Techniques of a twerp whisperer

Well, judging by the email I received yesterday, I can see that many of you feared for our lives and/or sanity. The good news is that the kiddos finally got out of the house and made their way to Pump it Up for several hours of controlled and, most importantly, tiring chaos. All in all, the kiddos, had a pretty good day. There was no bloodshed and we were all pretty effective at nabbing any questionable behavior in the bud. I think this may be the key.

We have to catch them before they reach the "red zone." Those of you that are Cesar Milan fans will know exactly what I mean but, for you others, here is the gist of it. When you are walking a dog and he starts going nuts barking and trying to get to another dog, it is very difficult (at that moment) to get them to calm down. For the most part you are left trying to hold on for dear life. However, had you tried to correct the behavior the moment the dog showed any inkling of interest in the other dog you would be much more successful. In other words, you have to correct the behaviour before the excitement level rises so high that they can't calm down.

I know this may sound strange but it is absolutely true. If I have seen it once in dogs, I have seen it a thousand times. You just have to catch them before they get out of control. If you can do that. You can be successful. You can achieve the holy grail of good and consistent dog behavior.

The problem with this method is correcting the behaviour early enough. You have to be on your toes. You have to pay attention. There is a limited window and timing is critical for success. This, too, seems to be an issue with the kiddos and very clearly my problem. They never register on my radar until they are out of control. However, when we catch them a bit earlier, we seem to achieve regular success.

The trick is not letting life get in the way of our parenting. That is not always easy.

However, that is what purpose is all about. What is really important?

The Happy Trojan Horse of Twerphood

It has rained much of the week here in beautiful Fort Worth, Texas. Yesterday was pretty clear with the exception of a few sprinkles. Yet, the kiddos still elected not to go swimming or play outside. This, has left them inside, doing the same things, over and over.

A new storm is brewing but, for a change, it is inside the house.

Our kiddos are going stir crazy.

Oh, I can see our mothers now - all happy and giddy. We are finally getting our just desserts. In their eyes, we are getting what we deserve and certainly no less than we gave. That is fine. But, don't think of us. Think of poor Miss Claudia who has been thrown to the hungry wolvelets. We are blood. We have to put up with it. Miss Claudia, luckily is not. And, we aren't paying her nearly enough. ( I hope she doesn't read that.)

They are taking over.

If it wasn't so embarrassing, this whole situation would truly be hilarious. My kiddos aren't bad. In fact, they are generally pretty great. As a threesome they are great fun. I don't know that I have necessarily ever seen a closer group of siblings. They love playing together. The problem is that they love it too much. It does not take long before the love turns to laughter, the laughter to chaos, and then, somehow, to violence. It is difficult to explain. You have these kiddos having a blast, giggling absolutely uncontrollably and, the next thing you know, it erupts into all out war. I can't say that I have ever experienced anything like it. It is day and night. It is the Trojan Horse of Twerphood.

The truly unfortunate part of all of this is that the giggleness seems to lead to obstinate behaviors. It becomes 'okay' not to list to your superiors. It seems funny to say 'no' when asked to settle down. It is as if they have swallowed some kind of giggle juice laced with a hint of bad kid. The next thing you know my wonderful twerps have turned into miscreant offspring.

We have to get them out of the house. We have to show them the light.

Purpose, give us strength.

Looking Outside In

Good morning! Ah, what a great night of sleep. I seriously think something may be wrong with me when I wake up at 3:45 AM and feel completely and utterly refreshed. None the less, I do. For me, yesterday was a busy day. Professionally, I have become involved with some pretty smart people with specialty in the non profit arena. Most specifically, they specialize in building non profit brands - I.e. Livestrong, the 3 Day, Team in Training, etc. One of them is even writing a book. These are clever people. I understand the concepts, the technology, and the know how to create something. I can build. I can do that. I can even be somewhat successful. But how, how, how do you create something that has truly national impact? How do you make neuroblastoma a common household name? I know how to make something big. How do you make it gigantic? I know where I want to start - and - I know where I want to end. How do I get there? It is for this reason that I have tried to begin to understand the strategic steps necessary to get where I want the name 'neuroblastoma' to be.

It is fun to dream and envision. It is invigorating. It has gotten my mind racing and I am ready to start pulling all of the pieces of the puzzle together. There are, very definitely, pieces I do not have. However, for the first time, in a very long time I can envision them and I can see how they can come together. This has brought me to the realization that stepping outside and looking back inside is absolutely critical. It can provide new insights and make you realize that the boundaries and obstacles that you once thought were there are, in fact, non existent.

It is funny, as the kids have gotten older, I have noticed the same thing with them. I am often frustrated by the chaos. It is very easy to become wrapped up in it. You can be very calm one moment and then it does not take but 1 or 2 fights from the twerp peanut gallery before you, yourself, become swallowed up in the nuttiness. From that perspective it is very hard to tread water. However, stepping outside of the situation and looking back in often gives you insight and the tools to accomplish the end goal - non loopy kiddos in a non deranged world.

Moral of the day - Don't forget to take a deep breath and look at your life from the outside.

Your purpose becomes clearer.

A New Neuroblastoma Vaccine Available

Last week a new vaccine trial opened for children with neuroblastoma. While I am yet to form an opinion on this particular option, I thought it was certainly worthy of mention. It may very well be an interesting option for you to discuss with your child's oncologist. But, act quickly, this one will likely be gone fast.

The trial "A Phase 1 Study to Determine the Immunologic Effects of a MAGE- A1, MAGE- A3, NY-ESO-1 Vaccine in Patients With High Risk Neuroblastoma, Osteogenic Sarcoma, and Rhabdomyosarcoma" is being offered at Penn State Hershey Children's Hospital. The purpose of this phase 1 study is to determine the safety and immunological effects of a new antibody targeted dendritic cell vaccine. The hypothesis behind the vaccine is that it could reduce the risk of relapse.

