Surprise surprise ...

Surprise surprise. Nobody was willing to swap their own appointment for a noon slot, so we've ended up being stuck with it. The FDG PET scan is at noon on Monday; the Octreotide scan is on Wednesday and Thursday. I spoke with Professor Pearson the head of the children's unit today, who has effectively been consulting on Adam since we reached the end of the road in terms of UK treatment. He was both apologetic and annoyed that these scans have taken so long, but we are where we are and there's nothing to be gained now by me making any more of a fuss about it. I'll just keep this episode tucked away in my back pocket in case it can buy me some goodwill in the future. The Nuclear Medicine team have told us that the fasting period need only be 4 hours instead of 6. So at least we can attempt to wake Adam up early and force feed him his breakfast.

I'm almost certain now that we will also go ahead with the bone biopsy; the only question is whether or not any results obtained by the Royal Marsden would be acceptable as far as the U.S. trial is concerned. It may seem like a no-brainer, I mean it's not as though the Royal Marsden don't know what they're doing, but stranger things have happened. Rules are rules, and it's generally advisable to find out what those rules are upfront rather than have to go through something like this twice because of bureaucratic red-tape. Most likely it will be fine, but best to double-check.

Most other things with Adam remain as they were. No real changes in terms of his general wellness; his bloods are much the same, he's eating, drinking, sleeping, and playing. For the past two Tuesdays Adam's had a friend from school come round to play. This was Adam's best friend during his reception year. The two of them were practically inseparable in the playground during break-times; but Adam hasn't been to school, other than for the odd hour here and there, since July 2009. And yet they played like it was a matter of weeks since they'd been regular pals, not the best part of two years. Yu-Gi-Oh!, beyblades, playstation, football. At bedtime I told Adam it was too late to watch anything on television before he had to go to sleep. Whereas he would normally offer some protest - "I am!" or "Just something short, Dad?" this time he simply looked up at me and said softly "It's ok Dad, you can decide. I had such a hugely enjoyable time today with Georgio." And yes, those really were his words. Spending most of his time in the company of adults has had a profound affect on Adam's vocabulary; some of the phrases he uses are both funny and at the same ever so slightly sad too. But whilst it upsets us that so much of Adam's childhood is being taken from him, for the most part he just gets on with whatever there is for him to get on with.

Grrr ...

There are some things that you have to wonder about. Just received the date for Adam's PET scan. Monday 16th May at midday. Read through the notes ... procedure will take between 2 and 4 hours ... nothing to be eaten for 6 hours beforehand. Could there be a worse time? Instead of eating bananas and nuts on that Monday morning, Adam will be going bananas and nuts. Earlier in the morning and we might have some chance of managing the situation. Later in the afternoon and we might have some chance of getting his breakfast done with the required 6 hours to spare. But nothing to eat from Sunday night until (sometime) Monday afternoon? That's asking for trouble. He'll probably refuse to get on the bed, let alone lie still for an hour.

Needless to say I have been on the phone to the hospital. The complication is that if the PET scan comes first it has to be conducted 48-hours before the Lutetium Dotetate scan; and if it's the other way round there has to be a 7 day gap. This is to prevent the tracer from the first scan interfering with the second. So we are just waiting to see if they can shuffle some other patient(s) around in order to get Adam scanned earlier in the day instead. If not they'd best be prepared ... it's not going to be pleasant. At least Alison will be taking him and not me I suppose.

Whilst it may seem like a triviality in the wider context of having a child with cancer, you'd be surprised just how many 'trivialities' there are that serve to make things that little bit more difficult than they need be.

No news is still no news ...

Still nothing substantive to report.To be honest I'm somewhat annoyed now, given my impatient disposition. Everybody seems to be in agreement that Adam needs to have these additional scans as soon as possible, and yet the wheels keep turning as slow as ever. We got the letter this week from Nuclear Medicine asking us to complete and return the form listing Adam's current medications - a prerequisite to them being able to book an appointment. I'm sure they are busy, I'm sure resources are stretched, I'm sure there are plenty of other patients that need fitting in, I'm sure Easter and the Royal Wedding has had an impact. And you know what? I DON'T CARE. JUST GET THE SCANS DONE SO WE CAN MOVE FORWARD.

It's looking very likely that we will go down the bone biopsy route. As much as I dislike the whole idea of grinding out a piece of Adam's thigh bone, it's the only way we'll know for sure what we're dealing with. If his cancer is still biologically active, but just smouldering, we are almost certainly going to end up in Philadelphia for six months (at least). It would be the best option under these circumstances, and we would need biopsy results in order for Adam to qualify for the trial anyway. My biggest fear is the PET and Lutetium scans are positive and lead us to biopsy, but the biopsy is inconclusive and we therefore can't proceed with the COG (Children's Oncology Group) trial in America. I don't quite know what we'd do in that case.

