuroblastoma that impact survival. They are unwritten because they are unproven. They are unproven because (a) there is no way to prove them in the real world , (b) nobody agrees on the rationale behind the successes or (c) no one can agree on how the successes should be measured. In other words, both sides have validity. Both have concrete arguments behind them as to why one way should or would be better than the other or vice versa. But, for some reason, one path always seems to do better than the other.

It is a dilemma. I hate it. I can't stand it.

So, for this reason, I have decided to start writing about the unwritten and unproven laws of neuroblastoma treatment.

Oh, yes, it is controversial. But, I offer this. I will still show both sides of every issue. I will provide all of the negative and positive research support. But, for these, I will also point out the intangibles - those things that can't be proven but certainly seem to have an impact. I will also share what I have seen as opposed to what is known. Furthermore, I will admit my bias.

Take it (and me) with a grain of salt. But I just can't keep my mouth shut when I believe it will help our kiddos.

I am finding that purpose can be compelling.

The stages of leg pain fear

Some days it is easier to write than others. I have two things in my life driving me nuts. Of course, it should come as absolutely no surprise that both of them have to do with neuroblastoma. One I know I can talk about. The other, well, I guess I am going to have to dig really deep not to make the entire world mad. So, for the sake of safety, I will start with the easier to talk about of the two. The second I will continue to think about - maybe tomorrow. It will probably shock you that this is the easiest one to talk about but here goes.

So, while I was in Chicago, Sydney apparently started having some leg pain. It wasn't crippling but she did limp at a few points during the day. When I saw her she was still having some issues but, to be honest, I did not pay too much attention to it. Over the years I have developed a balance. I have a tolerance for freaking out which has grown much larger over time. It takes something fairly significant to get the hairs on my neck to stand up. So, when I tell you that Sydney has leg pain it is something that I am acutely aware of but not something that makes me scream neuroblastoma. There is a process. There are steps and stages to terror. This was merely step number one.

Pain in the leg is significant. However, the cause can come from 1 million and 7 different things. There are lots of factors that we consider such as the location, appearance, and whether the pain changes with time. Frankly, using our eyes, hands, and a little thought we can usually find a cause that is probably not neuroblastoma related. But, when we have pain that is in a spot that is a known place for neuroblastoma related pain and we can't immediately rule it out, we begin to progress past step two.

Step three is the waiting game. In its most simple terms we are waiting for the pain to change. Ideally, we are hoping that it disappears. Thankfully, it usually does. However, sometimes it gets worse. Sometimes she wakes up in the middle of the night with leg pain.

That was Sunday night.

That is the scariest of all signs and the one that makes me the most nervous. However, you may also note that I am not running to the oncologist. I am not rattling off emails and I don't have phone calls in to 5 of the top neuroblastoma specialists on leg pain. We are waiting and watching.

Scary stuff huh.

The pain is in the middle of the right thigh - known location. It is intense enough that she limps. It is also enough that she woke up in the middle of the night from the pain. This is stage 4 fear.

Now, the good news - the news that makes you not freak out and makes you stop wondering why we aren't sitting in an oncologists office right now - is that we gave her Tylenol and the pain went away. We also made her go to Tae Kwon Do yesterday afternoon. We wanted to see what stretching it out would do. I can tell you that she only flinched once and frankly I would have flinched as well. The rest of the time she did absolutely everything expected of her. She did it well and she did it without reservation. In fact, she spent most of the lesson working on her snap kicks and round house kicks.

By the end, the pain was gone and she spent the rest of the evening without an ounce of pain. The big test now was making it through the night.

She did. In fact, she just came down and told me that she slept beautifully.

She does have pain. It is better.

I can't tell you what the rest of the day will hold. Honestly, I can't even tell you that this is absolutely not neuroblastoma. I can't even tell you that we are feeling much better.

This was a jolt to our psyche and something that we will watch closely but something I am so thankful was not worse.

My purpose still scares me. I am just better at being scared.

Back Home

Yesterday afternoon I returned home from Chicago. To be real honest, my brain is not functional yet. Between the three days I was there, I think I might have gotten 7 hours of sleep. I would love to blame that on something really exciting but I must be honest and say that I simply could not sleep. My brain was not keen on the idea of relaxing. The good news is that the meeting was productive. We accomplished a mountain of work. I am hopeful I will be better able to prioritize my time = making me more effective. I guess the bad news is that there is no less on my plate. I am hoping that changes soon. I often feel like I could do so much more if I wasn't pulled in so many different directions. We are moving there. It just takes time.

So, I made it home to my wonderful family. As always, I was so happy to be back with them. I know it sounds silly but I absolutely hate being without them. I love my kiddos and my wife. Unfortunately, sleep was not that much better in my own bed. For some unknown reason the kiddos were in our room no less than 3 times throughout the night.

Well, I had best be off. I have a mountain of email in which to attend.

With hope and purpose!