The study is in two parts. First, each patient will be screened for the presence of 3 antigens, MAGE-A1, MAGE-A3, and NY-ESO-1. These antigens can be found in fairly significant quantities on neuroblastoma, rhabdomyosarcoma, and osteogenic sarcoma cells. 70% of neuroblastoma tumors will express at least one of these antigens. Those testing positive for one or more of these antigens will then be consented for the treatment phase. An individualized vaccine will be developed and administered using your child's own dendritic cells. After about 1 month, each patient will receive a series of 3 vaccines containing 3,000,000-5,000,000 peptide pulsed dendritic cells at two week intervals. Prior to injection they will also receive Imiquimod, a topical cream, which is believed to help the immune cells travel to the tumor.

Understanding how tumor cell antigens and dendritic cell vaccines work together is a bit of a complicated subject. Essentially, dendritic cells break the antigens on the cancer cell surfaces into smaller pieces. The dendritic cells then act as most-wanted posters for the immune system, displaying those antigen pieces to the killer T cells. To make a dendritic cell vaccine, scientists extract some of the patient's dendritic cells and use immune cell stimulants to reproduce large amounts of dendritic cells in the lab. These dendritic cells are then exposed to antigens from the patient's cancer cells. This combination of dendritic cells and antigens is then injected into the patient, and the dendritic cells work to program the T cells, hopefully, forming an attack against the tumor cells.

Most important to any family of a child with neuroblastoma, however, are the questions of:

1. Will it work? and
2. What are the risks?

The answers to these questions are relatively unknown. Dendritic cell vaccines hold much promise but have, thus far, shown fairly lackluster performance in practice. However, recently there have been several examples of these vaccines providing the immune responses that we are looking for. There are even examples, in other cancers, of increased survival and reduced rates of relapse using this type of strategy. Side effects for vaccines such as this tend to be minor. Mild fever, muscle pain and fatigue are often seen. However, as with any phase 1 trial, the true risks are unknown. Only by talking to your oncologist or speaking with the trials primary investigator will you be able to get a good understanding of the risks and rewards of a trial such as this.

More information and contact information on this trial can be found here:
http://clinicaltrials.gov/ct2/show/NCT00944580

Batteries Recharged

Good morning! Wow, what a relaxing weekend. I can't always say that but, boy, this one sure was nice. It was good too. I needed a break. The other good news is that I did not even have to use my big mean daddy voice and the kiddos had a great time as well. And guess what, no chaos. They were much better the last few days of the week and spent the weekend in good spirits. Whether this is the calm before the storm is yet to be elucidated but we sure had a blast.

Friday night was busy. Graham had a birthday party where he was reunited with many of his old classmates. The party was held at one of those inflatable jumping wonderlands. He successfully jumped, hopped, ran and slid to his heart's content. By the end, he had been successfully drained of energy and that may, in fact, be the reasoning for such superb behavior that night.

Sydney spent Friday night at a sleepover with her best friend Jillian. Ainsley spent the early evening with mom at home. Eventually, we were reunited and had a nice dinner for four. Hmmm. Now I am starting to realize why this weekend was so easy. For half of it we only had four kiddos. I find it interesting that it is only now that I realized that. Wow, my old age is starting to show.

Saturday night we found the twerplets all back together. Lynley was feeling under the weather so I took the kiddos out to Mama's pizza with the Robertson's. The kiddos had fun playing the video games while the adults enjoyed some relaxing conversation. Sydney was sure to tell me on the way home that she stilled loved Truman. It was not in those exact words but, it was very clear that was her meaning. I knew I should have started her in Tae Kwon Do at an earlier age! I changed the subject as quickly as possible and made it home quickly to watch a movie and go to bed. Harry Potter was the movie of the night and I was hopeful it would successfully drain any romanticism that she was feeling.

Sunday was another relaxing day. We visited the duck pound, walked the dogs in the park and spent some time swimming. Later, Sydney would spend some time over at DeeDee's house. All in all, it was just a lackadaisical day at the Dungan's. I think we are ready to face another week.

Our purpose has been rejuvenated.

Does fun always have to end bad?

Well, well, well. With my trip out of town, I have been remiss in keeping everyone updated on the twerplets. You may recall that I last left them with the title of 'offspring.' It had not taken them very much time to revert to their old ways. For the most part, it was not that they were trying to be bad. In fact, often, it is just because they are having too much fun together and they just lose complete and utter control. They begin to make bad decisions. At the height of their chaos someone always seems to get hurt and then the screaming, yelling, and blaming begins. It is amazing how quickly this transpires. The fact remains: they are nuts. They push the envelope too far.

This eventually leads to several poor choices and bad behaviours.

Let me provide an example.

Graham is fundamentally a great little boy. Intensely great. He is kind, caring, and sweet. In the category of niceness I would put him up against any child and most religious leaders. He is just genuinely a great miniature human being.

Can you tell, I love my Dudely.

Anyway, even this miniature mountain of humble sweetness, is susceptible to the ways of kiddo crazy chaos. Furthermore, when this happens, there is little that can be done to turn the tide before it becomes unmanageable.

My hypothesis, at this point, is this: Children having too much fun make very poor decisions - even when they are great kiddos.

Journey with me.

Not to long ago, last week in fact, we were all at Tae Kwon Do. You may remember that one of the reasons that my kiddos are in Tae Kwon Do is because of the discipline. That still rings true. Their master, Master Adrian, is fierce. Not only is she an excellent instructor but she is also a very accomplished athlete. After all, she was a U.S. Open Gold Medalist. This is one tough teacher and not one that you would not want to face in a dark alley.

However, Master Adrian is great with the kids. She seems to know the balance of fun and discipline and can always wrangle the kiddos back into order when needed. Yet, she also has a playful side and can get them to giggle when they need it. During class she even sometimes spars with them. This is a good exercise for the kiddos as she knows exactly what moves to make to get them to learn how to apply the various punches and kicks to a combat situation. While she always lets them score, she also ultimately always wins. The winning point usually comes in dramatic fashion as she ends it with a combination that chases them back into their position in line at the end of the mat. Luckily, Graham is fast (he runs a bit like Forest Gump and has every bit of speed) and can usually make it off the mat before she scores her last point. He knows it is coming and he makes a run for it. Yes, Graham has prey instinct down. He is generally very proud of himself for outrunning the barage of kicks and spins and it always ends in giggles.