The little fella is still generally well; except for the fact that he doesn't attend school and has no hair he's a normal little boy. Though if he gets much taller I am going to have to stop referring to him as 'little'. When we checked a couple of weeks ago he was on the 75th percentile for his height (and 50th for his weight). Quite an achievement for a kid with neuroblastoma whose been subject to one of most intensive treatment regimens that modern medicine has to offer. Generally kids aren't supposed to grow, or put on weight, whilst in active treatment. His bloods are continuing to hold at the same levels. If only his platelets got some upward traction they would be as good as they have been since he started treatment.

No news is no news …

It’s that time of the week again, time for my regular update. There really isn’t anything to say on the treatment front. Nothing has moved forward since last week; we haven’t even received dates for the two additional scans yet. I’ve gone into hassle-and-chase mode on the basis that Adam is now D+80 post-transplant, and he will be off-treatment until we start in Germany or America. Without the scan results we can’t make a decision on whether or not to biopsy, let alone where we are heading off to. I’m just hoping that when we do get dates they are not two or three weeks hence, otherwise I’ll have to shift up into make-lots-of-noise-and-cause-lots-of-fuss mode. If needs must.

Adam has remained generally very well in himself, and the great weather over the Easter break definitely agreed with him. We were back down at the coast where the kids could get out on their bicycles, and spend time playing outside together, and with friends. On Saturday we took a trip to West Wittering where there is a lovely sandy beach. Needless to say it was absolutely mobbed, but we didn’t (as planned) arrive until later in the day so we missed the majority of the queues. Alan, Adam’s uncle, had brought an inflatable dinghy along, and naturally Adam was the first to have a go. I’m sure there were a few admiring glances as Adam stripped down to his pants and hickman line so we could wrap him in cling-film, to at least offer some protection against the sea water. He thoroughly enjoyed it, although he was a little unsure at first when he took a couple of bigger waves over the side on the way out. Thankfully we had no major catastrophes though; no capsize or boy overboard.

On the alternative treatment front we are currently having blood and stool samples analyzed by the lab once more now that Adam is well past high-dose. The results of these may give us further areas to work on in terms of Adam’s general health. Our goal is to make him better able to fight his cancer from within, and also to reduce side-effects and recovery time from conventional treatments. We should have the results in a week or two.

'Thank You' and 'Yes' ...

One thing we are incredibly fortunate about is that through the overwhelming generosity of people who have supported Adam's Appeal we don't have to worry about financial considerations at the moment. That said, once we leave the UK we are opening ourselves up to an indefinite period where we are liable for all treatment costs; and we know from the experience of others how quickly they can escalate. Not surprisingly the cost of taking Adam to America will be much higher than if we go to Germany. So thank you once again to everybody who has donated, supported, organised, collected, run, walked, cycled, baked, cooked, packed bags, washed cars, written letters, spoken to employers, and so much more besides. And thank you also to those people who have indicated that they are intending to help Adam's Appeal in the future. If you are sat wondering whether or not Adam (and I'm sad to say plenty of other children like him) still needs your help the answer I can assure you is a most emphatic 'yes'.

The plan to determine the plan ...

Apologies in advance because this is complicated. It's complicated because the situation we find ourselves in is complicated. As a consequence, it's more full of medical speak than ever before, but even if a lot of it goes over your head at least you'll (hopefully) get a flavour of what we are wrestling with right now. Think of it as more of a brain-dump than a thoughtfully constructed narrative ...

Here's where we're at; we are primarily considering two possible courses of action.

The first option is to take Adam to Germany for the ch14.18 + IL2 antibody (immunotherapy) trial. The primary role of antibody treatment is to consolidate remission, to mop up any minimal residual disease that remains undetectable but almost certainly exists and which if left will, sooner or later, result in a relapse. However, the scope of its use is being expanded to see whether or not antibodies can be effective in treating children who still have disease left after induction therapy. Unlike the groundbreaking U.S. trial (ch14.18 + IL2 + GM-CSF), that remains open only for children who achieve a remission having reached high-dose within nine months of diagnosis, the German trial is accepting children with refractory and relapsed neuroblastoma. Adam is eligible for, and has been accepted into, this trial if we decide it's the right thing to do.

