... that yesterday's update was somewhat incomplete. Not where the facts about Adam are concerned, but in a more general sense regarding where things are at now, and where we might be heading in the future.
That neuroblastoma is deadly is without question, but it also has a certain strangeness. It is one name but many diseases. It's not very well understood, and despite all the advances in medicine over the last couple of decades there remain lots of unknowns. It has an almost entirely benign form, and an ultra-aggressive form at the same time. The spectrum in between is vast, and there are very few absolutes. I find it incredibly difficult trying to understand enough to believe we are making intelligent and informed decisions for Adam, whilst at the same time accepting that I probably know next to nothing.
Here is some basic information to begin with; neuroblastomas are highly malignant tumours that originate from tissue that form the sympathetic nervous system. Ganglioneuromas are benign tumours that originate from the same. One is a mature form of the other i.e. neuroblastoma cells can mature into ganglioneuroma cells. Ganglioneuroma cells can dedifferentiate to become cancerous. Tumours can be formed by a combination of the two types of cells - this is referred to as ganglioneuroblastoma, where immature neuroblastoma cells are either mixed in with, or form clumps amongst, ganglioneuroma cells. It's already a minefield, and we've barely gotten started.
For many many years all children, including newborns and those very young, were treated the same. As though all neuroblastomas were the same, distinguished only by a few established markers such at N-MYC amplification, and by whether the disease was confined to a localized tumour or had metastasized to distant sites. All children were given intensive treatment, and some undoubtedly died as a result of these medical interventions rather than neuroblastoma itself. Subsequently it was discovered that in a number of very young children (usually < 12 months old) the most appropriate course of action was to do nothing, to adopt a watch-and-see approach. For in many cases amongst this particular group neuroblastoma spontaneously regresses and disappears without any treatment at all. As far as I understand it the why and how of this spontaneous regression remains unknown, but is assumed to be related to their early developmental stage. Of course there are now children for whom a wait-and-see approach is taken whose neuroblastoma does go on to become progressive. For them early intervention or tumour resection would, with the benefit of hindsight, have been the best course of action. This world is not, and never will be, perfect.
There is also another group of neuroblastoma patients; children for whom intensive and continued treatment does nothing to reduce their observable disease load. These children are collectively referred to as refractory. More and more clinical trials in the United States are being opened specifically to target refractory and recurrent/relapsed neuroblastoma. They are hard to treat successfully and the prognosis is generally very poor indeed. Treatment after frontline therapy has failed is an area where our NHS is way behind medical institutions across the Atlantic. Adam is in this refractory group.
It would seem natural and obvious that being in the refractory group is a universally bad thing, but it's not necessarily always the case. Within this group there is another smaller subset of children, albeit the exception rather than the norm, who become long-term survivors despite never ever reaching the panacea of NED (No Evidence of Disease). There are some of these children in the UK, there are plenty more in America. In general they are (re-)diagnosed with chronic neuroblastoma. It is assumed that their 'disease' has either undergone maturation or otherwise taken on a more indolent form. In this state, whilst it will still light up on MIBG scans, it is completely impervious to chemotherapy, radiation, and whatever else may be administered to try and combat it. The one thing these children do have in common with the 'wait-and-see' group is that their lives can be destroyed by endless rounds of unnecessary treatment.
So you can now really begin to see how difficult this really all is. To the point of being practically unfathomable. There are children who have a remarkable response to induction therapy - 80 days of on/off chemotherapy and all their disease completely disappears. And then back it comes, twice as fast, twice as aggressive, and there is nothing that can be done. There are children who respond to frontline therapy, go through high-dose, radiotherapy, immunotherapy having no evidence of disease and yet relapse days, weeks, months or years after. Most relapse within two years, but within five years is not uncommon and even beyond that remains a definite possibility. There are, of course, those who respond to frontline therapy and go on to become long-term survivors. Then there are those who have refractory disease, who remain stable for an extended period of time before eventually succumbing to progressive disease. And then there are long term survivors who move from childhood to adulthood with the same level of 'disease' that they had when they stopped treatment. Who, if they were scanned today would still look identical to a stage 4 neuroblastoma diagnosis.
As time has gone by I've got to wondering how long Adam had been living with neuroblastoma before he was diagnosed. Had it been with him all his life? Are we at this juncture because Adam has had slow growing disease for many years? He's never had a dramatic response to anything that's been pumped into him, and generally speaking cytotoxic agents used in the treatment of cancer tend to work on faster growing immature cells that are rapidly dividing. That's why they cause hair loss and bone marrow suppression because of their indiscriminate nature. Set against that his presentation on diagnosis with extensive bone marrow, lymph node and skeletal disease, coupled with his N-MYC amplification and the fact that his primary tumour wasn't ganglioneuroblastoma, is suggestive of something altogether different. Did he have a slow growing form of neuroblastoma that mutated into an a more aggressive strain? Are we treating the latter so that we remain with just the former? Is it even possible? So many questions, but the only truth is that whatever answers we come up with they are mere supposition, and we'll never ever know the true story.
So where does this leave Adam, and the prognosis for his future? We have to believe he is in that small subset of children who will go on to long-term wellness despite what shows up on his MIBG scan. I think we've come to a point where we can no longer harbour false hope that Adam will ever be clear in the conventional sense. We haven't reached a point where we have no hope, but rather we now have a different hope. Our baseline has moved from being no disease to being no more disease. It doesn't seem such a monumental change when thought about in those terms, does it? Whilst there is no progression, and no new disease in other areas, we can still have hope, we can still believe. It may not be the most probable scenario there is for Adam's future, but it's not one that is entirely beyond the realms of possibility. As one of the nurses at the Marsden said to us when we first started out on this journey and began to learn some of the awful truths about neuroblastoma - "Even if statistically the chance of long-term survivorship was only 1% you have got to believe that Adam will be in that 1%." And she was right. Hope that is not false hope, however small, is a very precious thing indeed.