Well, last week, right after Master Adrian worked with him and chased him off the mat, Graham ended in his usual fit of giggles. He was having great fun. As Master Adrian turned away and headed back to the front of the class Graham thought it would be a great time to throw a roundhouse kick right into her back side.

Yes, my son (the yellow belt) decided to give his instructor (an accomplished national champion second degree blackbelt) a kick to the posterior.

I could not believe it. In fact, we could not believe it so much that we all busted out in laughter. We hid it from his eyes but I must admit it was likely the funniest thing I had ever seen. Even Master Adrian was having difficulty keeping a straight face as she towered over Graham's sweet little body. She grabbed him up in one fell swoop. She feigned pummeling him to the ground. He just continue to giggled uncontrollably.

Lynley and I, of course, told him never to do that again. Away from his prying eyes, we all had a good chuckle, Master Adrian included.

This, however, is an excellent, supportive example of the type of behavior that somehow is released from my kiddos brains. I swear they were not taught this way.

It is the fun. It is the laughter. It always ends in bad decisions.

I haven't figured out exactly what to do.

I wish I had a magic purpose wand.

The world's greatest science ever!

Okay, so I have received a ton of email asking about the research I discussed while in Washington, D.C. Unfortunately, I signed a mountain of confidentiality agreements stating that I would not discuss it. The bottom line is this. I saw some incredibly interesting research that could have significant impact. Unfortunately, I also say some incredibly idiotic research. Yes, I said idiotic. And, if you know anything about me at all, you should know that I had no problem expressing my opinion at all. It actually made for some of the lighter moments in our discussions.

There were several proposals that presented some really flashy ideas - lasers, liposomes, and antibodies where my favorite. Unfortunately, for many of those, I did not see any significant impact on our lives. They were flashy. They were snazzy. In fact, they were really, really cool. Unfortunately, when you got right down to it they were completely useless to a child with neuroblastoma.

I sound bitter, don't I? Well, I don't mean to but let me give you a hypothetical example so you can understand. There were several proposals that fell into this category - again this is a hypothetical example.

A non surgical approach to removing neuroblastoma tumors with a laser.

Doesn't that sound cool? A laser that can successfully cut out and and evaporate a neuroblastoma tumor. Price tag - $2 million. Cheap considering the fact that you could now have surgeries - without surgery. No incision. No blood. No recovery. Magic!

Of course, this is what they would like for you to believe in the funding abstract. However, upon delving further, you would realize that this laser could only penetrate the skin to a depth of 1 centimeter at its maximum. So, in this sense, it may be great for the mice that they were testing it on. All of which had small tumors on the surface of the skin. Unfortunately, for child with neuroblastoma, a typical tumor of Sydney's size 5cm x 9cm, and located in a typical place (like the center of the abdomen); it would be completely and utterly worthless for children with neuroblastoma.

Like I said, really incredibly cool idea. Lasers are awesome.

Completely useless to children with neuroblastoma.

Ideas like this were at first met with excitement by many of the scientists. After all it was innovative. However, that was the reason that the clinicians and advocates were there - to gauge the impact on patients. We would get our point across and eventually it would be discovered that it was presented by a physician who specialized in skin cancer (a disease that would likely benefit from such an incredible tool) who, unfortunately, was only interested in getting a hold of some of the funding that was potentially set aside for neuroblastoma. I was amazed at the number of proposals which clearly utilized search and replace to insert the word neuroblastoma in for another disease in order to qualify.

Wow, all of that sounds really depressing. So, let me say that there was also a large group of truly innovative and meaningful proposals as well. Once again, there were several impressive collaborations - some from institutions that many would believe were at complete odds with each other. I was also impressed with the number of proposals which were focused on ideas that could truly increase efficacy while also reducing toxicity. Medical technology has come a long way and I was truly impressed by some of the innovative ways researchers were utilizing liposomes and antibodies to target therapy. There were voluminous examples.

I came away with two significant realizations. First, the clinical and patient experience are critical to making good funding decisions. I was amazed by the number of proposals with great science but little, if any, impact. In this way, I was also surprised by the number of proposals from scientific experts in the field which totally misunderstood the treatment of neuroblastoma. Second, I was amazed by how many of the titles and abstracts completely misrepresented the material that was actually found in the proposals. In many abstracts that include claims that were flat out false. There really should be some regulatory body for that. It was ridiculous. DId you notice my title to this entry. How does that make you feel? Cheated?

Overall it was a fun exercise and I walked away feeling like we made some very good decisions. I also believe that if our guidance is followed some very important and meaningful research will be making its way into our lives and the clinic.

Let's hope the DOD has purpose too.

Home again.

Ah, home sweet home. Last night I arrived home to my family. I was back in the swing of things. It was pretty clear that the kiddos were pretty glad to see me. They have learned through much practice that when Daddy leaves on a trip he brings back presents. They also know that if they ask for the presents as soon as I get in the car or walk through the door, that the process will be delayed indefinately. It is a game of give and take and I would be lying if I did not tell you that I enjoyed playing the game. I love acting like I forgot to purchase them trinkets in the airport gift shop. I really drag it on. I tell them how much I missed them and how much I love them. You can literally feel the anticipation build. The extremely nice feature of dragging on the gift giving is that, for 10 minutes, I have the absolute sweetest, kindest, and best behaved kiddos in the entire world. It is beautiful.

This time, however, my kiddos outsmarted me. As soon as I stepped opened the door and sat in the car they had gifts waiting for me. Yes, they figured that if they gave me gifts I would be forced to give in return. Yes, brilliant, this would surely speed up the process. My kiddos are clever ones, they are. I received a crisp new one dollar bill from Sydney - no doubt acquired from my change drawer in the armoire next to my bed. From Graham I received a brand new miniature sized leather football. It was nice. I should know. I got it for him as a gift last football season. Ainsley was not to be out done, though. Her gift to me was a stuffed kitty that she slept with. This gift, however, was only mine for the moment. As one might expect, after this, they looked at me lovingly and waited with baited breath.

and waited...

and waited...