The second option is to take Adam to America, most probably Philadelphia for a different type antibody trial. This involves ch14.18 + IL2 + GM-CSF, but the ch14.18 and IL2 are manufactured as a fusion protein. The cytokine (IL2) is fused onto the GD2 antibody (ch14.18) so it is taken direct to the neuroblastoma cells. The idea / hope is that this intrinsic coupling will result in a more potent and effective treatment. Results from a phase I trial of the ch14.18 + IL2 fusion protein alone were very encouraging, however a more recent phase II trial of the same was less so. The new trial, which opens in May, adds GM-CSF and 13-cis retonoic acid (accutane) as additional components alongside the fusion protein, hopefully resulting in improved efficacy compared to the previous trials.

There are other possibilities that we could look at more closely, but they are generally treatments in early-stages of development; phase I and phase II trials that may or may not become more standard treatments in the future. There may come a time when we turn to these as our main (or indeed only) hope, or if one of them emerges as a potential major breakthrough in neuroblastoma treatment, but I just don't see that we're there yet. One thing that is off the agenda at this moment in time, and whilst Adam's disease remains 'stable', is more intensive treatments that would have a significant adverse effect on Adam's fragile bone marrow. Having undergone both MIBG therapy and high-dose chemotherapy since the turn of the year his body needs time to recover. I would have liked to have been able to seriously consider humanized 3f8 antibody treatment at Memorial Sloan Kettering in New York, but this won't be available for another 3 to 6 months. Still it's something we may come back to in the future.

The obvious question then is why immunotherapy? Why are we considering putting Adam through a treatment whose primary (and only proven) purpose (thus far) has been to consolidate remission by clearing up minimal residual disease? It's a fair question. An important thing to keep aware of is there are no right answers to the situation we now face with Adam. There are no treatments proven to clear his remaining disease burden as seen by MIBG scan. There are, however, wrong answers. For example, all the evidence from the early phase trials of the ch14.18 + IL2 fusion protein indicate that it is ineffective against bulky tumours. If Adam had solid tumours or soft-tissue disease we shouldn't, and wouldn't, be considering it at all. Similarly, some of the oncolytic virus trials that are opening up in America involve direct injection of the virus into the tumour site, making them entirely inappropriate for the type of disease that Adam has. It's one of the defining characteristics of metastatic neuroblastoma that it has so many different manifestations; bone marrow infiltration, bone lesions which themselves can be either diffuse or well defined, infected lymph nodes, soft tissue disease, lung and liver metastases. A treatment that shows efficacy against one of these types of disease often has no benefit whatsoever against others.

The fundamental question, and the reason why we are most likely going down the immunotherapy route, is what are we hoping to achieve? Are we still trying to clear Adam's visible disease and get him to a point where he has clear scans? Or are we (for now at least) accepting that disease as stable, hoping it stays that way, and trying to prevent the cancer from taking hold elsewhere. It would be unrealistic to assume the cells that are observable on his MIBG scan are the only ones that remain in Adam's body. If a child who is NED (No Evidence of Disease) after induction therapy still has minimal residual disease that cannot be detected on any scans, it's safe to assume Adam has neuroblastoma cells lurking around in other places too. If these are not dealt with they could result in new areas of full-blown disease, and when neuroblastoma returns it often does so bigger and badder than before. Ideally, of course, we'd like something that might do both - clear the visible disease and wipe out the residual disease too - but that might be hoping for a little too much. There are no magic bullets.

The bottom line is there are no treatments that have been proven to clear children like Adam. The most effective, and most widely used, is I¹³¹ MIBG therapy and Adam has done that ... twice. Technically he is permitted to have a third administration, but given that the first two appear to have done nothing for him there would seem to be little justification in putting him through it yet again. If we assume, for one moment, that what lights up on Adam's scans is matured cells that have differentiated then immunotherapy becomes the obvious choice for what to do next. But we don't know that for certain, do we? And therein lies the crux of the matter. If it's MIBG-avid but not active neuroblastoma then choose whichever we believe will be the better at dealing with residual disease (we can't have the treatment that has been proven to deal with residual disease - it's just not available to Adam; not anywhere; not at any price). If it's MIBG-avid and it's active neuroblastoma the results from the phase I clinical trial would suggest the fusion protein is the best way to go in the first instance. It's possible we could do both treatments one after the other, but that very much depends on what adverse effects they have on Adam's body, which of course we won't know until we go through it.

So far it's as clear as mud then, and just to make matters worse only children with active disease are eligible for the new fusion protein immunotherapy trial. And whilst Adam has extensive MIBG uptake that is no longer (as per all my comments about mature or differentiated cells) conclusive proof of active disease. Which brings me to the title of this post; the plan to determine the plan ...

Adam is going to undergo two more scans; an FDG PET scan, and a Lutetium Dotatate scan. Whilst neither of these are currently part of the standard tests for neuroblastoma they may have something of relevance to offer in our current deliberations.  The FDG PET scan provides an image showing uptake of glucose, which is indicative of the metabolic activity in active cancer cells. The Lutetium Dotatate scan is similar to an MIBG scan but the radioactive tracer attaches to different receptors on the surface of neuroblastoma cells (somatostatin receptors for those that are interested!).