It was quite fun waiting. Unfortunately the temptation was just to much and it was not long before they all blurted out. "But, daddy, where are our presents."

Ah, home sweet home. This is what purpii are all about.

Dark Arts not so Dark

Good morning! Well, here I sit at my hotel desperately waiting for the breakfast area to open so I can get another shot of coffee before beginning another brisk day of peer review. Why hotel rooms only supply you with four packets of coffee is beyond me. Even at that, you can only only use the pre-made coffee packets twice. That is merely 8 cups off coffee. Who can live like that? Yesterday was a full 12 hours of work. I know that sounds awful but keep in mind we were given three 10 minute breaks and one 45 minute break for lunch. The rest of the time, however, the 20 some odd group of experts (and I) sat around and debated the various merits of a voluminous stack of research proposals. It has been fun but I must admit, tiring. Maintaining concentration and focus has, fortunately, not been particularly hard as much of the research is very interesting.

The difficulty, from my standpoint, is weeding out fact from fiction. Due to the availability of this research funding many researchers have crossed disease boundaries in an effort to grab a hold of some of the neuroblastoma dollars. I have never seen so many proposals on the subject of neuroblastoma coming from other cancer and disease specialists. This is good, in that it brings new ideas and perspectives to the neuroblastoma portfolio. It is frustrating because so many of them clearly lack basic understanding of the disease. In many cases these researchers have partnered with neuroblastoma experts but I would be lying if I said all. If I see another paper addressing how another interesting piece of research is going to save the lives of these "brain" cancer patients I am going to puke. So many miss the boat. However, many also bring new thoughts and directions. The group of neuroblastoma experts that are a part of this review are as about as tolerant as I and I can say we have honestly entered ever discussion with an open mind. There is significant talent in our room. These guys are smart and it is ,once again, assurance that our researchers are among the cream of the crop.

Today will be another excessively full day of debate. However, late this evening, I will be boarding a plane and heading home to a family that I miss very much. I can't wait to see them.

Trips like this are incredibly important but I must admit that I feel my purpose is split.

Defense against the dark arts

Good Morning! And this time I mean it. I am happy to say that I made it through all of my research proposals and I have written all of my reviews. Now I can take a deep breath and relax. This is, of course, until I have to stand in front of a group of oncologists that specialize in neuroblastoma and defend my point of view this weekend. It ought to be fun. To my pleasant surprise most of my reviews were very much in line with others opinions. However, there were two that there was some pretty significant differences with one of the expert reviewers. We will see how that goes but I am thinking that just may be his style. Regardless, I am looking forward to my trip.

With all of this neuroblastoma stuff I have neglected to update you on my offspring. Yes, you heard it. They have been demoted to 'offspring' again. The infighting amongst the 3 of them is ridiculous. The good news is that Lynley and I are having nothing to do with it. Punishment has been swift and severe. I am hoping a few days of this will show them that it is not worth it. At some point they will realize that it is easier to be nice to their siblings than it is to be mean to them.

I just hope it comes sooner than later.

For their sake, I also wish that this was not coming at such a busy time. With me out of town and Lynley in her busiest week of the year we can't spend as much time working on this with them as we would like. The good news is that tonight is family Tae Kwon Do. Perhaps, they can all beat it out of each other.

It is also time for my rematch with the 8 year old black belts. Don't laugh they will be tougher to defend against than my research opinions.

It is a purpii day of reckoning.

Research Rolls On

Good morning! Hold on, that seems too cheery for the way I feel this morning.

Morning.

There, that is more like it. I have a little too much neuroblastoma research on the brain. I think that next time I am going to have to break up my research researching a little more. I only made it through about half of the proposals yesterday and my reviews are all due today. Thankfully I have read them all and taken notes and now I am simply left with writing my reviews. Regardless, I am still knee deep in a race to get through the rest.

The good news is that, as I have dug through the research, I have actually found some pretty interesting and promising ideas. My stress about trying to identify the cream of the crop has been a bit easier than I was experiencing yesterday. However, I am still thoroughly annoyed that I have to accept some of the science as being true. I am happy to say that there are several interesting ideas that include oral drugs, with low toxicity, significant activity, and drug availability. For me that is the holy grail of neuroblastoma goodness - the quadrangle of success. Furthermore, there are even a few ideas that mention the word "cure" and "complete obliteration of neuroblastoma." While I am extremely skeptical of these ideas it is still great to see them in print and at this level of research. Many of the approaches I am seeing are truly innovative. They are new ideas that we have never seen or heard before. That, I like to see.

Unfortunately, I can't be more specific than that. I had to sign a mountain of non disclosure agreements when I agreed to sit on the review committee. None the less, I think it is important that, even though I am complaining incessantly about all of the reviewing, there is some very promising research on the horizon.

I am looking forward to my trip to Washington this weekend to discuss it.

Purpose abounds.

Neuroblastoma Research Conundrum

Good morning! This diary comes as a much needed break for me this morning. My eyes have begun to cross after reading mountains of research proposals. Don't get me wrong. I love reading neuroblastoma research. The problem is that I don't like reading all neuroblastoma research. Like any normal person I enjoy reading material that is interesting to me. Unfortunately, all neuroblastoma is not necessarily interesting.

My other issue is that with everything I read I am always reading it from a scientific perspective. Is it realistic, is it relevant, is it good science. I am great at punching holes in theory and assessing translational impact. However, with this group of scientific proposals, I am having to interpret it from the perspective as a patient advocate. I have to assume that the science is good and factual - frankly, I know in several cases it is not which is thoroughly irritating. Furthermore, in the scope of this review, it does not matter what I think. The perspective that I need to use is from the population of all patients and caregivers. What would they think? That is not easy for me. I am much better at what I think. Regardless, the point is that, I am having difficulty interpreting it from that perspective. I am not having nearly as much fun as I would ripping the research apart.

I know, sadistic, but true.

That is how I do it. I find promising research that I believe is meaningful to children with neuroblastoma and then rip it apart. I identify important questions and then evaluate the proposals ability to answer the question clearly. So, at the end of all of this, we actually have a meaningful answer. To me, that is good science. I then also assess the impact of potential new therapies on patient populations. I answer questions like. If this works, how meaningful would it be? Can it actually get into patients? How quickly? What is the cost (toxicity, etc.)? Will the drug be available? Would it be a good use of resources or would those dollars (and patients sadly) be better spent elsewhere?

As srtraight forward as that two step process seems to be it is more complicated. The answers aren't as clear as they seem. How do you factor in priority?

Ultimately, is the most important question: what has the most promise to make the most difference the most quickly? Or is it, what has the most potential to make the most difference in the long term?

There are drugs out there that could have an impact in the clinic right now. Potentially, they could save lives. However, they aren't the cure for neuroblastoma. They are just another tool in the tool belt. Do we prioritize those? Are those more meaningful? Or, do we prioritize research that does not have applicability in the clinic right now but holds significant promise in making a substantial difference in survival down the road?

It isn't an easy question. I know from personal experience that parents of children with relapsed neuroblastoma want treatments now - almost at any cost. Unfortunately, that does come at a cost. By pursuing that idea we are potentially losing out on another long term success.

Is it more important to find the genesis of neuroblastoma so we can learn how to stop it from the very beginning? Do we learn more about the stem cells and how to kill them? Or do we just focus on what we can kill right now?

I know what I think. The difficulty is in understanding what others would think?

Since I don't know the answer to that question it leaves me in the position of identifying something with a little of both - something that could have substantial impact and has a clear path to our children?

Seems simple, but you have no idea of how tall an order that is. Frankly, I don't know that I see that in this particular mountain of proposals.

Back to purpose.

Thoughts on Neuroblastoma Survival Curves

Fair warning, if you are a parent and you don't want to know about survival statistics this is probably not the diary entry for you. While I remember knowing the statistics relatively early on in Sydney's diagnosis, I remember it being quite a while before I admitted it to myself openly. If I remember correctly, it was even longer before Lynley and I discussed the real numbers. Early on, they were facts I knew but not ones that I wanted to share. Regardless, I am still pretty sensitive to that and it is for that reason that I felt I should devote an entire paragraph to warning you. Enter at your own risk. The good news is that I will be reviewing some of the shorter term statistics which are a bit higher.

I always try to be fair when debating different perspectives on neuroblastoma treatment. In fact, I feel very comfortable arguing either side of just about any issue. Generally, I always choose to argue the side that I feel is being misrepresented. Regardless, the problem always seems to arise that you make someone mad on the other side of the argument. I mention this because I am guessing that this will be a very sensitive subject and one that will draw fire.

After all of my discussions on the Sloan vs. COG or 'no transplant' vs. 'transplant' discussion, I received a significant amount of email. That was not surprising really. I actually expected more. As a result of that discussion though, it apparently got some people thinking, as I received support for an argument that I had not seen before in print. In fact, I had never even heard it discussed outside of a small group of people. Regardless, since I gave this person ample opportunity to post the information and they have not (Yes, I am calling this very intelligent person a chicken.), I will post it here.

For years, there have been many arguments that Sloan had higher survival rates than the rest of the COG. I think this argument came from some survival curves that were published on Sloan's website about 5 years ago which appeared to show an increase in survival of almost 15% for patients at Sloan Kettering. The problem with these statistics was that they fell victim to the same problems that I have been talking about for years. The statistics were not comparable. The survival statistics were over different time periods, included different patients, and fell victim to the differences between Event Free Survival and Progression Free Survival. None the less, many did not understand these differences and took them at face value. It became a mantra for many.

Today, there are finally some comparable survival curves and, oddly enough, they show the complete opposite of what was believed by many.

Until recently, the PFS survival curves from Sloan Kettering were always higher than the published EFS curves from the COG. It was still difficult to sort out the true differences though because of the differences in the types of curves that each used. Sloan uses progression free survival (PFS) which only shows the patients that did not progress with disease. The curve still includes all of the patients that had a secondary cancer or some other event - such as significant toxicities. The COG uses event free survival (EFS) curves which show survival after secondary cancers and other events. For this reason, even with the same exact group of patients, in the case of high risk neuroblastoma, an EFS curve would most likely be substantially lower than a PFS. How much is the question? After all, at one point, Sloan had a secondary cancer rate of roughly 8% (as compared to the COG's of less than 1%), Unfortunately, even today, we really do not know how many patients in Sloan's PFS curve have secondary cancers or other events. In this way, it continues to be difficult to compare.

The issue that we have before us today is that the 2 year EFS curve (2 years from randomization) from the COG as reported at ASCO this year in Dr. Yu's presentation is 66%. If you go back to the 2007 ASCO annual meeting in Dr. Cheung's presentation of "Reducing therapy for low-risk and advancing immunotherapy for high-risk neuroblastoma" you will see that Sloan published a curve which showed that their 2 year PFS curve was only about 60%.
This would seem to indicate that the COG survival curve is significantly higher than the Sloan survival curve. According to this data, following the COG standard of care would increase your odds of survival by at least 6%. I say 'at least' because we still do not know how many events and secondary cancers are included in the Sloan PFS curve. Sloan's comparable EFS could be significantly lower. I do know that recently they have reported that they have greatly reduced their secondary leukemia rate which would keep the curves closer together but, still, certainly no less than 6%. Additionally, Sloan's curve does not show patients in partial response. The COG's curves do. One would assume that this would also lower your survival curve and we do not know what impact this would have or how far it would reduce Sloan's survival curve.

Now, is this definitive? Well, at 2 years it is pretty clear. However, what we don't know is what will happen to these curves in another year or two. Additionally, we don't know how how much power the Sloan curve has. They make no mention of patient numbers. Finally, these curves are only talking about patients that had a CR, VGPR, or PR to induction. It does not discuss those patients with refractory or progressive disease. That could be a different story. Will the superior survival associated with the COG curve continue to hold?

Time will tell.

None the less, this is a very interesting perspective that I have not seen published anywhere. I think it is worth discussion.

That is what purpose is all about.