If both scans, and in particular the FDG PET scan, show positivity in the same way as the MIBG it will give us more evidence that what we are dealing with is active neuroblastoma. Then perhaps we would be better advised to head to America for the fusion protein immunotherapy trial in the first instance, and whatever else they can offer after that. Before we could do that, however, we would still require conclusive proof of active disease, and for that it would be necessary for Adam to undergo a bone biopsy. And for that biopsy to be positive for neuroblastoma. I hate the idea of a bone biopsy; the procedure itself, the pain and discomfort afterwards, the idea that performing it might in itself help re-ignite the cancer, and on top of all that we still might not get a conclusive result. Effectively we'll be on a hunting expedition trying to find some active neuroblastoma cells that will buy Adam a ticket to the U.S. trial.

On the other hand, if the additional scans are negative it would lead us to believe more strongly that the MIBG is being taken up by mature cells and we should be concentrating on immunotherapy as a means to deal with the minimal residual disease that undoubtedly exists within Adam's body. Whether that necessarily means Germany over America though is something of which I'm not entirely sure at the moment.

One final consideration to throw into the mix is this. As many of you know we've been pursuing a very different lifestyle for the past 9 months or so. One that involves us going organic as much as possible, cooking our food almost exclusively from scratch, eradicating the use of refined sugar and dairy from Adam's diet, using a daily routine of food supplements such as Avemar, Life Mel, Vitamin-D and Omega-3, removing harmful chemicals and toxins from our house, and much, much more besides. We know it's going to be very difficult to replicate this abroad. I refuse to believe it's impossible though, and to that extent I remain indifferent from a logistical perspective as to whether we end up going to Germany or America. We will take Adam to wherever we need to so that he can get the treatment that we believe is the best for him at this time. Our decision making process will be no different than it would have been had everything been available on our doorstep at the Royal Marsden. We will worry about the practicalities once we've got a plan ... the actual plan.

Written on location ...

Not much of substance to report this week really. We are away at the caravan at the moment getting some rest and relaxation (within the limits of what's possible with three children), and enjoying some family time together. Obviously I have taken a lot of time off work over the past year-and-a-half, but not much of it could be classed as 'holiday'.

I can't overstate how good having the caravan has been for us. It's such a lifeline to be able to get away from everything (but still be close enough to home to be within our comfort zone as far as Adam is concerned). The biggest benefit of all is we can live the same lifestyle, eat the same foods, do almost all the same things for Adam that we do at home. I just wish the kids would get with the program and stay in bed longer in the morning. Instead they fall naturally into the habit of going to bed later and yet waking up at the exact same time as usual. Bad, bad, bad.

Adam himself is doing great at the moment. I am aware that may seem at odds with recent posts, but apart from the first couple of months after diagnosis it's been like this throughout. If you lined up Adam's scans with a group of other NB children he might appear clinically to be in relatively bad shape. However, if you saw him, and observed his behaviour, you wouldn't suspect there was anything wrong with him. He's not quite back to how he was prior to high-dose, but he's not far off. Now the weather is improving, and the days are getting lighter, he's been spending more time playing outside with Jake and Jess. Consequently his general level of fitness, which took a big knock as he went through high-dose, has started to return. His energy levels and stamina are noticeably improved from what they were just a week or two ago.

On Tuesday we had a day at Chessington World of Adventures before travelling down here. We all had a great time, and Adam particularly enjoyed (1) me getting wet on bubble works after he'd assured me the water wasn't real, (2) me getting scared when he made the pink elephants go really high after he'd assured me we would stay low, and (3) me screaming with fear on the runaway train after he'd assured me that the second time round it only went 'really slowly'. You get the idea ... all in a paternal day's work.

Adam's blood counts have plateaued over the past fortnight. Hb is 10.3, neutrophils are 1.3 and platelets are holding around 80. Though not normal by any means the numbers are respectable considering how much treatment Adam's had, and we are now back to weekly bloods. I think in total Adam had 6 or 7 platelet transfusions since high-dose, which is a lot fewer than we would have forecast a few weeks ago.

We are still waiting for some more information from America before we can make a decision about where we go next. It's also been suggested that it might be useful for Adam to undergo some additional tests, although we don't know what, why or when yet! We're doing a good job of not fretting about how things are going to work out logistically over the next six to twelve months. It's going to be a pain in the proverbial for sure, but we'll muddle through and get it done. In the meantime we are just getting on with life one day at a time. Much like everybody else really.