The Dungan Five Reunited

On Friday, Sydney made it home from a week at camp. When she arrived off of the bus she was dog tired. Still, there were hugs and kisses to go around. She was relatively quiet on the way home, though. Truth be told, I was a little disappointed. I wanted dirt. I wanted to hear all of the stories. There really weren't any on the way home and most of our questions were followed by short answers.

"So, Sydney, tell us about your favorite activity at camp."

"Zip Line."

See what I mean, totally underwhelming. When we got home we had a family lunch. She didn't liven up much. After lunch we escorted Tweedle Dee and Tweedle Dum upstairs for their naps. By the time I made it back downstairs Sydney had already fallen asleep on the couch. If that was not a sign of how completely worn out she was, I don't know what was. She slept the longest of the Dungan clan.

When she woke up late Friday afternoon, my Sydney was back. She was full of snuggles and cuddles and her eyes lit up whenever she began talking about her trip. She had an absolute blast telling us about all of her favorite things and how she spent her days. It turns out that this was the trip of pottery. Apparently she only elected to do the pottery classes as she came home with some 20 (literally) hand made artifacts. She made bowls, cups, letters, starfish, and you name it. She absolutely delighted in telling us about each one and gave everyone at least two of her precious works of art for there very own.

The evening was very different from what she was like when we picked her up. She talked nonstop about all of her adventures.

It was great to have our Sydney back.

The weekend was relatively uneventful. We spent the majority of our time at the house together. In fact, I don't even recall leaving. We swam, chored, played on the Wii and even got in a few movies. It was perfectly relaxing. It was wonderful to have the Dungan five back together.

You may be wondering about the whole behavioral thing. Well, it is too early to tell. Ironically Graham and Ainsley were the culprits whenever an issue arose this weekend. I am happy to say that, when needed, our actions have been swift and we have yet to see any of the psychosis that proceeded the separation brought on by camp. Only time will tell, but we have been happy with the continued improvement.

For me, this week will be extremely busy as I review neuroblastoma research proposals for my upcoming trip to Washington D.C. this weekend.

Purpose overfloweth.

G and As First Trip to Camp Sanguinity

Good morning! I apologize for not writing yesterday morning but there was already enough chaos with trying to get the rugratigans out the door and on their way to Camp Sanguinity. It is funny how we have grown throughout this process of parenting. I vividly remember the first day that we sent Sydney off for a day at Camp Sanguinity. It was so surreal. I remember sitting at my office all day wondering and worrying about her. Would she be okay with out us? I was completely worthless the entire day. I could think of nothing else and Lynley and I spent the better part of the day chatting back and forth over our instant messengers. We were giant puddles of panic and worry.

I tell you that because on Graham and Ainsley's first trip to camp it was the complete opposite. No, it is not that we love them any less. First off, they made it easier. They were so incredibly excited to go to camp that they forgot to even give us hugs or kisses goodbye. We rectified that situation but, it was certainly not due to their need for parental comfort. They were ready to go. Second, we, too, have been hardened by years of parenting. We knew they would be just fine. They had each other and we knew they had Sydney once they got there. On top of all of this we also knew they had all of the Cook Children's nurses, physicians, and child life specialists to keep them happy and safe. If I am being completely honest, I never even had a second thought about it. I was utterly confident that they would have a great time.

They made it back at about 5:15 PM last night. They were worn out but happy to be home. Lynley used her new phone to interview them. Here you go, straight from the twerps themselves.

All in all, I consider this a great success. Today we should hear the rest of the story as Sydney returns from her week long adventure at about 11:00 AM. We can't wait to see her. The big question will still remain though. Can we make it through the weekend without them turning back into 'offspring.'

Not to worry, I have been rejuvenated. I overfloweth with twerp purpose.

I wish I could blame myself

Good morning! Twerp reconditioning day 3 has begun. I would like to tell you that we have taken some magnanimous steps to assert our control. I would love to brag about my superior parenting skills. I would be ecstatic to share with you my stories of twerpdom triumph. But, alas, I really have not done a single thing. It seems the disruption of the twerp nation has been all that was needed to jolt them back to reality. Outside of some typical 4 and 5 year old hyperactive craziness I could not describe my children as anything less than superbly angelic. In fact, I have been so impressed by their behavior that I have stopped referring to them as merely my 'offspring.' There is a spring in my step. It must be Daddy pride.

I do have two conundrums, however. I miss my Sydney. While I am sure she is having a tremendously good time at camp I miss her. I miss seeing her in the mornings and getting that first snuggle. I miss swimming in the pool with her and doing laps with her on my back. I miss my little compadre. On the other hand, I clearly don't miss the devilish 3 and I know that upon her return the gaggle will quickly regain its power and I fear falling back into the same behavioral rut. I have to find away to keep things shook up. I just haven't figured out what that is.

Yesterday, we received a bit of a surprise. Both Graham and Ainsley had been wait-listed by the camp that Sydney is attending. You may recall that I stated that they were booked full. Well, as it turns out, 2 spots opened up yesterday afternoon and it looks like they will get to go after all. Early tomorrow morning we will load them up on the bus to spend the day at Camp Sanguinity. Sydney will be completely and utterly excited to see them and I know they can't wait to see her as well. It will be an excellent reunion for them.

As for me, well, I really don't know what I will do with myself. Me, without rugrats? I don't even know what to think. I guess I will just bask in the glow of a little freedom. I know they will have a great time. I know they will be in good hands.

No worries.

I might just decide to spend the typing away on my computer in my jammies and flip flops.

Well, I had best be off. I have a few meetings today and a mountain of neuroblastoma research proposals to review. In fact, I have almost 30. That is approximately 3000 pages of medical jargon and I only have about a week to get all of my reviews in.

I am not going to be very exciting over the next few days. In fact, I may just be the most boring person on the planet.

But, I will have significant purpose.

Twerp Reconditioning

Good morning! Wow, I always forget how much easier it is taking care of two kids instead of three. Consider that, and the fact that their leader is the one that is away and all of a sudden they are like fish out of water. Seriously, it comes down to the simplest things. We have completely disrupted their systems of parental abuse. They are like putty in our hands.

You may think that I am overstating the impact for dramatic effect but I assure you no such motive exists. It is truly the dawn of a new day.

It comes down to the smallest of things. Take getting dressed in the morning for example. On a typical morning, as soon as I get out of the shower, the command comes down from high authority (me) "It is time to get dressed." On a normal day, they just sit there. You see, they are waiting for their leader to move. Until Sydney does something, nothing can be expected of them. This is not because Sydney is being difficult. Rather it is just because she is usually the last awake and the most tired. It takes some time to get her engine started and for her to become aware of surroundings. I get that. In fact, I ask twice before I turn on mean Daddy voice. After a delay, she is finally doing as I asked. Reality sets in. Sydney gets up and starts getting dressed. Like zombies, Tweedle Dee and Tweedle Dum follow her. It is annoying. It is as if they need Sydney's blessing before they do anything we ask.

So what changed in one simple day?

Well, yesterday morning began as usual. Sure enough, as I stepped out of the shower I made the announcement. I kid you not, they looked straight at each other as though completely baffled. They had no clue what to do. It was as if I asked them to solve a calculus problem. They clearly had no idea what to do. All of a sudden, with looks of shock and a complete lack of understanding they got up and began to put on their clothes. They kept looking at each other as if searching for answers.

I turned around and went back into the bathroom where I don't think I could have laughed harder. Throughout the day, this episode was replayed on several occasions. It seemed as though every time I asked them to start doing something they actually did it. The funny thing was that they looked as though they were being controlled by remote control. They had no idea what they were doing or why they were doing it.

The transformation is happening! (Evil Laugh)

Purpose is suddenly flowing through their veins they just don't know what it is.

The Birthday Girl

Well, today, marks another milestone in our lives. Lynley is one year older today. While from all outward appearances she seems to be handling another year fairly well I can tell that it is clearly not to her liking. She keeps referring to her self as old. As in, us "old" folks or my "old" body. It clearly isn't going as well as one might get the impression. I told her she was like fine wine only getting better with age. However, she just assumed that I though she was getting more vinegary. In all honesty, I think she is more like my grill outside. The longer she is on the hotter she gets. Of course, that just makes her think of me as a dirty old man and then that starts a whole other thing about how she is so old that her husband is a dirty old man. All I can say is that as long as I am married to her I will continue to be a dirty old man. She is hot in my book.

Okay, okay, enough about the old people. What is going on around the Dungan household? Well, we are down to 2 "offspring." Yesterday afternoon we delivered Sydney to Cooks and sent her off for a week of camp. She was ecstatic to go and it was not long before she had reconnected with many of her friends. She spent much of her time with Alaina, another neuroblastoma patient and one of their other friends. I was amazed by the size of the group that was heading out to camp. It was three bus loads. In fact,this year there was a waiting list for the camp. They did not have enough space for many, if not most, of the siblings this year. There are apparently too many survivors of cancer and now the space is limited to patients only.

That is pretty awesome if you ask me. We finally reached a point where that has become a problem. Of course, it also make me remember all of those that we have lost who were not able to be there. I also had the realization that more of her friends were gone than were there.

It was bitter sweet.

In the end, Sydney went off without a hitch. She was ready to go. I was a little saddened by all of this independence. Although it is good for her, I just don't know that I am ready for it. In the end though, she went running to the end of the bus to wave goodbye to us one more time. That's my girl. She will be back on Friday and, of course, we all ready miss her.

However, we won't be able to miss her for long. We are going to be busy with a little boot camp of our own. Now that their numbers have temporarily thinned it is time for aggressive man to man and woman to woman training. It is time for the parents to reassert their control and turn these offspring back into the wonderfully awesome little twerps that we know them to be.

Welcome to home twerp camp 2009! (evil laugh)

There will be plenty of purpose this week.

I dub thee offspring

Good morning! Well, here we are, heading into a holiday weekend. Once again, Lynley has usurped this holiday for her own benefit. Yes, she is claiming this as her own birthday. Why she would want to do this when it makes her a year older 2 days earlier is beyond me. However, I also know better than to argue with my blushing bride's logic, so I will let this one slip by. Therefore, tomorrow we will be celebrating Independence Day in concert with Lynley's XXth birthday.

Last night was a fairly late one for the kiddos. Unkie Jay had a 3 hour layover at DFW airport so we ran over there to take him out to dinner. The rugrats were incredibly happy to see him. Unfortunately, we did not get home until about 10:00PM so, even though we will let them sleep in, I am guessing that Claudia may have her hands full today.

This, unfortunately, would not be much different than she has experienced much of the week. My kiddos behavior has been out of control. I don't know whether it is the summer heat, the fact that there have spent 3 weeks together, or what the issue is but, my kids have gone from good to bad in a very short period of time. Lately I have written off Ainsley's behavior as being age related. (I guess I should have said hoped.) I still do not know that it is not the case, but it certainly has not improved. Worse yet, during this same period, both Graham and Sydney's behavior has begun to take a slide.

The are spoiled brats with bad attitudes.

There I said it and I said it about my own offspring. In fact, during this time of reconditioning, I think that is a good name for them. Right now the aren't cute enough to be twerps. Until I see a vast improvement in their behaviour they will no longer be known as the twerps. From here forth the shall be dubbed 'offspring'.

There, that makes me feel much better.

It is true they are grubby, little, misbehaving miscreants and neither Lynley nor I have figured out what to do about it. It isn't as though they have not met with resistance. Neither Lynley nor I have been tolerant of this behavior. I don't know what it is. I don't know whether we are not being consistent enough or whether this is just a tide that has flowed in due to the fact that it is summer and they are all back together. Regardless, I don't like it.

Not one little bit.

The good news is that next week things will be shook up a bit. Sydney is going to camp. This will be great for her and she is really looking forward to it. For the rest of the 'offspring' it is a good idea as well. Without their normal ring leader to listen to we will have a better opportunity to break through the veil of bad behavior. Additionally, for this week, we will not be outnumbered. We have a legitimate chance to regroup and retrain. We will no longer be playing zone. It is one on one baby. Twerp Hell Week - here we come.

Purpose is fun but always a challenge.

A delay in posting

Good morning! Well, for some reason, I was not able to reach my blog until late this morning so I did not get a chance to write. The good news is that the whole family is doing superbly. The twerps are a little questionable but other than that everything seems to be going just fine. Oh, and it isn't their health. It is their mental state.

More on that on the days to come.

In the meantime, I am off to purposefulness.

Another Perspective on the Induction Decision

As parents of children with neuroblastoma, we often make treatment decisions based primarily to two factors. The first is based on response. What treatment has the highest response rate? What treatment is going to create the biggest change? The second thing we consider is toxicity. What side effects come with this treatment? What is the impact on quality of life? Will something bad happen? We then take these two factors, mush them up in our brains, and spit out the answer for what treatment plan we follow.

Done. Easy answer.

Hold on. Unfortunately, this formula misses some very important considerations and often can lead you astray. The fact is that we don't live in a world which only has two factors - response and toxicity. Every decision we make has implications which will impact future decisions. In this way each decision also caries a significant risk factor. There is risk that a particular choice will make you ineligible for something later on down the road. There is risk that your child may not respond or the risk that something will happen that will preclude you from getting treatment. As I will try to demonstrate today, these are all extremely important factors that should weigh heavily on any decision. In today's high risk neuroblastoma treatment reality these may even be the most important factors to consider.

This is where my difference of opinion lies.

One of the appealing aspects of treatment at Sloan Kettering is the promise of no transplant. According to them, in their experience, they do not believe a transplant is necessary when antibodies (3F8) are used for consolidation of minimal residual disease. I should point out that this is in direct contradiction to three large randomized phase 3 trials which showed that transplant increased event free survival by 11% or more (these trials did not include the use of antibody, however.) Regardless, when analyzing the toxicities of transplant it is easy to be swayed by the allure of not having to have a transplant and the hope of achieving the same desired result. It is very appealing. People evaluate the response - children appear to achieve remission in similar numbers - and then they evaluate the toxicity - it isn't a transplant. The problem with this type of thinking is that it misses some extremely important factors. First and foremost, it misses the point that you are giving up on the proven standard. This is not additive treatment, this is "instead of" treatment. By not transplanting, you are risking the loss of an increase in survival of over 10%. It may very well turn out that the doctors at Sloan may be right. Someday, it may be proven that a transplant is not necessary given the medical technology at that time. But, in the meantime, you are very definitely adding more risk to your child's chance of success by not transplanting. You are gambling a 10 to 15 percent increase in survival in the hope that this other treatment (antibodies) will do the same job - a job that they are yet to be proven to accomplish. I think every one would agree that, in this case, if you looked at it from the perspective of this type of risk (the risk of decreasing survival), the best option would be to do both.

Another risk that many people do not think to consider is the risk of not being able to receive the treatment. This is one of the saddest realities of all. What if you decided to go to Sloan Kettering? What if you decide to reduce your risk of toxicity from transplant and forgo it? What if you decide to use 3F8 for consolidation instead?

What if you HAMA'd in the first or second round precluding further treatment?

This risk is significant. It happens. There are kids sitting in this scenario at this very moment - kids that could have been transplanted and received antibody. But, the question remains. You gave up transplant in the hopes of reducing toxicity in favor of a relatively unproven treatment (for this purpose) and now, because of a fluke, because of an immune reaction, you are no longer eligible to receive that treatment either. Or, you are no longer able to receive that treatment again with out some significantly high doses of chemotherapy - high doses of chemotherapy which offer significant toxicity but still do not provide you the benefit of a transplant or any guarantee that you will be able to get enough antibody to get the job done. In this scenario, the nightmare, you have actually increased your risk on at least two fronts. Your decision cost you the benefit of a transplant (11%+) and the benefit of antibody (20%). By choosing this route you have effectively reduced your chances of survival by over 30%. Could you go back and do a transplant? Probably. But, would you become eligible for the ch14.18 antibody? Not today.

That is a big gamble - an especially big gamble for something that is yet to be proven.

The third risk is the risk of treatment failure. I know this is something that no one wants to consider but, it too does happen. In fact, I have seen some articles quote numbers as high as 20% (or higher) of patients fall into this category. In this scenario, the standard therapy has failed in induction. You have done your due diligence yet, even given the best medical knowledge we have, your child has failed induction. What are the risks here? What impact did your decision of which path to take have in this scenario? I think the risk here is in eligibility. You see, if you fall into this category of patients the most important thing you can have is options. By participating in a standard induction you are naturally eligible for several options that you might not be otherwise. An example of this would be an MIBG/transplant regimen. This type of transplant has been extremely effective for a subset of these individuals. In fact, for some, this was the ticket that got them back onto the road to survival. I am not advertising this trial but simply pointing out that this is a treatment that is available and effective for a certain subset of the non responding population that may not be available to them if you decided on a different path from the beginning. It is just one example of risk in this group of patients.

Finally, before I run out of internet, I would be remiss if I did not address the most obvious but less publicized risk. By choosing not to participate in a COG trial, at this point in time, you run the risk of not being able to receive the ch14.18 antibody. This is the one antibody that has been proven in a randomized phase 3 trial to increase survival by an additional 20%. One could easily argue that choosing not to utilize ch14.18 carries inherent risk.

Now, please, don't send me email telling me that 3F8 can do everything that ch14.18 can do. Trust me, I know what it can do. The point is that by choosing 3F8 over ch14.18 you are taking on more risk. At this point in time ch14.18 is a proven commodity. We don't know whether 3F8 works better, the same, or worse. Furthermore, with 3F8, we also have the additive risk of an early HAMA - a risk that is greatly minimized by the ch14.18 antibody.

You see, today is not about response or toxicity. My arguments have absolutely nothing to do with which treatment is better. That is another discussion entirely. This entry is about reducing risk and increasing options.

Risk is the third ingredient of the treatment decision that we often forget to consider fully. This is unfortunate when, as I have demonstrated today, it just might be the most important component.

Let the email fly!

It is all part of the purpose equation.